Search results for: lipid disorders
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1967

Search results for: lipid disorders

1337 Understanding the Role of Nitric Oxide Synthase 1 in Low-Density Lipoprotein Uptake by Macrophages and Implication in Atherosclerosis Progression

Authors: Anjali Roy, Mirza S. Baig

Abstract:

Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid rich plaque enriched with necrotic core, modified lipid accumulation, smooth muscle cells, endothelial cells, leucocytes and macrophages. Macrophage foam cells play a critical role in the occurrence and development of inflammatory atherosclerotic plaque. Foam cells are the fat-laden macrophages in the initial stage atherosclerotic lesion formation. Foam cells are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening. The mechanisms that drive atherosclerotic plaque progression remain largely unknown. Dissecting the molecular mechanism involved in process of macrophage foam cell formation will help to develop therapeutic interventions for atherosclerosis. To investigate the mechanism, we studied the role of nitric oxide synthase 1(NOS1)-mediated nitric oxide (NO) on low-density lipoprotein (LDL) uptake by bone marrow derived macrophages (BMDM). Using confocal microscopy, we found that incubation of macrophages with NOS1 inhibitor, TRIM (1-(2-Trifluoromethylphenyl) imidazole) or L-NAME (N omega-nitro-L-arginine methyl ester) prior to LDL treatment significantly reduces the LDL uptake by BMDM. Further, addition of NO donor (DEA NONOate) in NOS1 inhibitor treated macrophages recovers the LDL uptake. Our data strongly suggest that NOS1 derived NO regulates LDL uptake by macrophages and foam cell formation. Moreover, we also checked proinflammatory cytokine mRNA expression through real time PCR in BMDM treated with LDL and copper oxidized LDL (OxLDL) in presences and absences of inhibitor. Normal LDL does not evoke cytokine expression whereas OxLDL induced proinflammatory cytokine expression which significantly reduced in presences of NOS1 inhibitor. Rapid NOS-1-derived NO and its stable derivative formation act as signaling agents for inducible NOS-2 expression in endothelial cells, leading to endothelial vascular wall lining disruption and dysfunctioning. This study highlights the role of NOS1 as critical players of foam cell formation and would reveal much about the key molecular proteins involved in atherosclerosis. Thus, targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages at early stage of disease and hence dampening the atherosclerosis progression.

Keywords: atherosclerosis, NOS1, inflammation, oxidized LDL

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1336 The GRIT Study: Getting Global Rare Disease Insights Through Technology Study

Authors: Aneal Khan, Elleine Allapitan, Desmond Koo, Katherine-Ann Piedalue, Shaneel Pathak, Utkarsh Subnis

Abstract:

Background: Disease management of metabolic, genetic disorders is long-term and can be cumbersome to patients and caregivers. Patient-Reported Outcome Measures (PROMs) have been a useful tool in capturing patient perspectives to help enhance treatment compliance and engagement with health care providers, reduce utilization of emergency services, and increase satisfaction with their treatment choices. Currently, however, PROMs are collected during infrequent and decontextualized clinic visits, which makes translation of patient experiences challenging over time. The GRIT study aims to evaluate a digital health journal application called Zamplo that provides a personalized health diary to record self-reported health outcomes accurately and efficiently in patients with metabolic, genetic disorders. Methods: This is a randomized controlled trial (RCT) (1:1) that assesses the efficacy of Zamplo to increase patient activation (primary outcome), improve healthcare satisfaction and confidence to manage medications (secondary outcomes), and reduce costs to the healthcare system (exploratory). Using standardized online surveys, assessments will be collected at baseline, 1 month, 3 months, 6 months, and 12 months. Outcomes will be compared between patients who were given access to the application versus those with no access. Results: Seventy-seven patients were recruited as of November 30, 2021. Recruitment for the study commenced in November 2020 with a target of n=150 patients. The accrual rate was 50% from those eligible and invited for the study, with the majority of patients having Fabry disease (n=48) and the remaining having Pompe disease and mitochondrial disease. Real-time clinical responses, such as pain, are being measured and correlated to disease-modifying therapies, supportive treatments like pain medications, and lifestyle interventions. Engagement with the application, along with compliance metrics of surveys and journal entries, are being analyzed. An interim analysis of the engagement data along with preliminary findings from this pilot RCT, and qualitative patient feedback will be presented. Conclusions: The digital self-care journal provides a unique approach to disease management, allowing patients direct access to their progress and actively participating in their care. Findings from the study can help serve the virtual care needs of patients with metabolic, genetic disorders in North America and the world over.

Keywords: eHealth, mobile health, rare disease, patient outcomes, quality of life (QoL), pain, Fabry disease, Pompe disease

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1335 Effect of a Polyherbal Gut Therapy Protocol in Changes of Gut and Behavioral Symptoms of Antibiotic Induced Dysbiosis of Autistic Babies

Authors: Dinesh K. S., D. R. C. V. Jayadevan

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Autism is the most prevalent of a subset of the disorders organized under the umbrella of pervasive developmental disorders. After the publication of Andrew Wakefield's paper in lancet, many critiques deny this connection even without looking in to the matter. The British Medical Journal even put an editorial regarding this issue. BMJ 2010; 340:c1807. But ayurveda has ample of evidences to believe this connectivity. Dysbiosis, yeast growth of the gut, nutritional deficiencies, enzyme deficiencies, essential fatty acid deficiencies, Gastro esophageal reflux disease, indigestion, inflammatory bowel, chronic constipation & its cascade are few of them to note. The purpose of this paper is to present the observed changes in the behavioural symptoms of autistic babies after a gut management protocol which is a usual programme of our autism treatment plan especially after dysbiotic changes after antibiotic administration. Is there any correlation between changes (if significant) in gut symptoms and behavioral problems of autistic babies especially after a dysbiosis induced by antibiotics. Retrospective analysis of the case sheets of autistic patients admitted in Vaidyaratnam P.S.Varier Ayurveda College hospital, kottakkal,kerala, india from September 2010 are taken for the data processing. Autistic patients are used to come to this hospital as a part of their usual course of treatment. We investigated 40 cases diagnosed as autistic by clinical psychologists from different institutions who had dysbiosis induced by antibiotics. Significant change in gut symptoms before and after treatment p<0.05 in most of its components Significant change in behavioral symptoms before and after treatments p<0.05 in most of the components Correlation between gut symptoms change and behavioral symptoms changes after treatment is + 0.86. Conclusion : Selected Polyherbal Ayurveda treatment has significant role to play to make changes abnormal behaviors in autistic babies and has a positive correlation with changes in gut symptoms induced by dysbiosis of antibiotic intake.

Keywords: ayurveda, autism, dysbiosis, antibiotic

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1334 The Ameliorative Effects of the Histamine H3 Receptor Antagonist/Inverse Agonist DL77 on MK801-Induced Memory Deficits in Rats

Authors: B. Sadek, N. Khan, Shreesh K. Ojha, Adel Sadeq, D. Lazewska, K. Kiec-Kononowicz

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The involvement of Histamine H3 receptors (H3Rs) in memory and the potential role of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer disease (AD) is well established. Therefore, the memory-enhancing effects of the H3R antagonist DL77 on MK801-induced cognitive deficits were evaluated in passive avoidance paradigm (PAP) and novel object recognition (NOR) tasks in adult male rats, applying donepezil (DOZ) as a reference drug. Animals pretreated with acute systemic administration of DL77 (2.5, 5, and 10 mg/kg, i.p.) were significantly ameliorated in regard to MK801-induced memory deficits in PAP. The ameliorative effect of most effective dose of DL77 (5 mg/kg, i.p.) was abrogated when animals were pretreated with a co-injection with the H3R agonist R-(α)-methylhistamine (RAMH, 10 mg/kg, i.p.). Moreover, and in the NOR paradigm, DL77 (5 mg/kg, i.p.) reversed MK801-induced deficits long-term memory (LTM), and the DL77-provided procognitive effect was comparable to that of reference drug DOZ, and was reversed when animals were co-injected with RAMH (10 mg/kg, i.p.). However, DL77(5 mg/kg, i.p.) failed to alter short-term memory (STM) impairment in NOR test. Furthermore, DL77 (5 mg/kg) failed to induce any alterations of anxiety and locomotor behaviors of animals naive to elevated-plus maze (EPM), indicating that the ameliorative effects observed in PAP or NOR tests were not associated to alterations in emotions or in natural locomotion of tested animals. These results reveal the potential contribution of H3Rs in modulating CNS neurotransmission systems associated with neurodegenerative disorders, e.g., AD.

Keywords: histamine H3 receptor, antagonist, learning and memory, Alzheimer's disease, neurodegeneration, passive avoidance paradigm, novel object recognition, behavioral research

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1333 Proximate Composition and Mineral Contents of Ocimum gratissimum Leaves (African Basil)

Authors: Adebola Ajayi

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Ocimum gratissimum belongs to the Lamiaceae family and is know generally as African Basil. Ocimum gratissimum leaves are widely used as local condiments in diets. The leaves were destalked sorted, washed with potable water to remove dirts, air dried for 14 days under ambient temperature and milled into powder. The proximate composition and mineral contents of Ocimum gratissimum leaves were investigated. The proximate analysis showed the moisture, crude, protein, total ash, crude fiber, crude lipid and total carbohydrate contents were 10.72±0.01%, 12.98±0.10%, 10.95±0.42, 10.21±0.04%, 4.81±0.04% and 49.01±0.25% respectively. The results of the analysis showed that Ocimum gratissimum could be a good source of important food nutrients.

Keywords: African Basil, drying, Ocimum gratissimum, proximate

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1332 Association between Substance Use Disorder, PTSD and the Effectiveness of Collaborative Care for Depression in Primary Care: A Systematic Literature Search and Narrative Review

Authors: J. Raub, H. Schillok, L. Kaupe, C. Jung-Sievers, G. Pitschel-Walz, M. Bühner, J. Gensichen, F. D. Pokal-Gruppe

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Introduction: In Germany, depression ranks among the top ten diseases with the highest disease burden and often occurs with comorbidities. Collaborative Care (CC), a concept developed in the United States for the primary care management of chronic diseases, has been identified as an efficient model for the treatment of depression in general medicine. A recent meta-analysis highlights research gaps regarding CC in patients with psychiatric multimorbidity. The highest prevalence of psychiatric comorbidities in depression is observed in anxiety disorders, post-traumatic stress disorder (PTSD), and substance use disorders. Methods: We conducted a literature search following the PRISMA guidelines with three components: Collaborative Care, Depression and randomized controlled trial on the common databases. We focused on the examination of psychiatric comorbidities in depression, specifically Posttraumatic Stress Disorder (PTSD) and Substance Use Disorder (SUD). Results: During the screening process, we identified nine relevant articles related to PTSD, the number of articles related to Substance Use Disorder (SUD) was ten. We examined a total of 8,634 individuals. Our literature review did not reveal any overall significant superiority of the Collaborative Care model compared to Usual Care in patients with depression with comorbid Substance Use Disorder (SUD) or Posttraumatic Stress Disorder (PTSD). Discussion: Five studies demonstrate a faster and statistically significant improvement in depression outcomes among patients with Substance Use Disorder (SUD) and Posttraumatic Stress Disorder (PTSD). Currently, several randomized controlled trials on the topic of Collaborative Care in depression with psychiatric comorbidity are ongoing, such as miCare, Claro and COMET.

Keywords: Depression, primary care, collaborative care, PTSD, Substance use Disorder

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1331 Pregnant Women and Mothers in Prison, Mother and Baby Units and Mental Health

Authors: Rachel Dolan

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Background: Over two thirds of women in prison in England are mothers, and estimates suggest between 100 and 200 women per year give birth during imprisonment. There are currently six mother and baby units (MBUs) in prisons in England which admit women and babies up to the age of 18 months. Although there are only 65 places available, and despite positive impacts, they are rarely full. Mental illness may influence the number of admissions, as may interpretation of admission criteria. They are the only current alternative to separation for imprisoned mothers and their babies. Aims: To identify the factors that affect the decision to apply for/be offered a place in a prison MBU; to measure the impact of a placement upon maternal mental health and wellbeing; To measure the Initial outcomes for mother and child. Methods: A mixed methods approach - 100 pregnant women in English prisons are currently being recruited from prisons in England. Quantitative measures will establish the prevalence of mental disorder, personality disorder, substance misuse and quality of life. Qualitative interviews will document the experiences of pregnancy and motherhood in prison. Results: Preliminary quantitative findings suggest the most prevalent mental disorders are anxiety and depression and approximately half the participants meet the criteria for one or more personality disorders. The majority of participants to date have been offered a place in a prison MBU, and those in a prison with an MBU prior to applying are more likely to be admitted. Those with a previous history of childcare issues, who are known to social services are less likely to be offered a place. Qualitative findings suggest that many women are often hungry and uncomfortable during pregnancy, many have feelings of guilt about having a child in prison and that feelings of anxiety and worry are exacerbated by lack of information.

Keywords: mothers, prison, mother and baby units, mental health

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1330 Assessing Autism Spectrum Disorders (ASD) Challenges in Young Children in Dubai: A Qualitative Study, 2016

Authors: Kadhim Alabady

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Background: Autism poses a particularly large public health challenge and an inspiring lifelong challenge for many families; it is a lifelong challenge of a different kind. Purpose: Therefore, it is important to understand what the key challenges are and how to improve the lives of children who are affected with autism in Dubai. Method: In order to carry out this research we have used a qualitative methodology. We performed structured in–depth interviews and focus groups with mental health professionals working at: Al Jalila hospital (AJH), Dubai Autism Centre (DAC), Dubai Rehabilitation Centre for Disabilities, Latifa hospital, Private Sector Healthcare (PSH). In addition to that, we conducted quantitative approach to estimate ASD prevalence or incidence data due to lack of registry. ASD estimates are based on research from national and international documents. This approach was applied to increase the validity of the findings by using a variety of data collection techniques in order to explore issues that might not be highlighted through one method alone. Key findings: Autism is the most common of the Pervasive Developmental Disorders. Dubai Autism Center estimates it affects 1 in 146 births (0.68%). If we apply these estimates to the total number of births in Dubai for 2014, it is predicted there would be approximately 199 children (of which 58 were Nationals and 141 were Non–Nationals) suffering from autism at some stage. 16.4% of children (through their families) seek help for ASD assessment between the age group 6–18+. It is critical to understand and address factors for seeking late–stage diagnosis, as ASD can be diagnosed much earlier and how many of these later presenters are actually diagnosed with ASD. Autism spectrum disorder (ASD) is a public health concern in Dubai. Families do not consult GPs for early diagnosis for a variety of reasons including cultural reasons. Recommendations: Effective school health strategies is needed and implemented by nurses who are qualified and experienced in identifying children with ASD. There is a need for the DAC to identify and develop a closer link with neurologists specializing in Autism, to work alongside and for referrals. Autism can be attributed to many factors, some of those are neurological. Currently, when families need their child to see a neurologist they have to go independently and search through the many that are available in Dubai and who are not necessarily specialists in Autism. Training of GP’s to aid early diagnosis of Autism and increase awareness. Since not all GP’s are trained to make such assessments increasing awareness about where to send families for a complete assessment and the necessary support. There is an urgent need for an adult autism center for when the children leave the safe environment of the school at 18 years. These individuals require a day center or suitable job training/placements where appropriate. There is a need for further studies to cover the needs of people with an Autism Spectrum Disorder (ASD).

Keywords: autism spectrum disorder, autism, pervasive developmental disorders, incidence

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1329 Autoimmune Diseases Associated with Primary Biliary Cirrhosis: A Retrospective Study of 51 Patients

Authors: Soumaya Mrabet, Imen Akkari, Amira Atig, Elhem Ben Jazia

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Introduction: Primary biliary cirrhosis (PBC) is a cholestatic cholangitis of unknown etiology. It is frequently associated with autoimmune diseases, which explains their systematic screening. The aim of our study was to determine the prevalence and the type of autoimmune disorders associated with PBC and to assess their impact on the prognosis of the disease. Material and methods: It is a retrospective study over a period of 16 years (2000-2015) including all patients followed for PBC. In all these patients we have systematically researched: dysthyroidism (thyroid balance, antithyroid autoantibodies), type 1 diabetes, dry syndrome (ophthalmologic examination, Schirmer test and lip biopsy in case of Presence of suggestive clinical signs), celiac disease(celiac disease serology and duodenal biopsies) and dermatological involvement (clinical examination). Results: Fifty-one patients (50 women and one men) followed for PBC were collected. The Mean age was 54 years (37-77 years). Among these patients, 30 patients(58.8%) had at least one autoimmune disease associated with PBC. The discovery of these autoimmune diseases preceded the diagnosis of PBC in 8 cases (26.6%) and was concomitant, through systematic screening, in the remaining cases. Autoimmune hepatitis was found in 12 patients (40%), defining thus an overlap syndrome. Other diseases were Hashimoto's thyroiditis (n = 10), dry syndrome (n = 7), Gougerot Sjogren syndrome (n=6), celiac disease (n = 3), insulin-dependent diabetes (n = 1), scleroderma (n = 1), rheumatoid arthritis (n = 1), Biermer Anemia (n=1) and Systemic erythematosus lupus (n=1). The two groups of patients with PBC with or without associated autoimmune disorders were comparable for bilirubin levels, Child-Pugh score, and response to treatment. Conclusion: In our series, the prevalence of autoimmune diseases in PBC was 58.8%. These diseases were dominated by autoimmune hepatitis and Hashimoto's thyroiditis. Even if their association does not seem to alter the prognosis, screening should be systematic in order to institute an early and adequate management.

Keywords: autoimmune diseases, autoimmune hepatitis, primary biliary cirrhosis, prognosis

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1328 Variation in pH Values and Tenderness of Meat of Cattle Fed Different Levels of Lipids

Authors: Erico Da Silva Lima, Tiago Neves Pereira Valente, Roberto De Oliveira Roça

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Introduction: Over the last few years the market has increased its demand for high quality meat. Based on this premise some producers have continuously improved their efficiency in breeding beef cattle with the purpose to support this demand. It is well recognized that final quality of beef is intimately linked to animal’s diet. The key objective of this study is to evaluate the influence of feeding animals with cottonseed and its lipids and the final results in terms of pH and shear forces of the meat. Materials and Methods: The study was carried out in the Chapéu de Couro Farm in Aguaí/SP, Brazil. A group of 39 uncastrated Nellore cattle. Mean age of the animals was 36 months and initial mean live weight was 494.1 ± 10.1. Animals were randomly assigned to one of three treatments, based on dry matter: feed with control diet 2.50% cottonseed, feed with 11.50% cottonseed, and feed with 3.13% cottonseed added of 1.77% protected lipid. Forage:concentrate ratio was 50:50 on a dry matter basis. Sugar cane chopped was used as forage. After slaughter, carcasses were identified and divided into two halves that were kept in a cold chamber for 24 h at 2°C. Using pH meter was determined post-mortem pH in Longissimus thoracis muscle between the 12th and 13th rib of the left half carcass. After, part of each animal was removed, and divided in three samples (steaks). Steaks were 2.5 cm thick and were identified and stored individually in plastic bags under vacuum. Samples were frozen in a freezer at -18°C. The same samples cooked were refrigerated by 12 h the 4°C, and then cut into cylinders 1.10 Øcm with the support of a drill press avoiding fats and nerves. Shear force was calculated in these samples cut into cylinders through the Brookfield texture CT3 Texture Analyzer 25 k equipped with a set of blade Warner-Bratzler. Results and Discussion: No differences (P > 0.05) in pH 24 h after slaughter were observed in the meat of Nellore cattle fed different sources of fat, and mean value for this variable was 5.59. However, for the shear force differences (P < 0.05) were founded. For diet with 2,50% cottonseed the lowest value found 5.10 (kg) while for the treatment with 11.50% cottonseed the great value found was 6.30 (kg). High shear force values mean greater texture of meat that indicates less tenderness. The texture of the meat can be influenced by age, weight to the slaughter of animals. For cattle breed Nellore Bos taurus indicus more high value of shear force. Conclusions: The add the cottonseed or protected lipid in diet is not affected pH values in meat. The whole cottonseed does not contribute to the improvement of tenderness of the meat. Acknowledgments: IFGoiano, FAPEG and CNPq (Brazil).

Keywords: beef quality, cottonseed, protected fat, shear force

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1327 Use of the Occupational Repetitive Action Method in Different Productive Sectors: A Literature Review 2007-2018

Authors: Aanh Eduardo Dimate-Garcia, Diana Carolina Rodriguez-Romero, Edna Yuliana Gonzalez Rincon, Diana Marcela Pardo Lopez, Yessica Garibello Cubillos

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Musculoskeletal disorders (MD) are the new epidemic of chronic diseases, are multifactorial and affect the different productive sectors. Although there are multiple instruments to evaluate the static and dynamic load, the method of repetitive occupational action (OCRA) seems to be an attractive option. Objective: It is aimed to analyze the use of the OCRA method and the prevalence of MD in workers of various productive sectors according to the literature (2007-2018). Materials and Methods: A literature review (following the PRISMA statement) of studies aimed at assessing the level of biomechanical risk (OCRA) and the prevalence of MD in the databases Scielo, Science Direct, Scopus, ProQuest, Gale, PubMed, Lilacs and Ebsco was realized; 7 studies met the selection criteria; the majority are quantitative (cross section). Results: it was evidenced (gardening and flower-growers) in this review that 79% of the conditions related to the task require physical requirements and involve repetitive movements. In addition, of the high appearance of DM in the high-low back, upper and lower extremities that are produced by the frequency of the activities carried out (footwear production). Likewise, there was evidence of 'very high risks' of developing MD (salmon industry) and a medium index (OCRA) for repetitive movements that require special care (U-Assembly line). Conclusions: the review showed the limited use of the OCRA method for the detection of MD in workers from different sectors, and this method can be used for the detection of biomechanical risk and the appearance of MD.

Keywords: checklist, cumulative trauma disorders, musculoskeletal diseases, repetitive movements

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1326 Evaluation of Antidiabetic Activity of a Combination Extract of Nigella Sativa & Cinnamomum Cassia in Streptozotocin Induced Type-I Diabetic Rats

Authors: Ginpreet Kaur, Mohammad Yasir Usmani, Mohammed Kamil Khan

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Diabetes mellitus is a disease with a high global burden and results in significant morbidity and mortality. In India, the number of people suffering with diabetes is expected to rise from 19 to 57 million in 2025. At present, interest in herbal remedies is growing to reduce the side effects associated with conventional dosage form like oral hypoglycemic agents and insulin for the treatment of diabetes mellitus. Our aim was to investigate the antidiabetic activities of combinatorial extract of N. sativa & C. cassia in Streptozotocin induced type-I Diabetic Rats. Thus, the present study was undertaken to screen postprandial glucose excursion potential through α- glucosidase inhibitory activity (In Vitro) and effect of combinatorial extract of N. sativa & C. cassia in Streptozotocin induced type-I Diabetic Rats (In Vivo). In addition changes in body weight, plasma glucose, lipid profile and kidney profile were also determined. The IC50 values for both extract and Acarbose was calculated by extrapolation method. Combinatorial extract of N. sativa & C. cassia at different dosages (100 and 200 mg/kg orally) and Metformin (50 mg/kg orally) as the standard drug was administered for 28 days and then biochemical estimation, body weights and OGTT (Oral glucose tolerance test) were determined. Histopathological studies were also performed on kidney and pancreatic tissue. In In-Vitro the combinatorial extract shows much more inhibiting effect than the individual extracts. The results reveals that combinatorial extract of N. sativa & C. cassia has shown significant decrease in plasma glucose (p<0.0001), total cholesterol and LDL levels when compared with the STZ group The decreasing level of BUN and creatinine revealed the protection of N. sativa & C. cassia extracts against nephropathy associated with diabetes. Combination of N. sativa & C. cassia significantly improved glucose tolerance to exogenously administered glucose (2 g/kg) after 60, 90 and 120 min interval on OGTT in high dose streptozotocin induced diabetic rats compared with the untreated control group. Histopathological studies shown that treatment with N. sativa & C. cassia extract alone and in combination restored pancreatic tissue integrity and was able to regenerate the STZ damaged pancreatic β cells. Thus, the present study reveals that combination of N. sativa & C. cassia extract has significant α- glucosidase inhibitory activity and thus has great potential as a new source for diabetes treatment.

Keywords: lipid levels, OGTT, diabetes, herbs, glucosidase

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1325 Examining the Relationship between Concussion and Neurodegenerative Disorders: A Review on Amyotrophic Lateral Sclerosis and Alzheimer’s Disease

Authors: Edward Poluyi, Eghosa Morgan, Charles Poluyi, Chibuikem Ikwuegbuenyi, Grace Imaguezegie

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Background: Current epidemiological studies have examined the associations between moderate and severe traumatic brain injury (TBI) and their risks of developing neurodegenerative diseases. Concussion, also known as mild TBI (mTBI), is however quite distinct from moderate or severe TBIs. Only few studies in this burgeoning area have examined concussion—especially repetitive episodes—and neurodegenerative diseases. Thus, no definite relationship has been established between them. Objectives : This review will discuss the available literature linking concussion and amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). Materials and Methods: Given the complexity of this subject, a realistic review methodology was selected which includes clarifying the scope and developing a theoretical framework, developing a search strategy, selection and appraisal, data extraction, and synthesis. A detailed literature matrix was set out in order to get relevant and recent findings on this topic. Results: Presently, there is no objective clinical test for the diagnosis of concussion because the features are less obvious on physical examination. Absence of an objective test in diagnosing concussion sometimes leads to skepticism when confirming the presence or absence of concussion. Intriguingly, several possible explanations have been proposed in the pathological mechanisms that lead to the development of some neurodegenerative disorders (such as ALS and AD) and concussion but the two major events are deposition of tau proteins (abnormal microtubule proteins) and neuroinflammation, which ranges from glutamate excitotoxicity pathways and inflammatory pathways (which leads to a rise in the metabolic demands of microglia cells and neurons), to mitochondrial function via the oxidative pathways.

Keywords: amyotrophic lateral sclerosis, Alzheimer's disease, mild traumatic brain injury, neurodegeneration

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1324 A Comparison of Three Protocols Weight-Loss Interventions for Obese Females

Authors: Nayera E. Hassan, Sahar A. El-Masry, Rokia El-Banna, Mohamed S. El Hussieny

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There are several different modalities for treatment of obesity. Common intervention methods for obesity include low-calorie diet, exercise. Also acupuncture has shown good therapeutic results in the treatment of obesity. A recent clinical observation showed that laser acupuncture could reduce body weight and body mass index in obese persons. So, the aim of this research is focused on body composition changes as related to type of intervention, before and after intentional weight loss in overweight and obesity. 76 subjects were included in the study analysis. The present study recommended that every obese female must do lipid profile and fasting blood sugar analysis before weight-loss intervention to take the decision of which method should be used.

Keywords: obesity, weight-loss, body composition, modalities

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1323 Improving Access to Training for Parents of Children with Autism Spectrum Disorders through Telepractice: Parental Perception

Authors: Myriam Rousseau, Marie-Hélène Poulin, Suzie McKinnon, Jacinthe Bourassa

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Context: There is a growing demand for effective training programs for parents of children with autism spectrum disorders. While traditional in-person training is effective, it can be difficult for some parents to participate due to distance, time, and cost. Telepractice, a form of distance education, could be a viable alternative to address these challenges. Research objective: The objective of this study is to explore the experiences of parents of children with autism who participated in a training program offered by telepractice in order to document: 1) the experience of parents who participated in a program telepractice training program for autistic children, 2) parental satisfaction with the telepractice modality, and 3) potential benefits of using telepractice to deliver training programs to parents of autistic children. Method: This study followed a qualitative research design, and Braun and Clarke's six-step procedure was used for the thematic analysis of the comments provided by parents. Data were collected through individual interviews with parents who participated in the project. The analysis focused on identifying patterns and themes in the comments in order to better understand parents' experiences with the telepractice modality. Results: The study revealed that parents were generally satisfied with the telepractice modality, as it was easy to use and enabled a better balance between work and family. This modality also enabled parents to share and receive mutual support. Despite the positive results, it is still relevant to offer training in different modalities to meet the different needs of parents. Conclusion: The study shows that parents of children with autism are generally satisfied with telepractice as a training modality. The results suggest that telepractice can be an effective alternative to traditional face-to-face training. The study highlights the importance of taking parents' needs and preferences into account when designing and implementing training programs.

Keywords: parents, children, training, telepractice

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1322 In silico Analysis towards Identification of Host-Microbe Interactions for Inflammatory Bowel Disease Linked to Reactive Arthritis

Authors: Anukriti Verma, Bhawna Rathi, Shivani Sharda

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Reactive Arthritis (ReA) is a disorder that causes inflammation in joints due to certain infections at distant sites in the body. ReA begins with stiffness, pain, and inflammation in these areas especially the ankles, knees, and hips. It gradually causes several complications such as conjunctivitis in the eyes, skin lesions in hand, feet and nails and ulcers in the mouth. Nowadays the diagnosis of ReA is based upon a differential diagnosis pattern. The parameters for differentiating ReA from other similar disorders include physical examination, history of the patient and a high index of suspicion. There are no standard lab tests or markers available for ReA hence the early diagnosis of ReA becomes difficult and the chronicity of disease increases with time. It is reported that enteric disorders such as Inflammatory Bowel Disease (IBD) that is inflammation in gastrointestinal tract namely Crohn’s Disease (CD) and Ulcerative Colitis (UC) are reported to be linked with ReA. Several microorganisms are found such as Campylobacter, Salmonella, Shigella and Yersinia causing IBD leading to ReA. The aim of our study was to perform the in-silico analysis in order to find interactions between microorganisms and human host causing IBD leading to ReA. A systems biology approach for metabolic network reconstruction and simulation was used to find the essential genes of the reported microorganisms. Interactomics study was used to find the interactions between the pathogen genes and human host. Genes such as nhaA (pathogen), dpyD (human), nagK (human) and kynU (human) were obtained that were analysed further using the functional, pathway and network analysis. These genes can be used as putative drug targets and biomarkers in future for early diagnosis, prevention, and treatment of IBD leading to ReA.

Keywords: drug targets, inflammatory bowel disease, reactive arthritis, systems biology

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1321 The Effect of the COVID-19 on Alzheimer’s Disease

Authors: Ayşe Defne Öz, Özlem Bozkurt

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Alzheimer's Disease (AD) is counted as one of the most important global health problems and the main cause of dementia. The term dementia refers to a wide spectrum of disorders characterized by global, chronic, and generally irreversible cognitive deterioration. It is estimated that %60 % to 80 of the cases of dementia are because of AD. Alzheimer's is a slowly progressive brain disease. The reason for AD is unknown to the author's best knowledge, yet it is one of the topics that is most researched. AD shows the histopathologically abnormal accumulation of the protein beta-amyloid (plague) outside neurons and twisted strands of the protein tau (tangles) inside neurons in the brain. These changes are accompanied by damage to the brain tissue and the death of neurons. AD causes people to have difficulty remembering names or conversations. Some of the later symptoms are difficulty in talking and walking. Alzheimer's Disease is elevated by the illness and mortality of COVID-19. COVID-19 has affected many lives globally and had profound effects on human lives. COVID-19 is caused by SARS-CoV-2, which is a virus that attacks the respiratory and central nervous system and has neuroinvasive potential. More than %80 of COVID-19 patients have ageusia or anosmia, representing the pathognomic features of the disease. Patients with dementia are frail, and with the COVID-19 pandemic, including isolation, cognitive decline may exacerbate. Furthermore, patients with AD can be unable to follow the directions, such as covering their mouth and nose while coughing and can live in nursing homes which makes them more open to being infected. As COVID-19 is highly infectious and its management requires isolation and quarantine, the need for caregivers for AD management conflicts with that of COVID-19 and adds an extra burden on AD patients, caregivers, families, society, and the economy. Due to the entry of SARS-CoV-2 into the central nervous system, inflammation caused by COVID-19, prolonged hospitalization, and delirium, it has been reported that COVID-19 causes many neurological disorders and predisposition to AD.

Keywords: Alzheimer's disease, COVID-19, dementia, SARS-CoV-2

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1320 Comparison between High Resolution Ultrasonography and Magnetic Resonance Imaging in Assessment of Musculoskeletal Disorders Causing Ankle Pain

Authors: Engy S. El-Kayal, Mohamed M. S. Arafa

Abstract:

There are various causes of ankle pain including traumatic and non-traumatic causes. Various imaging techniques are available for assessment of AP. MRI is considered to be the imaging modality of choice for ankle joint evaluation with an advantage of its high spatial resolution, multiplanar capability, hence its ability to visualize small complex anatomical structures around the ankle. However, the high costs and the relatively limited availability of MRI systems, as well as the relatively long duration of the examination all are considered disadvantages of MRI examination. Therefore there is a need for a more rapid and less expensive examination modality with good diagnostic accuracy to fulfill this gap. HRU has become increasingly important in the assessment of ankle disorders, with advantages of being fast, reliable, of low cost and readily available. US can visualize detailed anatomical structures and assess tendinous and ligamentous integrity. The aim of this study was to compare the diagnostic accuracy of HRU with MRI in the assessment of patients with AP. We included forty patients complaining of AP. All patients were subjected to real-time HRU and MRI of the affected ankle. Results of both techniques were compared to surgical and arthroscopic findings. All patients were examined according to a defined protocol that includes imaging the tendon tears or tendinitis, muscle tears, masses, or fluid collection, ligament sprain or tears, inflammation or fluid effusion within the joint or bursa, bone and cartilage lesions, erosions and osteophytes. Analysis of the results showed that the mean age of patients was 38 years. The study comprised of 24 women (60%) and 16 men (40%). The accuracy of HRU in detecting causes of AP was 85%, while the accuracy of MRI in the detection of causes of AP was 87.5%. In conclusions: HRU and MRI are two complementary tools of investigation with the former will be used as a primary tool of investigation and the latter will be used to confirm the diagnosis and the extent of the lesion especially when surgical interference is planned.

Keywords: ankle pain (AP), high-resolution ultrasound (HRU), magnetic resonance imaging (MRI) ultrasonography (US)

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1319 Transcriptomic and Translational Regulation of Peroxisome Proliferator-Activated Receptors after Different Feedings in Salmon

Authors: Mahsa Jalili, Essa Ehsan Khan, Signe Dille Lovmo, Augustine Akruwe, Egil Lien, Rolf Erik Olsen, Trygve Sigholt, Atle Magnus Bones

Abstract:

Data from the Norwegian Directorate of Fisheries reported that >1.2 million tons of Atlantic salmon were produced in Norway aquaculture industry in 2016. Peroxisome proliferator-activated receptors (PPARs) are one of the key transcription factor families that respond to nutritional ligands. Recent studies have shown the connection between PPARs with lipid and carbohydrate metabolism in aquaculture. To our knowledge, there is no published data about the effects of krill meal, soybean meal, Bactocell ® and butyrate feedings compared to control group on PPARs gene and protein expressions in Atlantic salmon. Fish, 1year +postsmolt, average weight 250 gram were cultured for 12 weeks after acclimatization by control commercial feeding in 2 weeks after hatchery. Water oxygen rate, salinity, and temperature were monitored every second day. At the end of the trial, fish were taken from tanks randomly, and four replicates per group were collected and stored in -80 freezers until analysis. Total RNA extracted from posterior part of dorsal fin muscle tissues and Nanodrop and Bioanalyzer was used to check the quality of RNA. Gene expression of PPAR α, β and γ were determined by RT-PCR. The expression of genes of interest was measured relative to control group after normalization to three reference genes. Total protein concentration was calculated by Bradford method, and protein expression was determined with primary PPARγ antibody by western blot. All data were analyzed by ANOVA followed by Benjamini-Hochberg and Bonferroni tests. Probability values <0.05 considered significant. Bactocell® and butyrate groups showed significantly lower PPARα expression. PPARβ and γ were not significantly different among groups. PPARγ mRNA expression was approximately consistent with protein expression pattern, except than butyrate group showed lower mRNA level. The order of PPARγ expression was Bactocell® > soy meal > butyrate > krill meal > control respectively. PPARβ gene expression decreased more in soy meal > butyrate > krill meal > Bactocell® > control groups respectively. In conclusion, the increased expression of PPARγ and α is proposed to represent a reduction tendency of lipid storage in fish fed by Bactocell®, butyrate, soy and krill meal.

Keywords: aquaculture, blotting western, gene expression, krill protein extract, prebiotics, probiotics, Salmo salar

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1318 A Method for Quantifying Arsenolipids in Sea Water by HPLC-High Resolution Mass Spectrometry

Authors: Muslim Khan, Kenneth B. Jensen, Kevin A. Francesconi

Abstract:

Trace amounts (ca 1 µg/L, 13 nM) of arsenic are present in sea water mostly as the oxyanion arsenate. In contrast, arsenic is present in marine biota (animals and algae) at very high levels (up to100,000 µg/kg) a significant portion of which is present as lipid-soluble compounds collectively termed arsenolipids. The complex nature of sea water presents an analytical challenge to detect trace compounds and monitor their environmental path. We developed a simple method using liquid-liquid extraction combined with HPLC-High Resolution Mass Spectrometer capable of detecting trace of arsenolipids (99 % of the sample matrix while recovering > 80 % of the six target arsenolipids with limit of detection of 0.003 µg/L.)

Keywords: arsenolipids, sea water, HPLC-high resolution mass spectrometry

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1317 Factors Affecting the Success of Premarital Screening Services in Middle Eastern Countries

Authors: Wafa Al Jabri

Abstract:

Background: In Middle Eastern Countries (MECs), there is a high prevalence of genetic blood disorders (GBDs), particularly sickle cell disease and thalassemia. The GBDs are considered a major public health concern that place a huge burden to individuals, families, communities, and health care systems. The high rates of consanguineous marriages, along with the unacceptable termination of at-risk pregnancy in MECs, reduce the possible solutions to control the high prevalence of GBDs. Since the early 1970s, most of MECs have started introducing premarital screening services (PSS) as a preventive measure to identify the asymptomatic carriers of GBDs and to provide genetic counseling to help couples plan for healthy families; yet, the success rate of PSS is very low. Purpose: This paper aims to highlight the factors that affect the success of PSS in MECs. Methods: An integrative review of articles located in CINAHL, PubMed, SCOPUS, and MedLine was carried out using the following terms: “premarital screening,” “success,” “effectiveness,” and “ genetic blood disorders”. Second, a hand search of the reference lists and Google searches were conducted to find studies that did not exist in the primary database searches. Only studies which are conducted in MECs and published after 2010 were included. Studies that were not published in English were excluded. Results: Eighteen articles were included in the review. The results showed that PSS in most of the MECs was successful in achieving its objective of identifying high-risk marriages; however, the service failed to meet its ultimate goal of reducing the prevalence of GBDs. Various factors seem to hinder the success of PSS, including poor public awareness, late timing of the screening, culture and social stigma, lack of prenatal diagnosis services and therapeutic abortion, emotional factors, religious beliefs, and lack of genetic counseling services. However, poor public awareness, late timing of the screening, religious misbeliefs, and the lack of adequate counseling services were the most common barriers identified. Conclusion and Implications: The review help in providing a framework for an effective preventive measure to reduce the prevalence of GBDs in MECS. This framework focuses primarily in overcoming the identified barriers by providing effective health education programs in collaboration with religious leaders, offering the screening test to young adults at an earlier stage, and tailoring the genetic counseling to consider people’s values, beliefs, and preferences.

Keywords: premarital screening, middle east, genetic blood disorders, factors

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1316 EGF Serum Level in Diagnosis and Prediction of Mood Disorder in Adolescents and Young Adults

Authors: Monika Dmitrzak-Weglarz, Aleksandra Rajewska-Rager, Maria Skibinska, Natalia Lepczynska, Piotr Sibilski, Joanna Pawlak, Pawel Kapelski, Joanna Hauser

Abstract:

Epidermal growth factor (EGF) is a well-known neurotrophic factor that involves in neuronal growth and synaptic plasticity. The proteomic research provided in order to identify novel candidate biological markers for mood disorders focused on elevated EGF serum level in patients during depression episode. However, the EGF association with mood disorder spectrum among adolescents and young adults has not been studied extensively. In this study, we aim to investigate the serum levels of EGF in adolescents and young adults during hypo/manic, depressive episodes and in remission compared to healthy control group. In our study, we involved 80 patients aged 12-24 years in 2-year follow-up study with a primary diagnosis of mood disorder spectrum, and 35 healthy volunteers matched by age and gender. Diagnoses were established according to DSM-IV-TR criteria using structured clinical interviews: K-SADS for child and adolescents, and SCID for young adults. Clinical and biological evaluations were made at baseline and euthymic mood (at 3th or 6th month of treatment and after 1 and 2 years). The Young Mania Rating Scale and Hamilton Rating Scale for Depression were used for assessment. The study protocols were approved by the relevant ethics committee. Serum protein concentration was determined by Enzyme-Linked Immunosorbent Assays (ELISA) method. Human EGF (cat. no DY 236) DuoSet ELISA kit was used (R&D Systems). Serum EGF levels were analysed with following variables: age, age under 18 and above 18 years old, sex, family history of affective disorders, drug-free vs. medicated. Shapiro-Wilk test was used to test the normality of the data. The homogeneity of variance was calculated with Levene’s test. EGF levels showed non-normal distribution and the homogeneity of variance was violated. Non-parametric tests: Mann-Whitney U test, Kruskall-Wallis ANOVA, Friedman’s ANOVA, Wilcoxon signed rank test, Spearman correlation coefficient was applied in the analyses The statistical significance level was set at p<0.05. Elevated EGF level at baseline (p=0.001) and at month 24 (p=0.02) was detected in study subjects compared with controls. Increased EGF level in women at month 12 (p=0.02) compared to men in study group have been observed. Using Wilcoxon signed rank test differences in EGF levels were detected: decrease from baseline to month 3 (p=0.014) and increase comparing: month 3 vs. 24 (p=0.013); month 6 vs. 12 (p=0.021) and vs. 24 (p=0.008). EGF level at baseline was negatively correlated with depression and mania occurrence at 24 months. EGF level at 24 months was positively correlated with depression and mania occurrence at 12 months. No other correlations of EGF levels with clinical and demographical variables have been detected. The findings of the present study indicate that EGF serum level is significantly elevated in the study group of patients compared to the controls. We also observed fluctuations in EGF levels during two years of disease observation. EGF seems to be useful as an early marker for prediction of diagnosis, course of illness and treatment response in young patients during first episode od mood disorders, which requires further investigation. Grant was founded by National Science Center in Poland no 2011/03/D/NZ5/06146.

Keywords: biological marker, epidermal growth factor, mood disorders, prediction

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1315 Circadian-Clock Controlled Drug Transport Across Blood-Cerebrospinal Fluid Barrier

Authors: André Furtado, Rafael Mineiro, Isabel Gonçalves, Cecília Santos, Telma Quintela

Abstract:

The development of therapies for central nervous system (CNS) disorders is one of the biggest challenges of current pharmacology, given the unique features of brain barriers, which limit drug delivery. Efflux transporters (ABC transporters) expressed at the blood-cerebrospinal fluid barrier (BCSFB), are the main obstacles for the delivery of therapeutic compounds into the CNS, compromising the effective treatment of brain cancer, brain metastasis from peripheral cancers, or even neurodegenerative disorders. It is thus extremely important to understand the regulation of these transporters for reducing their expression while treating a brain disorder or choosing the most appropriate conditions for drug administration. Based on the fact that the BCSFB have fine-tuned biological rhythms, studying the circadian variation of drug transport processes is critical for choosing the most appropriate time of the day for drug administration. In our study, using an in vitro model of the BCSFB, we characterized the circadian transport profile of methotrexate (MTX) and donepezil (DNPZ), two drugs involved in the treatment of cancer and Alzheimer’s Disease symptoms, respectively. We found that MTX is transported across the basal and apical membranes of the BCSFB in a circadian way. The circadian pattern of an ABC transporter, Abcc4, might be partially responsible for MTX circadian transport. Furthermore, regarding the DNPZ transport study, we observed that the regulation of Abcg2 expression by the circadian rhythm will impact the circadian-dependent transport of DNPZ across the BCSFB. Overall, our results will contribute to the current knowledge on brain pharmacoresistance at the BCSFB by disclosing how circadian rhythms control drug delivery to the brain, setting the grounds for a potential application of chronotherapy to brain diseases to enhance the efficacy of medications and minimize their side effects.

Keywords: blood-cerebrospinal fluid barrier, ABC transporters, drug transport, chronotherapy

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1314 Ethical Considerations in In-Utero Gene Editing

Authors: Shruti Govindarajan

Abstract:

In-utero gene editing with CRISPR-Cas9 opens up new possibilities for treating genetic disorders during pregnancy while still in mother’s womb. By targeting genetic mutations in the early stages of fetal development, this approach could potentially prevent severe conditions—like cystic fibrosis, sickle cell anemia, and muscular dystrophy—from causing harm. CRISPR-Cas9, which allows precise DNA edits, could be delivered into fetal cells through vectors such as adeno-associated viruses (AAVs) or nanoparticles, correcting disease-causing mutations and possibly offering lifelong relief from these disorders. For families facing severe genetic diagnoses, in-utero gene editing could provide a transformative option. However, technical challenges remain, including ensuring that gene editing only targets the intended cells and verifying long-term safety. Ethical considerations are also at the forefront of this technology. The editing of a fetus's genes brings up difficult questions about consent, especially since these genetic changes will affect the child’s entire life without their input. There's also concern over possible unintended side effects, or changes passed down to future generations. Moreover, if used beyond therapeutic purposes, this technology could be misused for ‘enhancements,’ like selecting for certain physical or cognitive traits, raising concerns about inequality and social pressures. In this way, in-utero gene editing brings both exciting potential and complex moral questions. As research progresses, addressing these scientific and ethical concerns will be key to ensuring that this technology is used responsibly, prioritizing safety, fairness, and a focus on alleviating genetic disease. A cautious and inclusive approach, along with clear regulations, will be essential to realizing the benefits of in-utero gene editing while protecting against unintended consequences.

Keywords: in-utero gene editing, CRISPR, bioethics, genetic disorder

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1313 The Clinical Characteristics and Their Relationship with Sleep Disorders in Patients with Parkinson Disease Accompanied with Cognitive Impairment

Authors: Peng Guo

Abstract:

Objective To investigate the clinical characteristics and changes of video-polysomnography (v-PSG) in Parkinson disease (PD) patients accompanied with cognitive impairment. Methods Three hundred and ninety-four patients with PD were enrolled in Beijing Tiantan Hospital, according to CI level, the patients were divided into PD without cognitive impairment (PD-NCI), PD with mild cognitive impairment (PD-MCI), and PD with dementia (PDD) group. Collect patient's demographic data, including gender, onset age, education level and duration. The cognitive function of PD patients was evaluated by Montreal cognitive assessment (MoCA) scale, and the overall cognitive function and cognitive domains of the three groups were compared.Using v-PSG to assess the sleep status of patients. Correlation analysis of MoCA Scale and v-PSG results in PD-CI group. Results 1. In 394 cases of PD, 94 cases (23.86%) in PD-NCI group , 177 cases(44.92%) in PD-MCI group , 123 cases (31.22%) in PDD group. 2.There was no significant difference in gender, age of onset, education level and duration in PD-NCI group, PD-MCI group and PDD group (P>0.05). 3. The total score of MoCA scale in PD-NCI group, PD-MCI group and PDD group decreased one by one. In PD-NCI group, PD-MCI group and PDD group, the scores of each cognitive domain in MoCA scale decreased significantly(P<0.05). 4.Compared with the PD-MCI group, PDD group had lower total sleep time, lower sleep efficiency (P<0.05). Compared with PD-NCI group, PDD group had lower total sleep time and lower sleep efficiency (P<0.05).5. The sleep efficiency of PD-CI patients is positively correlated with the total score of MoCA scale, visual spatial function, executive function, delayed recall and attention score(P<0.05). Conclusions The incidence of CI in PD patients was high; The cognitive function and cognitive domains of PD-CI patients were significantly impaired; In patients with PD-CI, total sleep time decreased, sleep efficiency decreased, and it was related to overall cognitive function and partial cognitive impairment.

Keywords: Parkinson disease, cognitive impairment, clinical characteristics, sleep disorders, video-polysomnography

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1312 Molecular Defects Underlying Genital Ambiguity in Egyptian Patients: A Systematic Review

Authors: Y. Z. Gad

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Disorders of Sex Development (DSD) are defined as congenital conditions in which development of chromosomal, gonadal or anatomical sex is atypical. The DSD are relatively prevalent in Egypt. In spite of that, the relative rarity of the individual disease types or their molecular pathologies frequently resulted in reporting on single or few cases. This augmented the challenging nature of phenotype-genotype correlation in this disease group and its utilization in the management of such medical emergency. Through critical assessment of the published DSD reports, the current review aims at analyzing the clinical characteristics of the various DSD forms in relation to the underlying molecular pathologies. A systematic literature search was done in Pubmed, using relevant keywords (Egypt versus DSD, genital ambiguity or ambiguous genitalia, the old terms of 'intersex, hermaphroditism and pseudohermaphroditism', and a list of the DSD entities and their related genes). The search yielded 24 reports of molecular data in Egyptian patients presenting with ambiguous genitalia. However, only 21 publications fulfilled the criteria of inclusion of detailed clinical descriptions and definitive molecular diagnoses of individual patients. Curation of the data yielded a total of 53 cases that were ascertained from 40 families. Fifty-one patients present with ambiguous genitalia only while 2 had multiple congenital anomalies. Parental consanguinity was noted in 60% of cases. Sex of rearing at initial presentation was female in 75% and 60% in 46,XY and 46,XX DSD cases, respectively. The external genital phenotype in 2/3 of the 46,XY DSD cases showed moderate undermasculinization [Quigley scores 3 & 4] and 1/3 had severe presentations [scores 5 & 6]. For 46,XX subjects, 1 had severe virilization of the external genitalia while 8 had moderate phenotype. Hormonal data were inconclusive or contradictory to final diagnosis in a forth of cases. Collectively, 31 families [31/40, 77.5%] with 46,XY DSD had molecular defects in the genes, 5 alpha reductase 2 (SRD5A2) [12/31], 17 beta-hydroxysteroid dehydrogenase 3 [8/31], androgen receptor [7/31], Steroidogenic factor 1 [2/31], luteinizing hormone receptor [1/31], and fibroblast growth factor receptor 1 [1/31]. In a multiethnic study, 9 families afflicted with 46,XX DSD due to 11 beta hydroxylase (CYP11B1) deficiency were documented. Two recurrent mutations, G34R and N160D, in SRD5A2 were present, respectively, in 42 and 17% of cases. Similarly, 4 recurrent mutations resulted in 89% of the CYP11B1 presentations. In conclusion, this analysis highlights the importance of autosomal recessive inheritance and inbreeding among DSD presentations, the importance of founder effect in at least 2 disorders, the difficulties in relating the genotype with the indeterminate genital phenotype, the under-reporting of some DSD subtypes, and the notion that the reported mutational profiles among Egyptian DSD cases are relatively different from those reported in other ethnic groups.

Keywords: disorders of sex development, genital ambiguity, mutation, molecular diagnosis, Egypt

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1311 Anti-Obesity Effects of Pteryxin in Peucedanum japonicum Thunb Leaves through Different Pathways of Adipogenesis In-Vitro

Authors: Ruwani N. Nugara, Masashi Inafuku, Kensaku Takara, Hironori Iwasaki, Hirosuke Oku

Abstract:

Pteryxin from the partially purified hexane phase (HP) of Peucedanum japonicum Thunb (PJT) was identified as the active compound related to anti-obesity. Thus, in this study we investigated the mechanisms related to anti-obesity activity in-vitro. The HP was fractionated, and effect on the triglyceride (TG) content was evaluated in 3T3-L1 and HepG2 cells. Comprehensive spectroscopic analyses were used to identify the structure of the active compound. The dose dependent effect of active constituent on the TG content, and the gene expressions related to adipogenesis, fatty acid catabolism, energy expenditure, lipolysis and lipogenesis (20 μg/mL) were examined in-vitro. Furthermore, higher dosage of pteryxin (50μg/mL) was tested against 20μg/mL in 3T3-L1 adipocytes. The mRNA were subjected to SOLiD next generation sequencer and the obtained data were analyzed by Ingenuity Pathway Analysis (IPA). The active constituent was identified as pteryxin, a known compound in PJT. However, its biological activities against obesity have not been reported previously. Pteryxin dose dependently suppressed TG content in both 3T3-L1 adipocytes and HepG2 hepatocytes (P < 0.05). Sterol regulatory element-binding protein-1 (SREBP1 c), Fatty acid synthase (FASN), and acetyl-CoA carboxylase-1 (ACC1) were downregulated in pteryxin-treated adipocytes (by 18.0, 36.1 and 38.2%; P < 0.05, respectively) and hepatocytes (by 72.3, 62.9 and 38.8%, respectively; P < 0.05) indicating its suppressive effects on fatty acid synthesis. The hormone-sensitive lipase (HSL), a lipid catabolising gene was upregulated (by 15.1%; P < 0.05) in pteryxin-treated adipocytes suggesting improved lipolysis. Concordantly, the adipocyte size marker gene, paternally expressed gene1/mesoderm specific transcript (MEST) was downregulated (by 42.8%; P < 0.05), further accelerating the lipolytic activity. The upregulated trend of uncoupling protein 2 (UCP2; by 77.5%; P < 0.05) reflected the improved energy expenditure due to pteryxin. The 50μg/mL dosage of pteryxin completely suppressed PPARγ, MEST, SREBP 1C, HSL, Adiponectin, Fatty Acid Binding Protein (FABP) 4, and UCP’s in 3T3-L1 adipocytes. The IPA suggested that pteryxin at 20μg/mL and 50μg/mL suppress obesity in two different pathways, whereas the WNT signaling pathway play a key role in the higher dose of pteryxin in preadipocyte stage. Pteryxin in PJT play the key role in regulating lipid metabolism related gene network and improving energy production in vitro. Thus, the results suggests pteryxin as a new natural compound to be used as an anti-obesity drug in pharmaceutical industry.

Keywords: obesity, peucedanum japonicum thunb, pteryxin, food science

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1310 Membrane Spanning DNA Origami Nanopores for Protein Translocation

Authors: Genevieve Pugh, Johnathan Burns, Stefan Howorka

Abstract:

Single-molecule sensing via protein nanopores has achieved a step-change in portable and label-free DNA sequencing. However, protein pores of both natural or engineered origin are not able to produce the tunable diameters needed for effective protein sensing. Here, we describe a generic strategy to build synthetic DNA nanopores that are wide enough to accommodate folded protein. The pores are composed of interlinked DNA duplexes and carry lipid anchors to achieve the required membrane insertion. Our demonstrator pore has a contiguous cross-sectional channel area of 50 nm2 which is 6-times larger than the largest protein pore. Consequently, transport of folded protein across bilayers is possible. The modular design is amenable for different pore dimensions and can be adapted for protein sensing or to create molecular gates in synthetic biology.

Keywords: biosensing, DNA nanotechnology, DNA origami, nanopore sensing

Procedia PDF Downloads 324
1309 Comparison of Two Home Sleep Monitors Designed for Self-Use

Authors: Emily Wood, James K. Westphal, Itamar Lerner

Abstract:

Background: Polysomnography (PSG) recordings are regularly used in research and clinical settings to study sleep and sleep-related disorders. Typical PSG studies are conducted in professional laboratories and performed by qualified researchers. However, the number of sleep labs worldwide is disproportionate to the increasing number of individuals with sleep disorders like sleep apnea and insomnia. Consequently, there is a growing need to supply cheaper yet reliable means to measure sleep, preferably autonomously by subjects in their own home. Over the last decade, a variety of devices for self-monitoring of sleep became available in the market; however, very few have been directly validated against PSG to demonstrate their ability to perform reliable automatic sleep scoring. Two popular mobile EEG-based systems that have published validation results, the DREEM 3 headband and the Z-Machine, have never been directly compared one to the other by independent researchers. The current study aimed to compare the performance of DREEM 3 and the Z-Machine to help investigators and clinicians decide which of these devices may be more suitable for their studies. Methods: 26 participants have completed the study for credit or monetary compensation. Exclusion criteria included any history of sleep, neurological or psychiatric disorders. Eligible participants arrived at the lab in the afternoon and received the two devices. They then spent two consecutive nights monitoring their sleep at home. Participants were also asked to keep a sleep log, indicating the time they fell asleep, woke up, and the number of awakenings occurring during the night. Data from both devices, including detailed sleep hypnograms in 30-second epochs (differentiating Wake, combined N1/N2, N3; and Rapid Eye Movement sleep), were extracted and aligned upon retrieval. For analysis, the number of awakenings each night was defined as four or more consecutive wake epochs between sleep onset and termination. Total sleep time (TST) and the number of awakenings were compared to subjects’ sleep logs to measure consistency with the subjective reports. In addition, the sleep scores from each device were compared epoch-by-epoch to calculate the agreement between the two devices using Cohen’s Kappa. All analysis was performed using Matlab 2021b and SPSS 27. Results/Conclusion: Subjects consistently reported longer times spent asleep than the time reported by each device (M= 448 minutes for sleep logs compared to M= 406 and M= 345 minutes for the DREEM and Z-Machine, respectively; both ps<0.05). Linear correlations between the sleep log and each device were higher for the DREEM than the Z-Machine for both TST and the number of awakenings, and, likewise, the mean absolute bias between the sleep logs and each device was higher for the Z-Machine for both TST (p<0.001) and awakenings (p<0.04). There was some indication that these effects were stronger for the second night compared to the first night. Epoch-by-epoch comparisons showed that the main discrepancies between the devices were for detecting N2 and REM sleep, while N3 had a high agreement. Overall, the DREEM headband seems superior for reliably scoring sleep at home.

Keywords: DREEM, EEG, seep monitoring, Z-machine

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1308 Usy-Cui Zeolite: An Efficient and Reusable Catalyst for Derivatives Indole Synthesis

Authors: Hassina Harkat, Samiha Taybe, Salima Loucif, Valérie Beneteau, Patrick Pale

Abstract:

Indole and its derivatives have attracted great interest because of their importance in the synthetic organic and medicinal chemistry. They are widely used as anti hypertension, anti tubercular, anticancer activity, antiviral, Alzheimer's disease, antioxidant properties, and free radical induced lipid peroxidation. Many drugs and natural products contain indole moiety, such as the vinca alkaloids, fungal metabolites and marine natural products. Generally applicable synthetic methods for indole moiety involve ring closure to form the pyrrole. Indole derivatives can also be accessed by further functionalization of the indole nucleus. Therefore we report a mild and efficient protocol for the synthesis of analogues of indole catalyzed via zeolithe USY doped with CuI under solvent-free conditions.

Keywords: indole, zeolithe, USY-CuI, heterogeneous catalysis

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