Search results for: Acute Respiratory Infection (ARI)
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2696

Search results for: Acute Respiratory Infection (ARI)

1286 Mycophenolate-Induced Disseminated TB in a PPD-Negative Patient

Authors: Megan L. Srinivas

Abstract:

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

Keywords: dermatomyositis, immunosuppressant medications, mycophenolate, disseminated tuberculosis

Procedia PDF Downloads 202
1285 The Stem Cell Transcription Co-factor Znf521 Sustains Mll-af9 Fusion Protein In Acute Myeloid Leukemias By Altering The Gene Expression Landscape

Authors: Emanuela Chiarella, Annamaria Aloisio, Nisticò Clelia, Maria Mesuraca

Abstract:

ZNF521 is a stem cell-associated transcription co-factor, that plays a crucial role in the homeostatic regulation of the stem cell compartment in the hematopoietic, osteo-adipogenic, and neural system. In normal hematopoiesis, primary human CD34+ hematopoietic stem cells display typically a high expression of ZNF521, while its mRNA levels rapidly decrease when these progenitors progress towards erythroid, granulocytic, or B-lymphoid differentiation. However, most acute myeloid leukemias (AMLs) and leukemia-initiating cells keep high ZNF521 expression. In particular, AMLs are often characterized by chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene, which MLL gene includes a variety of fusion oncogenes arisen from genes normally required during hematopoietic development; once they are fused, they promote epigenetic and transcription factor dysregulation. The chromosomal translocation t(9;11)(p21-22;q23), fusing the MLL gene with AF9 gene, results in a monocytic immune phenotype with an aggressive course, frequent relapses, and a short survival time. To better understand the dysfunctional transcriptional networks related to genetic aberrations, AML gene expression profile datasets were queried for ZNF521 expression and its correlations with specific gene rearrangements and mutations. The results showed that ZNF521 mRNA levels are associated with specific genetic aberrations: the highest expression levels were observed in AMLs involving t(11q23) MLL rearrangements in two distinct datasets (MILE and den Boer); elevated ZNF521 mRNA expression levels were also revealed in AMLs with t(7;12) or with internal rearrangements of chromosome 16. On the contrary, relatively low ZNF521 expression levels seemed to be associated with the t(8;21) translocation, that in turn is correlated with the AML1-ETO fusion gene or the t(15;17) translocation and in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. Invitro, we found that the enforced co-expression of ZNF521 in cord blood-derived CD34+ cells induced a significant proliferative advantage, improving MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome profiling of CD34+ cells transduced with either MLL-AF9, ZNF521, or a combination of the two transgenes highlighted specific sets of up- or down-regulated genes that are involved in the leukemic phenotype, including those encoding transcription factors, epigenetic modulators, and cell cycle regulators as well as those engaged in the transport or uptake of nutrients. These data enhance the functional cooperation between ZNF521 and MA9, resulting in the development, maintenance, and clonal expansion of leukemic cells. Finally, silencing of ZNF521 in MLL-AF9-transformed primary CD34+ cells inhibited their proliferation and led to their extinction, as well as ZNF521 silencing in the MLL-AF9+ THP-1 cell line resulted in an impairment of their growth and clonogenicity. Taken together, our data highlight ZNF521 role in the control of self-renewal and in the immature compartment of malignant hematopoiesis, which, by altering the gene expression landscape, contributes to the development and/or maintenance of AML acting in concert with the MLL-AF9 fusion oncogene.

Keywords: AML, human zinc finger protein 521 (hZNF521), mixed lineage leukemia gene (MLL) AF9 (MLLT3 or LTG9), cord blood-derived hematopoietic stem cells (CB-CD34+)

Procedia PDF Downloads 102
1284 LCA/CFD Studies of Artisanal Brick Manufacture in Mexico

Authors: H. A. Lopez-Aguilar, E. A. Huerta-Reynoso, J. A. Gomez, J. A. Duarte-Moller, A. Perez-Hernandez

Abstract:

Environmental performance of artisanal brick manufacture was studied by Lifecycle Assessment (LCA) methodology and Computational Fluid Dynamics (CFD) analysis in Mexico. The main objective of this paper is to evaluate the environmental impact during artisanal brick manufacture. LCA cradle-to-gate approach was complemented with CFD analysis to carry out an Environmental Impact Assessment (EIA). The lifecycle includes the stages of extraction, baking and transportation to the gate. The functional unit of this study was the production of a single brick in Chihuahua, Mexico and the impact categories studied were carcinogens, respiratory organics and inorganics, climate change radiation, ozone layer depletion, ecotoxicity, acidification/ eutrophication, land use, mineral use and fossil fuels. Laboratory techniques for fuel characterization, gas measurements in situ, and AP42 emission factors were employed in order to calculate gas emissions for inventory data. The results revealed that the categories with greater impacts are ecotoxicity and carcinogens. The CFD analysis is helpful in predicting the thermal diffusion and contaminants from a defined source. LCA-CFD synergy complemented the EIA and allowed us to identify the problem of thermal efficiency within the system.

Keywords: LCA, CFD, brick, artisanal

Procedia PDF Downloads 388
1283 Investigation of Clubroot Disease Occurrence under Chemical and Organic Soil Environment

Authors: Zakirul Islam, Yugo Kumokawa, Quoc Thinh Tran, Motoki Kubo

Abstract:

Clubroot is a disease of cruciferous plant caused by soil born pathogen Plasmodiophora brassicae and can significantly limit the production through rapid spreading. The present study was designed to investigate the effect of cultivation practices (chemical and organic soils) on clubroot disease development in Brassica rapa. Disease index and root bacterial composition were investigated for both chemical and organic soils. The bacterial biomass and diversity in organic soil were higher than those in chemical soil. Disease severity was distinct for two different cultivation methods. The number of endophytic bacteria decreased in the infected root for both soils. The increased number of endophytic bacterial number led to reduce the proliferation of pathogen spore inside the root and thus reduced the disease severity in organic plants.

Keywords: clubroot disease, bacterial biomass, root infection, disease index, chemical cultivation, organic cultivation

Procedia PDF Downloads 74
1282 Aerodynamic Design an UAV with Application on the Spraying Agricola with Method of Genetic Algorithm Optimization

Authors: Saul A. Torres Z., Eduardo Liceaga C., Alfredo Arias M.

Abstract:

Agriculture in the world falls within the main sources of economic and global needs, so care of crop is extremely important for owners and workers; one of the major causes of loss of product is the pest infection of different types of organisms. We seek to develop a UAV for agricultural spraying at a maximum altitude of 5000 meters above sea level, with a payload of 100 liters of fumigant. For the developing the aerodynamic design of the aircraft is using computational tools such as the "Vortex Lattice Athena" software, "MATLAB"," ANSYS FLUENT"," XFoil " package among others. Also methods are being used structured programming, exhaustive analysis of optimization methods and search. The results have a very low margin of error, and the multi- objective problems can be helpful for future developments. The program has 10 functions developed in MATLAB, these functions are related to each other to enable the development of design, and all these functions are controlled by the principal code "Master.m".

Keywords: aerodynamics design, optimization, algorithm genetic, multi-objective problem, stability, vortex

Procedia PDF Downloads 523
1281 The Use and Safety of Leave from an Acute Inpatient Psychiatry Unit: A Retrospective Review of Pass Outcomes Over Four Years Abstract

Authors: Vasilis C. Hristidis, Ricardo Caceda, Ji Soo Kim, Brian Bronson, Emily A. Hill

Abstract:

Objective: Leave passes to provide authorized leave for hospitalized patients from a psychiatric inpatient unit. Though providing day passes was once a relatively common practice, there is relatively little data describing their safety and efficacy. Methods: This descriptive study examines the use of leave passes in an adult inpatient unit at a university hospital between 2017 and 2021, with attention to reasons for granting the day pass, duration, and outcome of the pass. Results: During the study period, ten patients with primary psychotic or mood disorders received 12 passes for either housing coordination, COVID-19 vaccination, or major family events. There were no fatalities or elopements. One patient experienced severe agitation and engaged in non-suicidal self-injurious behavior. A second patient showed mild, redirectable psychomotor agitation upon return to the unit. The remaining 10 passes were uneventful. Conclusions: Our findings support the view that patients with diverse diagnoses can safely be provided leave from an inpatient setting with adequate planning and support, yielding a low incidence of adverse events.

Keywords: passes, inpatient, psychiatry, inpatient leave, outcome

Procedia PDF Downloads 192
1280 Medical Decision-Making in Advanced Dementia from the Family Caregiver Perspective: A Qualitative Study

Authors: Elzbieta Sikorska-Simmons

Abstract:

Advanced dementia is a progressive terminal brain disease that is accompanied by a syndrome of difficult to manage symptoms and complications that eventually lead to death. The management of advanced dementia poses major challenges to family caregivers who act as patient health care proxies in making medical treatment decisions. Little is known, however, about how they manage advanced dementia and how their treatment choices influence the quality of patient life. This prospective qualitative study examines the key medical treatment decisions that family caregivers make while managing advanced dementia. The term ‘family caregiver’ refers to a relative or a friend who is primarily responsible for managing patient’s medical care needs and legally authorized to give informed consent for medical treatments. Medical decision-making implies a process of choosing between treatment options in response to patient’s medical care needs (e.g., worsening comorbid conditions, pain, infections, acute medical events). Family caregivers engage in this process when they actively seek treatments or follow recommendations by healthcare professionals. Better understanding of medical decision-making from the family caregiver perspective is needed to design interventions that maximize the quality of patient life and limit inappropriate treatments. Data were collected in three waves of semi-structured interviews with 20 family caregivers for patients with advanced dementia. A purposive sample of 20 family caregivers was recruited from a senior care center in Central Florida. The qualitative personal interviews were conducted by the author in 4-5 months intervals. The ethical approval for the study was obtained prior to the data collection. Advanced dementia was operationalized as stage five or higher on the Global Deterioration Scale (GDS) (i.e., starting with the GDS score of five, patients are no longer able survive without assistance due to major cognitive and functional impairments). Information about patients’ GDS scores was obtained from the Center’s Medical Director, who had an in-depth knowledge of each patient’s health and medical treatment history. All interviews were audiotaped and transcribed verbatim. The qualitative data analysis was conducted to answer the following research questions: 1) what treatment decisions do family caregivers make while managing the symptoms of advanced dementia and 2) how do these treatment decisions influence the quality of patient life? To validate the results, the author asked each participating family caregiver if the summarized findings accurately captured his/her experiences. The identified medical decisions ranged from seeking specialist medical care to end-of-life care. The most common decisions were related to arranging medical appointments, medication management, seeking treatments for pain and other symptoms, nursing home placement, and accessing community-based healthcare services. The most challenging and consequential decisions were related to the management of acute complications, hospitalizations, and discontinuation of treatments. Decisions that had the greatest impact on the quality of patient life and survival were triggered by traumatic falls, worsening psychiatric symptoms, and aspiration pneumonia. The study findings have important implications for geriatric nurses in the context of patient/caregiver-centered dementia care. Innovative nursing approaches are needed to support family caregivers to effectively manage medical care needs of patients with advanced dementia.

Keywords: advanced dementia, family caregiver, medical decision-making, symptom management

Procedia PDF Downloads 117
1279 Microbiological Profile and Surgical Outcomes of Microbial Keratitis Associated Endophthalmitis

Authors: Prachi Abhishek Dave, Manisha Singh

Abstract:

Purpose: The purpose is to study the microbiological profile, prognostic factors, and outcomes of surgery for microbial keratitis (MK) associated endophthalmitis. Methods: It is a retrospective analysis of 39 MK associated endophthalmitis cases which underwent combined PKP with VR surgery. Results: The majority (84.6%) of patients had a history of previous ocular surgery, cataract surgery being the most common (51.2%). Six patients had a history of trauma and 8 patients had corneal graft infection. The culture positivity rate was 92.3%. Organisms isolated were Streptococcal sp (20.5%), Pseudomonas (15.3%), Staphylococcal sp (12.8%) and Fungus (35.8%). Final visual acuities ranged from NPL to 20/120. Poor anatomic success was seen in 15(38.46%) eyes (9-phthisis, 6-eviscerated). Fungal cases had a poor success rate (P-0.02). Conclusion: MK associated endophthalmitis is a sight threatening ocular condition. Fungal etiology carries a poorer prognosis. Timely surgical intervention can achieve favourable anatomical and functional results.

Keywords: endophthalmitis, microbial keratitis, penetrating keratoplasty, vitreo retinal surgery

Procedia PDF Downloads 37
1278 Physical Characterization of Indoor Dust Particles Using Scanning Electron Microscope (SEM)

Authors: Fatima S. Mohammed, Derrick Crump

Abstract:

Harmattan, a dusty weather condition characterized by thick smog-like suspended particles and dust storm are the peculiar events that happen during ¾ of the year in the Sahelian regions including Damaturu Town, Nigeria), resulting in heavy dust deposits especially indoors. The inhabitants of the Damaturu community are always inflicted with different ailments; respiratory tract infections, asthma, gastrointestinal infections and different ailments associated with the dusty nature of the immediate environment. This brought the need to investigate the nature of the settled indoor dust. Vacuum cleaner bag dust was collected from indoor of some Nigerian and UK homes, as well as outdoors including during seasonal dusty weather event (Harmattan and Storm dust). The dust was sieved, and the (150 µm size) particles were examined using scanning electron microscope (SEM). The physical characterization of the settled dust samples has revealed the various shapes and sizes, and elemental composition of the dust samples is indicating that some of the dust fractions were the respirable fractions and also the dust contained PM10 to PM 2.5 fractions with possible health effects. The elemental compositions were indicative of the diverse nature of the dust particle sources, which showed dust as a complex matrix.

Keywords: indoor dust, Harmattan dust, SEM, health effects

Procedia PDF Downloads 292
1277 Prevalence of Cryptosporidium spp. in Free-Living Wild Birds by Using Carbol Fuchsin Staining Methods in Konya, Turkey

Authors: Nermin Isik

Abstract:

Cryptosporidiosis is one of the most common parasitic infection in domesticated, caged, wild birds. Cryptosporidium sp. has been reported in over 30 avian species worldwide. Cryptosporidium meleagridis, Cryptosporidium baileyi and Cryptosporidium galli are recognised avian species of Cryptosporidium. This study was carried out to determine the prevalance of Cryptosporidium sp. in wild birds in Konya province, Turkey. Faecal samples were collected from 65 wild birds including 52 Podicipedidae (Podiceps cristatus), 11 Rallidae (Fulicia Atra), 2 Anitadia (Aytha ferina). Faecal samples were stained with Modified Ziehl-Neelsen staining technigue, they were examined under light microscope for the presence of Cryptosporidium sp. oocyts. Among the 65 faecal samples, 11 (16.9%) were found to be infected with Cryptosporidium sp. oocysts. The results of this study indicate that wild birds may play an important role in the epidemiology of Cryptosporidium. In conclusion, Cryptosporidiosis has suggested zoonotic potential and thus warrant further attention. In addition, biological and genetic studies are required to provide more information on Cryptosporidiosis.

Keywords: Cryptosporidium sp, wild birds, Konya, Turkey

Procedia PDF Downloads 349
1276 Management of Gastrointestinal Metastasis of Invasive Lobular Carcinoma

Authors: Sally Shepherd, Richard De Boer, Craig Murphy

Abstract:

Background: Invasive lobular carcinoma (ILC) can metastasize to atypical sites within the peritoneal cavity, gastrointestinal, or genitourinary tract. Management varies depending on the symptom presentation, extent of disease burden, particularly if the primary disease is occult, and patient wishes. Case Series: 6 patients presented with general surgical presentations of ILC, including incomplete large bowel obstruction, cholecystitis, persistent lower abdominal pain, and faecal incontinence. 3 were diagnosed with their primary and metastatic disease in the same presentation, whilst 3 patients developed metastasis from 5 to 8 years post primary diagnosis of ILC. Management included resection of the metastasis (laparoscopic cholecystectomy), excision of the primary (mastectomy and axillary clearance), followed by a combination of aromatase inhibitors, biologic therapy, and chemotherapy. Survival post diagnosis of metastasis ranged from 3 weeks to 7 years. Conclusion: Metastatic ILC must be considered with any gastrointestinal or genitourinary symptoms in patients with a current or past history of ILC. Management may not be straightforward to chemotherapy if the acute pathology is resulting in a surgically resectable disease.

Keywords: breast cancer, gastrointestinal metastasis, invasive lobular carcinoma, metastasis

Procedia PDF Downloads 140
1275 The Use of Hydrocolloid Dressing in the Management of Open Wounds in Big Cats

Authors: Catherine Portelli

Abstract:

Felines, such as Panthera tigris, Panthera leo and Puma concolor, have become common residents in animal parks and zoos. They often sustain injuries from other felines within the same, or adjacent enclosures and from playing with items of enrichment and structures of the enclosure itself. These open wounds, and their treatments, are often challenging in the veterinary practice, where feline-specific studies are lacking. This study is based on the author’s clinical experience gained while working at local animal parks in the past five years, and current evidence of hydrocolloid dressing applied to other species. Hydrocolloid dressing is used for secondary healing of chronic and acute wounds, where there is a considerable amount of tissue loss. The patients included in this study were sedated using medetomidine and ketamine every three to four days, for wound treatment and bandage change. Comparative studies of different techniques of open wound management will improve the healing process of exotic felines in the future by decreasing the time of recovery and incidence of other complications. Such studies will also aid with treatment of injuries sustained in wild felines, such as trap and bite wounds, found in natural conservation areas and wild animal sanctuaries.

Keywords: felines, hydrocolloid dressing, open wound, secondary healing

Procedia PDF Downloads 93
1274 Synthesis, Characterization, Computational Study, Antimicrobial Evaluation, in Vivo Toxicity Study of Manganese (II) and Copper (II) Complexes with Derivative Sulfa-drug

Authors: Afaf Bouchoucha, Karima Si Larbi, Mohamed Amine Bourouaia, Salah.Boulanouar, Safia.Djabbar

Abstract:

The synthesis, characterization and comparative biological study of manganese (II) and copper (II) complexes with an heterocyclic ligand used in pharmaceutical field (Scheme 1), were reported. Two kinds of complexes were obtained with derivative sulfonamide, [M (L)₂ (H₂O)₂].H₂O and [M (L)₂ (Cl)₂]3H₂O. These complexes have been prepared and characterized by elemental analysis, FAB mass, ESR magnetic measurements, FTIR, UV-Visible spectra and conductivity. Their stability constants have been determined by potentiometric methods in a water-ethanol (90:10 v/v) mixture at a 0.2 mol l-1 ionic strength (NaCl) and at 25.0 ± 0.1 ºC using Sirko program. DFT calculations were done using B3LYP/6-31G(d) and B3LYP/LanL2DZ. The antimicrobial activity of ligand and complexes against the species Escherichia coli, P. aeruginosa, Klebsiella pneumoniae, S. aureus, Bacillus subtilisan, Candida albicans, Candida tropicalis, Saccharomyces, Aspergillus fumigatus and Aspergillus terreus has been carried out and compared using agar-diffusion method. Also, the toxicity study was evaluated on synchesis complexes using Mice of NMRI strain.

Keywords: hetterocyclic ligand, complex, stability constant, antimicrobial activity, DFT, acute and genotoxicity study

Procedia PDF Downloads 112
1273 Performance of a Lytic Bacteriophage Cocktail against Pseudomonas aeruginosa in Conditions That Simulate the Cystic Fibrosis Lung Environment

Authors: Isaac Martin, Abigail Lark, Sandra Morales, Eric W. Alton, Jane C. Davies

Abstract:

Objectives: The cystic fibrosis (CF) lung is a unique microbiological niche, wherein harmful bacteria persist for many years despite antibiotic therapy. Pseudomonas aeruginosa (Pa), the major culprit leading to lung decline and increased mortality, thrives in the lungs of patients with CF due to several factors that have been linked with poor antibiotic performance. Our group is investigating alternative therapies including bacteriophage cocktails with which we have previously demonstrated efficacy against planktonic organisms. In this study, we explored the effects of a 4-phage cocktail on Pa grown in two different conditions, intended to mirror the CF lung: a) alongside standard antibiotic treatment in pre-formed biofilms (structures formed by Pa-secreted exopolysaccharides which provide both physical and cell division barriers to antimicrobials and host defenses and b) in an acidic environment postulated to be present in the CF airway due both to the primary defect in bicarbonate secretion and secondary effects of inflammation. Methods: 16 Pa strains from CF patients at the Royal Brompton Hospital were selected based on sensitivity to a) ceftazidime/ tobramycin and b) the phage cocktail in a conventional plaque assay. To assess efficacy of phage in biofilms, 96 well plates with Pa (5x10⁷ CFU/ ml) were incubated in static conditions, allowing adherent bacterial colonies to form for 24 hr. Ceftazidime and tobramycin (both at 2 × MIC) were added, +/- bacteriophage (4x10⁸ PFU/mL) for a further 24 hr. Cell viability and biomass were estimated using fluorescent resazurin and crystal violet assays, respectively. To evaluate the effect of pH, strains were grown planktonically in shaking 96 well plates at pH 6.0, 6.6, 7.0 and 7.5 with tobramycin or phage, at varying concentrations. Cell viability was quantified by fluorescent resazurin assay. Results: For the biofilm assay, treatment groups were compared with untreated controls and expressed as percent reduction in cell viability and biomass. Addition of the 4-phage cocktail resulted in a 1.3-fold reduction in cell viability and 1.7-fold reduction in biomass (p < 0.001) when compared to standard antibiotic treatment alone. Notably, there was a 50 ± 15% reduction in cell viability and 60 ± 12% reduction in biomass (95% CI) for the 4 biofilms demonstrating the most resistance to antibiotic treatment. 83% of strains tested (n=6) showed decreased bacterial killing by tobramycin at acidic pHs (p < 0.01). However, 25% of strains (n=12) showed improved phage killing at acidic pHs (p < 0.05), with none showing the pattern of reduced efficacy at acidic pH demonstrated by tobramycin. Conclusion: The 4-phage anti-Pa cocktail tested against Pa performs well in pre-formed biofilms and in acidic environments; two conditions intended to mimic the CF lung. To our knowledge, these are the first data looking at the effects of subtle pH changes on phage-mediated bacterial killing in the context of Pa infection. These findings contribute to a growing body of evidence supporting the use of nebulised lytic bacteriophage as a treatment in the context of lung infection.

Keywords: biofilm, cystic fibrosis, pH, Pseudomonas aeruginosa, lytic bacteriophage

Procedia PDF Downloads 171
1272 Topical Delivery of Griseofulvin via Lipid Nanoparticles

Authors: Yann Jean Tan, Hui Meng Er, Choy Sin Lee, Shew Fung Wong, Wen Huei Lim

Abstract:

Griseofulvin is a long standing fungistatic agent against dermatophytosis. Nevertheless, it has several drawbacks such as poor and highly variable bio availability, long duration of treatment, systemic side effects and drug interactions. Targeted treatment for the superficial skin infection, dermatophytosis via topical route could be beneficial. Nevertheless, griseofulvin is only available in the form of oral preparation. Hence, it generates interest in developing a topical formulation for griseofulvin, by using lipid nano particle as the vehicle. Lipid nanoparticle is a submicron colloidal carrier with a core that is solid in nature (lipid). It has combined advantages of various traditional carriers and is a promising vehicle for topical delivery. The griseofulvin loaded lipid nano particles produced using high pressure homogenization method were characterized and investigated for its skin targeting effect in vitro. It has a mean particle size of 179.8±4.9 nm with polydispersity index of 0.306±0.011. Besides, it showed higher skin permeation and better skin targeting effect compared to the griseofulvin suspension.

Keywords: lipid nanoparticles, griseofulvin, topical, dermatophytosis

Procedia PDF Downloads 448
1271 Development of Biosensor Chip for Detection of Specific Antibodies to HSV-1

Authors: Zatovska T. V., Nesterova N. V., Baranova G. V., Zagorodnya S. D.

Abstract:

In recent years, biosensor technologies based on the phenomenon of surface plasmon resonance (SPR) are becoming increasingly used in biology and medicine. Their application facilitates exploration in real time progress of binding of biomolecules and identification of agents that specifically interact with biologically active substances immobilized on the biosensor surface (biochips). Special attention is paid to the use of Biosensor analysis in determining the antibody-antigen interaction in the diagnostics of diseases caused by viruses and bacteria. According to WHO, the diseases that are caused by the herpes simplex virus (HSV), take second place (15.8%) after influenza as a cause of death from viral infections. Current diagnostics of HSV infection include PCR and ELISA assays. The latter allows determination the degree of immune response to viral infection and respective stages of its progress. In this regard, the searches for new and available diagnostic methods are very important. This work was aimed to develop Biosensor chip for detection of specific antibodies to HSV-1 in the human blood serum. The proteins of HSV1 (strain US) were used as antigens. The viral particles were accumulated in cell culture MDBK and purified by differential centrifugation in cesium chloride density gradient. Analysis of the HSV1 proteins was performed by polyacrylamide gel electrophoresis and ELISA. The protein concentration was measured using De Novix DS-11 spectrophotometer. The device for detection of antigen-antibody interactions was an optoelectronic two-channel spectrometer ‘Plasmon-6’, using the SPR phenomenon in the Krechman optical configuration. It was developed at the Lashkarev Institute of Semiconductor Physics of NASU. The used carrier was a glass plate covered with 45 nm gold film. Screening of human blood serums was performed using the test system ‘HSV-1 IgG ELISA’ (GenWay, USA). Development of Biosensor chip included optimization of conditions of viral antigen sorption and analysis steps. For immobilization of viral proteins 0.2% solution of Dextran 17, 200 (Sigma, USA) was used. Sorption of antigen took place at 4-8°C within 18-24 hours. After washing of chip, three times with citrate buffer (pH 5,0) 1% solution of BSA was applied to block the sites not occupied by viral antigen. It was found direct dependence between the amount of immobilized HSV1 antigen and SPR response. Using obtained biochips, panels of 25 positive and 10 negative for the content of antibodies to HSV-1 human sera were analyzed. The average value of SPR response was 185 a.s. for negative sera and from 312 to. 1264 a.s. for positive sera. It was shown that SPR data were agreed with ELISA results in 96% of samples proving the great potential of SPR in such researches. It was investigated the possibility of biochip regeneration and it was shown that application of 10 mM NaOH solution leads to rupture of intermolecular bonds. This allows reuse the chip several times. Thus, in this study biosensor chip for detection of specific antibodies to HSV1 was successfully developed expanding a range of diagnostic methods for this pathogen.

Keywords: biochip, herpes virus, SPR

Procedia PDF Downloads 415
1270 Amelioration of Arsenic and Mercury Induced Vasoconstriction by Eugenol, Linalool and Carvone

Authors: Swati Kundu, Seemi Farhat Basir, Luqman A. Khan

Abstract:

Acute and chronic exposure to arsenic and mercury is known to produce vasoconstriction. Pathways involved in this hypercontraction and their relative contribution are not understood. In this study, we measure agonist-induced contraction of isolated rat aorta exposed to arsenic and mercury aorta and delineate pathways mediating this effect. PE-induced hypercontraction of 37% and 32% was obtained with 25 µM As(III) and 6 nM Hg(II), respectively. Isometric contraction measurements in the presence of apocynin, verapamil and sodium nitroprusside indicates that the major cause of increased contraction is reactive oxygen species and depletion of nitric oxide. Calcium influx plays a minor role in both arsenic and mercury caused hypercontraction. In the unexposed aorta, eugenol causes relaxation by inhibiting ROS and elevating NO, linalool by blocking voltage dependent calcium channel (VDCC) and elevating NO, and carvone by blocking calcium influx through VDDC. Since arsenic and mercury caused hypercontraction is mediated by increased ROS and depletion of nitric oxide, we hypothesize that molecules which neutralize ROS or elevate NO will be better ameliorators. In line with this argument, we find eugenol to be the best ameliorator of arsenic and mercury hypercontraction followed by linalool and carvone.

Keywords: carvone, eugenol, linalool, mercury

Procedia PDF Downloads 315
1269 Human LACE1 Functions Pro-Apoptotic and Interacts with Mitochondrial YME1L Protease

Authors: Lukas Stiburek, Jana Cesnekova, Josef Houstek, Jiri Zeman

Abstract:

Cellular function depends on mitochondrial function and integrity that is therefore maintained by several classes of proteins possessing chaperone and/or proteolytic activities. In this work, we focused on characterization of LACE1 (lactation elevated 1) function in mitochondrial protein homeostasis maintenance. LACE1 is the human homologue of yeast mitochondrial Afg1 ATPase, a member of SEC18-NSF, PAS1, CDC48-VCP, TBP family. Yeast Afg1 was shown to be involved in mitochondrial complex IV biogenesis, and based on its similarity with CDC48 (p97/VCP) it was suggested to facilitate extraction of polytopic membrane proteins. Here we show that LACE1, which is a mitochondrial integral membrane protein, exists as part of three complexes of approx. 140, 400 and 500 kDa and is essential for maintenance of fused mitochondrial reticulum and lamellar cristae morphology. Using affinity purification of LACE1-FLAG expressed in LACE1 knockdown background we show that the protein physically interacts with mitochondrial inner membrane protease YME1L. We further show that human LACE1 exhibits significant pro-apoptotic activity and that the protein is required for normal function of the mitochondrial respiratory chain. Thus, our work establishes LACE1 as a novel factor with the crucial role in mitochondrial homeostasis maintenance.

Keywords: LACE1, mitochondria, apoptosis, protease

Procedia PDF Downloads 305
1268 The Robot Physician's (Rp - 7) Management and Care in Unstable ICU Oncology Patients

Authors: Alisher Agzamov, Hanan Al Harbi

Abstract:

BACKGROUND: The timely assessment and treatment of ICU Surgical and Medical Oncology patients is important for Oncology surgeons and Medical Oncologists and Intensivists. We hypothesized that the use of Robot Physician’s (RP - 7) ICU management and care in ICU can improve ICU physician rapid response to unstable ICU Oncology patients. METHODS: This is a prospective study using a before-after, cohort-control design to test the effectiveness of RP. We have used RP to make multidisciplinary ICU rounds in the ICU and for Emergency cases. Data concerning several aspects of the RP interaction including the latency of the response, the problem being treated, the intervention that was ordered, and the type of information gathered using the RP were documented. The effect of RP on ICU length of stay and cost was assessed. RESULTS: The use of RP was associated with a reduction in latency of attending physician face-to-face response for routine and urgent pages compared to conventional care (RP: 10.2 +/- 3.3 minutes vs conventional: 220 +/- 80 minutes). The response latencies to Oncology Emergency (8.0 +/- 2.8 vs 150 +/- 55 minutes) and for Respiratory Failure (12 +/- 04 vs 110 +/- 45 minutes) were reduced (P < .001), as was the LOS for patients with AML (5 days) and ARDS (10 day). There was an increase in ICU occupancy by 20 % compared with the prerobot era, and there was an ICU cost savings of KD2.5 million attributable to the use of RP. CONCLUSION: The use of RP enabled rapid face-to-face ICU Intensivist - physician response to unstable ICU Oncology patients and resulted in decreased ICU cost and LOS.

Keywords: robot physician, oncology patients, rp - 7 in icu management, cost and icu occupancy

Procedia PDF Downloads 77
1267 Outcomes of Combined Penetrating keratoplasty and Vitreo-Retinal Surgery in Management of Endophthalmitis with Obscured Corneal Clarity

Authors: Abhishek Dave, Manisha Singh

Abstract:

Purpose: The study aims to evaluate the outcomes of combined Penetrating keratoplasty (PKP) and Vitreo-Retinal (VR) surgery in patients having endophthalmitis with poor corneal clarity. Methods: PKP with VR Surgery was performed in 43 eyes. This is a retrospective analysis of their preoperative, intraoperative and microbiological characteristics and anatomical and functional outcomes. Results: Corneal opacification was due to corneal ulcer in 30 (69.7%), graft infection in 8 (18.6%), bullous keratopathy in 4 and corneal scar in 1 eye. Postoperative visual acuity improved in 20 (46.5%), not changed in 14 (32.5%) and deteriorated in 9 eyes (20.9%). Poor anatomic success was seen in 15 (34.88%) eyes (9-phthisis bulbi, 6-eviscerated). Graft remained clear in 24 eyes (1 year). Microbiology revealed bacteria in 26, fungus in 14 and no growth in 3 eyes. Six out of 11 patients having poor vision in the fellow eye, too, achieved functional success. Conclusion: PKP with VR surgery is a complex but globe-salvaging procedure for poor prognosis eyes, which otherwise would need evisceration.

Keywords: penetrating keratoplasty, VR surgery, endophthalmitis, corneal ulcer

Procedia PDF Downloads 42
1266 Ipsilateral Weakness Caused by Ipsilateral Stroke: A Case Series

Authors: Naim Izet Kajtazi

Abstract:

Introduction: There are few reported cases of ipsilateral weakness following ischemic or hemorrhagic stroke. In these rare cases, ipsilateral weakness is typically the result of damage to uncrossed components of the corticospinal tract (CST), which were recruited in response to previous CST injury. Patients and Methods: We report a series of six cases of acute ipsilateral weakness or numbness following a hemorrhagic or ischemic stroke from three medical institutions in Saudi Arabia. Results: Three of these patients presented with right-sided weakness caused by an ipsilateral right hemispheric stroke, while two exhibited left-sided symptoms and one had only left-sided numbness. In all six cases, the ipsilateral corona radiata, internal capsule, basal ganglia, insula, and thalamus were involved. No concomitant opposite hemisphere or brainstem lesion in none of the patients was evident. Two patients had previous strokes affecting the brainstem and left corona radiata, respectively. A complete stroke workup to reveal the cause of the stroke was carried out, however, no functional MRI was performed. Conclusion: Ischemic or hemorrhagic stroke may indeed result in ipsilateral weakness or numbness, though in very rare cases. We assume that the most likely mechanism of their ipsilateral weakness subsequent to the ipsilateral stroke was a functional reorganization favoring CST pathways within the ipsilateral hemisphere.

Keywords: stroke, weakness, MRI brain, stroke unit

Procedia PDF Downloads 82
1265 Investigation of Various Physical and Physiological Properties of Ethiopian Elite Men Distances Runners

Authors: Getaye Fisseha Gelaw

Abstract:

The purpose of this study was to investigate the key physical and physiological characteristics of 16 elite male Ethiopian national team distance runners, who have an average age of 28.1±4.3 years, a height of 175.0 ±5.6 cm, a weight of 59.1 ±3.9 kg, a BMI of 19.6 ±1.5, and training age of 10.1 ±5.1 yrs. The average weekly distance is 196.3±13.8 km, the average 10,000m time is 27:14±0.5 min sec, the average half marathon time is 59:30±0.6 min sec, the average marathon time is 2hr 03min 39sec±0.02. In addition, the average Cooper test (12-minute run test) is 4525.4±139.7 meters, and the average VO2 max is 90.8±3.1ml/kg/m. All athletes have a high profile and compete on the international label, and according to the World Athletics athletes' ranking system in 2021, 56.3% of the 16 participants were platinum label status, while the remaining 43.7 % were gold label status-completed an incremental treadmill test for the assessment of VO2peak, submaximal running, lactate threshold and test during which they ran continuously at 21 km/h. The laboratory determined VO2peak was 91.4 ± 1.7 mL/kg/min with anaerobic threshold of 74.2±1.6 mL/min/Kg and VO2max 81%. The speed at the AT is 15.9 ±0.6 Kmh and the altitude is 4,0%. The respiratory compensation RC point was reached at 88.7±1.1 mL/min/Kg and 97% of VO2 max. On RCP, the speed is 17.6 ±0.4 km/h and the altitude/slope are 5.5% percent, and the speed at Maximum effort is 19.5 ±1.5 and the elevation is 6.0%. The data also suggest that Ethiopian distance top athletes have considerably higher VO2 max values than those found in earlier research.

Keywords: long-distance running, Ethiopians, VO2 max, world athletics, anthropometric

Procedia PDF Downloads 121
1264 A phytochemical and Biological Study of Viscum schemperi Engl. Growing in Saudi Arabia

Authors: Manea A. I. Alqrad, Alaa Sirwi, Sabrin R. M. Ibrahim, Hossam M. Abdallah, Gamal A. Mohamed

Abstract:

Phytochemical study of the methanolic extract of the air dried powdered of the parts of Viscum schemperi Engl. (Family: Viscaceae) using different chromatographic techniques led to the isolation of five compounds: -amyrenone (1), betulinic acid (2), (3β)-olean-12-ene-3,23-diol (3), -oleanolic acid (4), and α-oleanolic acid (5). Their structures were established based on physical, chemical, and spectral data. Anti-inflammatory and anti-apoptotic activities of oleanolic acid in a mouse model of acute hepatorenal damage were assessed. This study showed the efficacy of oleanolic acid to counteract thioacetamide-induced hepatic and kidney injury in mice through the reduction of hepatocyte oxidative damage, suppression of inflammation, and apoptosis. More importantly, oleanolic acid suppressed thioacetamide-induced hepatic and kidney injury by inhibiting NF-κB/TNF-α-mediated inflammation/apoptosis and enhancing SIRT1/Nrf2/Heme-oxygenase signalling pathway. These promising pharmacological activities suggest the potential use of oleanolic acid against hepatorenal damage.

Keywords: oleanolic acid, viscum schimperi, thioacetamide, SIRT1/Nrf2/NF-κB, hepatorenal damage

Procedia PDF Downloads 88
1263 Risk Reduction of Household Refuse, a Case Study of Shagari Low-Cost, Mubi North (LGA) Adamawa State, Nigeria

Authors: Maryam Tijjani Kolo

Abstract:

Lack of refuse dumping points has made the residents of Shagari low-cost well armed with some health and environmental related hazards. These studies investigate the effect of household refuse on the resident of Shagari low-cost. A well structured questionnaire was administered to elicit views of the respondent in the study area through adopting cluster sampling method. A total of 100 questionnaires were selected and divided into 50, each to both sections of the study area. Interview was conducted to each household head. Data obtained were analyzed using simple parentages to determine the major hazard in the area. Result showed that majority of the household are civil servant and traders, earning reasonable monthly income. 68% of the respondent has experienced the effect of living close to waste dumping areas, which include unpleasant smell and polluted smoke when refuse is burnt, which causes eye and respiratory induction, human injury from broken bottles or sharp objects as well as water, insect and air borne diseases. Hence, the need to urgently address these menace before it overwhelms the capacities of the community becomes paramount. Thus, the community should be given more enlightenment and refuse dumping sites should be created by the local government area.

Keywords: household, refuse, refuse dumping points, Shagari low-cost

Procedia PDF Downloads 315
1262 Increasing Adherence to Preventative Care Bundles for Healthcare-Associated Infections: The Impact of Nurse Education

Authors: Lauren G. Coggins

Abstract:

Catheter-associated urinary tract infections (CAUTI) and central line-associated bloodstream infections (CLABSI) are among the most common healthcare-associated infections (HAI), contributing to prolonged lengths of stay, greater costs of patient care, and increased patient mortality. Evidence-based preventative care bundles exist to establish consistent, safe patient-care practices throughout an entire organization, helping to ensure the collective application of care strategies that aim to improve patient outcomes and minimize complications. The cardiac intensive care unit at a nationally ranked teaching and research hospital in the United States exceeded its annual CAUTI and CLABSI targets in the fiscal year 2019, prompting examination into the unit’s infection prevention efforts that included preventative care bundles for both HAIs. Adherence to the CAUTI and CLABSI preventative care bundles was evaluated through frequent audits conducted over three months, using standards and resources from The Joint Commission, a globally recognized leader in quality improvement in healthcare and patient care safety. The bundle elements with the lowest scores were identified as the most commonly missed elements. Three elements from both bundles, six elements in total, served as key content areas for the educational interventions targeted to bedside nurses. The CAUTI elements included appropriate urinary catheter order, appropriate continuation criteria, and urinary catheter care. The CLABSI elements included primary tubing compliance, needleless connector compliance, and dressing change compliance. An integrated, multi-platform education campaign featured content on each CAUTI and CLABSI preventative care bundle in its entirety, with additional reinforcement focused on the lowest scoring elements. One-on-one educational materials included an informational pamphlet, badge buddy, a presentation to reinforce nursing care standards, and real-time application through case studies and electronic health record demonstrations. A digital hub was developed on the hospital’s Intranet for quick access to unit resources, and a bulletin board helped track the number of days since the last CAUTI and CLABSI incident. Audits continued to be conducted throughout the education campaign, and staff were given real-time feedback to address any gaps in adherence. Nearly every nurse in the cardiac intensive care unit received all educational materials, and adherence to all six key bundle elements increased after the implementation of educational interventions. Recommendations from this implementation include providing consistent, comprehensive education across multiple teaching tools and regular audits to track adherence. The multi-platform education campaign brought focus to the evidence-based CAUTI and CLABSI bundles, which in turn will help to reduce CAUTI and CLABSI rates in clinical practice.

Keywords: education, healthcare-associated infections, infection, nursing, prevention

Procedia PDF Downloads 112
1261 Pulmonary Hydatid Cyst in a 13-Year-Old Child: A Case Report

Authors: Ghada Esheba, Bayan Hafiz, Ashwaq Al-Qarni, Abdulelah AlMalki, Esraa Kaheel

Abstract:

Hydatid disease is caused by genus Echinococcus, it is transmitted to human through sheep and cattle. People who lived in an endemic area should be suspected to have the disease. Pulmonary hydatid disease can be presented by respiratory manifestations as in our case. We report a case of child, 13 years old, who was presented by shortness of breath and non-productive cough 2 months ago. The patient had an attack of hemoptysis 3 months ago but there is no history of fever, other constitutional symptoms or any medical illness. The patient has had a close contact with a horse. On examination, the patient was oriented and vitally stable. Both side of chest were moving equally with decrease air entry on the left side of the chest. Cervical lymph node enlargement was also detected. The case was provisionally diagnosed as tuberculosis. The x-ray was normal, while CT scan showed two cysts in the left side. The patient was treated surgically with resection of both cysts without lobectomy. Broncho-alveolar lavage was done and together with plural effusion and both cysts were sent for histopathology. The patient received the following medication: albendazole 200MG/BID/Orally for 30 days and Cefuroxime 250MG/Q12H/Orally for 10 days.

Keywords: Echinococcus granulosus, hydatid disease, pediatrics, pulmonary hydatid cyst

Procedia PDF Downloads 268
1260 Biofilm Formation Due to the Proteome Changes Of Enterococcus Faecium in Response to Sub-Mic of Gentamicin

Authors: Amin Abbasi, Mahdi Asghari Ozma

Abstract:

Background and Objective:Enterococcus faecium is a normal flora of the human gastrointestinal tract that causes infection in the host body under conditions such as biofilm formation, in which the use of antibiotics causes changes in these pathogenic mechanisms. In this study, we aimed to evaluate comprehensively the changes in E.faecium when exposed to sub-MIC of the gentamicin,especiallythe biofilm formation rate. Materials and Methods: For this study, the keywords "Enterococcus faecium ", "Biofilm", and "Gentamicin" in the databases PubMed, Google Scholar, Sid, and MagIran between 2015 and 2021 were searched, and 14 articles were chosen, studied, and analyzed. Results: Gentamicin significantly had increased biofilm formation in most of the isolates in the studies. Increased expression of the genes (efaA and esp) and proteins involved in biofilm formation and decreased expression of the genes (gelE and cylA) involved in spreading and proteins involved in metabolism and cell division in E.faecium were the most significant cause of the biofilm formation, which were increased in sub-MIC gentamicin-treated situation. Conclusion: Inadequate use of gentamicin intensify biofilm formation of E.faecium, which can make the treatment of infections caused by this bacterium difficult.

Keywords: biofilm, enterococcus faecium, gentamicin, proteome

Procedia PDF Downloads 105
1259 The Pigeon Circovirus Evolution and Epidemiology under Conditions of One Loft Race Rearing System: The Preliminary Results

Authors: Tomasz Stenzel, Daria Dziewulska, Ewa Łukaszuk, Joy Custer, Simona Kraberger, Arvind Varsani

Abstract:

Viral diseases, especially those leading to impairment of the immune system, are among the most important problems in avian pathology. However, there is not much data available on this subject other than commercial poultry bird species. Recently, increasing attention has been paid to racing pigeons, which have been refined for many years in terms of their ability to return to their place of origin. Currently, these birds are used for races at distances from 100 to 1000 km, and winning pigeons are highly valuable. The rearing system of racing pigeons contradicts the principles of biosecurity, as birds originating from various breeding facilities are commonly transported and reared in “One Loft Race” (OLR) facilities. This favors the spread of multiple infections and provides conditions for the development of novel variants of various pathogens through recombination. One of the most significant viruses occurring in this avian species is the pigeon circovirus (PiCV), which is detected in ca. 70% of pigeons. Circoviruses are characterized by vast genetic diversity which is due to, among other things, the recombination phenomenon. It consists of an exchange of fragments of genetic material among various strains of the virus during the infection of one organism. The rate and intensity of the development of PiCV recombinants have not been determined so far. For this reason, an experiment was performed to investigate the frequency of development of novel PiCV recombinants in racing pigeons kept in OLR-type conditions. 15 racing pigeons originating from 5 different breeding facilities, subclinically infected with various PiCV strains, were housed in one room for eight weeks, which was supposed to mimic the conditions of OLR rearing. Blood and swab samples were collected from birds every seven days to recover complete PiCV genomes that were amplified through Rolling Circle Amplification (RCA), cloned, sequenced, and subjected to bioinformatic analyses aimed at determining the genetic diversity and the dynamics of recombination phenomenon among the viruses. In addition, virus shedding rate/level of viremia, expression of the IFN-γ and interferon-related genes, and anti-PiCV antibodies were determined to enable the complete analysis of the course of infection in the flock. Initial results have shown that 336 full PiCV genomes were obtained, exhibiting nucleotide similarity ranging from 86.6 to 100%, and 8 of those were recombinants originating from viruses of different lofts of origin. The first recombinant appeared after seven days of experiment, but most of the recombinants appeared after 14 and 21 days of joint housing. The level of viremia and virus shedding was the highest in the 2nd week of the experiment and gradually decreased to the end of the experiment, which partially corresponded with Mx 1 gene expression and antibody dynamics. The results have shown that the OLR pigeon-rearing system could play a significant role in spreading infectious agents such as circoviruses and contributing to PiCV evolution through recombination. Therefore, it is worth considering whether a popular gambling game such as pigeon racing is sensible from both animal welfare and epidemiological point of view.

Keywords: pigeon circovirus, recombination, evolution, one loft race

Procedia PDF Downloads 66
1258 Challenges to Tuberculosis Control in Angola: The Narrative of Medical Professionals

Authors: Domingos Vita, Patrick Brady

Abstract:

Background: There is a tuberculosis (TB) epidemic in Angola that has been getting worse for more than a decade despite the active implementation of the DOTS strategy. The aim of this study was to directly interrogate healthcare workers involved in TB control on what they consider to be the drivers of the TB epidemic in Angola. Methods: Twenty four in-depth qualitative interviews were conducted with medical staff working in this field in the provinces of Luanda and Benguela. Results: The healthcare professionals see the migrant working poor as a particular problem for the control of TB. These migrants are constructed as ‘Rural People’ and are seen as non-compliant and late-presenting. This is a stigmatized and marginal group contending with the additional stigma associated with TB infection. The healthcare professionals interviewed also see the interruption of treatment and self medication generally as a better explanation for the TB epidemic than urbanization or lack of medication. Conclusions: The local narrative is in contrast to previous explanations used elsewhere in the developing world. To be effective policy must recognize the local issues of the migrant workforce, interruption of treatment and the stigma associated with TB in Angola.

Keywords: Africa, Angola, migrants, qualitative, research, tuberculosis

Procedia PDF Downloads 154
1257 Targeting Matrix Metalloprotease-9 to Reduce Coronary Artery Manifestations of Kawasaki’s Disease

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

Abstract:

Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD.

Keywords: MMP-9, coronary artery aneurysm, Kawasaki’s disease, curcumin, AMPK, immune system, NF-κB, MAPK

Procedia PDF Downloads 300