Search results for: genetic disorder

Authors: Ora Geiger

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Reading is a cognitive process of deciphering visual signs to produce meaning. During the reading process, written information of symbols and signs is received in the person’s eye and processed in the brain. This definition is relevant to both the reading of letters and the reading of musical notation. But while the letters of the alphabet are signs determined arbitrarily, notes are recorded systematically on a staff, with the location of each note on the staff indicating its relative pitch. In this paper, the researcher specifies the characteristics of alphabet reading in comparison to musical notation reading, and discusses the question whether a person diagnosed with dyslexia will necessarily have difficulty in reading musical notes. Dyslexia is a learning disorder that makes it difficult to acquire alphabet-reading skills due to difficulties expressed in the identification of letters, spelling, and other language deciphering skills. In order to read, one must be able to connect a symbol with a sound and to join the sounds into words. A person who has dyslexia finds it difficult to translate a graphic symbol into the sound that it represents. When teaching reading to children diagnosed with dyslexia, the multi-sensory approach, supporting the activation and involvement of most of the senses in the learning process, has been found to be particularly effective. According to this approach, when most senses participate in the reading learning process, it becomes more effective. During years of experience, the researcher, who is a music specialist, has been following the music reading learning process of elementary school age students, some of them diagnosed with Dyslexia, while studying to play soprano (descant) recorder. She argues that learning music reading while studying to play a musical instrument is a multi-sensory experience by its nature. The senses involved are: sight, hearing, touch, and the kinesthetic sense (motion), which provides the brain with information on the relative positions of the body. In this way, the learner experiences simultaneously visual, auditory, tactile, and kinesthetic impressions. The researcher concludes that there should be no contra-indication for teaching standard music reading to children with dyslexia if an appropriate process is offered. This conclusion is based on two main characteristics of music reading: (1) musical notation system is a systematic, logical, relative set of symbols written on a staff; and (2) music reading learning connected with playing a musical instrument is by its nature a multi-sensory activity since it combines sight, hearing, touch, and movement. This paper describes music reading teaching procedures and provides unique teaching methods that have been found to be effective for students who were diagnosed with Dyslexia. It provides theoretical explanations in addition to guidelines for music education practices.

Keywords: alphabet reading, dyslexia, multisensory teaching method, music reading, recorder playing

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Authors: Peter C. St. John, Michael F. Crowley, Yannick J. Bomble

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Production of chemicals from engineered organisms in a batch culture typically involves a trade-off between productivity, yield, and titer. However, strategies for strain design typically involve designing mutations to achieve the highest yield possible while maintaining growth viability. Such approaches tend to follow the principle of designing static networks with minimum metabolic functionality to achieve desired yields. While these methods are computationally tractable, optimum productivity is likely achieved by a dynamic strategy, in which intracellular fluxes change their distribution over time. One can use multi-stage fermentations to increase either productivity or yield. Such strategies would range from simple manipulations (aerobic growth phase, anaerobic production phase), to more complex genetic toggle switches. Additionally, some computational methods can also be developed to aid in optimizing two-stage fermentation systems. One can assume an initial control strategy (i.e., a single reaction target) in maximizing productivity - but it is unclear how close this productivity would come to a global optimum. The calculation of maximum theoretical yield in metabolic engineering can help guide strain and pathway selection for static strain design efforts. Here, we present a method for the calculation of a maximum theoretical productivity of a batch culture system. This method follows the traditional assumptions of dynamic flux balance analysis: that internal metabolite fluxes are governed by a pseudo-steady state and external metabolite fluxes are represented by dynamic system including Michealis-Menten or hill-type regulation. The productivity optimization is achieved via dynamic programming, and accounts explicitly for an arbitrary number of fermentation stages and flux variable changes. We have applied our method to succinate production in two common microbial hosts: E. coli and A. succinogenes. The method can be further extended to calculate the complete productivity versus yield Pareto surface. Our results demonstrate that nearly optimal yields and productivities can indeed be achieved with only two discrete flux stages.

Keywords: A. succinogenes, E. coli, metabolic engineering, metabolite fluxes, multi-stage fermentations, succinate

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Authors: S. Hussain, C. Grieco, M. Brosnan

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Background and Aims: Autism is a complex neurobehavioural disorder, characterised by impairments in the development of language and communication skills. The study involved a state-of-art systematic review, in addition to qualitative data analysis, to establish the evidence for social stories as an intervention strategy for autistic children. An up-to-date review of the use of digital technologies in the delivery of interventions to autistic children was also carried out; to propose the efficacy of digital technologies and the use of social stories to improve intervention outcomes for autistic children. Methods: Two student researchers reviewed a range of randomised control trials and observational studies. The aim of the review was to establish if there was adequate evidence to justify recommending social stories to autistic patients. Students devised their own search strategies to be used across a range of search engines, including Ovid-Medline, Google Scholar and PubMed. Students then critically appraised the generated literature. Additionally, qualitative data obtained from a comprehensive online questionnaire on social stories was also thematically analysed. The thematic analysis was carried out independently by each researcher, using a ‘bottom-up’ approach, meaning contributors read and analysed responses to questions and devised semantic themes from reading the responses to a given question. The researchers then placed each response into a semantic theme or sub-theme. The students then joined to discuss the merging of their theme headings. The Inter-rater reliability (IRR) was calculated before and after theme headings were merged, giving IRR for pre- and post-discussion. Lastly, the thematic analysis was assessed by a third researcher, who is a professor of psychology and the director for the ‘Centre for Applied Autism Research’ at the University of Bath. Results: A review of the literature, as well as thematic analysis of qualitative data found supporting evidence for social story use. The thematic analysis uncovered some interesting themes from the questionnaire responses, relating to the reasons why social stories were used and the factors influencing their effectiveness in each case. However, overall, the evidence for digital technologies interventions was limited, and the literature could not prove a causal link between better intervention outcomes for autistic children and the use of technologies. However, they did offer valid proposed theories for the suitability of digital technologies for autistic children. Conclusions: Overall, the review concluded that there was adequate evidence to justify advising the use of social stories with autistic children. The role of digital technologies is clearly a fast-emerging field and appears to be a promising method of intervention for autistic children; however, it should not yet be considered an evidence-based approach. The students, using this research, developed ideas on social story interventions which aim to help autistic children.

Keywords: autistic children, digital technologies, intervention, social stories

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Authors: Dina Magnaye

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In the Philippines, the performance of the agricultural sector is gauged through crop productivity and returns from farm production rather than the biodiversity in the agricultural ecosystem. Agricultural development hinges on the overall goal of increasing productivity through intensive agriculture, monoculture system, utilization of high yielding varieties in plants, and genetic upgrading in animals. This merits an analysis of the role of agro-biodiversity in terms of increasing productivity, food security and economic returns from community-based pro-biodiversity enterprises. These enterprises conserve biodiversity while equitably sharing production income in the utilization of biological resources. The study aims to determine how community-based pro-biodiversity enterprises become instrumental in local climate change adaptation and agro-biodiversity conservation as input to local green economic development planning. It also involves an assessment of the role of agrobiodiversity in terms of increasing productivity, food security and economic returns from community-based pro-biodiversity enterprises. The perceptions of the local community members both in urban and upland rural areas on community-based pro-biodiversity enterprises were evaluated. These served as a basis in developing a planning modality that can be mainstreamed in the management of local green economic enterprises to benefit the environment, provide local income opportunities, conserve species diversity, and sustain environment-friendly farming systems and practices. The interviews conducted with organic farmer-owners, entrepreneur-organic farmers, and organic farm workers revealed that pro-biodiversity enterprise such as organic farming involved the cyclic use of natural resources within the carrying capacity of a farm; recognition of the value of tradition and culture especially in the upland rural area; enhancement of socio-economic capacity; conservation of ecosystems in harmony with nature; and climate change mitigation. The suggested planning modality for community-based pro-biodiversity enterprises for a green economy encompasses four (4) phases to include community resource or capital asset profiling; stakeholder vision development; strategy formulation for sustained enterprises; and monitoring and evaluation.

Keywords: agro-biodiversity, agro-biodiversity conservation, local green economy, organic farming, pro-biodiversity enterprise

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Authors: Josiane N. Muller, Allan K. R. Galardo, Tatiane A. Barbosa, Evan P. Ferro, Wellington M. Dos Santos, Ana Paula S. A. Correa, Edinaldo C. Rego, Jose B. P. Lima

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The susceptibility status of an insect population to any larvicide depends on several factors such includes genetic constitution, environmental conditions and others. The mosquito Aedes aegypti is the primary vector of three important viral diseases, Zika, Dengue, and Chikungunya. The frequent outbreaks of those diseases in different parts of Brazil demonstrate the importance of testing the susceptibility of vectors in different environments. Since the control of this mosquito leads to the control of disease, alternatives for vector control that value the different Brazilian environmental conditions are needed for effective actions. The aim of this study was to evaluate a new commercial formulation of Bacillus thuringiensis israelenses (DengueTech: Brazilian innovative technology) in the Brazilian Legal Amazon considering the climate conditions. Semi-field tests were conducted in the Institute of Scientific and Technological Research of the State of Amapa in two different environments, one in a shaded area and the other exposed to sunlight. The mosquito larvae were exposed to larvicide concentration and a control; each group was tested in three containers of 40 liters each. To assess persistence 50 third instar larvae of Aedes aegypti laboratory lineages (Rockefeller) and 50 larvae of Aedes aegypti collected in the municipality of Macapa, Brazil’s Amapa state, were added weekly and after 24 hours the mortality was assessed. In total 16 tests were performed, where 12 were done with replacement of water (1/5 of the volume, three times per week). The effectiveness of the product was determined through mortality of ≥ 80%, as recommend by the World Health Organization. The results demonstrated that high-water temperatures (26-35 °C) on the containers influenced the residual time of the product, where the maximum effect achieved was 21 days in the shaded area; and no effectiveness of 60 days was found in any of the tests, as expected according to the larvicide company. The test with and without water replacement did not present significant differences in the mortality rate. Considering the different environments and climate, these results stimulate the need to test larvicide and its effectiveness in specific environmental settings in order to identify the parameters required for better results. Thus, we see the importance of semi-field researches considering the local climate conditions for a successful control of Aedes aegypti.

Keywords: Aedes aegypti, bioassay, larvicida, vector control

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Authors: R. Hurtado-Ortiz, D. Clermont, M. Schüngel, C. Bizet, D. Smith, E. Stackebrandt

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Microbiological resources and their derivatives are the essential raw material for the advancement of human health, agro-food, food security, biotechnology, research and development in all life sciences. Microbial resources, and their genetic and metabolic products, are utilised in many areas such as production of healthy and functional food, identification of new antimicrobials against emerging and resistant pathogens, fighting agricultural disease, identifying novel energy sources on the basis of microbial biomass and screening for new active molecules for the bio-industries. The complexity of public collections, distribution and use of living biological material (not only living but also DNA, services, training, consultation, etc.) and service offer, demands the coordination and sharing of policies, processes and procedures. The Microbial Resource Research Infrastructure (MIRRI) is an initiative within the European Strategy Forum Infrastructures (ESFRI), bring together 16 partners including 13 European public microbial culture collections and biological resource centres (BRCs), supported by several European and non-European associated partners. The objective of MIRRI is to support innovation in microbiology by provision of a one-stop shop for well-characterized microbial resources and high quality services on a not-for-profit basis for biotechnology in support of microbiological research. In addition, MIRRI contributes to the structuring of microbial resources capacity both at the national and European levels. This will facilitate access to microorganisms for biotechnology for the enhancement of the bio-economy in Europe. MIRRI will overcome the fragmentation of access to current resources and services, develop harmonised strategies for delivery of associated information, ensure bio-security and other regulatory conditions to bring access and promote the uptake of these resources into European research. Data mining of the landscape of current information is needed to discover potential and drive innovation, to ensure the uptake of high quality microbial resources into research. MIRRI is in its Preparatory Phase focusing on governance and structure including technical, legal governance and financial issues. MIRRI will help the Biological Resources Centres to work more closely with policy makers, stakeholders, funders and researchers, to deliver resources and services needed for innovation.

Keywords: culture collections, microbiology, infrastructure, microbial resources, biotechnology

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Authors: Angelis P. Barlampas

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Objective: The confusion of terms is a common practice in many situations of the everyday life. But, in some circumstances, such as in medicine, the precise meaning of a word curries a critical role for the health of the patient. Fahr disease and Fahr syndrome are often falsely used interchangeably, but they are two different conditions with different physical histories of different etiology and different medical management. A case of the seldom Fahr disease is presented, and a comparison with the more common Fahr syndrome follows. Materials and method: A 72 years old patient came to the emergency department, complaining of some kind of non specific medal disturbances, like anxiety, difficulty of concentrating, and tremor. The problems had a long course, but he had the impression of getting worse lately, so he decided to check them. Past history and laboratory tests were unremarkable. Then, a computed tomography examination was ordered. Results: The CT exam showed bilateral, hyperattenuating areas of heavy, dense calcium type deposits in basal ganglia, striatum, pallidum, thalami, the dentate nucleus, and the cerebral white matter of frontal, parietal and iniac lobes, as well as small areas of the pons. Taking into account the absence of any known preexisting illness and the fact that the emergency laboratory tests were without findings, a hypothesis of the rare Fahr disease was supposed. The suspicion was confirmed with further, more specific tests, which showed the lack of any other conditions which could probably share the same radiological image. Differentiating between Fahr disease and Fahr syndrome. Fahr disease: Primarily autosomal dominant Symmetrical and bilateral intracranial calcifications The patient is healthy until the middle age Absence of biochemical abnormalities. Family history consistent with autosomal dominant Fahr syndrome :Earlier between 30 to 40 years old. Symmetrical and bilateral intracranial calcifications Endocrinopathies: Idiopathic hypoparathyroidism, secondary hypoparathyroidism, hyperparathyroidism, pseudohypoparathyroidism ,pseudopseudohypoparathyroidism, e.t.c The disease appears at any age There are abnormal laboratory or imaging findings. Conclusion: Fahr disease and Fahr syndrome are not the same illness, although this is not well known to the inexperienced doctors. As clinical radiologists, we have to inform our colleagues that a radiological image, along with the patient's history, probably implies a rare condition and not something more usual and prompt the investigation to the right route. In our case, a genetic test could be done earlier and reveal the problem, and thus avoiding unnecessary and specific tests which cost in time and are uncomfortable to the patient.

Keywords: fahr disease, fahr syndrome, CT, brain calcifications

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Authors: Nouha Bouayed Abdelmoula, Rim Louati, Nawel Abdellaoui, Balkiss Abdelmoula, Oldez Kaabi, Walid Smaoui, Samir Aloulou

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Background and Aims: Cardiofaciocutaneous syndrome (CFC) is an autosomal dominant disorder with the vast majority of cases arising by a new mutation of BRAF, MEK1, MEK2, or rarely, KRAS genes. Here, we report a rare Tunisian case of CFC syndrome for whom we identify SOS1 mutation. Methods: Genomic DNA was obtained from peripheral blood collected in an EDTA tube and extracted from leukocytes using the phenol/chloroform method according to standard protocols. High resolution melting (HRM) analysis for screening of mutations in the entire coding sequence of PTPN11 was conducted first. Then, HRM assays to look for hot spot mutations coding regions of the other genes of the RAS-MAPK pathway (RAt Sarcoma viral oncogene homolog Mitogen-Activated Protein Kinases Pathway): SOS1, SHOC2, KRAS, RAF1, KRAS, NRAS, CBL, BRAF, MEK1, MEK2, HRAS, and RIT1, were applied. Results: Heterozygous SOS1 point mutation clustered in exon 10, which encodes for the PH domain of SOS1, was identified: c.1655 G > A. The patient was a 9-year-old female born from a consanguineous couple. She exhibited pulmonic valvular stenosis as congenital heart disease. She had facial features and other malformations of Noonan syndrome, including macrocephaly, hypertelorism, ptosis, downslanting palpebral fissures, sparse eyebrows, a short and broad nose with upturned tip, low-set ears, high forehead commonly associated with bitemporal narrowing and prominent supraorbital ridges, short and/or webbed neck and short stature. However, the phenotype is also suggestive of CFC syndrome with the presence of more severe ectodermal abnormalities, including curly hair, keloid scars, hyperkeratotic skin, deep plantar creases, and delayed permanent dentition with agenesis of the right maxillary first molar. Moreover, the familial history of the patient revealed recurrent brain malignancies in the paternal family and epileptic disease in the maternal family. Conclusions: This case report of an overlapping RASopathy associated with SOS1 mutation and familial history of brain tumorigenesis is exceptional. The evidence suggests that RASopathies are truly cancer-prone syndromes, but the magnitude of the cancer risk and the types of cancer partially overlap.

Keywords: cardiofaciocutaneous syndrome, CFC, SOS1, brain cancer, germline mutation

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Authors: K. Thiel, P. Patrikainen, C. Nagy, D. Fitzpatrick, E.-M. Aro, P. Kallio

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Photosynthetic cyanobacteria have been recognized as potential future biotechnological hosts for the direct conversion of CO₂ into chemicals of interest using sunlight as the solar energy source. However, in order to develop commercially viable systems, the flux of electrons from the photosynthetic light reactions towards specified target chemicals must be significantly improved. The objective of the study was to investigate whether the autotrophic production efficiency of specified end-metabolites can be improved in engineered cyanobacterial cells by rescuing excited electrons that are normally lost to molecular oxygen due to the cyanobacterial flavodiiron protein Flv1/3. Natively Flv1/3 dissipates excess electrons in the photosynthetic electron transfer chain by directing them to molecular oxygen in Mehler-like reaction to protect photosystem I. To evaluate the effect of flavodiiron inactivation on autotrophic production efficiency in the cyanobacterial host Synechocystis sp. PCC 6803 (Synechocystis), sucrose was selected as the quantitative reporter and a representative of a potential end-product of interest. The concept is based on the native property of Synechocystis to produce sucrose as an intracellular osmoprotectant when exposed to high external ion concentrations, in combination with the introduction of a heterologous sucrose permease (CscB from Escherichia coli), which transports the sucrose out from the cell. In addition, cell growth, photosynthetic gas fluxes using membrane inlet mass spectrometry and endogenous storage compounds were analysed to illustrate the consequent effects of flv deletion on pathway flux distributions. The results indicate that a significant proportion of the electrons can be lost to molecular oxygen via Flv1/3 even when the cells are grown under high CO₂ and that the inactivation of flavodiiron activity can enhance the photosynthetic electron flux towards optionally available sinks. The flux distribution is dependent on the light conditions and the genetic context of the Δflv mutants, and favors the production of either sucrose or one of the two storage compounds, glycogen or polyhydroxybutyrate. As a conclusion, elimination of the native Flv1/3 reaction and concomitant introduction of an engineered product pathway as an alternative sink for excited electrons could enhance the photosynthetic electron flux towards the target endproduct without compromising the fitness of the host.

Keywords: cyanobacterial engineering, flavodiiron proteins, redirecting electron flux, sucrose

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Authors: Sigal Gat-Lazer, Ronny Geva, Dan Ramon, Eitan Gur, Daniel Stein

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Introduction: Eating disorders (ED) are common psychopathologies which involve distorted body image and eating disturbances. Binge-purge eating disorders (B/P ED) are characterized by repetitive events of binge eating followed by purges. Patients with B/P ED behavior may be seen as impulsive especially when relate to food stimulation and affective conditions. The current study included innovative modification of the day-night task targeted to assess inhibitory control among patients with B/P ED. Methods: This prospective study included 50 patients with B/P ED during acute phase of illness (T1) upon their admission to specialized ED department in tertiary center. 34 patients repeated the study towards discharge to ambulatory care (T2). Treatment effect was evaluated by BMI and emotional questionnaires regarding depression and anxiety by the Beck Depression Inventory and State Trait Anxiety Inventory questionnaires. Control group included 36 healthy controls with matched demographic parameters who performed both T1 and T2 assessments. The current modification is based on the emotional day-night task (EDNT) which involves five emotional stimulation added to the sun and moon pictures presented to participants. In the current study, we designed the food-emotional modification day night task (F-EDNT) food stimulations of egg and banana which resemble the sun and moon, respectively, in five emotional states (angry, sad, happy, scrambled and neutral). During this computerized task, participants were instructed to push on “day” bottom in response to moon and banana stimulations and on “night” bottom when sun and egg were presented. Accuracy (A) and reaction time (RT) were evaluated and compared between EDNT and F-EDNT as a reflection of participants’ inhibitory control. Results: Patients with B/P ED had significantly improved BMI, depression and anxiety scores on T2 compared to T1 (all p<0.001). Task performance was similar among patients and controls in the EDNT without significant A or RT differences in both T1 and T2. On F-EDNT during T1, B/P ED patients had significantly reduced accuracy in 4/5 emotional stimulation compared to controls: angry (73±25% vs. 84±15%, respectively), sad (69±25% vs. 80±18%, respectively), happy (73±24% vs. 82±18%, respectively) and scrambled (74±24% vs. 84±13%, respectively, all p<0.05). Additionally, patients’ RT to food stimuli was significantly faster compared to neutral ones, in both cry and neutral emotional stimulations (356±146 vs. 400±141 and 378±124 vs. 412±116 msec, respectively, p<0.05). These significant differences between groups as a function of stimulus type were diminished on T2. Conclusion: Having to process food related content, in particular in emotional context seems to be impaired in patients with B/P ED during the acute phase of their illness and elicits greater impulsivity. Innovative modification using such procedures seem to be sensitive to patients’ illness phase and thus may be implemented during screening and follow up through the clinical management of these patients.

Keywords: binge purge eating disorders, day night task modification, eating disorders, food related stimulations

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Authors: Abhimanyu Kumar

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The relationship between religion and medicine is much evident in the context of Buddhism. This paper is an attempt to look at the processes of social and cultural evolution of scientific creativity in the field of medicine and institutionalization of medical practices. The objective of the paper is to understand the Buddhist responses towards health as understood from the Vinaya Piṭaka and the Jātaka. This work is a result of the analysis of two important Buddhist texts: the Vinaya Piṭaka and the Jātaka. Broadly the Vinaya Piṭaka is concerned with the growth of Buddhist monasticism. The Vinaya Piṭaka is considered one of the most important sacred texts of the Buddhists, and contains rules for monastic life. These rules deal with such aspects as formal meetings of the saṃgha (monastery), expiation, confession, training, and legal questions. The Jātaka stories, on the other hand, are in the form of folk narratives, and provide a major source of medical consultation for all classes. These texts help us to ascertain the ‘proficiency and perceptions’ of the prevailing medical traditions. The Jātakas are a collection of 547 stories about the past lives of the Buddha, who is represented in anthropomorphic and animal form. The Jātaka connects itself between existing cognitive environments related to ethics and Buddhist didacticism. These stories are a reflection of the connection between the past and contemporary times (in the sense of time of creation of the story) as well. This is visible through the narrative strategy of the text, where every story is sub-divided into the story of the past and story of the present, and there is a significant identification element or connection that established at the end of each story. The minimal presence of philosophical content and the adoption of a narrative strategy make it possible for more of everyday life. This study gives me an opportunity to raise questions about how far were the body and mind closely interrelated in the Buddhist perceptions, and also did the society act like a laboratory for the Buddhists to practice healing activities? How far did religious responses to afflictions, be they leprosy or plague or anger, influence medical care; what impact did medical practitioners, religious authorities and the regulation of medical activity and practice have on healing the body and the mind; and, how has the healing environment been viewed. This paper is working with the idea that medical science in early India was not only for the curative purpose of diseases, but it fulfilled a greater cause of promoting, maintaining and restoring human health. In this regard, studying these texts gives an insight regarding religious responses to epidemics, from leprosy to plague, as well as to behavioral disorder such as anger. In other words, it deals with the idea about healing the body and healing the soul from a religious perspective.

Keywords: food for health, folk narratives, human body, materia medica, social sickness

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Authors: Kalangi Rodrigo

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Sri Lanka has been known as an island which has a diverse variety of prehistoric occupation among ecological zones. Defining the paleoecology of the past societies has been an archaeological thought developed in the 1960s. It is mainly concerned with the reconstruction from available geological and biological evidence of past biota, populations, communities, landscapes, environments, and ecosystems. Sri Lanka has dealt with this subject, and considerable research has been already undertaken. The fossil and material record of Sri Lanka’s Wet Zone tropical forests continues from c. 38,000–34,000 ybp. This early and persistent human fossil, technical, and cultural florescence, as well as a collection of well-preserved tropical-forest rock shelters with associated 'on-site' palaeoenvironmental records, makes Sri Lanka a central and unusual case study to determine the extent and strength of early human tropical forest encounters. Excavations carried out in prehistoric caves in the low country wet zone has shown that in the last 50,000 years, the temperature in the lowland rainforests has not exceeded 5°C. When taking Batadombalena alone, the entire seven layers have yielded an uninterrupted occupation of Acavus sp and Canerium zeylanicum, a plant that grows in the middle of the rainforest. Acavus, which is highly sensitive to rainforest ecosystems, has been well documented in many of the lowland caves, confirming that the wetland rainforest environment has remained intact at least for the last 50,000 years. If the dry and arid conditions in the upper hills regions affected the wet zone, the Tufted Gray Lunger (semnopithecus priam), must also meet with the prehistoric caves in the wet zone thrown over dry climate. However, the bones in the low country wet zone do not find any of the fragments belonging to Turfed Gray Lunger, and prehistoric human consumption is bestowed with purple-faced leaf monkey (Trachypithecus vetulus) and Toque Macaque (Macaca Sinica). The skeletal remains of Lyriocephalus scutatus, a full-time resident in rain forests, have also been recorded among lowland caves. But, in zoological terms, these remains may be the remains of the Barking deer (Muntiacus muntjak), which is currently found in the wet zone. For further investigations, the mtDNA test of genetic diversity (Bottleneck effect) and pollen study from lowland caves should determine whether the wet zone climate has persisted over the last 50,000 years, or whether the dry weather affected in the mountainous region has invaded the wet zone.

Keywords: paleoecology, prehistory, zooarchaeology, reconstruction, palaeo-climate

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Authors: Katri K. Cornelissen, Lise Gulli Brokjob, Kristofor McCarty, Jiri Gumancik, Martin J. Tovee, Piers L. Cornelissen

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Recent research has shown that body size estimation of healthy women is driven by independent attitudinal and perceptual components. The attitudinal component represents psychological concerns about body, coupled to low self-esteem and a tendency towards depressive symptomatology, leading to over-estimation of body size, independent of the Body Mass Index (BMI) someone actually has. The perceptual component is a normal bias known as contraction bias, which, for bodies is dependent on actual BMI. Women with a BMI less than the population norm tend to overestimate their size, while women with a BMI greater than the population norm tend to underestimate their size. Women whose BMI is close to the population mean are most accurate. This is indexed by a regression of estimated BMI on actual BMI with a slope less than one. It is well established that body dissatisfaction, i.e. an attitudinal distortion, leads to body size overestimation in eating disordered individuals. However, debate persists as to whether women with eating disorders may also suffer a perceptual body distortion. Therefore, the current study was set to ask whether women with eating disorders exhibit the normal contraction bias when they estimate their own body size. If they do not, this would suggest differences in the way that women with eating disorders process the perceptual aspects of body shape and size in comparison to healthy controls. 100 healthy controls and 33 women with a history of eating disorders were recruited. Critically, it was ensured that both groups of participants represented comparable and adequate ranges of actual BMI (e.g. ~18 to ~40). Of those with eating disorders, 19 had a history of anorexia nervosa, 6 bulimia nervosa, and 8 OSFED. 87.5% of the women with a history of eating disorders self-reported that they were either recovered or recovering, and 89.7% of them self-reported that they had had one or more instances of relapse. The mean time lapsed since first diagnosis was 5 years and on average participants had experienced two relapses. Participants were asked to fill number of psychometric measures (EDE-Q, BSQ, RSE, BDI) to establish the attitudinal component of their body image as well as their tendency to internalize socio-cultural body ideals. Additionally, participants completed a method of adjustment psychophysical task, using photorealistic avatars calibrated for BMI, in order to provide an estimate of their own body size and shape. The data from the healthy controls replicate previous findings, revealing independent contributions to body size estimation from both attitudinal and perceptual (i.e. contraction bias) body image components, as described above. For the eating disorder group, once the adequacy of their actual BMI ranges was established, a regression of estimated BMI on actual BMI had a slope greater than 1, significantly different to that from controls. This suggests that (some) eating disordered individuals process the perceptual aspects of body image differently from healthy controls. It therefore is necessary to develop interventions which are specific to the perceptual processing of body shape and size for the management of (some) individuals with eating disorders.

Keywords: body image distortion, perception, recovery, relapse, BMI, eating disorders

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Authors: Michelle Belinda S. Weerawardana, Gobika Thiripuranathar, Priyani A. Paranagama

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Most of fresh vegetables and fruits available in the retail markets undergo a physiological disorder in its appearance and coloration, which indeed discourages consumer purchase. A loss of millions of dollars yearly to the food industry had been due to this pronounced color reaction called Enzymatic Browning which is driven due to the catalytic activity by an oxidoreductase enzyme, polyphenol oxidase (PPO). The enzyme oxidizes the phenolic compounds which are abundantly available in fruits and vegetables as substrates into quinones, which could react with proteins in its surrounding to generate black pigments, called melanins, which are highly UV-active compounds. Annona muricata (Katu anoda) and Musa acuminata (Ash plantains) is a fruit and a vegetable consumed by Sri Lankans widely due to their high nutritional values, medicinal properties and economical importance. The objective of the present study was to evaluate and determine the effective natural anti-browning inhibitors that could prevent PPO activity in the selected fruit and vegetable. Enzyme extracts from Annona muricata (Katu anoda) and Musa acuminata (Ash plantains), were prepared by homogenizing with analytical grade acetone, and pH of each enzyme extract was maintained at 7.0 using a phosphate buffer. The extracts of inhibitors were prepared using powdered ginger rhizomes and essential oil from the bark of Cinnamomum zeylanicum. Water extracts of ginger were prepared and the essential oil from Ceylon cinnamon bark was extracted using steam distillation method. Since the essential oil is not soluble in water, 0.1µl of cinnamon bark oil was mixed with 0.1µl of Triton X-100 emulsifier and 5.00 ml of water. The effect of each inhibitor on the PPO activity was investigated using catechol (0.1 mol dm-3) as the substrate and two samples of enzyme extracts prepared. The dosages of the prepared Cinnamon bark oil, and ginger (2 samples) which were used to measure the activity were 0.0035 g/ml, 0.091 g/ml and 0.087 g/ml respectively. The measurements of the inhibitory activity were obtained at a wavelength of 525 nm using the UV-visible spectrophotometer. The results evaluated thus revealed that % inhibition observed with cinnamon bark oil, and ginger for Annona muricata was 51.97%, and 60.90% respectively. The effects of cinnamon bark oil, and ginger extract on PPO activity of Musa acuminata were 49.51%, and 48.10%. The experimental findings thus revealed that Cinnamomum zeylanicum bark oil was a more effective inhibitor for PPO enzyme present in Musa acuminata and ginger was effective for PPO enzyme present in Annona muricata. Overall both the inhibitors were proven to be more effective towards the activities of PPO enzyme present in both samples. These inhibitors can thus be corroborated as effective, natural, non-toxic, anti-browning extracts, which when added to the above fruit and vegetable will increase the shelf life and also the acceptance of the product by the consumers.

Keywords: anti-browning agent, enzymatic browning, inhibitory activity, polyphenol oxidase

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Authors: Savitha Janakiraman, Shivakumar M. C

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Anidulafungin, an advanced class of antifungal agent used for the treatment of chronic fungal infections, is derived from Echinocandin B nucleus, an intermediate metabolite of Echinocandin B produced by Aspergillus nidulans. The enzyme acylase derived from the fermentation broth of Actinoplanes utahensis (NRRL 12052) plays a key role in the bioconversion of echinocandin B to echinocandin B nucleus. The membrane-bound nature of acylase and low levels of expression contributes to the rate-limiting process of enzymatic deacylation, hence low yields of ECB nucleus and anidulafungin. In the present study, this is addressed through novel genetic engineering approaches of overexpression and heterologous expression studies, immobilization of whole cells of Actinoplanes utahensis (NRRL 12052) and Co-cultivation studies. Overexpression of the acylase gene in Actinoplanes utahensis (NRRL 12052) was done by increasing the gene copy number to increase the echinocandin B nucleus production. Echinocandin B acylase gene, under the control of a PermE* promoter, was cloned in pSET152 vector and introduced into Actinoplanes utahensis (NRRL12052) by a ɸC31-directed site-specific recombination method. The resultant recombinant strain (C2-18) showed a 3-fold increase in acylase expression, which was confirmed by HPLC analysis. Pichia pastoris is one of the most effective and versatile host systems for the production of heterologous proteins. The ECB acylase gene was cloned into pPIC9K vector with AOX1 promoter and was transformed into Pichia pastoris (GS115). The acylase expression was confirmed by protein expression and bioconversion studies. The heterologous expression of acylase in Pichia pastoris, is a milestone in the development of antifungals. Actively growing cells of Actinoplanes utahensis (NRRL 12052) were immobilized and tested for bioconversion ability which showed >90% conversion in each cycle. The stability of immobilized cell beads retained the deacylation ability up to 60 days and reusability was confirmed up to 4 cycles. The significant findings from the study have revealed that immobilization of whole cells of Actinoplanes utahensis (NRRL 12052) could be an alternative option for bioconversion of echinocandin B to echinocandin B nucleus, which has not been reported to date. The concept of co-cultivation of Aspergillus nidulans and Actinoplanes utahensis strains for the production of the echinocandin B nucleus was also carried out in order to produce echinocandin B nucleus. The process completely reduced the ECB purification step and, therefore, could be recommended as an ingenious method to improve the yield of the ECB nucleus.

Keywords: acylase, anidulafungin, antifungals, Aspergillus nidulans

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Authors: Valencia Fernandes, Dharmendra Kumar Khatri, Shashi Bala Singh

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Background and Aim: Epigenetics are the inaudible signatures of several pathological processes in the brain. This study understands the influence of DNA methylation, a major epigenetic modification, in the prefrontal cortex and hippocampus of the diabetic brain and its notable effect on the cellular chaperones and synaptic proteins. Method: Chronic high fat diet and STZ-induced diabetic mice were studied for cognitive dysfunction, and global DNA methylation, as well as DNA methyltransferase (DNMT) activity, were assessed. Further, the cellular chaperones and synaptic proteins were examined using DNMT inhibitor, 5-aza-2′-deoxycytidine (5-aza-dC)-via intracerebroventricular injection. Moreover, % methylation of these synaptic proteins were also studied so as to correlate its epigenetic involvement. Computationally, its interaction with the DNMT enzyme were also studied using bioinformatic tools. Histological studies for morphological alterations and neuronal degeneration were also studied. Neurogenesis, a characteristic marker for new learning and memory formation, was also assessed via the BrdU staining. Finally, the most important behavioral studies, including the Morris water maze, Y maze, passive avoidance, and Novel object recognition test, were performed to study its cognitive functions. Results: Altered global DNA methylation and increased levels of DNMTs within the nucleus were confirmed in the cortex and hippocampus of the diseased mice, suggesting hypermethylation at a genetic level. Treatment with AzadC, a global DNA demethylating agent, ameliorated the protein and gene expression of the cellular chaperones and synaptic fidelity. Furthermore, the methylation analysis profile showed hypermethylation of the hsf1 protein, a master regulator for chaperones and thus, confirmed the epigenetic involvement in the diseased brain. Morphological improvements and decreased neurodegeneration, along with enhanced neurogenesis in the treatment group, suggest that epigenetic modulations do participate in learning and memory. This is supported by the improved behavioral test battery seen in the treatment group. Conclusion: DNA methylation could possibly accord in dysregulating the memory-associated proteins at chronic stages in type 2 diabetes. This could suggest a substantial contribution to the underlying pathophysiology of several metabolic syndromes like insulin resistance, obesity and also participate in transitioning this damage centrally, such as cognitive dysfunction.

Keywords: epigenetics, cognition, chaperones, DNA methylation

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Authors: Idowu R. Akomolafe, Naven Chetty

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Background: The widespread medical application of ionizing radiation has raised public concern about radiation exposure and, thus, associated cancer risk. The production of reactive oxygen species and free radicals as a result of radiation exposure can cause severe damage to deoxyribonucleic acid (DNA) of cells, thus leading to biological effect. Radiotherapy is an excellent modality in the treatment of cancerous cells, comes with a few challenges. A significant challenge is the exposure of healthy cells surrounding the tumour to radiation. The last few decades have witnessed lots of attention shifted to plants, herbs, and natural product as an alternative to synthetic compound for radioprotection. Thus, the study investigated the radioprotective efficacy of Costus afer against whole-body radiation-induced haematological, histopathological disorder in mice. Materials and Method: Fifty-four mice were randomly divided into nine groups. Animals were pretreated with the extract of Costus afer by oral gavage for six days before irradiation. Control: 6 mice received feed and water only; 6 mice received feed, water, and 3Gy; 6 mice received feed, water, and 6Gy; experimental: 6 mice received 250 mg/kg extract; 6 mice received 500 mg/kg extract; 6 mice received 250 mg/kg extract and 3Gy; 6 mice received 500 mg/kg extract and 3Gy; 6 mice received 250 mg/kg extract and 6Gy; 6 mice received 500 mg/kg extract and 6Gy in addition to feeding and water. The irradiation was done at the Radiotherapy and Oncology Department of Grey's Hospital using linear accelerator (LINAC). Thirty-six mice were sacrificed by cervical dislocation 48 hours after irradiation, and blood was collected for haematology tests. Also, the liver and kidney of the sacrificed mice were surgically removed for histopathology tests. The remaining eighteen (18) mice were used for mortality and survival studies. Data were analysed by one-way ANOVA, followed by Tukey's multiple comparison test. Results: Prior administration of Costus afer extract decreased the symptoms of radiation sickness and caused a significant delay in the mortality as demonstrated in the experimental mice. The first mortality was recorded on day-5 post irradiation, and this happened to the group E- that is, mice that received 6Gy but no extract. There was significant protection in the experimental mice, as demonstrated in the blood counts against hematopoietic and gastrointestinal damage when compared with the control. The protection was seen in the increase in blood counts of experimental animals and the number of survivor. The protection offered by Costus afer may be due to its ability to scavenge free radicals and restore gastrointestinal and bone marrow damage produced by radiation. Conclusions: The study has demonstrated that exposure of mice to radiation could cause modifications in the haematological and histopathological parameters of irradiated mice. However, the changes were relieved by the methanol extract of Costus afer, probably through its free radical scavenging and antioxidant properties.

Keywords: costus afer, hematological, mortality, radioprotection, radiotherapy

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Authors: J. H. Bang, H. J. Baek, K. I. Kim, B. J. Lee, H. J. Jung, H. J. Jang, S. K. Jung

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Asthma is a chronic inflammatory lung disease characterized by airway hyper responsiveness (AHR), airway obstruction and airway wall remodeling responsible for significant morbidity and mortality worldwide. Genetic and environment factors may result in asthma, but there are no the exact causes of asthma. Chungpye-tang (CPT) has been prescribed as a representative aerosol agent for patients with dyspnea, cough and phlegm in the respiratory clinic at Kyung Hee Korean Medicine Hospital. This Korean herbal medicines have the effect of dispelling external pathogen and dampness pattern. CPT is composed of 4 species of herbal medicines. The 4 species of herbal medicines are Ephedrae herba, Pogostemonis(Agatachis) herba, Caryophylli flos and Zingiberis rhizoma crudus. CPT suppresses neutrophil infiltration and the production of pro-inflammatory cytokines in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Moreover, the anti-inflammatory effects of CPT on a mouse model of Chronic Obstructive Pulmonary Disease (COPD) was proved. Activation of the NF-κB has been proven that it plays an important role in inflammation via inducing transcription of pro-inflammatory genes. Over-expression of NF-κB has been believed be related to many inflammatory diseases such as arthritis, gastritis, asthma and COPD. So we firstly hypothesize whether CPT has an anti-inflammatory effect on asthmatic human airway epithelial tissue via inhibiting NF-κB pathway. In this study, CPT was extracted with distilled water for 3 hours at 100°C. After process of filtration and evaporation, it was freeze dried. And asthmatic human lung tissues were provided by MatTek Corp. We investigated the precise mechanism of the anti-inflammatory effect of CPT by western blotting analysis. We observed whether the decoction extracts could reduce NF-κB activation, COX-2 protein expression and NF-κB-mediated pro-inflammatory cytokines such as TNF-α, eotaxin, IL-4, IL-9 and IL-13 in asthmatic human lung tissue. As results of this study, there was a trend toward decreased NF-κB expression in asthmatic human airway epithelial tissue. We found that the inhibition effects of CPT on COX-2 expression was not determined. IL-9 and IL-13 secretion was significantly reduced in the asthmatic human lung tissue treated with CPT. Overall, our results indicate that CPT has an anti-inflammatory effect through blocking the signaling pathway of NF-κB, thereby CPT may be a potential remedial agent for allergic asthma.

Keywords: Chungpye-tang, allergic asthma, asthmatic human airway epithelial tissue, nuclear factor kappa B (NF-κB) pathway, COX-2

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Authors: Franco Van De Velde, Debora Esposito, Maria E. Pirovani, Mary A. Lila

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The physiology of various inflammatory diseases is a complex process mediated by inflammatory and immune cells such as macrophages and monocytes. Chronic inflammation, as observed in many cardiovascular and autoimmune disorders, occurs when the low-grade inflammatory response fails to resolve with time. Because of the complexity of the chronic inflammatory disease, major efforts have focused on identifying novel anti-inflammatory agents and dietary regimes that prevent the pro-inflammatory process at the early stage of gene expression of key pro-inflammatory mediators and cytokines. The ability of the extracts of three blackberry cultivars (‘Jumbo’, ‘Black Satin’ and ‘Dirksen’), and one strawberry cultivar (‘Camarosa’) to inhibit four well-known genetic biomarkers of inflammation: inducible nitric oxide synthase (iNOS), cyclooxynase-2 (Cox-2), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in an in vitro lipopolysaccharide-stimulated murine RAW 264.7 macrophage model were investigated. Moreover, the effect of latter extracts on the intracellular reactive oxygen species (ROS) and nitric oxide (NO) production was assessed. Assay was conducted with 50 µg/mL crude extract concentration, an amount that is easily achievable in the gastrointestinal tract after berries consumption. The mRNA expression levels of Cox-2 and IL-6 were reduced consistently (more than 30%) by extracts of ‘Jumbo’ and ‘Black Satin’ blackberries. Strawberry extracts showed high reduction in mRNA expression levels of IL-6 (more than 65%) and exhibited moderate reduction in mRNA expression of Cox-2 (more than 35%). The latter behavior mirrors the intracellular ROS production of the LPS stimulated RAW 264.7 macrophages after the treatment with blackberry ‘Black Satin’ and ‘Jumbo’, and strawberry ‘Camarosa’ extracts, suggesting that phytochemicals from these fruits may play a role in the health maintenance by reducing oxidative stress. On the other hand, effective inhibition in the gene expression of IL-1β and iNOS was not observed by any of blackberry and strawberry extracts. However, suppression in the NO production in the activated macrophages among 5–25% was observed by ‘Jumbo’ and ‘Black Satin’ blackberry extracts and ‘Camarosa’ strawberry extracts, suggesting a higher NO suppression property by phytochemicals of these fruits. All these results suggest the potential beneficial effects of studied berries as functional foods with antioxidant and anti-inflammatory roles. Moreover, the underlying role of phytochemicals from these fruits in the protection of inflammatory process will deserve to be further explored.

Keywords: cyclooxygenase-2, functional foods, interleukin-6, reactive oxygen species

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Authors: Maha J. Balgoon, Gehan A. Raouf, Safaa Y. Qusti, Soad S. Ali

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The main cause of Alzheimer disease (AD) was believed to be mainly due to the accumulation of free radicals owing to oxidative stress (OS) in brain tissue. The mechanism of the neurotoxicity of Aluminum chloride (AlCl3) induced AD in hippocampus Albino wister rat brain tissue, the curative & the protective effects of Lipidium sativum group (LS) water extract were assessed after 8 weeks by attenuated total reflection spectroscopy ATR-IR and histologically by light microscope. ATR-IR results revealed that the membrane phospholipid undergo free radical attacks, mediated by AlCl3, primary affects the polyunsaturated fatty acids indicated by the increased of the olefinic -C=CH sub-band area around 3012 cm-1 from the curve fitting analysis. The narrowing in the half band width(HBW) of the sνCH2 sub-band around 2852 cm-1 due to Al intoxication indicates the presence of trans form fatty acids rather than gauch rotomer. The degradation of hydrocarbon chain to shorter chain length, increasing in membrane fluidity, disorder and decreasing in lipid polarity in AlCl3 group were indicated by the detected changes in certain calculated area ratios compared to the control. Administration of LS was greatly improved these parameters compared to the AlCl3 group. Al influences the Aβ aggregation and plaque formation, which in turn interferes to and disrupts the membrane structure. The results also showed a marked increase in the β-parallel and antiparallel structure, that characterize the Aβ formation in Al-induced AD hippocampal brain tissue, indicated by the detected increase in both amide I sub-bands around 1674, 1692 cm-1. This drastic increase in Aβ formation was greatly reduced in the curative and protective groups compared to the AlCl3 group and approaches nearly the control values. These results were supported too by the light microscope. AlCl3 group showed significant marked degenerative changes in hippocampal neurons. Most cells appeared small, shrieked and deformed. Interestingly, the administration of LS in curative and protective groups markedly decreases the amount of degenerated cells compared to the non-treated group. Also the intensity of congo red stained cells was decreased. Hippocampal neurons looked more/or less similar to those of control. This study showed a promising therapeutic effect of Lipidium sativum group (LS) on AD rat model that seriously overcome the signs of oxidative stress on membrane lipid and restore the protein misfolding.

Keywords: aluminum chloride, alzheimer disease, ATR-IR, Lipidium sativum

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Authors: Apurva Singh, S. P. Jaiswar, Apala Priyadarshini, Akancha Pandey

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Objective: The aim of this study is to find the association of PON1 gene polymorphism with pesticides In RPL subjects. Background: Recurrent pregnancy loss (RPL) is defined as three or more sequential abortions before the 20th week of gestation. Pesticides and its derivatives (organochlorine and organophosphate) are proposed to accommodate a ruler chemical for RPL in the sub-humid region of India. The paraoxonase-1 enzyme (PON1) plays an important role in the toxicity of some organophosphate pesticides, with low PON1 activity being associated with higher pesticide sensitivity Methodology: This is a case-control study done in Department of Obstetrics & Gynaecology & Department of Biochemistry, K.G.M.U, Lucknow, India. The subjects were enrolled after fulfilling the inclusion & exclusion criteria. Inclusion criteria: Cases- Subject having two or more spontaneous abortions & Control- Healthy female having one or more alive child was selected. Exclusion criteria: Cases & Control- Subject having the following disease will be excluded from the study Diabetes mellitus, Hypertension, Tuberculosis, Immunocompromised patients, any endocrine disorder and genital, colon or breast cancer any other malignancies. Blood samples were collected in EDTA tubes from cases & healthy control women & genomic DNA was extracted by phenol-chloroform method. The estimation of pesticides residue from blood was done by HPLC. Biochemical estimation was also performed. Genotyping of PON1 gene polymorphism was performed by RFLP. Statistical analysis of the data was performed using the SPSS16.3 software. Results: A sum of total 14 pesticides (12 organochlorine and 2 organophosphate) selected on the basis of their persistent nature and consumption rate. The significant level of pesticide (ppb) estimated by the Mann whiney test and it was found to be significant at higher level of β-HCH (p:0.04), γ-HCH (p:0.001), δ-HCH (p: 0.002), chloropyrifos (p:0.001), pp-DDD (p:0.001) and fenvalrate (p: 0.001) in case group compare to its control. The level of antioxidant enzymes were found to be significantly decreased among the cases. Wild homozygous TT was more frequent and prevalent among control groups. However, heterozygous group (Tt) was more in cases than control groups (CI-0.3-1.3) (p=0.06). Conclusion: Higher levels of pesticides with endocrine disrupting potential in cases indicate the possible role of these compounds as one of the causes of recurrent pregnancy loss. Possibly, increased pesticide level appears to indicate increased levels of oxidative damage that has been associated with the possible cause of Recurrent Miscarriage, it may reflect indirect evidence of toxicity rather than the direct cause. Since both factors are reported to increase risk, individuals with higher levels of these 'Toxic compounds' especially in 'high-risk genotypes' might be more susceptible to recurrent pregnancy loss.

Keywords: paraoxonase, pesticides, PON1, RPL

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Authors: Yesim Sucullu Karadag, Pinar Kurt, Sule Bilen, Nese Subutay Oztekin, Fikri Ak

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Background: Primary cervical dystonia is thought to be a purely motor disorder. But recent studies revealed that patients with dystonia had additional non-motor features. Sensory and psychiatric disturbances could be included into the non-motor spectrum of dystonia. The Basal Ganglia receive inputs from all cortical areas and throughout the thalamus project to several cortical areas, thus participating to circuits that have been linked to motor as well as sensory, emotional and cognitive functions. However, there are limited studies indicating cognitive impairment in patients with cervical dystonia. More evidence is required regarding neurocognitive functioning in these patients. Objective: This study is aimed to investigate neurocognitive profile of cervical dystonia patients in comparison to healthy controls (HC) by employing a detailed set of neuropsychological tests in addition to self-reported instruments. Methods: Totally 29 (M/F: 7/22) cervical dystonia patients and 30 HC (M/F: 10/20) were included into the study. Exclusion criteria were depression and not given informed consent. Standard demographic, educational data and clinical reports (disease duration, disability index) were recorded for all patients. After a careful neurological evaluation, all subjects were given a comprehensive battery of neuropsychological tests: Self report of neuropsychological condition (by visual analogue scale-VAS, 0-100), RAVLT, STROOP, PASAT, TMT, SDMT, JLOT, DST, COWAT, ACTT, and FST. Patients and HC were compared regarding demographic, clinical features and neurocognitive tests. Also correlation between disease duration, disability index and self report -VAS were assessed. Results: There was no difference between patients and HCs regarding socio-demographic variables such as age, gender and years of education (p levels were 0.36, 0.436, 0.869; respectively). All of the patients were assessed at the peak of botulinum toxine effect and they were not taking an anticholinergic agent or benzodiazepine. Dystonia patients had significantly impaired verbal learning and memory (RAVLT, p<0.001), divided attention and working memory (ACTT, p<0.001), attention speed (TMT-A and B, p=0.008, 0.050), executive functions (PASAT, p<0.001; SDMT, p= 0.001; FST, p<0.001), verbal attention (DST, p=0.001), verbal fluency (COWAT, p<0.001), visio-spatial processing (JLOT, p<0.001) in comparison to healthy controls. But focused attention (STROOP-spontaneous correction) was not different between two groups (p>0.05). No relationship was found regarding disease duration and disability index with any neurocognitive tests. Conclusions: Our study showed that neurocognitive functions of dystonia patients were worse than control group with the similar age, sex, and education independently clinical expression like disease duration and disability index. This situation may be the result of possible cortical and subcortical changes in dystonia patients. Advanced neuroimaging techniques might be helpful to explain these changes in cervical dystonia patients.

Keywords: cervical dystonia, neurocognitive impairment, neuropsychological test, dystonia disability index

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Authors: Nalini Kaul, Barrie Drewitt, Elsie Kohoot

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Hyperpigmentation is the third most common pigmentary disorder where dermatologic treatment is sought. It affects all ages resulting in skin darkening because of melanin accumulation. An uneven skin tone because of either exposure to the sun (solar lentigos/age spots/sun spots or skin disruption following acne, or rashes (post-inflammatory hyperpigmentation -PIH) or hormonal changes (melasma) can lead to significant psychosocial impairment. Dyschromia is a result of various alterations in biochemical processes regulating melanogenesis. Treatments include the daily use of sunscreen with lightening, brightening, and exfoliating products. Depigmentation is achieved by various depigmenting agents: common examples are hydroquinone, arbutin, azelaic acid, aloesin, mulberry, licorice extracts, kojic acid, niacinamide, ellagic acid, arbutin, green tea, turmeric, soy, ascorbic acid, and tranexamic acid. These agents affect pigmentation by interfering with mechanisms before, during, and after melanin synthesis. While immediate correction is much sought after, patience and diligence are key. Our objective was to assess the effects of a facial product with pigmentation treatment and UV protection in 35 healthy F (35-65y), meeting the study criteria. Subjects with mild to moderate hyperpigmentation and fine lines with no use of skin-lightening products in the last six months or any dermatological procedures in the last twelve months before the study started were included. Efficacy parameters included expert clinical grading for hyperpigmentation, radiance, skin tone & smoothness, fine lines, and wrinkles bioinstrumentation (Corneometer®, Colorimeter®), digital photography and imaging (Visia-CR®), and self-assessment questionnaires. Safety included grading for erythema, edema, dryness & peeling and self-assessments for itching, stinging, tingling, and burning. Our results showed statistically significant improvement in clinical grading scores, bioinstrumentation, and digital photos for hyperpigmentation-brown spots, fine lines/wrinkles, skin tone, radiance, pores, skin smoothness, and overall appearance compared to baseline. The product was also well-tolerated and liked by subjects. Conclusion: Facial hyperpigmentation is of great concern, and treatment strategies are increasingly sought. Clinical trials with both subjective and objective assessments, imaging analyses, and self-perception are essential to distinguish evidence-based products. The multifunctional cosmetic product tested in this clinical study showed efficacy, tolerability, and subject satisfaction in reducing hyperpigmentation and global photoaging.

Keywords: hyperpigmentation; photoaging, clinical testing, expert visual evaluations, bio-instruments

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Authors: Christine P. Gibson, Ramona Alex, Michael Farney, Johana Vallejo-Elias, Mitra Esfandiarei

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Aortic aneurysm is the leading cause of death in Marfan syndrome (MFS), a connective tissue disorder caused by mutations in fibrillin-1 gene (FBN1). MFS aneurysm is characterized by weakening of the aortic wall due to elastin fibers fragmentation and disorganization. The above-average height and distinct physical features make young adults with MFS desirable candidates for competitive sports; but little is known about the exercise limit at which they will be at risk for aortic rupture. On the other hand, aerobic cardiovascular exercise has been shown to have protective effects on the heart and aorta. We have previously reported that mild aerobic exercise can delay the formation of aortic aneurysm in a mouse model of MFS. In this study, we aimed to investigate the effects of various levels of exercise intensity on the progression of aortic aneurysm in the mouse model. Starting at 4 weeks of age, we subjected control and MFS mice to different levels of exercise intensity (8m/min, 10m/min, 15m/min, and 20m/min, corresponding to 55%, 65%, 75%, and 85% of VO2 max, respectively) on a treadmill for 30 minutes per day, five days a week for the duration of the study. At 24 weeks of age, aortic tissue were isolated and subjected to structural and functional studies using histology and wire myography in order to evaluate the effects of different exercise routines on elastin fragmentation and organization and aortic wall elasticity/stiffness. Our data shows that exercise training at the intensity levels between 55%-75% significantly reduces elastin fragmentation and disorganization, with less recovery observed in 85% MFS group. The reversibility of elasticity was also significantly restored in MFS mice subjected to 55%-75% intensity; however, the recovery was less pronounced in MFS mice subjected to 85% intensity. Furthermore, our data shows that smooth muscle cells (SMCs) contractilion in response to vasoconstrictor agent phenylephrine (100nM) is significantly reduced in MFS aorta (54.84 ± 1.63 mN/mm2) as compared to control (95.85 ± 3.04 mN/mm2). At 55% of intensity, exercise did not rescue SMCs contraction (63.45 ± 1.70 mN/mm2), while at higher intensity levels, SMCs contraction in response to phenylephrine was restored to levels similar to control aorta [65% (81.88 ± 4.57 mN/mm2), 75% (86.22 ± 3.84 mN/mm2), and 85% (83.91 ± 5.42 mN/mm2)]. This study provides the first time evidence that high intensity exercise (e.g. 85%) may not provide the most beneficial effects on aortic function (vasoconstriction) and structure (elastin fragmentation, aortic wall elasticity) during the progression of aortic aneurysm in MFS mice. On the other hand, based on our observations, medium intensity exercise (e.g. 65%) seems to provide the utmost protective effects on aortic structure and function in MFS mice. These findings provide new insights into the potential capacity, in which MFS patients could participate in various aerobic exercise routines, especially in young adults affected by cardiovascular complications particularly aortic aneurysm. This work was funded by Midwestern University Research Fund.

Keywords: aerobic exercise, aortic aneurysm, aortic wall elasticity, elastin fragmentation, Marfan syndrome

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

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

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

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Authors: Claire Sciberras

Abstract:

Introduction: Autism Spectrum Disorder (ASD) has become recognized as being the most common childhood neurological condition. Indeed, numerous studies demonstrate an increase in the prevalence rate of children diagnosed with ASD. Concurrent with these findings, the European Agency for Special Needs and Inclusive Education reported a similar escalating tendency in prevalence also in Malta. Such an increase within the educational context in Malta has led the European Agency to call for increased support within educational settings in Malta. However, although research has addressed the positive impact of mainstream education on learners with ASD, empirical studies vis-à-vis the internal and external strengths and weaknesses present within the support provided in mainstream settings in Malta is distinctly limited. In light of the aforementioned argument, Malta would benefit from research which focuses on analysing the strengths, weaknesses, opportunities, and threats (SWOTs) which are present within the support provision of learners with ASD in mainstream primary schools. Such SWOT analysis is crucial as lack of appropriate opportunities might jeopardize the educational and social experiences of persons with ASD throughout their schooling. Methodology: A mixed methodological approach would be well suited to examine the provision of support of learners with ASD as the combination of qualitative and quantitative approaches allows researchers to collect a comprehensive range of data and validate their results. Hence, it is intended that questionnaires will be distributed to all the stakeholders involved so as to acquire a broader perspective to be collected from a wider group who provide support to students with ASD across schools in Malta. Moreover, the use of a qualitative approach in the form of interviews with a sample group will be implemented. Such an approach will be considered as it would potentially allow the researcher to gather an in-depth perspective vis-à-vis to the nature of the services which are currently provided to learners with ASD. The intentions of the study: Through the analysis of the data collected vis-à-vis to the SWOTs within the provision of support of learners with ASD it is intended that; i) a description in regards to the educational provision for learners with ASD within mainstream primary schools in Malta in light of the experiences and perceptions of the stakeholders involved will be acquired; ii) an analysis of the SWOTs which exist within the services for learners with ASD in primary state schools in Malta is carried out and iii) based on the SWOT analysis, recommendations that can lead to improvements in practice in the field of ASD in Malta and beyond will be provided. Conclusion: Due to the heterogeneity of individuals with ASD which spans across several deficits related to the social communication and interaction domain and also across areas linked to restricted, repetitive behavioural patterns, educational settings need to alter their standards according to the needs of their students. Thus, the standards established by schools throughout prior phases do not remain applicable forever, and therefore these need to be reviewed periodically in accordance with the diversities and the necessities of their learners.

Keywords: autism spectrum disorders, mainstream educational settings, provision of support, SWOT analysis

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Authors: A. M. Tarola, R. Preti, A. M. Girelli, P. Campana

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Safeguarding, studying and enhancing biodiversity play an important and indispensable role in re-launching agriculture. The ancient local varieties are therefore a precious resource for genetic and health improvement. In order to protect biodiversity through the recovery and valorization of autochthonous varieties, in this study we analyzed 12 samples of four ancient apple cultivars representative of Friuli Venezia Giulia, selected by local farmers who work on a project for the recovery of ancient apple cultivars. The aim of this study is to evaluate the polyphenolic profile and the antioxidant capacity that characterize the organoleptic and functional qualities of this fruit species, besides having beneficial properties for health. In particular, for each variety, the following compounds were analyzed, both in the skins and in the pulp: gallic acid, catechin, chlorogenic acid, epicatechin, caffeic acid, coumaric acid, ferulic acid, rutin, phlorizin, phloretin and quercetin to highlight any differences in the edible parts of the apple. The analysis of individual phenolic compounds was performed by High Performance Liquid Chromatography (HPLC) coupled with a diode array UV detector (DAD), the antioxidant capacity was estimated using an in vitro essay based on a Free Radical Scavenging Method and the total phenolic compounds was determined using the Folin-Ciocalteau method. From the results, it is evident that the catechins are the most present polyphenols, reaching a value of 140-200 μg/g in the pulp and of 400-500 μg/g in the skin, with the prevalence of epicatechin. Catechins and phlorizin, a dihydrohalcone typical of apples, are always contained in larger quantities in the peel. Total phenolic compounds content was positively correlated with antioxidant activity in apple pulp (r² = 0,850) and peel (r² = 0,820). Comparing the results, differences between the varieties analyzed and between the edible parts (pulp and peel) of the apple were highlighted. In particular, apple peel is richer in polyphenolic compounds than pulp and flavonols are exclusively present in the peel. In conclusion, polyphenols, being antioxidant substances, have confirmed the benefits of fruit in the diet, especially as a prevention and treatment for degenerative diseases. They demonstrated to be also a good marker for the characterization of different apple cultivars. The importance of protecting biodiversity in agriculture was also highlighted through the exploitation of native products and ancient varieties of apples now forgotten.

Keywords: apple, biodiversity, polyphenols, antioxidant activity, HPLC-DAD, characterization

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Authors: Sijie Chen, Xiaofang Chen, Juan Wang, Yingying Zhang, Yu Hong, Wanyu Zhuang, Xinxin Huang, Ping Ou, Longsheng Huang

Abstract:

Purpose: Autistic symptom improvement can be observed in children treated with acupuncture, but the mechanism is still being explored. In the present study, we used scalp acupuncture to treat autism rat model, and then their improvement in the abnormal behaviors and specific mechanisms behind were revealed by detecting animal behaviors, analyzing the RNA sequencing of the prefrontal cortex(PFC), and observing the ultrastructure of PFC neurons under the transmission electron microscope. Methods: On gestational day 12.5, Wistar rats were given valproic acid (VPA) by intraperitoneal injection, and their offspring were considered to be reliable rat models of autism. They were randomized to VPA or VPA-acupuncture group (n=8). Offspring of Wistar pregnant rats that were simultaneously injected with saline were randomly selected as the wild-type group (WT). VPA_acupuncture group rats received acupuncture intervention at 23 days of age for 4 weeks, and the other two groups followed without intervention. After the intervention, all experimental rats underwent behavioral tests. Immediately afterward, they were euthanized by cervical dislocation, and their prefrontal cortex was isolated for RNA sequencing and transmission electron microscopy. Results: The main results are as follows: 1. Animal behavioural tests: VPA group rats showed more anxiety-like behaviour and repetitive, stereotyped behaviour than WT group rats. While VPA group rats showed less spatial exploration ability, activity level, social interaction, and social novelty preference than WT group rats. It was gratifying to observe that acupuncture indeed improved these abnormal behaviors of autism rat model. 2. RNA-sequencing: The three groups of rats differed in the expression and enrichment pathways of multiple genes related to synaptic function, neural signal transduction, and circadian rhythm regulation. Our experiments indicated that acupuncture can alleviate the major symptoms of ASD by improving these neurological abnormalities. 3. Under the transmission electron microscopy, several lysosomes and mitochondrial structural abnormalities were observed in the prefrontal neurons of VPA group rats, which were manifested as atrophy of the mitochondrial membran, blurring or disappearance of the mitochondrial cristae, and even vacuolization. Moreover, the number of synapses and synaptic vesicles was relatively small. Conversely, the mitochondrial structure of rats in the WT group and VPA_acupuncture was normal, and the number of synapses and synaptic vesicles was relatively large. Conclusion: Acupuncture effectively improved the abnormal behaviors of autism rat model and the ultrastructure of the PFC neurons, which might worked by improving their abnormal synaptic function, synaptic plasticity and promoting neuronal signal transduction.

Keywords: autism spectrum disorder, acupuncture, animal behavior, RNA sequencing, transmission electron microscope

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Authors: Justin Fu, Thomas Mazzuchi, Shahram Sarkani

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A key factor in technological immaturity in defense weapons acquisition is lack of understanding critical integrations at the subsystem and component level. To address this shortfall, recent research in integration readiness level (IRL) combines with technology readiness level (TRL) to form a system readiness level (SRL). SRL can be enriched with more robust quantitative methods to provide the program manager a useful tool prior to committing to major weapons acquisition programs. This research harnesses previous mathematical models based on graph theory, Petri nets, and tropical algebra and proposes a modification of the desirable SRL mathematical properties such that a tightly integrated (multitude of interfaces) subsystem can display a lower SRL than an inherently less coupled subsystem. The synthesis of these methods informs an improved decision tool for the program manager to commit to expensive technology development. This research ties the separately developed manufacturing readiness level (MRL) into the network representation of the system and addresses shortfalls in previous frameworks, including the lack of integration weighting and the over-importance of a single extremely immature component. Tropical algebra (based on the minimum of a set of TRLs or IRLs) allows one low IRL or TRL value to diminish the SRL of the entire system, which may not be reflective of actuality if that component is not critical or tightly coupled. Integration connections can be weighted according to importance and readiness levels are modified to be a cardinal scale (based on an analytic hierarchy process). Integration arcs’ importance are dependent on the connected nodes and the additional integrations arcs connected to those nodes. Lack of integration is not represented by zero, but by a perfect integration maturity value. Naturally, the importance (or weight) of such an arc would be zero. To further explore the impact of grouping subsystems, a multi-objective genetic algorithm is then used to find various clusters or communities that can be optimized for the most representative subsystem SRL. This novel calculation is then benchmarked through simulation and using past defense acquisition program data, focusing on the newly introduced Middle Tier of Acquisition (rapidly field prototypes). The model remains a relatively simple, accessible tool, but at higher fidelity and validated with past data for the program manager to decide major defense acquisition program milestones.

Keywords: readiness, maturity, system, integration

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Authors: Henry Venter, Murali Thyloth, Alceu Casseb

Abstract:

Historically, mental and substance use disorders were not a global health priority. Since the 1993 World Development Report, the importance of the contribution of mental health and substance abuse on the relative global burden associated with disease morbidity has been recognized with 300 million people worldwide suffering from depression alone. This led to an international effort to improve the mental health of populations around the world. Despite these efforts some countries remain at the top of the list of countries with the highest rate of mental illness. Important research questions were asked: Would there be commonalities regarding mental health between these countries; would there be common factors leading to the high prevalence of mental illness; and how prepared are these countries with mental health delivery? Findings from this research can aid organizations and institutions preparing mental health service providers to focus training and preparation to address specific needs revealed by the study. Methods: Researchers decided to compare three distinctly different countries at the top of the list of countries with the highest rate of mental illness, the USA, India and Brazil, situated on three different continents with different economies and lifestyles. Data were collected using archival research methodology, reviewing records and findings of international and national health and mental health studies to subtract and compare data and findings. Results: The findings indicated that India is the most depressed country in the world, followed by the USA (and China) with Brazil in Latin America with the greatest number of depressed individuals. By 2020 roughly 20% of India, acountry of over one billion citizens, will suffer from some form of mental illnees, yet there are less than 4,000 experts available. In the USA 164.8 million people were substance abusers and an estimate of 47.6 million adults, 18 or older, had any mental illness in 2018. That means that about one in five adults in the USA experiences some form of mental illness each year, but only 41% of those affected received mental health care or services in the past year. Brazil has the greatest number of depressed individuals, in Latin America. Adults living in Sao Paulo megacity has prevalence of mental disorders at greater levels than similar surveys conducted in other areas of the world with more than one million adults with serious impairment levels. Discussion: The results show that, despite the vast socioeconomic differences between the three countries, there are correlations regarding mental health prevalence and difficulty to provide adequate services including a lack of awareness of how serious mental illness is, stigma for seeking mental illness, with comorbidity a common phenomenon, and a lack of partnership between different levels of service providers, which weakens mental health service delivery. The findings also indicate that mental health training institutions have a monumental task to prepare personnel to address the future mental health needs in each of the countries compared, which will constitute the next phase of the research.

Keywords: mental health epidemiology, mental health disorder, mental health prevalence, mental health treatment

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