Search results for: death
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1282

Search results for: death

172 Anti-DNA Antibodies from Patients with Schizophrenia Hydrolyze DNA

Authors: Evgeny A. Ermakov, Lyudmila P. Smirnova, Valentina N. Buneva

Abstract:

Schizophrenia associated with dysregulation of neurotransmitter processes in the central nervous system and disturbances in the humoral immune system resulting in the formation of antibodies (Abs) to the various components of the nervous tissue. Abs to different neuronal receptors and DNA were detected in the blood of patients with schizophrenia. Abs hydrolyzing DNA were detected in pool of polyclonal autoantibodies in autoimmune and infectious diseases, such catalytic Abs were named abzymes. It is believed that DNA-hydrolyzing abzymes are cytotoxic, cause nuclear DNA fragmentation and induce cell death by apoptosis. Abzymes with DNAase activity are interesting because of the mechanism of formation and the possibility of use as diagnostic markers. Therefore, in our work we have set following goals: to determine the level anti-DNA Abs in the serum of patients with schizophrenia and to study DNA-hydrolyzing activity of IgG of patients with schizophrenia. Materials and methods: In our study there were included 41 patients with a verified diagnosis of paranoid or simple schizophrenia and 24 healthy donors. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the serum proteins on protein G-Sepharose and gel filtration. The levels of anti-DNA Abs were determined using ELISA. DNA-hydrolyzing activity was detected as the level of supercoiled pBluescript DNA transition in circular and linear forms, the hydrolysis products were analyzed by agarose electrophoresis followed by ethidium bromide stain. To correspond the registered catalytic activity directly to the antibodies we carried out a number of strict criteria: electrophoretic homogeneity of the antibodies, gel filtration (acid shock analysis) and in situ activity. Statistical analysis was performed in ‘Statistica 9.0’ using the non-parametric Mann-Whitney test. Results: The sera of approximately 30% of schizophrenia patients displayed a higher level of Abs interacting with single-stranded (ssDNA) and double-stranded DNA (dsDNA) compared with healthy donors. The average level of Abs interacting with ssDNA was only 1.1-fold lower than that for interacting with dsDNA. IgG of patient with schizophrenia were shown to possess DNA hydrolyzing activity. Using affinity chromatography, electrophoretic analysis of isolated IgG homogeneity, gel filtration in acid shock conditions and in situ DNAse activity analysis we proved that the observed activity is intrinsic property of studied antibodies. We have shown that the relative DNAase activity of IgG in patients with schizophrenia averaged 55.4±32.5%, IgG of healthy donors showed much lower activity (average of 9.1±6.5%). It should be noted that DNAase activity of IgG in patients with schizophrenia with a negative symptoms was significantly higher (73.3±23.8%), than in patients with positive symptoms (43.3±33.1%). Conclusion: Anti-DNA Abs of patients with schizophrenia not only bind DNA, but quite efficiently hydrolyze the substrate. The data show a correlation with the level of DNase activity and leading symptoms of patients with schizophrenia.

Keywords: anti-DNA antibodies, abzymes, DNA hydrolysis, schizophrenia

Procedia PDF Downloads 328
171 Toxicity Evaluation of Reduced Graphene Oxide on First Larval Stages of Artemia sp.

Authors: Roberta Pecoraro

Abstract:

The focus of this work was to investigate the potential toxic effect of titanium dioxide-reduced graphene oxide (TiO₂-rGO) nanocomposites on nauplii of microcrustacean Artemia sp. In order to assess the nanocomposite’s toxicity, a short-term test was performed by exposing nauplii to solutions containing TiO₂-rGO. To prepare titanium dioxide-reduced graphene oxide (TiO₂-rGO) nanocomposites, a green procedure based on solar photoreduction was proposed; it allows to obtain the photocatalysts by exploiting the photocatalytic properties of titania activated by the solar irradiation in order to avoid the high temperatures and pressures required for the standard hydrothermal synthesis. Powders of TiO₂-rGO supplied by the Department of Chemical Sciences (University of Catania) are indicated as TiO₂-rGO at 1% and TiO₂-rGO at 2%. Starting from a stock solution (1mg rGO-TiO₂/10 ml ASPM water) of each type, we tested four different concentrations (serial dilutions ranging from 10⁻¹ to 10⁻⁴ mg/ml). All the solutions have been sonicated for 12 min prior to use. Artificial seawater (called ASPM water) was prepared to guarantee the hatching of the cysts and to maintain nauplii; the durable cysts used in this study, marketed by JBL (JBL GmbH & Co. KG, Germany), were hydrated with ASPM water to obtain nauplii (instar II-III larvae). The hatching of the cysts was carried out in the laboratory by immersing them in ASPM water inside a 500 ml beaker and keeping them constantly oxygenated thanks to an aerator for the insufflation of microbubble air: after 24-48 hours, the cysts hatched, and the nauplii appeared. The nauplii in the second and third stages of development were collected one-to-one, using stereomicroscopes, and transferred into 96-well microplates where one nauplius per well was added. The wells quickly have been filled with 300 µl of each specific concentration of the solution used, and control samples were incubated only with ASPM water. Replication was performed for each concentration. Finally, the microplates were placed on an orbital shaker, and the tests were read after 24 and 48 hours from inoculating the solutions to assess the endpoint (immobility/death) for the larvae. Nauplii that appeared motionless were counted as dead, and the percentages of mortality were calculated for each treatment. The results showed a low percentage of immobilization both for TiO₂-rGO at 1% and TiO₂-rGO at 2% for all concentrations tested: for TiO₂-rGO at 1% was below 12% after 24h and below 15% after 48h; for TiO₂-rGO at 2% was below 8% after 24h and below 12% after 48h. According to other studies in the literature, the results have not shown mortality nor toxic effects on the development of larvae after exposure to rGO. Finally, it is important to highlight that the TiO₂-rGO catalysts were tested in the solar photodegradation of a toxic herbicide (2,4-Dichlorophenoxyacetic acid, 2,4-D), obtaining a high percentage of degradation; therefore, this alternative approach could be considered a good strategy to obtain performing photocatalysts.

Keywords: Nauplii, photocatalytic properties, reduced GO, short-term toxicity test, titanium dioxide

Procedia PDF Downloads 183
170 Approaching a Tat-Rev Independent HIV-1 Clone towards a Model for Research

Authors: Walter Vera-Ortega, Idoia Busnadiego, Sam J. Wilson

Abstract:

Introduction: Human Immunodeficiency Virus type 1 (HIV-1) is responsible for the acquired immunodeficiency syndrome (AIDS), a leading cause of death worldwide infecting millions of people each year. Despite intensive research in vaccine development, therapies against HIV-1 infection are not curative, and the huge genetic variability of HIV-1 challenges to drug development. Current animal models for HIV-1 research present important limitations, impairing the progress of in vivo approaches. Macaques require a CD8+ depletion to progress to AIDS, and the maintenance cost is high. Mice are a cheaper alternative but need to be 'humanized,' and breeding is not possible. The development of an HIV-1 clone able to replicate in mice is a challenging proposal. The lack of human co-factors in mice impedes the function of the HIV-1 accessory proteins, Tat and Rev, hampering HIV-1 replication. However, Tat and Rev function can be replaced by constitutive/chimeric promoters, codon-optimized proteins and the constitutive transport element (CTE), generating a novel HIV-1 clone able to replicate in mice without disrupting the amino acid sequence of the virus. By minimally manipulating the genomic 'identity' of the virus, we propose the generation of an HIV-1 clone able to replicate in mice to assist in antiviral drug development. Methods: i) Plasmid construction: The chimeric promoters and CTE copies were cloned by PCR using lentiviral vectors as templates (pCGSW and pSIV-MPCG). Tat mutants were generated from replication competent HIV-1 plasmids (NHG and NL4-3). ii) Infectivity assays: Retroviral vectors were generated by transfection of human 293T cells and murine NIH 3T3 cells. Virus titre was determined by flow cytometry measuring GFP expression. Human B-cells (AA-2) and Hela cells (TZMbl) were used for infectivity assays. iii) Protein analysis: Tat protein expression was determined by TZMbl assay and HIV-1 capsid by western blot. Results: We have determined that NIH 3T3 cells are able to generate HIV-1 particles. However, they are not infectious, and further analysis needs to be performed. Codon-optimized HIV-1 constructs are efficiently made in 293T cells in a Tat and Rev independent manner and capable of packaging a competent genome in trans. CSGW is capable of generating infectious particles in the absence of Tat and Rev in human cells when 4 copies of the CTE are placed preceding the 3’LTR. HIV-1 Tat mutant clones encoding different promoters are functional during the first cycle of replication when Tat is added in trans. Conclusion: Our findings suggest that the development of an HIV-1 Tat-Rev independent clone is challenging but achievable aim. However, further investigations need to be developed prior presenting our HIV-1 clone as a candidate model for research.

Keywords: codon-optimized, constitutive transport element, HIV-1, long terminal repeats, research model

Procedia PDF Downloads 308
169 Safety Assessment of Traditional Ready-to-Eat Meat Products Vended at Retail Outlets in Kebbi and Sokoto States, Nigeria

Authors: M. I. Ribah, M. Jibir, Y. A. Bashar, S. S. Manga

Abstract:

Food safety is a significant and growing public health problem in the world and Nigeria as a developing country, since food-borne diseases are important contributors to the huge burden of sickness and death of humans. In Nigeria, traditional ready-to-eat meat products (RTE-MPs) like balangu, tsire, guru and dried meat products like kilishi, dambun nama, banda, were reported to be highly appreciated because of their eating qualities. The consumption of these products was considered as safe due to the treatments that are usually involved during their production process. However, during processing and handling, the products could be contaminated by pathogens that could cause food poisoning. Therefore, a hazard identification for pathogenic bacteria on some traditional RTE-MPs was conducted in Kebbi and Sokoto States, Nigeria. A total of 116 RTE-MPs (balangu-38, kilishi-39 and tsire-39) samples were obtained from retail outlets and analyzed using standard cultural microbiological procedures in general and selective enrichment media to isolate the target pathogens. A six-fold serial dilution was prepared and using the pour plating method, colonies were counted. Serial dilutions were selected based on the prepared pre-labeled Petri dishes for each sample. A volume of 10-12 ml of molten Nutrient agar cooled to 42-45°C was poured into each Petri dish and 1 ml each from dilutions of 102, 104 and 106 for every sample was respectively poured on a pre-labeled Petri plate after which colonies were counted. The isolated pathogens were identified and confirmed after series of biochemical tests. Frequencies and percentages were used to describe the presence of pathogens. The General Linear Model was used to analyze data on pathogen presence according to RTE-MPs and means were separated using the Tukey test at 0.05 confidence level. Of the 116 RTE-MPs samples collected, 35 (30.17%) samples were found to be contaminated with some tested pathogens. Prevalence results showed that Escherichia coli, salmonella and Staphylococcus aureus were present in the samples. Mean total bacterial count was 23.82×106 cfu/g. The frequency of individual pathogens isolated was; Staphylococcus aureus 18 (15.51%), Escherichia coli 12 (10.34%) and Salmonella 5 (4.31%). Also, among the RTE-MPs tested, the total bacterial counts were found to differ significantly (P < 0.05), with 1.81, 2.41 and 2.9×104 cfu/g for tsire, kilishi, and balangu, respectively. The study concluded that the presence of pathogenic bacteria in balangu could pose grave health risks to consumers, and hence, recommended good manufacturing practices in the production of balangu to improve the products’ safety.

Keywords: ready-to-eat meat products, retail outlets, public health, safety assessment

Procedia PDF Downloads 133
168 Acceptability of ‘Fish Surimi Peptide’ in Under Five Children Suffering from Moderate Acute Malnutrition in Bangladesh

Authors: M. Iqbal Hossain, Azharul Islam Khan, S. M. Rafiqul Islam, Tahmeed Ahmed

Abstract:

Objective: Moderate acute malnutrition (MAM) is a major cause of morbidity and mortality in under-5 children of low-income countries. Approximately 14.6% of all under-5 mortality worldwide is attributed to MAM with >3 times increased risk of death compared to well-nourished peers. Prevalence of MAM among under-5 children in Bangladesh is ~12% (~1.7 million). Providing a diet containing adequate nutrients is the mainstay of treatment of children with MAM. It is now possible to process fish into fish peptides with longer shelf-life without refrigerator, known as ‘Fish Surimi peptide’ and this could be an attractive alternative to supply fish protein in the diet of children in low-income countries like Bangladesh. We conducted this study to assess the acceptability of Fish Surimi peptide given with various foods/meals in 2-5 years old children with MAM. Design/methods: Fish Surimi peptide is broken down from white fish meat using plant-derived enzyme and the ingredient is just fish meat consisted of 20 different kinds of amino acids including nine essential amino acids. In a convenience sample of 34 children we completed the study ward of Dhaka Hospital of icddr,b in Bangladesh during November 2014 through February 2015. For each child the study was for two consecutive days: i.e. direct observation of food intake of two lunches and two suppers. In a randomly and blinded manner and cross over design an individual child received Fish Surimi peptide (5g at lunch and 5g at supper) mixed meal [e.g. 30g rice and 30g dahl (thick lentil soup) or 60g of a vegetables-lentil-rice mixed local dish known as khichuri in one day and the same meal on other day without any Fish Surimi peptide. We observed the completeness and eagerness of eating and any possible side effect (e.g. allergy, vomiting, diarrhea etc.) over these two days. Results: The mean±SD age of the enrolled children was 38.4±9.4 months, weight 11.22±1.41 kg, height 91.0±6.3 cm, and WHZ was -2.13±0.76. Their mean±SD total feeding time (minutes) for lunch was 25.4±13.6 vs. 20.6±11.1 (p=0.130) and supper was 22.3±9.7 vs. 19.7±11.2 (p=0.297), and total amount (g) of food eaten in lunch and supper was found similar 116.1±7.0 vs. 117.7±8.0 (p=3.01) in A (Fish Surimi) and B group respectively. Score in Hedonic scale by mother on test of food given to children at lunch or supper was 3.9±0.2 vs. 4.0±0.2 (p=0.317) and on overall acceptance (including the texture, smell, and appearance) of food at lunch or supper was 3.9±0.2 vs. 4.0±0.2 (p=0.317) for A and B group respectively. No adverse event was observed in any food group during the study period. Conclusions: Fish Surimi peptide may be a cost effective supplementary food, which should be tested by appropriately designed randomized community level intervention trial both in wasted children and stunted children.

Keywords: protein-energy malnutrition, moderate acute malnutrition, weight-for-height z-score, mid upper arm circumference, acceptability, fish surimi peptide, under-5 children

Procedia PDF Downloads 412
167 Missed Opportunities for Immunization of under Five Children in Calabar South County Cros River State, Nigeria, the Way Forward

Authors: Celestine Odigwe, Epoke Lincoln, Rhoda-Dara Ephraim

Abstract:

Background; Immunization against the childhood killer diseases is the cardinal strategy for the prevention of these diseases all over the world in under five children, these diseases include; Tuberculosis, Measles, Polio, Tetanus, Diphthria, Pertusis, Yellow Fever, Hepatitis B, Haemophilus Influenza type B. 6.9 million children die before their fifth birthday , 80% of the worlds death in children under 5 years occur in 25 countries most in Africa and Asia and 2 million children can be saved each year with routine immunization Therefore failure to achieve total immunization coverage puts several children at risk. Aim; The aim of the study was to ascertain the prevalence, Investigate the various reasons and causes why several under five children in a suburb of calabar municipal county fail to get the required immunizations as at and when due and possibly the consequences, so that efforts can be re-directed towards the solution of the problems so identified. Methods; the study was a community based cross sectional study. The respondents were the mothers/guardians of the sampled children who were all aged 0-59 months. To be eligible for recruitment into the study, the parent or guardian was required to give an informed consent, reside within the Calabar South County with his/her children aged 0-59 months. We calculated our sample size using the Leslie-Kish formula and we used a two-staged sampling method, first to ballot for the wards to be involved and then to select four of the most populated ones in the wards chosen. Data collection was by interviewer administered structured questionnaire (Appendix I), Data collected was entered and analyzed using Statistical Package for the Social Sciences (SPSS) Version 20. Percentages were calculated and represented using charts and tables Results; The number of children sampled was 159. We found that 150 were fully immunized and 9 were not, the prevalence of missed opportunity was 32% from the study. The reasons for missed opportunities were varied, ranging from false contraindications, logistical problems resulting in very poor access roads to health facilities and poor organization of health centers together with negative health worker attitudes. Some of the consequences of these missed opportunities were increased susceptibility to vaccine preventable diseases, resurgence of the above diseases and increased morbidity and mortality of children aged less than 5 years. Conclusion; We found that ignorance on the part of both parents/guardians and health care staff together with infrastructural inadequacies in the county such as- roads, poor electric power supply for storage of vaccines were hugely responsible for most missed opportunities for immunization. The details of these and suggestions for improvement and the way forward are discussed.

Keywords: missed opportunity, immunization, under five, Calabar south

Procedia PDF Downloads 324
166 Choking among Babies, Toddlers and Children with Special Needs: A Review of Mechanisms, Implications, Incidence, and Recommendations of Professional Prevention Guidelines

Authors: Ella Abaev, Shany Segal, Miri Gabay

Abstract:

Background: Choking is a blockage of airways that prevents efficient breathing and air flow to the lungs. Choking may be partial or full and is an emergency situation. Complete or prolonged choking leads to apnea, lack of oxygen in the tissues of the body and brain, and can cause death. There are three mechanisms of choking: obstruction of internal respiratory tracts by food or object aspiration, any material that blocks or covers external air passages, external pressure on the neck or trapping between objects. Children's airways are narrower than that of adults and therefore the risk of choking is greater, due to the aspiration of food and other foreign bodies into the lungs. In the Child Development Center at Safra Children’s Hospital, Tel Hashomer in Israel are treated infants, toddlers, and children aged 0-18 years with various developmental disabilities. Due to the increase in reports of ‘almost an event’ of choking in the past year and the serious consequences of choking event, it was decided to give an emphasis to the issue. Incidence and methods: The number of reports of ‘almost an event’ or a choking event was examined at the center during the years 2013-2018 and a thorough research work was conducted on the subject in order to build a prevention program. Findings: Between 2013 and 2018 the center reported about ten cases of ‘almost choking events’. In the middle of 2018 alone three cases of ‘almost an event’ were reported. Objective: Providing knowledge leads to awareness raise, change of perception, change in behavior and prevention. The center employs more than 130 staff members from various sectors so that it is the work of multi-professional teams to promote the quality and safety of the treatment. The familiarity of the staff with risk factors, prevention guidelines, identification of choking signs, and treatment are most important and significant in determining the outcome of a choking event. Conclusions and recommendations: After in-depth research work was carried out in cooperation with the Risk Management Unit on the subject of choking, which include a description of the definitions, mechanisms, risk factors, treatment methods and extensive recommendations for prevention (e.g. using treatment and stimulation accessories with standards association stamps and adjustment of the type of food and the way it is served to match to the child's age and the ability to swallow). The expected stages of development and emphasis on the population of children with special needs were taken into account. The research findings will be published by the staff and parents of the patients, professional publications, and lectures and there is an expectation to decrease the number of choking events in the next years.

Keywords: children with special needs, choking, educational system, prevention guidelines

Procedia PDF Downloads 179
165 Verification of Low-Dose Diagnostic X-Ray as a Tool for Relating Vital Internal Organ Structures to External Body Armour Coverage

Authors: Natalie A. Sterk, Bernard van Vuuren, Petrie Marais, Bongani Mthombeni

Abstract:

Injuries to the internal structures of the thorax and abdomen remain a leading cause of death among soldiers. Body armour is a standard issue piece of military equipment designed to protect the vital organs against ballistic and stab threats. When configured for maximum protection, the excessive weight and size of the armour may limit soldier mobility and increase physical fatigue and discomfort. Providing soldiers with more armour than necessary may, therefore, hinder their ability to react rapidly in life-threatening situations. The capability to determine the optimal trade-off between the amount of essential anatomical coverage and hindrance on soldier performance may significantly enhance the design of armour systems. The current study aimed to develop and pilot a methodology for relating internal anatomical structures with actual armour plate coverage in real-time using low-dose diagnostic X-ray scanning. Several pilot scanning sessions were held at Lodox Systems (Pty) Ltd head-office in South Africa. Testing involved using the Lodox eXero-dr to scan dummy trunk rigs at various degrees and heights of measurement; as well as human participants, wearing correctly fitted body armour while positioned in supine, prone shooting, seated and kneeling shooting postures. The verification of sizing and metrics obtained from the Lodox eXero-dr were then confirmed through a verification board with known dimensions. Results indicated that the low-dose diagnostic X-ray has the capability to clearly identify the vital internal structures of the aortic arch, heart, and lungs in relation to the position of the external armour plates. Further testing is still required in order to fully and accurately identify the inferior liver boundary, inferior vena cava, and spleen. The scans produced in the supine, prone, and seated postures provided superior image quality over the kneeling posture. The X-ray-source and-detector distance from the object must be standardised to control for possible magnification changes and for comparison purposes. To account for this, specific scanning heights and angles were identified to allow for parallel scanning of relevant areas. The low-dose diagnostic X-ray provides a non-invasive, safe, and rapid technique for relating vital internal structures with external structures. This capability can be used for the re-evaluation of anatomical coverage required for essential protection while optimising armour design and fit for soldier performance.

Keywords: body armour, low-dose diagnostic X-ray, scanning, vital organ coverage

Procedia PDF Downloads 122
164 Healthcare Associated Infections in an Intensive Care Unit in Tunisia: Incidence and Risk Factors

Authors: Nabiha Bouafia, Asma Ben Cheikh, Asma Ammar, Olfa Ezzi, Mohamed Mahjoub, Khaoula Meddeb, Imed Chouchene, Hamadi Boussarsar, Mansour Njah

Abstract:

Background: Hospital acquired infections (HAI) cause significant morbidity, mortality, length of stay and hospital costs, especially in the intensive care unit (ICU), because of the debilitated immune systems of their patients and exposure to invasive devices. The aims of this study were to determine the rate and the risk factors of HAI in an ICU of a university hospital in Tunisia. Materials/Methods: A prospective study was conducted in the 8-bed adult medical ICU of a University Hospital (Sousse Tunisia) during 14 months from September 15th, 2015 to November 15th, 2016. Patients admitted for more than 48h were included. Their surveillance was stopped after the discharge from ICU or death. HAIs were defined according to standard Centers for Disease Control and Prevention criteria. Risk factors were analyzed by conditional stepwise logistic regression. The p-value of < 0.05 was considered significant. Results: During the study, 192 patients had admitted for more than 48 hours. Their mean age was 59.3± 18.20 years and 57.1% were male. Acute respiratory failure was the main reason of admission (72%). The mean SAPS II score calculated at admission was 32.5 ± 14 (range: 6 - 78). The exposure to the mechanical ventilation (MV) and the central venous catheter were observed in 169 (88 %) and 144 (75 %) patients, respectively. Seventy-three patients (38.02%) developed 94 HAIs. The incidence density of HAIs was 41.53 per 1000 patient day. Mortality rate in patients with HAIs was 65.8 %( n= 48). Regarding the type of infection, Ventilator Associated Pneumoniae (VAP) and central venous catheter Associated Infections (CVC AI) were the most frequent with Incidence density: 14.88/1000 days of MV for VAP and 20.02/1000 CVC days for CVC AI. There were 5 Peripheral Venous Catheter Associated Infections, 2 urinary tract infections, and 21 other HAIs. Gram-negative bacteria were the most common germs identified in HAIs: Multidrug resistant Acinetobacter Baumanii (45%) and Klebsiella pneumoniae (10.96%) were the most frequently isolated. Univariate analysis showed that transfer from another hospital department (p= 0.001), intubation (p < 10-4), tracheostomy (p < 10-4), age (p=0.028), grade of acute respiratory failure (p=0.01), duration of sedation (p < 10-4), number of CVC (p < 10-4), length of mechanical ventilation (p < 10-4) and length of stay (p < 10-4), were associated to high risk of HAIS in ICU. Multivariate analysis reveals that independent risk factors for HAIs are: transfer from another hospital department: OR=13.44, IC 95% [3.9, 44.2], p < 10-4, duration of sedation: OR= 1.18, IC 95% [1.049, 1.325], p=0.006, high number of CVC: OR=2.78, IC 95% [1.73, 4.487], p < 10-4, and length of stay in ICU: OR= 1.14, IC 95% [1.066,1.22], p < 10-4. Conclusion: Prevention of nosocomial infections in ICUs is a priority of health care systems all around the world. Yet, their control requires an understanding of epidemiological data collected in these units.

Keywords: healthcare associated infections, incidence, intensive care unit, risk factors

Procedia PDF Downloads 369
163 The Mitigation of Quercetin on Lead-Induced Neuroinflammation in a Rat Model: Changes in Neuroinflammatory Markers and Memory

Authors: Iliyasu Musa Omoyine, Musa Sunday Abraham, Oladele Sunday Blessing, Iliya Ibrahim Abdullahi, Ibegbu Augustine Oseloka, Nuhu Nana-Hawau, Animoku Abdulrazaq Amoto, Yusuf Abdullateef Onoruoiza, Sambo Sohnap James, Akpulu Steven Peter, Ajayi Abayomi

Abstract:

The neuroprotective role of inflammation from detrimental intrinsic and extrinsic factors has been reported. However, the overactivation of astrocytes and microglia due to lead toxicity produce excessive pro-inflammatory cytokines, mediating neurodegenerative diseases. The present study investigated the mitigatory effects of quercetin on neuroinflammation, correlating with memory function in lead-exposed rats. In this study, Wistar rats were administered orally with Quercetin (Q: 60 mg/kg) and Succimer as a standard drug (S: 10 mg/kg) for 21 days after lead exposure (Pb: 125 mg/kg) of 21 days or in combination with Pb, once daily for 42 days. Working and reference memory was assessed using an Eight-arm radial water maze (8-ARWM). The changes in brain lead level, the neuronal nitric oxide synthase (nNOS) activity, and the level of neuroinflammatory markers such as tumour necrosis factor-alpha (TNF-α) and Interleukin 1 Beta (IL-1β) were determined. Immunohistochemically, astrocyte expression was evaluated. The results showed that the brain level of lead was increased significantly in lead-exposed rats. The expression of astrocytes increased in the CA3 and CA1 regions of the hippocampus, and the levels of brain TNF-α and IL-1β increased in lead-exposed rats. Lead impaired reference and working memory by increasing reference memory errors and working memory incorrect errors in lead-exposed rats. However, quercetin treatment effectively improved memory and inhibited neuroinflammation by reducing astrocytes’ expression and the levels of TNF-α and IL-1β. The expression of astrocytes and the levels of TNF-α and IL-1β correlated with memory function. The possible explanation for quercetin’s anti-neuroinflammatory effect is that it modulates the activity of cellular proteins involved in the inflammatory response; inhibits the transcription factor of nuclear factor-kappa B (NF-κB), which regulates the expression of proinflammatory molecules; inhibits kinases required for the synthesis of Glial fibrillary acidic protein (GFAP) and modifies the phosphorylation of some proteins, which affect the structure and function of intermediate filament proteins; and, lastly, induces Cyclic-AMP Response Element Binding (CREB) activation and neurogenesis as a compensatory mechanism for memory deficits and neuronal cell death. In conclusion, the levels of neuroinflammatory markers negatively correlated with memory function. Thus, quercetin may be a promising therapy in neuroinflammation and memory dysfunction in populations prone to lead exposure.

Keywords: lead, quercetin, neuroinflammation, memory

Procedia PDF Downloads 53
162 Tuberculosis (TB) and Lung Cancer

Authors: Asghar Arif

Abstract:

Lung cancer has been recognized as one of the greatest common cancers, causing the annual mortality rate of about 1.2 million people in the world. Lung cancer is the most prevalent cancer in men and the third-most common cancer among women (after breast and digestive cancers).Recent evidences have shown the inflammatory process as one of the potential factors of cancer. Tuberculosis (TB), pneumonia, and chronic bronchitis are among the most important inflammation-inducing factors in the lungs, among which TB has a more profound role in the emergence of cancer.TB is one of the important mortality factors throughout the world, and 205,000 death cases are reported annually due to this disease. Chronic inflammation and fibrosis due to TB can induce genetic mutation and alternations. Parenchyma tissue of lung is involved in both diseases of TB and lung cancer, and continuous cough in lung cancer, morphological vascular variations, lymphocytosis processes, and generation of immune system mediators such as interleukins, are all among the factors leading to the hypothesis regarding the role of TB in lung cancer Some reports have shown that the induction of necrosis and apoptosis or TB reactivation, especially in patients with immune-deficiency, may result in increasing IL-17 and TNF_α, which will either decrease P53 activity or increase the expression of Bcl-2, decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. It has been also indicated that following the injection of BCG vaccine, the host immune system will be reinforced, and in particular, the rates of gamma interferon, nitric oxide, and interleukin-2 are increased. Therefore, CD4 + lymphocyte function will be improved, and the person will be immune against cancer.Numerous prospective studies have so far been conducted on the role of TB in lung cancer, and it seems that this disease is effective in that particular cancer.One of the main challenges of lung cancer is its correct and timely diagnosis. Unfortunately, clinical symptoms (such as continuous cough, hemoptysis, weight loss, fever, chest pain, dyspnea, and loss of appetite) and radiological images are similar in TB and lung cancer. Therefore, anti-TB drugs are routinely prescribed for the patients in the countries with high prevalence of TB, like Pakistan. Regarding the similarity in clinical symptoms and radiological findings of lung cancer, proper diagnosis is necessary for TB and respiratory infections due to nontuberculousmycobacteria (NTM). Some of the drug resistive TB cases are, in fact, lung cancer or NTM lung infections. Acid-fast staining and histological study of phlegm and bronchial washing, culturing and polymerase chain reaction TB are among the most important solutions for differential diagnosis of these diseases. Briefly, it is assumed that TB is one of the risk factors for cancer. Numerous studies have been conducted in this regard throughout the world, and it has been observed that there is a significant relationship between previous TB infection and lung cancer. However, to prove this hypothesis, further and more extensive studies are required. In addition, as the clinical symptoms and radiological findings of TB, lung cancer, and non-TB mycobacteria lung infections are similar, they can be misdiagnosed as TB.

Keywords: TB and lung cancer, TB people, TB servivers, TB and HIV aids

Procedia PDF Downloads 73
161 Contentious Politics during a Period of Transition to Democracy from an Authoritarian Regime: The Spanish Cycle of Protest of November 1975-December 1978

Authors: Juan Sanmartín Bastida

Abstract:

When a country experiences a period of transition from authoritarianism to democracy, involving an earlier process of political liberalization and a later process of democratization, a cycle of protest usually outbreaks, as there is a reciprocal influence between that kind of political change and the frequency and scale of social protest events. That is what happened in Spain during the first years of its transition to democracy from the Francoist authoritarian regime, roughly between November 1975 and December 1978. Thus, the object of this study is to show and explain how that cycle of protest started, developed, and finished in relation to such a political change, and offer specific information about the main features of all protest cycles: the social movements that arose during that period, the number of protest events by month, the forms of collective action that were utilized, the groups of challengers that engaged in contentious politics, the reaction of the authorities to the action and claims of those groups, etc. The study of this cycle of protest, using the primary sources and analytical tools that characterize the model of research of protest cycles, will make a contribution to the field of contentious politics and its phenomenon of cycles of contention, and more broadly to the political and social history of contemporary Spain. The cycle of protest and the process of political liberalization of the authoritarian regime began around the same time, but the first concluded long before the process of democratization was completed in 1982. The ascending phase of the cycle and therefore the process of liberalization started with the death of Francisco Franco and the proclamation of Juan Carlos I as King of Spain in November 1975; the peak of the cycle was around the first months of 1977; the descending phase started after the first general election of June 1977; and the level of protest stabilized in the last months of 1978, a year that finished with a referendum in which the Spanish people approved the current democratic constitution. It was then when we can consider that the cycle of protest came to an end. The primary sources are the news of protest events and social movements in the three main Spanish newspapers at the time, other written or audiovisual documents, and in-depth interviews; and the analytical tools are the political opportunities that encourage social protest, the available repertoire of contention, the organizations and networks that brought together people with the same claims and allowed them to engage in contentious politics, and the interpretative frames that justify, dignify and motivates their collective action. These are the main four factors that explain the beginning, development and ending of the cycle of protest, and therefore the accompanying social movements and events of collective action. Among those four factors, the political opportunities -their opening, exploitation, and closure-proved to be most decisive.

Keywords: contentious politics, cycles of protest, political opportunities, social movements, Spanish transition to democracy

Procedia PDF Downloads 138
160 Determining the Threshold for Protective Effects of Aerobic Exercise on Aortic Structure in a Mouse Model of Marfan Syndrome Associated Aortic Aneurysm

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

Abstract:

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

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

Procedia PDF Downloads 381
159 Inpatient Glycemic Management Strategies and Their Association with Clinical Outcomes in Hospitalized SARS-CoV-2 Patients

Authors: Thao Nguyen, Maximiliano Hyon, Sany Rajagukguk, Anna Melkonyan

Abstract:

Introduction: Type 2 Diabetes is a well-established risk factor for severe SARS-CoV-2 infection. Uncontrolled hyperglycemia in patients with established or newly diagnosed diabetes is associated with poor outcomes, including increased mortality and hospital length of stay. Objectives: Our study aims to compare three different glycemic management strategies and their association with clinical outcomes in patients hospitalized for moderate to severe SARS-CoV-2 infection. Identifying optimal glycemic management strategies will improve the quality of patient care and improve their outcomes. Method: This is a retrospective observational study on patients hospitalized at Adventist Health White Memorial with severe SARS-CoV-2 infection from 11/1/2020 to 02/28/2021. The following inclusion criteria were used: positive SARS-CoV-2 PCR test, age >18 yrs old, diabetes or random glucose >200 mg/dL on admission, oxygen requirement >4L/min, and treatment with glucocorticoids. Our exclusion criteria included: ICU admission within 24 hours, discharge within five days, death within five days, and pregnancy. The patients were divided into three glycemic management groups: Group 1, managed solely by the Primary Team, Group 2, by Pharmacy; and Group 3, by Endocrinologist. Primary outcomes were average glucose on Day 5, change in glucose between Days 3 and 5, and average insulin dose on Day 5 among groups. Secondary outcomes would be upgraded to ICU, inpatient mortality, and hospital length of stay. For statistics, we used IBM® SPSS, version 28, 2022. Results: Most studied patients were Hispanic, older than 60, and obese (BMI >30). It was the first CV-19 surge with the Delta variant in an unvaccinated population. Mortality was markedly high (> 40%) with longer LOS (> 13 days) and a high ICU transfer rate (18%). Most patients had markedly elevated inflammatory markers (CRP, Ferritin, and D-Dimer). These, in combination with glucocorticoids, resulted in severe hyperglycemia that was difficult to control. Average glucose on Day 5 was not significantly different between groups primary vs. pharmacy vs. endocrine (220.5 ± 63.4 vs. 240.9 ± 71.1 vs. 208.6 ± 61.7 ; P = 0.105). Change in glucose from days 3 to 5 was not significantly different between groups but trended towards favoring the endocrinologist group (-26.6±73.6 vs. 3.8±69.5 vs. -32.2±84.1; P= 0.052). TDD insulin was not significantly different between groups but trended towards higher TDD for the endocrinologist group (34.6 ± 26.1 vs. 35.2 ± 26.4 vs. 50.5 ± 50.9; P=0.054). The endocrinologist group used significantly more preprandial insulin compared to other groups (91.7% vs. 39.1% vs. 65.9% ; P < 0.001). The pharmacy used more basal insulin than other groups (95.1% vs. 79.5% vs. 79.2; P = 0.047). There were no differences among groups in the clinical outcomes: LOS, ICU upgrade, or mortality. Multivariate regression analysis controlled for age, sex, BMI, HbA1c level, renal function, liver function, CRP, d-dimer, and ferritin showed no difference in outcomes among groups. Conclusion: Given high-risk factors in our population, despite efforts from the glycemic management teams, it’s unsurprising no differences in clinical outcomes in mortality and length of stay.

Keywords: glycemic management, strategies, hospitalized, SARS-CoV-2, outcomes

Procedia PDF Downloads 448
158 The Effect of Slum Neighborhoods on Pregnancy Outcomes in Tanzania: Secondary Analysis of the 2015-2016 Tanzania Demographic and Health Survey Data

Authors: Luisa Windhagen, Atsumi Hirose, Alex Bottle

Abstract:

Global urbanization has resulted in the expansion of slums, leaving over 10 million Tanzanians in urban poverty and at risk of poor health. Whilst rural residence has historically been associated with an increased risk of adverse pregnancy outcomes, recent studies found higher perinatal mortality rates in urban Tanzania. This study aims to understand to what extent slum neighborhoods may account for the spatial disparities seen in Tanzania. We generated a slum indicator based on UN-HABITAT criteria to identify slum clusters within the 2015-2016 Tanzania Demographic and Health Survey. Descriptive statistics, disaggregated by urban slum, urban non-slum, and rural areas, were produced. Simple and multivariable logistic regression examined the association between cluster residence type and neonatal mortality and stillbirth. For neonatal mortality, we additionally built a multilevel logistic regression model, adjusting for confounding and clustering. The neonatal mortality ratio was highest in slums (38.3 deaths per 1000 live births); the stillbirth rate was three times higher in slums (32.4 deaths per 1000 births) than in urban non-slums. Neonatal death was more likely to occur in slums than in urban non-slums (aOR=2.15, 95% CI=1.02-4.56) and rural areas (aOR=1.78, 95% CI=1.15-2.77). Odds of stillbirth were over five times higher among rural than urban non-slum residents (aOR=5.25, 95% CI=1.31-20.96). The results suggest that slums contribute to the urban disadvantage in Tanzanian neonatal health. Higher neonatal mortality in slums may be attributable to lack of education, lower socioeconomic status, poor healthcare access, and environmental factors, including indoor and outdoor air pollution and unsanitary conditions from inadequate housing. However, further research is required to ascertain specific causalities as well as significant associations between residence type and other pregnancy outcomes. The high neonatal mortality, stillbirth, and slum formation rates in Tanzania signify that considerable change is necessary to achieve international goals for health and human settlements. Disparities in access to adequate housing, safe water and sanitation, high standard antenatal, intrapartum, and neonatal care, and maternal education need to urgently be addressed. This study highlights the spatial neonatal mortality shift from rural settings to urban informal settlements in Tanzania. Importantly, other low- and middle-income countries experiencing overwhelming urbanization and slum expansion may also be at risk of a reversing trend in residential neonatal health differences.

Keywords: urban health, slum residence, neonatal mortality, stillbirth, global urbanisation

Procedia PDF Downloads 64
157 Benefits of Using Social Media and Collaborative Online Platforms in PBL

Authors: Susanna Graziano, Lydia Krstic Ward

Abstract:

The purpose of this presentation is to demonstrate the steps of using multimedia and collaborative platforms in project-based learning. The presentation will demonstrate the stages of the learning project with various components of independent and collaborative learning, where students research the topic, share information, prepare a survey, use social media (Facebook, Instagram, WhasApp) and collaborative platforms (wikispaces.com and Google docs) to collect, analyze and process data, then produce reports and logos to be displayed as a final product. At the beginning of the presentation participants will answer a questionnaire about project based learning and share their experience on using social media, real–world project work and collaborative learning. Using a PPP, the presentation will walk participants through the steps of a completed project where tertiary education students are involved in putting together a multimedia campaign for safe driving in Kuwait. The research component of the project entails taking a holistic view on the problem of the high death rate in traffic accidents. The final goal of the project is to lead students to raise public awareness about the importance of safe driving. The project steps involve using the social media and collaborative platforms for collecting data and sharing the required materials to be used in the final product – a display of written reports, slogans and videos, as well as oral presentations. The same structure can be used to organize a multimedia campaign focusing on other issues, whilst scaffolding on students’ ability to brainstorm, retrieve information, organize it and engage in collaborative/ cooperative learning whilst being immersed in content-based learning as well as in authentic tasks. More specifically, the project we carried out at Box Hill College was a real-world one and involved a multimedia Campaign for Safe Driving since reckless driving is one of the major problems in the country. The idea for the whole project started by a presentation given by a board member of the Kuwaiti Society for Traffic Safety who was invited to college and spoke about: • Driving laws in the country, • What causes car accidents, • Driving safety tips. The principal goal of this project was to let students consider problems of traffic in Kuwait from different points of view. They also had to address the number and causes of accidents, evaluate the effectiveness of the local traffic law in order to send a warning about the importance of safe driving and, finally, suggest ways of its improvement. Benefits included: • Engagement, • Autonomy, • Motivation, • Content knowledge, • Language mastery, • Enhanced critical thinking, • Increased metacognitive awareness, • Improved social skills, • Authentic experience.

Keywords: social media, online learning platforms, collaborative platforms, project based learning

Procedia PDF Downloads 425
156 The Application of Patterned Injuries in Reconstruction of Motorcycle Accidents

Authors: Chun-Liang Wu, Kai-Ping Shaw, Cheng-Ping Yu, Wu-Chien Chien, Hsiao-Ting Chen, Shao-Huang Wu

Abstract:

Objective: This study analyzed three criminal judicial cases. We applied the patterned injuries of the rider to demonstrate the facts of each accident, reconstruct the scenes, and pursue the truth. Methods: Case analysis, a method that collects evidence and reasons the results in judicial procedures, then the importance of the pattern of injury as evidence will be compared and evaluated. The patterned injuries analysis method is to compare the collision situation between an object and human body injuries to determine whether the characteristics can reproduce the unique pattern of injury. Result: Case 1: Two motorcycles, A and B, head-on collided; rider A dead, and rider B was accused. During the prosecutor’s investigation, the defendant learned that rider A had an 80 mm open wound on his neck. During the court trial, the defendant requested copies of the case file and found out that rider A had a large contusion on his chest wall, and the cause of death was traumatic hemothorax and abdominal wall contusion. The defendant compared all the evidence at the scene and determined that the injury was obviously not caused by the collision of the body or the motorcycle of rider B but that rider was out of control and injured himself when he crossed the double yellow line. In this case, the defendant was innocent in the High Court judgment in April 2022. Case 2: Motorcycles C and D head-on crashed, and rider C died of massive abdominal bleeding. The prosecutor decided that rider C was driving under the influence (DUI), but rider D was negligent and sued rider D. The defendant requested the copies’ file and found the special phenomenon that the front wheel of motorcycle C was turned left. The defendant’s injuries were a left facial bone fracture, a left femur fracture, and other injuries on the left side. The injuries were of human-vehicle separation and human-vehicle collision, which proved that rider C suddenly turned left when the two motorcycles approached, knocked down motorcycle D, and the defendant flew forward. Case 3: Motorcycle E and F’s rear end collided, the front rider E was sentenced to 3 months, and the rear rider F sued rider E for more than 7 million N.T. The defendant found in the copies’ file that the injury of rider F was the left tibial platform fracture, etc., and then proved that rider F made the collision with his left knee, causing motorcycle E to fall out of control. This evidence was accepted by the court and is still on trial. Conclusion: The application of patterned injuries in the reconstruction of a motorcycle accident could discover the truth and provide the basis for judicial justice. The cases and methods could be the reference for the policy of preventing traffic accident casualties.

Keywords: judicial evidence, patterned injuries analysis, accident reconstruction, fatal motorcycle injuries

Procedia PDF Downloads 84
155 Domestic Violence Against Women (With Special Reference to India): A Human Rights Issue

Authors: N. B. Chandrakala

Abstract:

Domestic violence is one of the most under-reported crimes. Problem with domestic violence is that it is not even considered as abuse in many parts of the world especially certain parts of Asia, Africa and Middle East. It is viewed as “doing the needful”. Domestic violence could be in form of emotional harassment, physical injury or psychological abuse perpetrated by one of the family members to another. It is a worldwide phenomenon mainly targeting women. The acts of violence have terrible negative impact on women. It is also an infringement of women’s rights and can be safely termed as human rights abuse. In cases pertaining to domestic violence, male adults often misuses his authority and power to control another using physical or psychological means. Violence and other forms of abuse are common in domestic violence. Sexual assaults, molestation and battering are common in these cases. Domestic violence is a human rights issue and a serious deterrent to development. Domestic violence could also take place in subtle forms like making the person feel worthless or not giving the victims any personal space or freedom. The problematic aspect is cases of domestic violence are very rarely reported. The majority of the victims are women but children are also made to suffer silently. They are abused and neglected. Their innocent minds are adversely affected with the incidents of domestic violence. According to a report by World Health Organization (WHO), sexual trafficking, female feticide, dowry death, public humiliation and physical torture are some of the most common forms of domestic violence against Indian women. Such acts belie our growth and claim as an economic superpower. It is ironic that we claim to be one of the most rapidly advancing countries in the world and yet we have done hardly anything of note against social hazards like domestic violence. Laws are not that stringent when it comes to reporting acts of domestic violence. Even if the report is filed it turns out to be a long drawn process and not every victim has that much resource to fight till the end. It is also a social taboo to make your family matters public. The big challenge in front now is to enforce it in true sense. Steps that are actually needed; tough laws against domestic violence, speedy execution and change in the mindset of society only then we can expect to have some improvement in such inhuman cases. An effective response to violence must be multi-sectoral; addressing the immediate practical needs of women experiencing abuse; providing long-term follow up and assistance; and focusing on changing those cultural norms, attitudes and legal provisions that promote the acceptance of and even encourage violence against women, and undermine women's enjoyment of their full human rights and freedoms. Hence the responses to the problem must be based on integrated approach. The effectiveness of measures and initiatives will depend on coherence and coordination associated with their design and implementation.

Keywords: domestic violence, human rights, sexual assaults, World Health Organization

Procedia PDF Downloads 542
154 The Effect of TiO₂ Nanoparticles on Zebrafish Embryos

Authors: Elena Maria Scalisi

Abstract:

Currently, photodegradation by nanoparticles (NPs) is a common solution for wastewater treatment. Nanoparticles are efficient for removing organic and inorganic pollutants, heavy metals from wastewater and killing microorganisms through environmentally friendly. In this context, the major representative of photocatalytic technology for industrial wastewater treatment are TiO₂ nanoparticles (TiO₂-NPs). TiO₂-NPs have a strong catalytic activity that depends to their physicochemical properties. Thanks to their small size (between 1-100 nm), nanoparticles occupy less volume, then their surface area increases. The increase in the surface-to-volume ratio results in the increase of the particle surface energy, which improve their reactivity potential. However, these unique properties represent risks to the ecosystems and organisms when unintentionally TiO₂-NPs are release into the environment and absorbed by living organisms. Several studies confirm that there is a high level of interest concerning the safety of TiO₂-NPs in the aquatic environment, furthermore, ecotoxicological tools are useful to correctly evaluate their toxicity. In the current study, we aimed to characterize potential toxic effects of TiO₂-NP suspension to zebrafish during embryo-larval stages to evaluate parameters such as survival rates, malformation, hatching, the overall length of the larvae heartbeat, and biochemical biomarkers that reflect the acute toxicity and sublethal effects of TiO₂-NPs. Zebrafish embryos were exposed to titanium dioxide nanoparticles (TiO₂-NPs at 1mg/L, 2mg/L, and 4mg/L) from fertilization to the free swimming stage (144hpf). Every day, we recorded the toxicological endpoints, moreover, immunohistochemical analysis has been performed at the end of the exposure. In particular, we have evaluate the expression of the following biomarkers: Heat Shock Protein 70 (HSP70), Poly ADP-Ribose Polymerase-1 (PARP-1), Metallothioneins (MTs). Our results have shown that hatch ability, survival, and malformation rate were not affected by TiO₂ NPs at these exposure levels. However, TiO₂-NPs caused an increase of heartbeat and reduction of body length; at the same time, TiO₂-NPs have inducted the production of ROS and the expression of oxidative stress biomarkers HSP70 and PARP-1. Hight positivity for PARP-1 at all concentration tested was observed. As regards MT, positivity was found in the expression of this biomarker in the whole body of the embryo, with the exception of the end of the tail. Metallothioneins (MT) are biomarkers widely used in environmental monitoring programs for aquatic creatures. At the light of our results i.e. no death until the end of the experiment (144hpf), no malformation and expression of the biomarkers mentioned, it is evident that zebrafish larvae with their natural detoxification pathways are able to resist the presence of toxic substances and then they can tolerate the presence of metal concentrations. However, an excessive oxidative state can compromise cell function, therefore the uncontrolled release of nanoparticles into the environment is severe and must be constantly monitored.

Keywords: nanoparticles, embryo zebrafish, HSP70, PARP-1

Procedia PDF Downloads 139
153 Differentially Expressed Protein Biomarkers in Early and Advanced Stage Young Triple-Negative Breast Cancer Patients

Authors: Shamim Mushtaq, Moazzam Shahid

Abstract:

Breast cancer (BC) claims the lives of half a million women every year and is the most common cause of death in the developing world. In 2019, it was estimated that BC alone accounts for 15% of all cancer deaths in younger women (aged < 45 years old) with advanced-stage lung metastasis. According to the World Health Organization & International Union against Cancer, in Asia, a high number of cancer-related deaths will be observed in 2020, whereas the burden will be reduced in Western countries due to awareness about the disease, better health facilities and advanced treatments. In the last 15 years, it has been reported that the incidence of BC has increased by 1.1% among Asian compared to the US population from 2003 to 2012. To date, several BC biological subtypes have been reported so far, which are associated with different treatment responses. The heterogeneity and diversity of BC reflected these different subtypes, including Luminal A (23.7% prevalence) and B (38.8% prevalence) that have pathological estrogen receptor (ER+)-positive tumors, the human epidermal growth factor receptor 2 (HER2) (11.2% prevalence) and triple-negative breast cancer (TNBC) (25% prevalence). According to Shaukat Khanum Memorial Cancer Hospital and Research Centre – Pakistan, ten years of data showed that among 636 BC patients, 30.5% had TNBC who were <40 years of age, which is an extremely alarming situation. Therefore, there is a dire need to explore and develop therapeutic targets for the treatment of early TNBC. Since the last decade, unfortunately, there has been little success in understanding the complexity of TNBC and in discovering new biological therapeutic targets. However, conventional chemotherapy is the only choice of treatment for TNBC patients. Many investigators revealed advances in multi-omics (multiple "omes", e.g., genome, proteome, transcriptome, epigenome, and microbiome) which were later identified as actionable targets and increased prevalence in TNBC patients. However, various drugs have been identified so far which are related to a particular diagnostic and prognostic biomarker. For example, Epidermal growth factor receptor ( EGFR or ErbB-1), HER-2/neu (ErbB-2), HER-3 (ErbB-3), and HER-4 (ErbB-4). Protein Transglin-2 (TAGLN 2 ) and Profilins-1 (Pfn-1 ) are the ubiquitously expressed large family of proteins present in all eukaryotes, enabling actin cytoskeletal reorganization. It is known that the oncogenic transformation of cells is accompanied by alteration in the actin cytoskeleton. There are causal connections between altered expression of actin cytoskeletal regulators and cancer progression. Our case-control study identified TAGLN-2 and Pfn-1 proteins in TNBC blood by mass spectrometry. Both TAGLN-2 and Pfn-1 proteins are differentially expressed in early and advanced stages of TNBS patients, which could be potential predictors or therapeutic targets for TNBC.

Keywords: TNBC, blood biomarkers, mass spectrometry, qPCR, ELISA

Procedia PDF Downloads 43
152 In vivo Estimation of Mutation Rate of the Aleutian Mink Disease Virus

Authors: P.P. Rupasinghe, A.H. Farid

Abstract:

The Aleutian mink disease virus (AMDV, Carnivore amdoparvovirus 1) causes persistent infection, plasmacytosis, and formation and deposition of immune complexes in various organs in adult mink, leading to glomerulonephritis, arteritis and sometimes death. The disease has no cure nor an effective vaccine, and identification and culling of mink positive for anti-AMDV antibodies have not been successful in controlling the infection in many countries. The failure to eradicate the virus from infected farms may be caused by keeping false-negative individuals on the farm, virus transmission from wild animals, or neighboring farms. The identification of sources of infection, which can be performed by comparing viral sequences, is important in the success of viral eradication programs. High mutation rates could cause inaccuracies when viral sequences are used to trace back an infection to its origin. There is no published information on the mutation rate of AMDV either in vivo or in vitro. The in vivo estimation is the most accurate method, but it is difficult to perform because of the inherent technical complexities, namely infecting live animals, the unknown numbers of viral generations (i.e., infection cycles), the removal of deleterious mutations over time and genetic drift. The objective of this study was to determine the mutation rate of AMDV on which no information was available. A homogenate was prepared from the spleen of one naturally infected American mink (Neovison vison) from Nova Scotia, Canada (parental template). The near full-length genome of this isolate (91.6%, 4,143 bp) was bidirectionally sequenced. A group of black mink was inoculated with this homogenate (descendant mink). Spleen sampled were collected from 10 descendant mink after 16 weeks post-inoculation (wpi) and from anther 10 mink after 176 wpi, and their near-full length genomes were bi-directionally sequenced. Sequences of these mink were compared with each other and with the sequence of the parental template. The number of nucleotide substitutions at 176 wpi was 3.1 times greater than that at 16 wpi (113 vs 36) whereas the estimates of mutation rate at 176 wpi was 3.1 times lower than that at 176 wpi (2.85×10-3 vs 9.13×10-4 substitutions/ site/ year), showing a decreasing trend in the mutation rate per unit of time. Although there is no report on in vivo estimate of the mutation rate of DNA viruses in animals using the same method which was used in the current study, these estimates are at the higher range of reported values for DNA viruses determined by various techniques. These high estimates are logical based on the wide range of diversity and pathogenicity of AMDV isolates. The results suggest that increases in the number of nucleotide substitutions over time and subsequent divergence make it difficult to accurately trace back AMDV isolates to their origin when several years elapsed between the two samplings.

Keywords: Aleutian mink disease virus, American mink, mutation rate, nucleotide substitution

Procedia PDF Downloads 124
151 Direct Current Electric Field Stimulation against PC12 Cells in 3D Bio-Reactor to Enhance Axonal Extension

Authors: E. Nakamachi, S. Tanaka, K. Yamamoto, Y. Morita

Abstract:

In this study, we developed a three-dimensional (3D) direct current electric field (DCEF) stimulation bio-reactor for axonal outgrowth enhancement to generate the neural network of the central nervous system (CNS). By using our newly developed 3D DCEF stimulation bio-reactor, we cultured the rat pheochromocytoma cells (PC12) and investigated the effects on the axonal extension enhancement and network generation. Firstly, we designed and fabricated a 3D bio-reactor, which can load DCEF stimulation on PC12 cells embedded in the collagen gel as extracellular environment. The connection between the electrolyte and the medium using salt bridges for DCEF stimulation was introduced to avoid the cell death by the toxicity of metal ion. The distance between the salt bridges was adopted as the design variable to optimize a structure for uniform DCEF stimulation, where the finite element (FE) analyses results were used. Uniform DCEF strength and electric flux vector direction in the PC12 cells embedded in collagen gel were examined through measurements of the fabricated 3D bio-reactor chamber. Measurement results of DCEF strength in the bio-reactor showed a good agreement with FE results. In addition, the perfusion system was attached to maintain pH 7.2 ~ 7.6 of the medium because pH change was caused by DCEF stimulation loading. Secondly, we disseminated PC12 cells in collagen gel and carried out 3D culture. Finally, we measured the morphology of PC12 cell bodies and neurites by the multiphoton excitation fluorescence microscope (MPM). The effectiveness of DCEF stimulation to enhance the axonal outgrowth and the neural network generation was investigated. We confirmed that both an increase of mean axonal length and axogenesis rate of PC12, which have been exposed 5 mV/mm for 6 hours a day for 4 days in the bioreactor. We found following conclusions in our study. 1) Design and fabrication of DCEF stimulation bio-reactor capable of 3D culture nerve cell were completed. A uniform electric field strength of average value of 17 mV/mm within the 1.2% error range was confirmed by using FE analyses, after the structure determination through the optimization process. In addition, we attached a perfusion system capable of suppressing the pH change of the culture solution due to DCEF stimulation loading. 2) Evaluation of DCEF stimulation effects on PC12 cell activity was executed. The 3D culture of PC 12 was carried out adopting the embedding culture method using collagen gel as a scaffold for four days under the condition of 5.0 mV/mm and 10mV/mm. There was a significant effect on the enhancement of axonal extension, as 11.3% increase in an average length, and the increase of axogenesis rate. On the other hand, no effects on the orientation of axon against the DCEF flux direction was observed. Further, the network generation was enhanced to connect longer distance between the target neighbor cells by DCEF stimulation.

Keywords: PC12, DCEF stimulation, 3D bio-reactor, axonal extension, neural network generation

Procedia PDF Downloads 184
150 Use of Misoprostol in Pregnancy Termination in the Third Trimester: Oral versus Vaginal Route

Authors: Saimir Cenameri, Arjana Tereziu, Kastriot Dallaku

Abstract:

Introduction: Intra-uterine death is a common problem in obstetrical practice, and can lead to complications if left to resolve spontaneously. The cervix is unprepared, making inducing of labor difficult. Misoprostol is a synthetic prostaglandin E1 analogue, inexpensive, and is presented valid thanks to its ability to bring about changes in the cervix that lead to the induction of uterine contractions. Misoprostol is quickly absorbed when taken orally, resulting in high initial peak serum concentrations compared with the vaginal route. The vaginal misoprostol peak serum concentration is not as high and demonstrates a more gradual serum concentration decline. This is associated with many benefits for the patient; fast induction of labor; smaller doses; and fewer side effects (dose-depended). Mostly it has been used the regime of 50 μg/4 hour, with a high percentage of success and limited side effects. Objective: Evaluation of the efficiency of the use of oral and vaginal misoprostol in inducing labor, and comparing it with its use not by a previously defined protocol. Methods: Participants in this study included patients at U.H.O.G. 'Koco Gliozheni', Tirana from April 2004-July 2006, presenting with an indication for inducing labor in the third trimester for pregnancy termination. A total of 37 patients were randomly admitted for birth inducing activity, according to protocol (26), oral or vaginal protocol (10 vs. 16), and a control group (11), not subject to the protocol, was created. Oral or vaginal misoprostol was administered at a dose of 50 μg/4 h, while the fourth group participants were treated individually by the members of the medical staff. The main result of interest was the time between induction of labor to birth. Kruskal-Wallis test was used to compare the average age, parity, women weight, gestational age, Bishop's score, the size of the uterus and weight of the fetus between the four groups in the study. The Fisher exact test was used to compare day-stay and causes in the four groups. Mann-Whitney test was used to compare the time of the expulsion and the number of doses between oral and vaginal group. For all statistical tests used, the value of P ≤ 0.05 was considered statistically significant. Results: The four groups were comparable with regard to woman age and weight, parity, abortion indication, Bishop's score, fetal weight and the gestational age. There was significant difference in the percentage of deliveries within 24 hours. The average time from induction to birth per route (vaginal, oral, according to protocol and not according to the protocol) was respectively; 10.43h; 21.10h; 15.77h, 21.57h. There was no difference in maternal complications in groups. Conclusions: Use of vaginal misoprostol for inducing labor in the third trimester for termination of pregnancy appears to be more effective than the oral route, and even more to uses not according to the protocols approved before, where complications are greater and unjustified.

Keywords: inducing labor, misoprostol, pregnancy termination, third trimester

Procedia PDF Downloads 185
149 Hospital Malnutrition and its Impact on 30-day Mortality in Hospitalized General Medicine Patients in a Tertiary Hospital in South India

Authors: Vineet Agrawal, Deepanjali S., Medha R., Subitha L.

Abstract:

Background. Hospital malnutrition is a highly prevalent issue and is known to increase the morbidity, mortality, length of hospital stay, and cost of care. In India, studies on hospital malnutrition have been restricted to ICU, post-surgical, and cancer patients. We designed this study to assess the impact of hospital malnutrition on 30-day post-discharge and in-hospital mortality in patients admitted in the general medicine department, irrespective of diagnosis. Methodology. All patients aged above 18 years admitted in the medicine wards, excluding medico-legal cases, were enrolled in the study. Nutritional assessment was done within 72 h of admission, using Subjective Global Assessment (SGA), which classifies patients into three categories: Severely malnourished, Mildly/moderately malnourished, and Normal/well-nourished. Anthropometric measurements like Body Mass Index (BMI), Triceps skin-fold thickness (TSF), and Mid-upper arm circumference (MUAC) were also performed. Patients were followed-up during hospital stay and 30 days after discharge through telephonic interview, and their final diagnosis, comorbidities, and cause of death were noted. Multivariate logistic regression and cox regression model were used to determine if the nutritional status at admission independently impacted mortality at one month. Results. The prevalence of malnourishment by SGA in our study was 67.3% among 395 hospitalized patients, of which 155 patients (39.2%) were moderately malnourished, and 111 (28.1%) were severely malnourished. Of 395 patients, 61 patients (15.4%) expired, of which 30 died in the hospital, and 31 died within 1 month of discharge from hospital. On univariate analysis, malnourished patients had significantly higher morality (24.3% in 111 Cat C patients) than well-nourished patients (10.1% in 129 Cat A patients), with OR 9.17, p-value 0.007. On multivariate logistic regression, age and higher Charlson Comorbidity Index (CCI) were independently associated with mortality. Higher CCI indicates higher burden of comorbidities on admission, and the CCI in the expired patient group (mean=4.38) was significantly higher than that of the alive cohort (mean=2.85). Though malnutrition significantly contributed to higher mortality on univariate analysis, it was not an independent predictor of outcome on multivariate logistic regression. Length of hospitalisation was also longer in the malnourished group (mean= 9.4 d) compared to the well-nourished group (mean= 8.03 d) with a trend towards significance (p=0.061). None of the anthropometric measurements like BMI, MUAC, or TSF showed any association with mortality or length of hospitalisation. Inference. The results of our study highlight the issue of hospital malnutrition in medicine wards and reiterate that malnutrition contributes significantly to patient outcomes. We found that SGA performs better than anthropometric measurements in assessing under-nutrition. We are of the opinion that the heterogeneity of the study population by diagnosis was probably the primary reason why malnutrition by SGA was not found to be an independent risk factor for mortality. Strategies to identify high-risk patients at admission and treat malnutrition in the hospital and post-discharge are needed.

Keywords: hospitalization outcome, length of hospital stay, mortality, malnutrition, subjective global assessment (SGA)

Procedia PDF Downloads 149
148 Socio-Cultural Factors Influencing Adherence to Anti-Retroviral Therapy among HIV Patients in a University Teaching Hospital in South-Western Nigeria

Authors: Okunola Oluseye Ademola

Abstract:

The study investigated various socio-cultural factors influencing adherence to antiretroviral drugs among people living with HIV in a University Teaching Hospital in South-western Nigeria. The objectives are to examine the perception of people living with HIV/AIDS (PLWHA) of antiretroviral therapy (ART) in Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, investigate the influence of socio-cultural factors on adherence of PLWHA to treatment regimen in the study area and assess the prevalence of adherence to ART among PLWHA in the study area. It was a cross-sectional where both qualitative and quantitative research methods were adopted. The participants were HIV diagnosed patients attending clinic at the Obafemi Awolowo University Teaching Hospitals Complex in Ile-Ife between the ages of 18 and 60 years. Also three healthcare delivery personnel working in the clinic were interviewed. Out of the 3007 patients receiving treatment, using Fischer’s formula of sampling technique, 336 patients living with HIV/AIDS were selected for the study. These participants had been on antiretroviral drugs for more than six months prior to the study and were selected using simple random sampling technique. Two focus group discussion sessions comprising of 10 male and 10 female living with HIV and currently on ART were conducted. These groups were purposively selected based on their being on ART for more than one year. Also in-depth interviews were conducted among three purposively selected healthcare givers (an experienced nurse, a doctor and a pharmacist) who are working in this clinic. All the participants were interviewed at the clinic on the various clinic days. Data were collected using a structured questionnaire, an interview guide and tape-recorder. The quantitative data were analysed using descriptive and inferential statistics. Content analysis was employed to analyse responses from IDI and FGD sessions. The findings from the study revealed a very positive perception to ART among PLWHA which was about 86.3% while the level of adherence to ART was 89.0% among the respondents. There was a very strong relationship between social and family supports and the degree of adherence to ART in the PLWHA. Nutrition, polygamy, difficulty in financing transportation fare to the clinic, unemployment, drug hawkers, religion, excuse duty from work and waking up very early were highlighted as socio-cultural barriers to adherence to ART. Fear of death, strong family support, religion belief, not seeking alternative treatment, absence of rituals and perceived improved health status were identified as very strong facilitators to adherence. The study concluded that to achieve a very optimal outcome in the management of HIV among PLWHA, various social and cultural contexts should be taken into consideration as this study was able to ascertain the influence of various socio-cultural factors militating and facilitating adherence to ART.

Keywords: ART, HIV, PLWHA, socio-cultural

Procedia PDF Downloads 278
147 COVID-19 Laws and Policy: The Use of Policy Surveillance For Better Legal Preparedness

Authors: Francesca Nardi, Kashish Aneja, Katherine Ginsbach

Abstract:

The COVID-19 pandemic has demonstrated both a need for evidence-based and rights-based public health policy and how challenging it can be to make effective decisions with limited information, evidence, and data. The O’Neill Institute, in conjunction with several partners, has been working since the beginning of the pandemic to collect, analyze, and distribute critical data on public health policies enacted in response to COVID-19 around the world in the COVID-19 Law Lab. Well-designed laws and policies can help build strong health systems, implement necessary measures to combat viral transmission, enforce actions that promote public health and safety for everyone, and on the individual level have a direct impact on health outcomes. Poorly designed laws and policies, on the other hand, can fail to achieve the intended results and/or obstruct the realization of fundamental human rights, further disease spread, or cause unintended collateral harms. When done properly, laws can provide the foundation that brings clarity to complexity, embrace nuance, and identifies gaps of uncertainty. However, laws can also shape the societal factors that make disease possible. Law is inseparable from the rest of society, and COVID-19 has exposed just how much laws and policies intersects all facets of society. In the COVID-19 context, evidence-based and well-informed law and policy decisions—made at the right time and in the right place—can and have meant the difference between life or death for many. Having a solid evidentiary base of legal information can promote the understanding of what works well and where, and it can drive resources and action to where they are needed most. We know that legal mechanisms can enable nations to reduce inequities and prepare for emerging threats, like novel pathogens that result in deadly disease outbreaks or antibiotic resistance. The collection and analysis of data on these legal mechanisms is a critical step towards ensuring that legal interventions and legal landscapes are effectively incorporated into more traditional kinds of health science data analyses. The COVID-19 Law Labs see a unique opportunity to collect and analyze this kind of non-traditional data to inform policy using laws and policies from across the globe and across diseases. This global view is critical to assessing the efficacy of policies in a wide range of cultural, economic, and demographic circumstances. The COVID-19 Law Lab is not just a collection of legal texts relating to COVID-19; it is a dataset of concise and actionable legal information that can be used by health researchers, social scientists, academics, human rights advocates, law and policymakers, government decision-makers, and others for cross-disciplinary quantitative and qualitative analysis to identify best practices from this outbreak, and previous ones, to be better prepared for potential future public health events.

Keywords: public health law, surveillance, policy, legal, data

Procedia PDF Downloads 141
146 The Social Ecology of Serratia entomophila: Pathogen of Costelytra giveni

Authors: C. Watson, T. Glare, M. O'Callaghan, M. Hurst

Abstract:

The endemic New Zealand grass grub (Costelytra giveni, Coleoptera: Scarabaeidae) is an economically significant grassland pest in New Zealand. Due to their impacts on production within the agricultural sector, one of New Zealand's primary industries, several methods are being used to either control or prevent the establishment of new grass grub populations in the pasture. One such method involves the use of a biopesticide based on the bacterium Serratia entomophila. This species is one of the causative agents of amber disease, a chronic disease of the larvae which results in death via septicaemia after approximately 2 to 3 months. The ability of S. entomophila to cause amber disease is dependant upon the presence of the amber disease associated plasmid (pADAP), which encodes for the key virulence determinants required for the establishment and maintenance of the disease. Following the collapse of grass grub populations within the soil, resulting from either natural population build-up or application of the bacteria, non-pathogenic plasmid-free Serratia strains begin to predominate within the soil. Whilst the interactions between S. entomophila and grass grub larvae are well studied, less information is known on the interactions between plasmid-bearing and plasmid-free strains, particularly the potential impact of these interactions upon the efficacy of an applied biopesticide. Using a range of constructed strains with antibiotic tags, in vitro (broth culture) and in vivo (soil and larvae) experiments were conducted using inoculants comprised of differing ratios of isogenic pathogenic and non-pathogenic Serratia strains, enabling the relative growth of pADAP+ and pADAP- strains under competition conditions to be assessed. In nutrient-rich, the non-pathogenic pADAP- strain outgrew the pathogenic pADAP+ strain by day 3 when inoculated in equal quantities, and by day 5 when applied as the minority inoculant, however, there was an overall gradual decline in the number of viable bacteria for both strains over a 7-day period. Similar results were obtained in additional experiments using the same strains and continuous broth cultures re-inoculated at 24-hour intervals, although in these cultures, the viable cell count did not diminish over the 7-day period. When the same ratios were assessed in soil microcosms with limited available nutrients, the strains remained relatively stable over a 2-month period. Additionally, in vivo grass grub co-infections assays using the same ratios of tagged Serratia strains revealed similar results to those observed in the soil, but there was also evidence of horizontal transfer of pADAP from the pathogenic to the non-pathogenic strain within the larval gut after a period of 4 days. Whilst the influence of competition is more apparent in broth cultures than within the soil or larvae, further testing is required to determine whether this competition between pathogenic and non-pathogenic Serratia strains has any influence on efficacy and disease progression, and how this may impact on the ability of S. entomophila to cause amber disease within grass grub larvae when applied as a biopesticide.

Keywords: biological control, entomopathogen, microbial ecology, New Zealand

Procedia PDF Downloads 156
145 Pediatric Drug Resistance Tuberculosis Pattern, Side Effect Profile and Treatment Outcome: North India Experience

Authors: Sarika Gupta, Harshika Khanna, Ajay K Verma, Surya Kant

Abstract:

Background: Drug-resistant tuberculosis (DR-TB) is a growing health challenge to global TB control efforts. Pediatric DR-TB is one of the neglected infectious diseases. In our previously published report, we have notified an increased prevalence of DR-TB in the pediatric population at a tertiary health care centre in North India which was estimated as 17.4%, 15.1%, 18.4%, and 20.3% in (%) in the year 2018, 2019, 2020, and 2021. Limited evidence exists about a pattern of drug resistance, side effect profile and programmatic outcomes of Paediatric DR-TB treatment. Therefore, this study was done to find out the pattern of resistance, side effect profile and treatment outcome. Methodology: This was a prospective cohort study conducted at the nodal drug-resistant tuberculosis centre of a tertiary care hospital in North India from January 2021 to December 2022. Subjects included children aged between 0-18 years of age with a diagnosis of DR-TB, on the basis of GeneXpert (rifampicin [RIF] resistance detected), line probe assay and drug sensitivity testing (DST) of M. tuberculosis (MTB) grown on a culture of body fluids. Children were classified as monoresistant TB, polyresistant TB (resistance to more than 1 first-line anti-TB drug, other than both INH and RIF), MDR-TB, pre-XDR-TB and XDR-TB, as per the WHO classification. All the patients were prescribed DR TB treatment as per the standard guidelines, either shorter oral DR-TB regimen or a longer all-oral MDR/XDR-TB regimen (age below five years needed modification). All the patients were followed up for side effects of treatment once per month. The patient outcomes were categorized as good outcomes if they had completed treatment and cured or were improving during the course of treatment, while bad outcomes included death or not improving during the course of treatment. Results: Of the 50 pediatric patients included in the study, 34 were females (66.7%) and 16 were male (31.4%). Around 33 patients (64.7%) were suffering from pulmonary TB, while 17 (33.3%) were suffering from extrapulmonary TB. The proportions of monoresistant TB, polyresistant TB, MDR-TB, pre-XDR-TB and XDR-TB were 2.0%, 0%, 50.0%, 30.0% and 18.0%, respectively. Good outcome was reported in 40 patients (80.0%). The 10 bad outcomes were 7 deaths (14%) and 3 (6.0%) children who were not improving. Adverse events (single or multiple) were reported in all the patients, most of which were mild in nature. The most common adverse events were metallic taste 16(31.4%), rash and allergic reaction 15(29.4%), nausea and vomiting 13(26.0%), arthralgia 11 (21.6%) and alopecia 11 (21.6%). Serious adverse event of QTc prolongation was reported in 4 cases (7.8%), but neither arrhythmias nor symptomatic cardiac side effects occurred. Vestibular toxicity was reported in 2(3.9%), and psychotic symptoms in 4(7.8%). Hepatotoxicity, hypothyroidism, peripheral neuropathy, gynaecomastia, and amenorrhea were reported in 2 (4.0%), 4 (7.8%), 2 (3.9%), 1(2.0%), and 2 (3.9%) respectively. None of the drugs needed to be withdrawn due to uncontrolled adverse events. Conclusion: Paediatric DR TB treatment achieved favorable outcomes in a large proportion of children. DR TB treatment regimen drugs were overall well tolerated in this cohort.

Keywords: pediatric, drug-resistant, tuberculosis, adverse events, treatment

Procedia PDF Downloads 66
144 Relationship between Iron-Related Parameters and Soluble Tumor Necrosis Factor-Like Weak Inducer of Apoptosis in Obese Children

Authors: Mustafa M. Donma, Orkide Donma

Abstract:

Iron is physiologically essential. However, it also participates in the catalysis of free radical formation reactions. Its deficiency is associated with amplified health risks. This trace element establishes some links with another physiological process related to cell death, apoptosis. Both iron deficiency and iron overload are closely associated with apoptosis. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) has the ability to trigger apoptosis and plays a dual role in the physiological versus pathological inflammatory responses of tissues. The aim of this study was to investigate the status of these parameters as well as the associations among them in children with obesity, a low-grade inflammatory state. The study was performed on groups of children with normal body mass index (N-BMI) and obesity. Forty-three children were included in each group. Based upon age- and sex-adjusted BMI percentile tables prepared by World Health Organization, children whose values varied between 85 and 15 were included in N-BMI group. Children whose BMI percentile values were between 99 and 95 comprised obese (OB) group. Institutional ethical committee approval and informed consent forms were taken prior to the study. Anthropometric measurements (weight, height, waist circumference, hip circumference, head circumference, neck circumference) and blood pressure values (systolic blood pressure and diastolic blood pressure) were recorded. Routine biochemical analysis including serum iron, total iron binding capacity (TIBC), transferrin saturation percent (Tf Sat %), and ferritin were performed. Soluble tumor necrosis factor-like weak inducer of apoptosis levels were determined by enzyme-linked immunosorbent assay. Study data was evaluated using appropriate statistical tests performed by the statistical program SPSS. Serum iron levels were 91±34 mcrg/dl and 75±31 mcrg/dl in N-BMI and OB children, respectively. The corresponding values for TIBC, Tf Sat %, ferritin were 265 mcrg/dl vs 299 mcrg/dl, 37.2±19.1 % vs 26.7±14.6 %, and 41±25 ng/ml vs 44±26 ng/ml. in N-BMI and OB groups, sTWEAK concentrations were measured as 351 ng/L and 325 ng/L, respectively (p>0.05). Correlation analysis revealed significant associations between sTWEAK levels and iron related parameters (p<0.05) except ferritin. In conclusion, iron contributes to apoptosis. Children with iron deficiency have decreased apoptosis rate in comparison with that of healthy children. sTWEAK is inducer of apoptosis. Obese children had lower levels of both iron and sTWEAK. Low levels of sTWEAK are associated with several types of cancers and poor survival. Although iron deficiency state was not observed in this study, the correlations detected between decreased sTWEAK and decreased iron as well as Tf Sat % values were valuable findings, which point out decreased apoptosis. This may induce a proinflammatory state, potentially leading to malignancies in the future lives of obese children.

Keywords: apoptosis, children, iron-related parameters, obesity, soluble tumor necrosis factor-like weak inducer of apoptosis

Procedia PDF Downloads 132
143 Acute Antihyperglycemic Activity of a Selected Medicinal Plant Extract Mixture in Streptozotocin Induced Diabetic Rats

Authors: D. S. N. K. Liyanagamage, V. Karunaratne, A. P. Attanayake, S. Jayasinghe

Abstract:

Diabetes mellitus is an ever increasing global health problem which causes disability and untimely death. Current treatments using synthetic drugs have caused numerous adverse effects as well as complications, leading research efforts in search of safe and effective alternative treatments for diabetes mellitus. Even though there are traditional Ayurvedic remedies which are effective, due to a lack of scientific exploration, they have not been proven to be beneficial for common use. Hence the aim of this study is to evaluate the traditional remedy made of mixture of plant components, namely leaves of Murraya koenigii L. Spreng (Rutaceae), cloves of Allium sativum L. (Amaryllidaceae), fruits of Garcinia queasita Pierre (Clusiaceae) and seeds of Piper nigrum L. (Piperaceae) used for the treatment of diabetes. We report herein the preliminary results for the in vivo study of the anti-hyperglycaemic activity of the extracts of the above plant mixture in Wistar rats. A mixture made out of equal weights (100 g) of the above mentioned medicinal plant parts were extracted into cold water, hot water (3 h reflux) and water: acetone mixture (1:1) separately. Male wistar rats were divided into six groups that received different treatments. Diabetes mellitus was induced by intraperitoneal administration of streptozotocin at a dose of 70 mg/ kg in male Wistar rats in group two, three, four, five and six. Group one (N=6) served as the healthy untreated and group two (N=6) served as diabetic untreated control and both groups received distilled water. Cold water, hot water, and water: acetone plant extracts were orally administered in diabetic rats in groups three, four and five, respectively at different doses of 0.5 g/kg (n=6), 1.0 g/kg(n=6) and 1.5 g/kg(n=6) for each group. Glibenclamide (0.5 mg/kg) was administered to diabetic rats in group six (N=6) served as the positive control. The acute anti-hyperglycemic effect was evaluated over a four hour period using the total area under the curve (TAUC) method. The results of the test group of rats were compared with the diabetic untreated control. The TAUC of healthy and diabetic rats were 23.16 ±2.5 mmol/L.h and 58.31±3.0 mmol/L.h, respectively. A significant dose dependent improvement in acute anti-hyperglycaemic activity was observed in water: acetone extract (25%), hot water extract ( 20 %), and cold water extract (15 %) compared to the diabetic untreated control rats in terms of glucose tolerance (P < 0.05). Therefore, the results suggest that the plant mixture has a potent antihyperglycemic effect and thus validating their used in Ayurvedic medicine for the management of diabetes mellitus. Future studies will be focused on the determination of the long term in vivo anti-diabetic mechanisms and isolation of bioactive compounds responsible for the anti-diabetic activity.

Keywords: acute antihyperglycemic activity, herbal mixture, oral glucose tolerance test, Sri Lankan medicinal plant extracts

Procedia PDF Downloads 179