Search results for: abnormalities

Authors: Eda Jazexhiu-Postoli, Gladiola Hoxha, Ada Simeoni, Sonila Biba

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Background Neonatal hypotonia represents a commonly encountered issue in the Neonatal Intensive Care Unit and newborn nursery. The differential diagnosis is broad, encompassing chromosome abnormalities, primary muscular dystrophies, neuropathies and inborn errors of metabolism. Aim of study Our study describes some of the main clinical features of hypotonia in newborns and presents clinical cases of neonatal hypotonia we treated in our Neonatal unit in the last 3 years. Case reports Four neonates born in our hospital presented with hypotonia after birth, one preterm newborn 35-36 weeks of gestational age and three other term newborns (38-39 weeks of gestational age). Prenatal data revealed a decrease in fetal movements in both cases. Intrapartum meconium-stained amniotic fluid was found in 75% of our hypotonic newborns. Clinical features included inability to establish effective respiratory movements and need for resuscitation in the delivery room, respiratory distress syndrome, feeding difficulties and need for oro-gastric tube feeding, dysmorphic features, hoarse voice and moderate to severe muscular hypotonia. The genetic workup revealed the diagnosis of Autosomal Recessive Congenital Myasthenic Syndrome 1-B, Sotos Syndrome, Spinal Muscular Atrophy Type 1 and Transient Hypotonia of the Newborn. Two out of four hypotonic neonates were transferred to the Pediatric Intensive Care Unit and died at the age of three to five months old. Conclusion Hypotonia is a concerning finding in neonatal care and it is suggested by decreased intrauterine fetal movements, failure to establish first breaths, respiratory distress and feeding difficulties in the neonate. Prognosis is determined by its etiology and time of diagnosis and intervention.

Keywords: hypotonic neonate, respiratory distress, feeding difficulties, fetal movements

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Authors: Ana Neves, John Leander, Ignacio Gonzalez, Raid Karoumi

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Systematic monitoring and inspection are needed to assess the present state of a structure and predict its future condition. If an irregularity is noticed, repair actions may take place and the adequate intervention will most probably reduce the future costs with maintenance, minimize downtime and increase safety by avoiding the failure of the structure as a whole or of one of its structural parts. For this to be possible decisions must be made at the right time, which implies using systems that can detect abnormalities in their early stage. In this sense, Structural Health Monitoring (SHM) is seen as an effective tool for improving the safety and reliability of infrastructures. This paper explores the decision-making problem in SHM regarding the maintenance of civil engineering structures. The aim is to assess the present condition of a bridge based exclusively on measurements using the suggested method in this paper, such that action is taken coherently with the information made available by the monitoring system. Artificial Neural Networks are trained and their ability to predict structural behavior is evaluated in the light of a case study where acceleration measurements are acquired from a bridge located in Stockholm, Sweden. This relatively old bridge is presently still in operation despite experiencing obvious problems already reported in previous inspections. The prediction errors provide a measure of the accuracy of the algorithm and are subjected to further investigation, which comprises concepts like clustering analysis and statistical hypothesis testing. These enable to interpret the obtained prediction errors, draw conclusions about the state of the structure and thus support decision making regarding its maintenance.

Keywords: artificial neural networks, clustering analysis, model-free damage detection, statistical hypothesis testing, structural health monitoring

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Authors: Mohammad Alkhatatbeh, Nehad Ayoub, Nizar Mhaidat, Nesreen Saadeh, Lisa Lincz

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CD36 is involved in the development of atherosclerosis by enhancing macrophage endocytosis of oxidized-low density lipoproteins and foam cell formation. Soluble CD36 (sCD36) was found to be elevated in type 2 diabetic patients and was supposed to act as a marker of insulin resistance and atherosclerosis. In young subjects, sCD36 was associated with cardiovascular risk factors including obesity and hypertriglyceridemia. This study was conducted to further investigate the relationship between plasma sCD36 and cardiovascular risk factors among middle-aged patients with metabolic syndrome (MetS) and healthy controls. SCD36 concentrations were determined by enzyme-linked immunosorbent assays (ELISA) for 41 patients with MetS and 36 healthy controls. Data for other variables were obtained from patients' medical records. SCD36 concentrations were relatively low compared to most other studies and were not significantly different between the MetS group and controls (P-value=0.17). SCD36 was also not correlated with age, body mass index, glucose, lipid profile, serum electrolytes and blood counts. SCD36 was not significantly different between subjects with obesity, hyperglycemia, dyslipidemia, hypertension or cardiovascular disease and those without these abnormalities (P-value > 0.05). The inconsistency between results reported in this study and other studies may be unique to the study population or be a result of the lack of a reliable standardized method for determining absolute sCD36 concentrations. However, further investigations are required to assess CD36 tissue expression in the study population and to assess the accuracy of various commercially available sCD36 ELISA kits. Thus, the availability of a standardized simple sCD36 ELISA that could be performed in any basic laboratory would be more favorable to the specialized flow cytometry methods that detect CD36+ microparticles if it was to be used as a biomarker.

Keywords: metabolic syndrome, CD36, cardiovascular risk, obesity, type 2 diabetes mellitus

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Authors: Akshada Amit Koparde, Candrakant S. Magdum

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Objective: To investigate the anti-arthritic activity of chloroform extract and Isolate 1 of Eulophia ochreata Lindl and dichloromethane extract and Isolate 2 of Zingiber cassumunar Roxb in adjuvant arthritic (AA) rat model induced by Freund’s complete adjuvant (FCA). Methods: Forty two healthy albino rats were selected and randomly divided into six groups. Freund’s complete adjuvant (FCA) was used to induce arthritis and then treated with chloroform extract, isolate 1 and dichloromethane extract, isolate 2 for 28 days. The various parameters like paw volume, haematological parameters (RBC, WBC, Hb and ESR), were studied. Structural elucidation of active constituents isolate 1 and isolate 2 from Eulophia ochreata Lindl and Zingiber cassumunar Roxb will be done using GCMS and H1NMR. Results: In FCA induced arthritic rats, there was significant increase in rat paw volume whereas chloroform extract and Isolate 1 of Eulophia ochreata Lindl and dichloromethane extract and Isolate 2 of Zingiber cassumunar Roxb treated groups showed strong significant reduction in paw volume. The altered haematological parameters in the arthritic rats were significantly recovered to near normal by the treatment with extracts at the dose of 200 mg/kg. Further histopathological studies revealed the anti-arthritic activity of Eulophia ochreata Lindl and Zingiber cassumunar Roxb by preventing cartilage and bone destruction of the arthritic joints of AA rats. Conclusion: Extracts and isolates of Eulophia ochreata Lindl and Zingiber cassumunar Roxb have shown anti-arthritic activity. Decrease in paw volume and normalization of haematological abnormalities in adjuvant induced arthritic rats is significantly seen in the experiment. Further histopathological studies confirmed the anti-arthritic activity of Eulophia ochreata Lindl and Zingiber cassumunar Roxb.

Keywords: arthritis, Eulophia ochreata Lindl, Freund's complete adjuvant, paw volume, Zingiber cassumunar Roxb

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Authors: Ali Kassem, Mohamed Alsenbasy, Ahmed Nagaah

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Background: Diabetic foot is one of the often neglected complications of diabetes mellitus It was reported that patients of diabetic foot ulcer (DFU) have considerable morbidity and mortality. Due to arterial abnormalities, diabetic neuropathy, as well as the tendency to delayed wound healing, foot infection and or gangrene is relatively common in diabetic patients. Foot related problems are responsible for up to 50% of diabetic related hospital admissions. Aim of work: The aim of the present study is to assess the risk factors for DFU in diabetic patients attending Sohag University Hospitals (Upper Egypt) Material and methods: The present study includes 100 diabetic foot patients attending the diabetic outpatient clinic of Sohag University Hospitals. For all of the studied patients the following were done: Full medical history and clinical examination; thorough foot examination; Laboratory tests including: Blood glucose level, HBA1c, serum lipids and renal function tests, ECG and Echocardiography, Doppler study on the lower limbs. Results: Sixty eight percent of the affected patients were males versus 32 % female patients. All male patients and none of the female were smoker. Seventy nine percent of patients were living in rural areas versus 14 % in urban areas. Duration of diabetes was more than 12 years in 74%, less than 12 years in 26% of patients. Fifty percent of patients have associated hypertension, 46% have dyslipidemia, 18% have ischemic heart disease or old myocardial infarction and 8% have impaired renal function. History of previous foot ulcers was reported in 11 % and foot amputation in 2% of patients. Conclusion: Male gender, low socioeconomic status, smoking, long duration of diabetes, other cardiovascular risk factors particularly hypertension and previous history of foot ulceration are the major risk factors for diabetic foot in our locality.

Keywords: diabetic foot, diabetic neuropathy, foot gangrene, risk factors for diabetic complications

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Authors: Abir Dey, Shams Noman

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Introduction: Offshore Island is the remote and isolated area from the terrestrial mainland. They are deprived of their needs. The children from an offshore island are usually underserved in the case of health care because it is a remote area where the health care systems are quite poor compared to mainland. So, the proper information is required for appropriate planning to reduce underlying causes behind visual deprivation among the surviving children of the Offshore Island. Purpose: The purpose of this study was to determine ocular morbidities, knowledge, and barriers of eye care services among children in an Offshore Island. Methods: The study team visited, and all data were collected from different rural communities at Sandwip Upazila, Chittagong district for screening the children aged 5-16 years old by doing spot examination. The whole study was conducted in both qualitative and quantitative methods. To determine ocular status of children, examinations were done under skilled Ophthalmologists and Optometrists. A focus group discussion was held. The sample size was 490. It was a community based descriptive study and the sampling method was purposive sampling. Results: In total 490 children, about 56.90% were female and 43.10% were male. Among them 456 were school-going children (93.1%) and 34 were non-school going children (6.9%). In this study the most common ocular morbidity was Allergic Conjunctivitis (35.2%). Other mentionable ocular morbidities were Refractive error (27.7%), Blepharitis (13.8%), Meibomian Gland Dysfunction (7.5%), Strabismus (6.3%) and Amblyopia (6.3%). Most of the non-school going children were involved in different types of domestic work like farming, fishing, etc. About 90.04% children who had different ocular abnormalities could not attend to the doctor due to various reasons. Conclusions: The ocular morbidity was high in rate on the offshore island. Eye health care facility was also not well established there. Awareness should be raised about necessity of maintaining hygiene and eye healthcare among the island people. Timely intervention through available eye care facilities and management can reduce the ocular morbidity rate in that area.

Keywords: morbidities, screening, barriers, offshore island, knowledge

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Authors: Krzysztof Plesiewicz, Izabela Plesiewicz, Krzysztof Chiżyński, Marzenna Zielińska

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Background: Obesity is an independent risk factor for cardiovascular diseases. There are several anthropometric parameters proposed to estimate the level of obesity, but until now there is no agreement which one is the best predictor of cardiometabolic risk. Scientists defined metabolically obese normal weight, who suffer from metabolic abnormalities, the same as obese individuals, and defined this syndrome as normal weight obesity (NWO). Aim of the study: The aim of our study was to determine the occurrence of overweight and obesity in a cohort of young, adult women, using standard and complementary methods of obesity assessment and to indicate those, who are at risk of obesity. The second aim of our study was to test additional methods of obesity assessment and proof that body mass index using alone is not sufficient parameter of obesity assessment. Materials and methods: 384 young women, aged 18-32, were enrolled into the study. Standard anthropometric parameters (waist to hips ratio (WTH), waist to height ratio (WTHR)) and two other methods of body fat percentage measurement (BFPM) were used in the study: electrical bioimpendance analysis (BIA) and skinfold measurement test by digital fat body mass clipper (SFM). Results: In the study group 5% and 7% of participants had waist to hips ratio and accordingly waist to height ratio values connected with visceral obesity. According to BMI 14% participants were overweight and obese. Using additional methods of body fat assessment, there were 54% and 43% of obese for BIA and SMF method. In the group of participants with normal BMI and underweight (not overweight, n =340) there were individuals with the level of BFPM above the upper limit, for the BIA 49% (n =164) and for the SFM 36 % (n=125). Statistical analysis revealed strong correlation between BIA and SFM methods. Conclusion: BMI using alone is not a sufficient parameter of obesity assessment. High percentage of young women with normal BMI values seem to be normal weight obese.

Keywords: electrical bioimpedance, normal weight obesity, skin-fold measurement test, women

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Authors: Rita Emília Szabó, Róbert Polanek, Tünde Tőkés, Zoltán Szabó, Szabolcs Czifrus, Katalin Hideghéty

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Purpose: Several feature of zebrafish are making them amenable for investigation on therapeutic approaches such as ionizing radiation. The establishment of zebrafish model for comprehensive radiobiological research stands in the focus of our investigation, comparing the radiation effect curves of neutron and photon irradiation. Our final aim is to develop an appropriate vertebrate model in order to investigate the relative biological effectiveness of laser driven ionizing radiation. Methods and Materials: After careful dosimetry series of viable zebrafish embryos were exposed to a single fraction whole-body neutron-irradiation (1,25; 1,875; 2; 2,5 Gy) at the research reactor of the Technical University of Budapest and to conventional 6 MeV photon beam at 24 hour post-fertilization (hpf). The survival and morphologic abnormalities (pericardial edema, spine curvature) of each embryo were assessed for each experiment at 24-hour intervals from the point of fertilization up to 168 hpf (defining the dose lethal for 50% (LD50)). Results: In the zebrafish embryo model LD50 at 20 Gy dose level was defined and the same lethality were found at 2 Gy dose from the reactor neutron beam resulting RBE of 10. Dose-dependent organ perturbations were detected on macroscopic (shortening of the body length, spine curvature, microcephaly, micro-ophthalmia, micrognathia, pericardial edema, and inhibition of yolk sac resorption) and microscopic (marked cellular changes in skin, cardiac, gastrointestinal system) with the same magnitude of dose difference. Conclusion: In our observations, we found that zebrafish embryo model can be used for investigating the effects of different type of ionizing radiation and this system proved to be highly efficient vertebrate model for preclinical examinations.

Keywords: ionizing radiation, LD50, relative biological effectiveness, zebrafish embryo

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Authors: Archana. S, Usha Rani. G, Anand Balakrishnan, Sanjana.R, Solomon F, Vijayalakshmi. J

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Background: There is evidence that male factors contribute to the infertility of up to 50% of couples, who are evaluated and treated for infertility using advanced assisted reproductive technologies. Genetic abnormalities, including sperm chromosome aneuploidy as well as structural aberrations, are one of the major causes of male infertility. Recent advances in technology expedite the evaluation of sperm aneuploidy. The purpose of the study was to de-termine the prevalence of sperm aneuploidy in infertile males and the degree of association between DNA fragmentation and sperm aneuploidy. Methods: In this study, 75 infertile men were included, and they were divided into four abnormal groups (Oligospermia, Terato-spermia, Asthenospermia and Oligoasthenoteratospermia (OAT)). Men with children who were normozoospermia served as the control group. The Fluorescence in situ hybridization (FISH) method was used to test for sperm aneuploidy, and the Sperm Chromatin Dispersion Assay (SCDA) was used to measure the fragmentation of sperm DNA. Spearman's correla-tion coefficient was used to evaluate the relationship between sperm aneuploidy and sperm DNA fragmentation along with age. P < 0.05 was regarded as significant. Results: 75 partic-ipants' ages varied from 28 to 48 years old (35.5±5.1). The percentage of spermatozoa bear-ing X and Y was determined to be statistically significant (p-value < 0.05) and was found to be 48.92% and 51.18% of CEP X X 1 – nucish (CEP XX 1) [100] and CEP Y X 1 – nucish (CEP Y X 1) [100]. When compared to the rate of DNA fragmentation, it was discovered that infertile males had a greater frequency of sperm aneuploidy. Asthenospermia and OAT groups in sex chromosomal aneuploidy were significantly correlated (p<0.05). Conclusion: Sperm FISH and SCDA assay results showed increased sperm aneuploidy frequency, and DNA fragmentation index in infertile men compared with fertile men. There is a significant relationship observed between sperm aneuploidy and DNA fragmentation in OAT patients. When evaluating male variables and idiopathic infertility, the sperm FISH screening method can be used as a valuable diagnostic tool.

Keywords: ale infertility, dfi (dna fragmentation assay) (scd-sperm chromatin dispersion).art (artificial reproductive technology), trisomy, aneuploidy, fish (fluorescence in-situ hybridization), oat (oligoasthoteratospermia)

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Authors: Nazihe Sedighi, Mohsen Nokhbatolphoghaei

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Bisphenol A (BPA) is a monomer used in the manufacture of polycarbonate plastics. Due to having properties such as transparency, heat and impact resistance, it is used widely in medicine, sorts, electronic components, and food containers. It is also used in the production of resins which is applied for lining cans. BPA releases from resins and polycarbonate when it is heated or continuously used the containers from which BPA can enter the body. There are several reports indicating the presence of BPA in the placenta, amniotic fluid, and the embryo itself. While researchers investigated the teratogenic effect of BPA on embryos, very limited work has been done on the effects of BPA when applied from early stages of development. In this study, The teratogenic effect of BPA was investigated at earliest preimplantation (day zero) through day 15.5 of the development of Balb/C mouse embryos. After ensuring the pregnancy via observing vaginal plug, Pregnant mice were divided into five groups. For the three experimental groups, the amount of 500, 750, and 1000 mg/kg/d Bisphenol A was given orally according to body weight. The sham group that was treated with sesame oil, which was used as vehicle and control group remained intact. On day 18.5 of gestation, embryos were removed from the uterus. Randomly half of the embryo were fixed in Bouin for tissue analysis. The other half were prepared for skeletal system staining using Alizarin Red and alcian blue dies. The results showed that the embryonic weight and the crown-rump length of embryos decreased significantly (P < 0.05) in all experimental groups compared to the control group and the sham. In this study, skeletal abnormalities such as delay in ossification of skull and limbs as well as the deviation in the backbone were seen. This research suggests that pregnant mothers need to be aware of possible teratogenic effects of BPA at any stage of pregnancy especially from early to mid stages. In this case, pregnant mothers may need to stop using any manufacture of polycarbonate plastics, as a container for food or drinking.

Keywords: bisphenol A, development, polycarbonate plastic, skeletal system, teratogenicity

Procedia PDF Downloads 257

Authors: Angelis P. Barlampas

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Purpose or Learning Objective It is well known that previous examinations play a major role in futural diagnosis, thus avoiding unnecessary new exams that cost in time and money both for the patient and the health system. A case is presented in which past patient’s results, in combination with the least needed new tests, give an easy final diagnosis. Methods or Background A middle aged man visited the emergency department complaining of hard controlled, persisting fever for the last few days. Laboratory tests showed an elevated number of white blood cells with neutrophil shift and abnormal CRP. The patient was admitted to hospital a month ago for continuing lungs symptomatology after a recent covid-19 infection. Results or Findings Computed tomography scanning showed a solid mass with spiculating margins in right lower lobe. After intravenous iodine contrast administration, there was mildly peripheral enhancement and eccentric non enhancing area. A pneumonic cancer was suspected. Comparison with the patient’s latest computed tomography revealed no mass in the area of interest but only signs of recent post covid-19 lung parenchyma abnormalities. Any new mass that appears in a month’s time span can not be a cancer but a benign lesion. It was obvious that an abscess was the most suitable explanation. The patient was admitted to hospital, and antibiotic therapy was given, with very good results. After a few days, the patient was afebrile and in good condition. Conclusion In this case , a PET scan or a biopsy was avoided, thanks to the patient’s medical history and the availability of previous examinations. It is worthy encouraging the patients to keep their medical records and organizing more efficiently the health system with the current technology of archiving the medical examinations, too.

Keywords: covid-19, chest ct, cancer, abscess, fever

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

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Introduction: Celiac disease (CD) is a chronic autoimmune inflammatory enteropathy caused by gluten. The clinical presentation is very variable. Malabsorption in the MC is responsible for an alteration of the bone metabolism. Our purpose is to study the osteoarticular manifestations related to this condition. Material and methods: It is a retrospective study of 41 cases of CD diagnosed on clinical, immunological, endoscopic and histological arguments, in the Internal Medicine and Gastroenterology Department of Farhat Hached Hospital between September 2005 and January 2016. Results: Osteoarticular manifestations were found in 9 patients (22%) among 41 patients presenting CD. These were 7 women and 2 men with an average age of 35.7 years (25 to 67 years). These manifestations were revelatory of CD in 3 cases. Abdominal pain and diarrhea were present in 6 cases. Inflammatory polyarthralgia of wrists and knees has been reported in 7 patients. Mechanical mono arthralgia was noted in 2 patients. Biological tests revealed microcytic anemia by iron deficiency in 7 cases, hypocalcemia in 5 cases, Hypophosphatemia in 3 cases and elevated alkaline phosphatases in 3 cases. Upper gastrointestinal endoscopy with duodenal biopsy found villous atrophy in all cases. In immunology, Anti-transglutaminase antibodies were positive in all patients, Anti-endomysium in 7 cases. Measurement of bone mineral density (BMD) by biphotonic X-ray absorptiometer with evaluation of the T-score and the Z-score was performed in Twenty patients (48.8%). It was normal in 7 cases (33%) and showed osteopenia in 5 patients (25%) and osteoporosis in 2 patients (10%). All patients were treated with a Gluten-free diet associated with vitamin D and calcium substitution in 5 cases. The evolution was favorable in all cases with reduction of bone pain and normalization of the phosphocalcic balance. Conclusion: The bone impact of CD is frequent but often asymptomatic. Patients with CD should be evaluated by the measurement of bone mineral density and monitored for calcium and vitamin D deficiencies.

Keywords: bone mineral density, celiac disease, osteoarticular manifestations, vitamin D and calcium

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Authors: Ahsan Khan, Nazish Shah, Muhammad Salman

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The present study deals with the toxicological effects of copper, lead and chromium on brain and liver tissues of grass carp (Ctenopharyngodon idella). The average length of experimental fish was 8.5 ± 5.5 cm and weighed 9.5 ± 6.5 g. Grass carp was exposed to lethal concentration (LC₁₅) of copper, lead and chromium for 24, 48, 72 and 96 hours respectively. (LC₁₅) for copper was 1.5, 1.4, 1.2 and 1mgL⁻¹. Similarly, LC₁₅ of lead was 250, 235, 225 and 216mgL⁻¹ while (LC₁₅) for chromium was 25.5, 22.5, 20 and 18mgL⁻¹ respectively. During the time of exposure against various doses of heavy metals the grass carp showed some behavioral changes. In the initial stages of experiment, the rapid movements and gulping of air were observed. Several times the fish tried to jump to scat from the toxic median. In addition, the accumulation of heavy metals in different tissues of grass carp particularly in liver and brain tissues were observed. Lead was highly accumulated in brain tissue after the exposure of fish for 24 and 48 hours, while highly accumulated in liver tissues after the exposure of fish for 72 and 96 hours. Chromium was highly accumulated in the liver tissues after the exposure of fish for 24 hours while its accumulation was found highly in the brain tissues after the exposure of fish for 48, 72 and 96 hours. Similarly, accumulation of copper concentration was found highly in brain tissues after the exposure of 48 and 96 hours while its accumulation was high in liver tissues after the exposure of 24 and 72 hours. Comparatively maximum accumulation of lead was found in brain and liver tissues of grass carp followed by chromium and copper. Furthermore, accumulation of these metals caused many abnormalities like gliosis, destruction of cell, change in cell shape and shrinkage of cells in brain tissue while in liver tissues aggregation in hepatocytes, widen space between cells and also destruction of cell was observed. These experiments and observations can be useful to monitor the aquatic pollution and quality of aquatic environment system.

Keywords: brain, grass carp, liver, lethal concentration, toxicity

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Authors: M. Borgie, Z. Dagher, F. Ledoux, A. Verdin, F. Cazier, H. Greige, P. Shirali, D. Courcot

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In October 2013, the International Agency for Research on Cancer (IARC) classified outdoor air pollution and fine particulate matter (PM2.5) as carcinogenic to humans. Despite the clearly relationship established by epidemiological studies between PM exposure and the onset of respiratory and cardiovascular diseases, uncertainties remain about the physiopathological mechanisms responsible for these diseases. The aim of this work was to evaluate the toxicological effects of two samples of atmospheric PM2.5 collected at urban and rural sites on human bronchial epithelial cells, BEAS-2B, especially to investigate the metabolic activation of organic compounds, the alteration of epigenetic mechanisms (i.e. microRNAs genes expression), the phosphorylation of H2AX and the telomerase activity. Our results showed a significant increase in CYP1A1, CYP1B1, and AhRR genes expression, miR-21 gene expression, H2AX phosphorylation and telomerase activity in BEAS-2B cells after their exposure to PM2.5, both in a dose and site-dependent manner. These results showed that PM2.5, especially urban PM, are able to induce the expression of metabolizing enzymes which can provide metabolic biotransformation of organic compounds into more toxic and carcinogenic metabolites, and to induce the expression of the oncomiR miR-21 which promotes cell growth and enhances tumor invasion and metastasis in lung cancer. In addition, our results have highlighted the role of PM2.5 in the activation of telomerase, which can maintain the telomeres length and subsequently preventing cell death, and have also demonstrated the ability of PM2.5 to induce DNA breaks and thus to increase the risk of mutations or chromosomal translocations that lead to genomic instability. All these factors may contribute to cell abnormalities, and thus the development of cancer.

Keywords: BEAS-2B cells, carcinogenesis, epigenetic alterations and genotoxicity, PM2.5

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Authors: Min L. Stewart, Patrick Johnston

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Predictive coding has been proposed as a general explanatory framework for understanding the neural mechanisms of perception. As such, an underweighting of perceptual priors has been hypothesised to underpin a range of differences in inferential and sensory processing in autism spectrum disorders. However, empirical evidence to support this has not been well established. The present study uses an electroencephalography paradigm involving changes of facial identity and person category (actors etc.) to explore how levels of autistic traits (AT) affect predictive coding at multiple stages in the visual processing hierarchy. The study uses a rapid serial presentation of faces, with hierarchically structured sequences involving both periodic and aperiodic repetitions of different stimulus attributes (i.e., person identity and person category) in order to induce contextual expectations relating to these attributes. It investigates two main predictions: (1) significantly larger and late neural responses to change of expected visual sequences in high-relative to low-AT, and (2) significantly reduced neural responses to violations of contextually induced expectation in high- relative to low-AT. Preliminary frequency analysis data comparing high and low-AT show greater and later event-related-potentials (ERPs) in occipitotemporal areas and prefrontal areas in high-AT than in low-AT for periodic changes of facial identity and person category but smaller ERPs over the same areas in response to aperiodic changes of identity and category. The research advances our understanding of how abnormalities in predictive coding might underpin aberrant perceptual experience in autism spectrum. This is the first stage of a research project that will inform clinical practitioners in developing better diagnostic tests and interventions for people with autism.

Keywords: hierarchical visual processing, face processing, perceptual hierarchy, prediction error, predictive coding

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Authors: M. P. Dandekar, A. P. Bharne, P. T. Borkar, D. M. Kokare, N. K. Subhedar

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Ethanol ingestion by the mother ensue adverse consequences for her offspring. Herein, we examine the behavioral phenotype and neural substrate of the offspring of the mother on ethanol. Female rats were fed with ethanol-containing liquid diet from 8 days prior of conception and continued till 25 days post-parturition to coincide with weaning. Behavioral changes associated with anxiety, depression and learning and memory were assessed in the offspring, after they attained adulthood (day 85), using elevated plus maze (EPM), forced swim (FST) and novel object recognition tests (NORT), respectively. The offspring of the alcoholic mother, compared to those of the pair-fed mother, spent significantly more time in closed arms of EPM and showed more immobility time in FST. Offspring at the age of 25 and 85 days failed to discriminate between novel versus familiar object in NORT, thus reflecting anxiogenic, depressive and amnesic phenotypes. Neuropeptide cocaine- and amphetamine-regulated transcript peptide (CART) is known to be involved in central effects of ethanol and hence selected for the current study. Twenty-five days old pups of the alcoholic mother showed significant augmentation in CART-immunoreactivity in the cells of Edinger-Westphal (EW) nucleus and lateral hypothalamus. However, a significant decrease in CART-immunoreactivity was seen in nucleus accumbens shell (AcbSh), lateral part of bed nucleus of the stria terminalis (BNSTl), locus coeruleus (LC), hippocampus (CA1, CA2 and CA3), and arcuate nucleus (ARC) of the pups and/or adults offspring. While no change in the CART-immunoreactive fibers of AcbSh and BNSTl, CA2 and CA3 was noticed in the 25 days old pups, the CART-immunoreactive cells in EW and paraventricular nucleus (PVN), and fibers in the central nucleus of amygdala of 85 days old offspring remained unaffected. We suggest that the endogenous CART system in these discrete areas, among other factors, may be a causal to the abnormalities in the next generation of an alcoholic mother.

Keywords: anxiety, depression, CART, ethanol, immunocytochemistry

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Authors: Sahar M. El-Gowilly, Mai M. Helmy, Hanan M. El-Gowelli

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Methotrexate (MTX) is widely used in treatment of cancers and autoimmune diseases. However, nephrotoxicity is one of the most important side effects of MTX. The peroxisome proliferator-activated receptor gamma agonist, pioglitazone (PIO), is known to exert anti-inflammatory and reno-protective effects in various kidney injuries. The purpose of this study was to investigate the potential involvement of endothelial damage in MTX-induced renal injury and to elaborate the possible protective effect of PIO against MTX-induced nephropathy. Compared with saline-treated rats, treatment with MTX (7 mg/kg for 3 day) caused significant elevations in serum levels of urea and creatinine, increased renal nitrate/nitrite level and impaired renovascular responsiveness of isolated perfused kidney to endothelium-dependent vasodilations induced by acetylcholine (0.01-2.43 nmol) and isoprenaline (1µmol). These effects were abolished by concurrent treatment with PIO (2.5 mg/kg, for 5 days starting two days before MTX). Alternatively, MTX treatment did not affect endothelium-independent renovascular relaxation induced by sodium nitroprusside (1-30 μmole). The possibility that alterations in renal antioxidants, circulating cytokine and apoptotic factor (Fas) levels contributed to MTX-PIO interaction was assessed. PIO treatment abrogated renal oxidative stress (decreased reduced glutathione and catalase activity and increased malondialdehyde), elevated serum cytokine (interleukin-6, interleukin-10, tumor necrosis factor-alpha and transforming growth factor-beta1) and Fas induced by MTX. Histologically, MTX caused defused tubular cells swelling and vacuolization associated with endothelial damage in renal arterioles. These effects disappeared upon co-treated with PIO. Collectively, PIO abolished MTX-induced endothelium dysfunction and nephrotoxicity via ameliorating oxidative stress and rectifying cytokines and Fas abnormalities caused by MTX.

Keywords: methotrexate, pioglitazone, endothelium, kidney

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Authors: Sahar M. El-Gowilly, Mai M. Helmy, Hanan M. El-Gowelli

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Methotrexate (MTX) is widely used in treatment of cancers and autoimmune diseases. However, nephrotoxicity is one of its most important side effects. The peroxisome proliferator-activated receptor gamma agonist, pioglitazone, is known to exert antiinflammatory and reno-protective effects in various kidney injuries. The purpose of this study was to investigate the potential involvement of endothelial damage in MTX-induced renal injury and to elaborate the possible protective effect of pioglitazone against MTX-induced endothelial impairment. Compared with saline-treated rats, treatment with MTX (7 mg/kg for 3 day) caused significant elevations in serum levels of urea and creatinine, increased renal nitrate/nitrite level and impaired renovascular responsiveness of isolated perfused kidney to endothelium-dependent vasodilations induced by acetylcholine (0.01-2.43 nmol) and isoprenaline (1µmol). These effects were abolished by concurrent treatment with pioglitazone (2.5 mg/kg, for 5 days starting two days before MTX). Alternatively, MTX treatment did not affect endothelium-independent renovascular relaxation induced by sodium nitroprusside (0.001-10 μmole). The possibility that alterations in renal antioxidants, circulating cytokine and apoptotic factor (Fas) levels contributed to MTX-pioglitazone interaction was assessed. Pioglitazone treatment abrogated renal oxidative stress (decreased reduced glutathione and catalase activity and increased malondialdehyde), elevated serum cytokine (interleukin-6, interleukin-10, tumor necrosis factor-alpha and transforming growth factor-beta1) and Fas induced by MTX. Histologically, MTX caused defused tubular cells swelling and vacuolization associated with endothelial damage in renal arterioles. These effects disappeared upon co-treated with pioglitazone. Collectively, pioglitazone abolished MTX-induced endothelium dysfunction and nephrotoxicity via ameliorating oxidative stress and rectifying cytokines and Fas abnormalities caused by MTX.

Keywords: methotrexate, pioglitazone, endothelium, kidney

Procedia PDF Downloads 477

Authors: Peter David Reiss

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The concept of the psychosis prodrome has allowed for the identification of adolescent and young adult patients who have a significantly elevated risk of developing schizophrenia spectrum disorders. A number of different interventions have been tested in order to prevent or delay progression of symptoms. To date, there has been no consistent meta-analytical evidence to support efficacy of antipsychotic treatment for patients in the prodromal state, and their use remains therefore inconclusive. Although antipsychotics may manage symptoms transiently, they have not been found to prevent or delay onset of psychotic disorders. Furthermore, pharmacological intervention in high-risk individuals remains controversial, because of the antipsychotic side effect profile in a population in which only about 20 to 35 percent will eventually convert to psychosis over a two-year period, with even after two years conversion rates not exceeding 30 to 40 percent. This general estimate is additionally problematic, in that it ignores the fact that there is significant variation in individual risk among clinical high-risk cases. The current lack of reliable tests for at-risk patients makes it difficult to justify individual treatment decisions. Preventive treatment should ideally be dictated by an individual’s risk while minimizing potentially harmful medication exposure. This requires more accurate predictive assessments by using valid and accessible prognostic markers. The following will compare prediction and risk modification potential of behavioral biomarkers such as disturbances of basic sense of self and emotion awareness, neurocognitive biomarkers such as attention, working and declarative memory, and neurophysiological biomarkers such as glutamatergic abnormalities and NMDA receptor dysfunction. Identification of robust biomarkers could therefore not only provide more reliable means of psychosis prediction, but also help test and develop new clinical interventions targeted at the prodromal state.

Keywords: at-risk mental state, biomarkers, glutamatergic system, NMDA receptor, psychosis prodrome, schizophrenia

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Authors: Rona Hanani Simamora, Bahagia Loebis, M. Surya Husada

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Background: The exact cause of schizophrenia is not known, although several etiology theories have been proposed for the disease, including immune dysfunction or autoimmune mechanisms. Cytokines including Tnf-α has an important role in the pathophysiology of schizophrenia and the effects of pharmacological treatment with antipsychotics. Nicotine is widespread effects on the brain, immune system and cytokine levels. Smoking among schizophrenic patients could play a role in the altered cytokine profiles of schizophrenia such as Tnf-α. Aims: To determine differences of serum Tnf-α levels between schizophrenic patients with smoking in male and healthy control. Methods: This study was a comparative analytic study, divided into two groups: 1) group of male schizophrenic patients with smoking (n1=30) with inclusion criteria were patients who have been diagnosed schizophrenic based PPDGJ-III, 20-60 years old, male, smoking, chronic schizophrenic patients in the stable phase and willing to participate this study. Exclusion criteria were having other mental disorders and comorbidity with other medical illnesses. 2) healthy control group (n2=30) with inclusion criteria were 20-60 years old, male, smoking, willing to participate this study. Exclusion criteria were having mental disorder, a family history of psychiatric disorders, the other medical illnesses, a history of alcohol and other substances abuse (except caffeine and nicotine). Serum Tnf-α were analyzed using the Quantikine HS Human Tnf –α Immunoassay. Results: Serum Tnf-α level measure in patient schizophrenia male with smoking and compared with the healthy control subjects. Tnf-α levels were significantly higher in patients schizophrenic male with smoking (25,79±27,96) to healthy control subjects (2,74±2,19), by using the Mann Whitney U test showed a statistically significant difference was observed for serum Tnf-α level (p < 0,001). Conclusions: Schizophrenia is a highly heterogeneous disorder, and this study shows an increase Tnf-α as pro-inflammation cytokines in schizophrenics. These results suggest an immune abnormalities may be involved in the etiology and pathophysiology of schizophrenia.

Keywords: male, schizophrenic, smoking, Tnf Alpha

Procedia PDF Downloads 204

Authors: Amirreza Fazely Hamedani, Muzzamil Aziz, Philipp Wieder, Ramin Yahyapour

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Software-defined networking in recent years came into the sight of so many network designers as a successor to the traditional networking. Unlike traditional networks where control and data planes engage together within a single device in the network infrastructure such as switches and routers, the two planes are kept separated in software-defined networks (SDNs). All critical decisions about packet routing are made on the network controller, and the data level devices forward the packets based on these decisions. This type of network is vulnerable to DDoS attacks, degrading the overall functioning and performance of the network by continuously injecting the fake flows into it. This increases substantial burden on the controller side, and the result ultimately leads to the inaccessibility of the controller and the lack of network service to the legitimate users. Thus, the protection of this novel network architecture against denial of service attacks is essential. In the world of cybersecurity, attacks and new threats emerge every day. It is essential to have tools capable of managing and analyzing all this new information to detect possible attacks in real-time. These tools should provide a comprehensive solution to automatically detect, predict and prevent abnormalities in the network. Big data encompasses a wide range of studies, but it mainly refers to the massive amounts of structured and unstructured data that organizations deal with on a regular basis. On the other hand, it regards not only the volume of the data; but also that how data-driven information can be used to enhance decision-making processes, security, and the overall efficiency of a business. This paper presents an intelligent big data framework as a solution to handle illegitimate traffic burden on the SDN network created by the numerous DDoS attacks. The framework entails an efficient defence and monitoring mechanism against DDoS attacks by employing the state of the art machine learning techniques.

Keywords: apache spark, apache kafka, big data, DDoS attack, machine learning, SDN network

Procedia PDF Downloads 138

Authors: Oktavian Prasetia Wardana, Martono Tri Utomo, Risa Etika, Kartika Darma Handayani, Dina Angelika, Wurry Ayuningtyas

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Background: Critically ill neonates are newborn babies with high-risk factors that potentially cause disability and/or death. Scoring systems for determining the severity of the disease have been widely developed as well as some designs for use in neonates. The SNAPPE-II method, which has been used as a mortality predictor scoring system in several referral centers, was found to be slow in assessing the outcome of critically ill neonates in the Neonatal Intensive Care Unit (NICU). Objective: To analyze the predictive value of MSNS on the outcome of critically ill neonates at the time of arrival up to 24 hours after being admitted to the NICU. Methods: A longitudinal observational analytic study based on medical record data was conducted from January to August 2022. Each sample was recorded from medical record data, including data on gestational age, mode of delivery, APGAR score at birth, resuscitation measures at birth, duration of resuscitation, post-resuscitation ventilation, physical examination at birth (including vital signs and any congenital abnormalities), the results of routine laboratory examinations, as well as the neonatal outcomes. Results: This study involved 105 critically ill neonates who were admitted to the NICU. The outcome of critically ill neonates was 50 (47.6%) neonates died, and 55 (52.4%) neonates lived. There were more males than females (61% vs. 39%). The mean gestational age of the subjects in this study was 33.8 ± 4.28 weeks, with the mean birth weight of the subjects being 1820.31 ± 33.18 g. The mean MSNS score of neonates with a deadly outcome was lower than that of the lived outcome. ROC curve with a cut point MSNS score <10.5 obtained an AUC of 93.5% (95% CI: 88.3-98.6) with a sensitivity value of 84% (95% CI: 80.5-94.9), specificity 80 % (CI 95%: 88.3-98.6), Positive Predictive Value (PPV) 79.2%, Negative Predictive Value (NPV) 84.6%, Risk Ratio (RR) 5.14 with Hosmer & Lemeshow test results p>0.05. Conclusion: The MSNS score has a good predictive value and good calibration of the outcomes of critically ill neonates admitted to the NICU.

Keywords: critically ill neonate, outcome, MSNS, NICU, predictive value

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Authors: Kohkan Shamsi

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Background: MRI and PET are now extensively utilized in Alzheimer's disease (AD) trials for patient eligibility, efficacy assessment, and safety evaluations but including imaging in AD trials impacts site selection process, patient recruitment, and patient retention. Methods: PET/MRI are performed at baseline and at multiple follow-up timepoints. This requires prospective site imaging qualification, evaluation of phantom data, training and continuous monitoring of machines for acquisition of standardized and consistent data. This also requires prospective patient/caregiver training as patients must go to multiple facilities for imaging examinations. We will share our experience form one of the largest AD programs. Lesson learned: Many neurological diseases have a similar presentation as AD or could confound the assessment of drug therapy. The inclusion of wrong patients has ethical and legal issues, and data could be excluded from the analysis. Centralized eligibility evaluation read process will be discussed. Amyloid related imaging abnormalities (ARIA) were observed in amyloid-β trials. FDA recommended regular monitoring of ARIA. Our experience in ARIA evaluations in large phase III study at > 350 sites will be presented. Efficacy evaluation: MRI is utilized to evaluate various volumes of the brain. FDG PET or amyloid PET agents has been used in AD trials. We will share our experience about site and central independent reads. Imaging logistic issues that need to be handled in the planning phase will also be discussed as it can impact patient compliance thereby increasing missing data and affecting study results. Conclusion: imaging must be prospectively planned to include standardizing imaging methodologies, site selection process and selecting assessment criteria. Training should be transparently conducted and documented. Prospective patient/caregiver awareness of imaging requirement is essential for patient compliance and reduction in missing imaging data.

Keywords: Alzheimer's disease, ARIA, MRI, PET, patient recruitment, retention

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Authors: Minhal Abidi, Moinuddin

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Diabetes mellitus (DM) induced metabolic abnormalities causes oxidative stress which leads to the pathogenesis of complications associated with diabetes like retinopathy, nephropathy periodontitis etc. Combination of glycation and oxidation 'glycoxidation' occurs when oxidative reactions affect the early state of glycation products. Low density lipoprotein (LDL) is prone to glycoxidative attack by sugars and methylglyoxal (MGO) being a strong glycating agent may have severe impact on its structure and consequent role in diabetes. Pro-inflammatory cytokines like IL1β and TNFα produced by the action of gram negative bacteria in periodontits (PD) can in turn lead to insulin resistance. This work discusses modifications to LDL as a result of glycoxidation. The changes in the protein molecule have been characterized by various physicochemical techniques and the immunogenicity of the modified molecules was also evaluated as they presented neo-epitopes. Binding of antibodies present in diabetes patients to the native and glycated LDL has been evaluated. Role of modified epitopes in the generation of antibodies in diabetes and periodontitis has been discussed. The structural perturbations induced in LDL were analyzed by UV–Vis, fluorescence, circular dichroism and FTIR spectroscopy, molecular docking studies, thermal denaturation studies, Thioflavin T assay, isothermal titration calorimetry, comet assay. MALDI-TOF, ketoamine moieties, carbonyl content and HMF content were also quantitated in native and glycated LDL. IL1β and TNFα levels were also measured in the type 2 DM and PD patients. We report increased carbonyl content, ketoamine moieties and HMF content in glycated LDL as compared to native analogue. The results substantiate that in hyperglycemic state MGO modification of LDL causes structural perturbations making the protein antigenic which could obstruct normal physiological functions and might contribute in the development of secondary complications in diabetic patients like periodontitis.

Keywords: advanced glycation end products, diabetes mellitus, glycation, glycoxidation, low density lipoprotein, periodontitis

Procedia PDF Downloads 169

Authors: Noreen Noreen, Aamir Ijaz, Hamza Akhtar

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Background: Screening plays a major role to detect chromosomal abnormalities, Down syndrome, neural tube defects and other inborn diseases of the newborn. Serum biomarkers in the second trimester are useful in determining risk of most common chromosomal anomalies; these test include Alpha-fetoprotein (AFP), Human chorionic gonadotropin (hCG), Unconjugated Oestriol (UEȝ)and inhibin-A. Quadruple biomarkers are worth test in diagnosing the congenital pathology during pregnancy, these procedures does not form a part of routine health care of pregnant women in Pakistan, so the median value is lacking for population in Pakistan. Objective: To determine median values of biochemical maternal serum markers in local population during second trimester maternal screening. Study settings: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology (AFIP) Rawalpindi. Methods: Cross-Sectional study for estimation of reference values. Non-probability consecutive sampling, 155 healthy pregnant women, of 30-40 years of age, will be included. As non-parametric statistics will be used, the minimum sample size is 120. Result: Total 155 women were enrolled into this study. The age of all women enrolled ranged from 30 to39 yrs. Among them, 39 per cent of women were less than 34 years. Mean maternal age 33.46±2.35 SD and maternal body weight were 54.98±2.88. Median value of quadruple markers calculated from 15-18th week of gestation that will be used for calculation of MOM for screening of trisomy21 in this gestational age. Median value at 15 week of gestation were observed hCG 36650 mIU/ml, AFP 23.3 IU/ml, UEȝ 3.5 nmol/L, InhibinA 198 ng/L, at 16 week of gestation hCG 29050 mIU/ml, AFP 35.4 IU/ml, UEȝ 4.1 nmol/L, InhibinA 179 ng/L, at 17 week of gestation hCG 28450 mIU/ml, AFP 36.0 IU/ml, UEȝ 6.7 nmol/L, InhibinA 176 ng/L and at 18 week of gestation hCG 25200 mIU/ml, AFP 38.2 IU/ml, UEȝ 8.2 nmol/L, InhibinA 190 ng/L respectively.All the comparisons were significant (p-Value <0.005) with 95% confidence Interval (CI) and level of significance of study set by going through literature and set at 5%. Conclusion: The median values for these four biomarkers in Pakistani pregnant women can be used to calculate MoM.

Keywords: screening, down syndrome, quadruple test, second trimester, serum biomarkers

Procedia PDF Downloads 152

Authors: Parul Kapoor, Dheeraj Bhardwaj

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Delhi and other Indian cities accommodate thousands of Central Government employees in housing complexes called ‘General Pool Residential Accommodation’ (GPRA), located in prime parcels of the city. These residential colonies are now undergoing redevelopment at a massive scale, significantly impacting the ecology of the surrounding areas. Essentially, these colonies were low-rise, low-density planned developments with a dense tree cover and minimal parking requirements. But with increasing urbanisation and spike in parking demand, the proposed built form is an aggregate of high-rise gated complexes, redefining the skyline of the city which is a huge departure from the mediocre setup of Low-rise Walk-up apartments. The complexity of these developments is further aggravated by the need for parking which necessitates cutting huge number of trees to accommodate multiple layers of parking beneath the structures thus sidelining the authentic character of these areas which is laden with a dense tree cover. The aftermath of this whole process is the generation of a huge carbon footprint on the surrounding areas, which is unaccounted for, in the planning and design practice. These developments are currently planned as mix-use compounds with large commercial built-up spaces which have additional parking requirements over and above the residential parking. Also, they are perceived as gated complexes and not as neighborhood units, thus project isolated images of high-rise, dense systems with little context to the surroundings. The paper would analyze case studies of GPRA Redevelopment projects in Delhi, and the lack of relevant development control regulations which have led to abnormalities and complications in the entire redevelopment process. It would also suggest policy guidelines which can establish comprehensive codes for effective planning of these settlements.

Keywords: gated complexes, GPRA Redevelopment projects, increased densities, huge carbon footprint, mixed-use development

Procedia PDF Downloads 90

Authors: Godwin Dennison, C. E. Boulind, O. Gould, B. de Lacy Costello, J. Allison, P. White, P. Ewings, A. Wicaksono, N. J. Curtis, A. Pullyblank, D. Jayne, J. A. Covington, N. Ratcliffe, N. K. Francis

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Background: Colorectal symptoms are common but only infrequently represent serious pathology, including colorectal cancer (CRC). A large number of invasive tests are presently performed for reassurance. We investigated the feasibility of urinary volatile organic compound (VOC) testing as a potential triage tool in patients fast-tracked for assessment for possible CRC. Methods: A prospective, multi-centre, observational feasibility study was performed across three sites. Patients referred on NHS fast-track pathways for potential CRC provided a urine sample which underwent Gas Chromatography Mass Spectrometry (GC-MS), Field Asymmetric Ion Mobility Spectrometry (FAIMS) and Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) analysis. Patients underwent colonoscopy and/or CT colonography and were grouped as either CRC, adenomatous polyp(s), or controls to explore the diagnostic accuracy of VOC output data supported by an artificial neural network (ANN) model. Results: 558 patients participated with 23 (4.1%) CRC diagnosed. 59% of colonoscopies and 86% of CT colonographies showed no abnormalities. Urinary VOC testing was feasible, acceptable to patients, and applicable within the clinical fast track pathway. GC-MS showed the highest clinical utility for CRC and polyp detection vs. controls (sensitivity=0.878, specificity=0.882, AUROC=0.884). Conclusion: Urinary VOC testing and analysis are feasible within NHS fast-track CRC pathways. Clinically meaningful differences between patients with cancer, polyps, or no pathology were identified therefore suggesting VOC analysis may have future utility as a triage tool. Acknowledgment: Funding: NIHR Research for Patient Benefit grant (ref: PB-PG-0416-20022).

Keywords: colorectal cancer, volatile organic compound, gas chromatography mass spectrometry, field asymmetric ion mobility spectrometry, selected ion flow tube mass spectrometry

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Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

Procedia PDF Downloads 178

Authors: Mona K. Fehling, Jakob Unger, Dietmar J. Hecker, Bernhard Schick, Joerg Lohscheller

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Voice disorders origin from disturbances of the vibration patterns of the two vocal folds located within the human larynx. Consequently, the visual examination of vocal fold vibrations is an integral part within the clinical diagnostic process. For an objective analysis of the vocal fold vibration patterns, the two-dimensional vocal fold dynamics are captured during sustained phonation using an endoscopic high-speed camera. In this work, we present an approach allowing a fully automatic analysis of the high-speed video data including a computerized classification of healthy and pathological voices. The approach bases on a wavelet-based analysis of so-called phonovibrograms (PVG), which are extracted from the high-speed videos and comprise the entire two-dimensional vibration pattern of each vocal fold individually. Using a principal component analysis (PCA) strategy a low-dimensional feature set is computed from each phonovibrogram. From the PCA-space clinically relevant measures can be derived that quantify objectively vibration abnormalities. In the first part of the work it will be shown that, using a machine learning approach, the derived measures are suitable to distinguish automatically between healthy and pathological voices. Within the approach the formation of the PCA-space and consequently the extracted quantitative measures depend on the clinical data, which were used to compute the principle components. Therefore, in the second part of the work we proposed a strategy to achieve a normalization of the PCA-space by registering the PCA-space to a coordinate system using a set of synthetically generated vibration patterns. The results show that owing to the normalization step potential ambiguousness of the parameter space can be eliminated. The normalization further allows a direct comparison of research results, which bases on PCA-spaces obtained from different clinical subjects.

Keywords: Wavelet-based analysis, Multiscale product, normalization, computer assisted classification, high-speed laryngoscopy, vocal fold analysis, phonovibrogram

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Authors: Erwin Geroleo, Higinio Mappala

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Introduction Overt Hepatic Encephalopathy (OHE) is the most dreaded outcome of liver cirrhosis. Aside from the triggering factors which are already known to precipitate OHE, there is growing evidence that an altered gut microbiota profile (dysbiosis) can also trigger OHE. MHE is the mildest form of hepatic encephalopathy(HE), affecting about one-third of patients with cirrhosis, and close 80% of patients with cirrhosis and manifests as abnormalities in central nervous system function. Since these symptoms are subclinical most patients are not being treated to prevent OHE. The gut microbiota have been evaluated by several studies as a therapeutic option for MHE, especially in decreasing the levels of ammonia, thus preventing progression to OHE Objectives This study aims to evaluate the efficacy of probiotics in terms of reduction of ammonia levels in patient with minimal hepatic encephalopathies and to determine if Probiotics has role in the prevention of progression to overt hepatic encephalopathy in adult patients with minimal hepatic encephalopathy (MHE) Methods and Analysis The literature search strategy was restricted to human studies in adults subjects from 2004 to 2022. The Jadad Score Calculation was utilized in the assessment of the final studies included in this study. Eight (8) studies were included. Cochrane’s Revman Web, the Fixed Effects model and the Ztest were all used in the overall analysis of the outcomes. A p value of less than 0.0005 was statistically significant. Results. These results show that Probiotics significantly lowers the level of Ammonia in Cirrhotic patients with OHE. It also shows that the use of Probiotics significantly prevents the progression of MHE to OHE. The overall risk of bias graph indicates low risk of publication bias among the studies included in the meta-analysis. Main findings This research found that plasma ammonia concentration was lower among participants treated with probiotics (p<0.00001).) Ammonia level of the probiotics group is lower by 13.96 μmol/ on the average. Overall risk of developing overt hepatic encephalopathy in the probiotics group is shown to be decreased by 15% as compared to the placebo group Conclusion The analysis showed that compared with placebo, probiotics can decrease serum ammonia, may improve MHE and may prevent OHE.

Keywords: minimal hepatic encephalopathy, probiotics, liver cirrhosis, overt hepatic encephalopathy

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