Search results for: bloodstream

Authors: Umut Kokbas, Mustafa Nisari

Abstract:

Immunoglobulins, also known as antibodies, are glycoprotein molecules produced by activated B cells that transform into plasma cells and result in them. Antibodies are critical molecules of the immune response to fight, which help the immune system specifically recognize and destroy antigens such as bacteria, viruses, and toxins. Immunoglobulin classes differ in their biological properties, structures, targets, functions, and distributions. Five major classes of antibodies have been identified in mammals: IgA, IgD, IgE, IgG, and IgM. Evaluation of the immunoglobulin isotype can provide a useful insight into the complex humoral immune response. Evaluation and knowledge of immunoglobulin structure and classes are also important for the selection and preparation of antibodies for immunoassays and other detection applications. The immunoglobulin test measures the level of certain immunoglobulins in the blood. IgA, IgG, and IgM are usually measured together. In this way, they can provide doctors with important information, especially regarding immune deficiency diseases. Hypogammaglobulinemia (HGG) is one of the main groups of primary immunodeficiency disorders. HGG is caused by various defects in B cell lineage or function that result in low levels of immunoglobulins in the bloodstream. This affects the body's immune response, causing a wide range of clinical features, from asymptomatic diseases to severe and recurrent infections, chronic inflammation and autoimmunity Transient infant hypogammaglobulinemia (THGI), IgM deficiency (IgMD), Bruton agammaglobulinemia, IgA deficiency (SIgAD) HGG samples are a few. Most patients can continue their normal lives by taking prophylactic antibiotics. However, patients with severe infections require intravenous immune serum globulin (IVIG) therapy. The IgE level may rise to fight off parasitic infections, as well as a sign that the body is overreacting to allergens. Also, since the immune response can vary with different antigens, measuring specific antibody levels also aids in the interpretation of the immune response after immunization or vaccination. Immune deficiencies usually occur in childhood. In Immunology and Allergy clinics, apart from the classical methods, it will be more useful in terms of diagnosis and follow-up of diseases, if it is fast, reliable and especially in childhood hypogammaglobulinemia, sampling from children with a method that is more convenient and uncomplicated. The antibodies were attached to the electrode surface via the poly hydroxyethyl methacrylamide cysteine nanopolymer. It was used to evaluate the anodic peak results obtained in the electrochemical study. According to the data obtained, immunoglobulin determination can be made with a biosensor. However, in further studies, it will be useful to develop a medical diagnostic kit with biomedical engineering and to increase its sensitivity.

Keywords: biosensor, immunosensor, immunoglobulin, infection

Procedia PDF Downloads 65

Authors: Jessica A. Hellings, Piyushkumar Jani

Abstract:

Background: Systemic autoimmune disorders are increasingly implicated in neuropsychiatric illness, especially in the setting of treatment resistance in individuals of all ages. Gluten allergy in fullest extent results in celiac disease, affecting multiple organs including central nervous system (CNS). Clinicians often lack awareness of the association between neuropsychiatric illness and gluten allergy, partly since many such research studies are published in immunology and gastroenterology journals. Methods: Following a Pubmed literature search and online searches on celiac disease websites, 40 articles are critically reviewed in detail. This work reviews celiac disease, gluten intolerance and current evidence of their relationship to neuropsychiatric and systemic illnesses. The review also covers current work-up and diagnosis, as well as dietary interventions, gluten restriction outcomes, and future research directions. Results: Gluten allergy in susceptible individuals damages the small intestine, producing a leaky gut and malabsorption state, as well as allowing antibodies into the bloodstream, which attack major organs. Lack of amino acid precursors for neurotransmitter synthesis together with antibody-associated brain changes and hypoperfusion may result in neuropsychiatric illness. This is well documented; however, studies in neuropsychiatry are often small. In the large CATIE trial, subjects with schizophrenia had significantly increased antibodies to tissue transglutaminase (TTG), and antigliadin antibodies, both significantly greater gluten antibodies than in control subjects. On later follow up, TTG-6 antibodies were identified in these subjects’ brains but not in their intestines. Significant evidence mostly from small studies also exists for gluten allergy and celiac-related depression, anxiety disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, ataxia, and epilepsy. Dietary restriction of gluten resulted in remission in several published cases, including for treatment-resistant schizophrenia. Conclusions: Ongoing and larger studies are needed of the diagnosis and treatment efficacy of the gluten-free diet in neuropsychiatric illness. Clinicians should ask about the patient history of anemia, hypothyroidism, irritable bowel syndrome and family history of benefit from the gluten-free diet, not limited to but especially in cases of treatment resistance. Obtaining gluten antibodies by a simple blood test, and referral for gastrointestinal work-up in positive cases should be considered.

Keywords: celiac, gluten, neuropsychiatric, translational

Procedia PDF Downloads 131

Authors: P. Uma Devi, S. Sujith, K. Rahul, T. S. Dipu, V. Anil Kumar , Vidya Menon

Abstract:

Introduction: Candida is an important cause of bloodstream infections (BSIs), causing significant mortality and morbidity. The epidemiology of Candida infection is also changing, mainly in relation to the number of episodes caused by species Candida non-albicans. However, in India, the true burden of candidemia is not clear. Thus, this study was conducted to evaluate the clinical characteristics, species distribution, antifungal susceptibility and outcome of candidemia at our hospital. Methodology: Between January 2012 and April 2014, adult patients with at least one positive blood culture for Candida species were identified through the microbiology laboratory database (for each patient only the first episode of candidemia was recorded). Patient data was collected by retrospective chart review of clinical characteristics including demographic data, risk factors; species distribution, resistance to antifungals and survival. Results: A total of 165 episodes of Candida BSI were identified, with 115 episodes occurring in adult patients. Most of the episodes occurred in males (69.6%). Nearly 82.6% patients were between 41 to 80 years and majority of the patients were in the intensive care unit (65.2%) at the time of diagnosis. On admission, 26.1% and 18.3% patients had pneumonia and urinary tract infection, respectively. Majority of the candidemia episodes were found in the general medicine department (23.5%) followed by gastrointestinal surgery (13.9%) and medical oncology & haematology (13%). Risk factors identified were prior hospitalization within one year (83.5%), antibiotic therapy within the last one month (64.3%), indwelling urinary catheter (63.5%), central venous catheter use (59.1%), diabetes mellitus (53%), severe sepsis (45.2%), mechanical ventilation (43.5%) and surgery (36.5%). C. tropicalis (30.4%) was the leading cause of infection followed by C. parapsilosis (28.7%) and C. albicans (13%). Other non-albicans species isolated included C. haemulonii (7.8%), C. glabrata (7%), C. famata (4.3%) and C. krusei (1.7%). Antifungal susceptibility to fluconazole was 87.9% (C. parapsilosis), 100% (C. tropicalis) and 93.3% (C. albicans). Mortality was noted in 51 patients (44.3%). Early mortality (within 7 days) was noted in 32 patients while late mortality (between 7 and 30 days) was noted in 19 patients. Conclusion: In recent years, candidemia has been flourishing in critically ill patients. Comparison of data from our own hospital from 2005 shows a doubling of the incidence. Rapid changes in the rate of infection, potential risk factors, and emergence of non-albicans Candida demand continued surveillance of this serious BSI. High index of suspicion and sensitive diagnostics are essential to improve outcomes in resource limited settings with emergence of non-albicans Candida.

Keywords: antifungal susceptibility, candida albicans, candidemia, non-albicans candida

Procedia PDF Downloads 429

Authors: Harmeet Pal Singh Dhooria, Deepinder Chinna, UPS Sidhu, Alok Jain

Abstract:

Serious infections caused by gram-negative bacteria are a significant cause of mortality and morbidity in the hospital setting. In acute care facilities like in intensive care units (ICUs), the intensity of antimicrobial use together with a population highly susceptible to infection, creates an environment, which facilitates both emergence and transmission of Extended Spectrum -lactamase (ESBL) producing Enterobacteriaceae species. The study was conducted in the Medical Intensive Care Unit (MICU) and the Pulmonary Critical Care Unit (PCCU) of the Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab, India. Out of a total of 1108 samples of urine, blood and respiratory tract secretions received for culture and sensitivity analysis from Medical Intensive Care Unit and Pulmonary Critical Care Unit, a total of 170 isolates of Enterobacteriaceae species were obtained which were then included in our study. Out of these 170 isolates, confirmed ESBL production was seen in 116 (68.24%) cases. E.coli was the most common species isolated (56.47%) followed by Klebsiella (32.94%), Enterobacter (5.88%), Citrobacter (3.53%), Enterobacter (0.59%) and Morganella (0.59%) among the total isolates. The rate of ESBL production was more in Klebsiella (78.57%) as compared to E.coli (60.42%). ESBL producers were found to be significantly more common in patients with prior history of hospitalization, antibiotic use, and prolonged ICU stay. Also significantly increased the prevalence of ESBL related infections was observed in patients with a history of catheterization or central line insertion but not in patients with the history of intubation. Patients who had an underlying malignancy had significantly higher prevalence of ESBL related infections as compared to other co-morbid illnesses. A slightly significant difference in the rate of mortality/LAMA was observed in the ESBL producer versus the non-ESBL producer group. The rate of mortality/LAMA was significantly higher in the ESBL related UTI but not in the ESBL related respiratory tract and bloodstream infections. ESBL producing isolates had significantly higher rates of resistance to Cefepime and Piperacillin/Tazobactum, and to non β-lactum antibiotics like Amikacin and Ciprofloxacin. The level of resistance to Imipenem was lower as compared to other antibiotics. However, it was noted that ESBL producing isolates had higher levels of resistance to Imipenem as compared to non-ESBL producing isolates. Conclusion- The prevalence of ESBL producing organisms was found to be very high (68.24%) among Enterobacteriaceae isolates in our ICU setting as among other ICU care settings around the world.

Keywords: enterobacteriaceae, extended spectrum B-lactamase (ESBL), ICU, antibiotic resistance

Procedia PDF Downloads 242

Authors: Shilpee Jain, Sachin Latiyan, Kaushik Suneet

Abstract:

Unlike traditional robots, medical microbots are not only smaller in size, but they also possess various unique properties, for example, biocompatibility, stability in the biological fluids, navigation opposite to the bloodstream, wireless control over locomotion, etc. The idea behind their usage in the medical field was to build a minimally invasive method for addressing the post-operative complications, including longer recovery time, infection eruption and pain. Herein, the present study demonstrates the fabrication of dual nature magneto-conducting Fe3O4 magnetic nanoparticles (MNPs) and SU8 derived carbon-based Janus microbots for the efficient intracellular delivery of biomolecules. The low aspect ratio with feature size 2-5 μm microbots were fabricated by using a photolithography technique. These microbots were pyrolyzed at 900°C, which converts SU8 into amorphous carbon. The pyrolyzed microbots have dual properties, i.e., the half part is magneto-conducting and another half is only conducting for sufficing the therapeutic payloads efficiently with the application of external electric/magnetic field stimulations. For the efficient intracellular delivery of the microbots, the size and aspect ratio plays a significant role. However, on a smaller scale, the proper control over movement is difficult to achieve. The dual nature of Janus microbots allowed to control its maneuverability in the complex fluids using external electric as well as the magnetic field. Interestingly, Janus microbots move faster with the application of an external electric field (44 µm/s) as compared to the magnetic field (18 µm/s) application. Furthermore, these Janus microbots exhibit auto-fluorescence behavior that will help to track their pathway during navigation. Typically, the use of MNPs in the microdevices enhances the tendency to agglomerate. However, the incorporation of Fe₃O₄ MNPs in the pyrolyzed carbon reduces the chances of agglomeration of the microbots. The biocompatibility of the medical microbots, which is the essential property of any biosystems, was determined in vitro using HeLa cells. The microbots were found to compatible with HeLa cells. Additionally, the intracellular uptake of microbots was higher in the presence of an external electric field as compared to without electric field stimulation. In summary, the cytocompatible Janus microbots were fabricated successfully. They are stable in the biological fluids, wireless controllable navigation with the help of a few Guess external magnetic fields, their movement can be tracked because of autofluorescence behavior, they are less susceptible to agglomeration and higher cellular uptake could be achieved with the application of the external electric field. Thus, these carriers could offer a versatile platform to suffice the therapeutic payloads under wireless actuation.

Keywords: amorphous carbon, electric/magnetic stimulations, Janus microbots, magnetic nanoparticles, minimally invasive procedures

Procedia PDF Downloads 96

Authors: Khethiwe Mtshali, Zamantungwa T. H. Khumalo, Stanford Kwenda, Ismail Arshad, Oriel M. M. Thekisoe

Abstract:

Ecologically, the gut, mammary glands and bloodstream consist of distinct microbial communities of commensals, mutualists and pathogens, forming a complex ecosystem of niches. The by-products derived from these body sites i.e. faeces, milk and blood, respectively, have many uses in rural communities where they aid in the facilitation of day-to-day household activities and occasional rituals. Thus, although livestock rearing plays a vital role in the sustenance of the livelihoods of rural communities, it may serve as a potent reservoir of different pathogenic organisms that could have devastating health and economic implications. This study aimed to simultaneously explore the microbial profiles of corresponding faecal, milk and blood samples from lactating cows using 16S rRNA metagenomic sequencing. Bacterial communities were inferred through the Divisive Amplicon Denoising Algorithm 2 (DADA2) pipeline coupled with SILVA database v138. All downstream analyses were performed in R v3.6.1. Alpha-diversity metrics showed significant differences between faeces and blood, faeces and milk, but did not vary significantly between blood and milk (Kruskal-Wallis, P < 0.05). Beta-diversity metrics on Principal Coordinate Analysis (PCoA) and Non-Metric Dimensional Scaling (NMDS) clustered samples by type, suggesting that microbial communities of the studied niches are significantly different (PERMANOVA, P < 0.05). A number of taxa were significantly differentially abundant (DA) between groups based on the Wald test implemented in the DESeq2 package (Padj < 0.01). The majority of the DA taxa were significantly enriched in faeces than in milk and blood, except for the genus Anaplasma, which was significantly enriched in blood and was, in turn, the most abundant taxon overall. A total of 30 phyla, 74 classes, 156 orders, 243 families and 408 genera were obtained from the overall analysis. The most abundant phyla obtained between the three body sites were Firmicutes, Bacteroidota, and Proteobacteria. A total of 58 genus-level taxa were simultaneously detected between the sample groups, while bacterial signatures of at least 8 of these occurred concurrently in corresponding faeces, milk and blood samples from the same group of animals constituting a pool. The important taxa identified in this study could be categorized into four potentially pathogenic clusters: i) arthropod-borne; ii) food-borne and zoonotic; iii) mastitogenic and; iv) metritic and abortigenic. This study provides insight into the microbial composition of bovine faeces, milk, and blood and its extent of overlapping. It further highlights the potential risk of disease occurrence and transmission between the animals and the inhabitants of the sampled rural community, pertaining to their unsanitary practices associated with the use of cattle by-products.

Keywords: microbial profiling, 16S rRNA, NGS, feces, milk, blood, lactating cows, small-scale farmers

Procedia PDF Downloads 81

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 85

Authors: Michelle Maurer, Antonia Last, Mark S. Gresnigt, Bernhard Hube, Alexander S. Mosig

Abstract:

The intestinal epithelium forms an essential barrier to prevent translocation of microorganisms, toxins or other potentially harmful molecules into the bloodstream. In particular, dendritic cells of the intestinal epithelium orchestrate an adapted response of immune tolerance to commensals and immune defense against invading pathogens. Systemic inflammation is typically associated with a dysregulation of this adapted immune response and is accompanied by a disruption of the epithelial and endothelial gut barrier which enables dissemination of pathogens within the human body. To understand the pathophysiological mechanisms underlying the inflammation-associated gut barrier breakdown, it is crucial to elucidate the complex interplay of the host and the intestinal microbiome. A microfluidically perfused three-dimensional intestine-on-chip model was established to emulate these processes in the presence of immune cells, commensal bacteria, and facultative pathogens. Multi-organ tissue flow (MOTiF) biochips made from polystyrene were used for microfluidic perfusion of the intestinal tissue model. The biochips are composed of two chambers separated by a microporous membrane. Each chamber is connected to inlet and outlet channels allowing independent perfusion of the individual channels and application of microfluidic shear stress. Human umbilical vein endothelial cells (HUVECs), monocyte-derived macrophages and intestinal epithelial cells (Caco-2) were assembled on the biochip membrane. Following 7 – 14 days of growth in the presence of physiological flow conditions, the epithelium was colonized with the commensal bacterium Lactobacillus rhamnosus, while the endothelium was perfused with peripheral blood mononuclear cells (PBMCs). Additionally, L. rhamnosus was co-cultivated with the opportunistic fungal pathogen Candida albicans. Within one week of perfusion, the epithelial cells formed self-organized and well-polarized villus- and crypt-like structures that resemble essential morphological characteristics of the human intestine. Dendritic cells were differentiated in the epithelial tissue that specifically responds to bacterial lipopolysaccharide (LPS) challenge. LPS is well-tolerated at the luminal epithelial side of the intestinal model without signs of tissue damage or induction of an inflammatory response, even in the presence of circulating PBMC at the endothelial lining. In contrast, LPS stimulation at the endothelial side of the intestinal model triggered the release of pro-inflammatory cytokines such as TNF, IL-1β, IL-6, and IL-8 via activation of macrophages residing in the endothelium. Perfusion of the endothelium with PBMCs led to an enhanced cytokine release. L. rhamnosus colonization of the model was tolerated in the immune competent tissue model and was demonstrated to reduce damage induced by C. albicans infection. A microfluidic intestine-on-chip model was developed to mimic a systemic infection with a dysregulated immune response under physiological conditions. The model facilitates the colonization of commensal bacteria and co-cultivation with facultative pathogenic microorganisms. Both, commensal bacteria alone and facultative pathogens controlled by commensals, are tolerated by the host and contribute to cell signaling. The human intestine-on-chip model represents a promising tool to mimic microphysiological conditions of the human intestine and paves the way for more detailed in vitro studies of host-microbiota interactions under physiologically relevant conditions.

Keywords: host-microbiota interaction, immune tolerance, microfluidics, organ-on-chip

Procedia PDF Downloads 106

Authors: Adela Diepoltova, Klara Konecna, Ondrej Jandourek, Petr Nachtigal

Abstract:

A loss of control over antibiotic-resistant pathogens has become a global issue due to severe and often untreatable infections. This state is reflected in complicated treatment, health costs, and higher mortality. All these factors emphasize the urgent need for the discovery and development of new anti-infectives. One of the most common pathogens mentioned in the phenomenon of antibiotic resistance are bacteria of the genus Staphylococcus. These bacterial agents have developed several mechanisms against the effect of antibiotics. One of them is biofilm formation. In staphylococci, biofilms are associated with infections such as endocarditis, osteomyelitis, catheter-related bloodstream infections, etc. To author's best knowledge, no validated and standardized methodology evaluating candidate compound activity against staphylococcal biofilms exists. However, a variety of protocols for in vitro drug activity testing has been suggested, yet there are often fundamental differences. Based on our experience, a key methodological step that leads to credible results is to form a robust biofilm with appropriate attributes such as firm adherence to the substrate, a complex arrangement in layers, and the presence of extracellular polysaccharide matrix. At first, for the purpose of drug antibiofilm activity evaluation, the focus was put on various conditions (supplementation of cultivation media by human plasma/fetal bovine serum, shaking mode, the density of initial inoculum) that should lead to reproducible and robust in vitro staphylococcal biofilm formation in microtiter plate model. Three model staphylococcal reference strains were included in the study: Staphylococcus aureus (ATCC 29213), methicillin-resistant Staphylococcus aureus (ATCC 43300), and Staphylococcus epidermidis (ATCC 35983). The total biofilm biomass was quantified using the Christensen method with crystal violet, and results obtained from at least three independent experiments were statistically processed. Attention was also paid to the viability of the biofilm-forming staphylococcal cells and the presence of extracellular polysaccharide matrix. The conditions that led to robust biofilm biomass formation with attributes for biofilms mentioned above were then applied by introducing an alternative method analogous to the commercially available test system, the Calgary Biofilm Device. In this test system, biofilms are formed on pegs that are incorporated into the lid of the microtiter plate. This system provides several advantages (in situ detection and quantification of biofilm microbial cells that have retained their viability after drug exposure). Based on our preliminary studies, it was found that the attention to the peg surface and substrate on which the bacterial biofilms are formed should also be paid to. Therefore, further steps leading to the optimization were introduced. The surface of pegs was coated by human plasma, fetal bovine serum, and L-polylysine. Subsequently, the willingness of bacteria to adhere and form biofilm was monitored. In conclusion, suitable conditions were revealed, leading to the formation of reproducible, robust staphylococcal biofilms in vitro for the microtiter model and the system analogous to the Calgary biofilm device, as well. The robustness and typical slime texture could be detected visually. Likewise, an analysis by confocal laser scanning microscopy revealed a complex three-dimensional arrangement of biofilm forming organisms surrounded by an extracellular polysaccharide matrix.

Keywords: anti-biofilm drug activity screening, in vitro biofilm formation, microtiter plate model, the Calgary biofilm device, staphylococcal infections, substrate modification, surface coating

Procedia PDF Downloads 121