Search results for: immune stimulation

Authors: Soraia V. M. de Sá, Miguel A. Faria, José O. Fernandes, Sara C. Cunha

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Cereals play a vital role in fulfilling the nutritional needs of children, supplying essential nutrients crucial for their growth and development. However, concerns arise due to children's heightened vulnerability due to their unique physiology, specific dietary requirements, and relatively higher intake in relation to their body weight. This vulnerability exposes them to harmful food contaminants, particularly mycotoxins, prevalent in cereals. Because of the thermal stability of mycotoxins, conventional industrial food processing often falls short of eliminating them. Children, especially those aged 4 months to 12 years, frequently encounter mycotoxins through the consumption of specialized food products, such as instant foods, breakfast cereals, bars, cookie snacks, fruit puree, and various dairy items. A close monitoring of this demographic group's exposure to mycotoxins is essential, as toxins ingestion may weaken children’s immune systems, reduce their resistance to infectious diseases, and potentially lead to cognitive impairments. The severe toxicity of mycotoxins, some of which are classified as carcinogenic, has spurred the establishment and ongoing revision of legislative limits on mycotoxin levels in food and feed globally. While EU Commission Regulation 1881/2006 addresses well-known mycotoxins in processed cereal-based foods and infant foods, the absence of regulations specifically addressing emerging mycotoxins underscores a glaring gap in the regulatory framework, necessitating immediate attention. Emerging mycotoxins have gained mounting scrutiny in recent years due to their pervasive presence in various foodstuffs, notably cereals and cereal-based products. Alarmingly, exposure to multiple mycotoxins is hypothesized to exhibit higher toxicity than isolated effects, raising particular concerns for products primarily aimed at children. This study scrutinizes the presence of 22 mycotoxins of the diverse range of chemical classes in 148 processed cereal-based foods, including 39 breakfast cereals, 25 infant formulas, 27 snacks, 25 cereal bars, and 32 cookies commercially available in Portugal. The analytical approach employed a modified QuEChERS procedure followed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. Given the paucity of information on the risk assessment of children to multiple mycotoxins in cereal and cereal-based products consumed by children of Portugal pioneers the evaluation of this critical aspect. Overall, aflatoxin B1 (AFB1) and aflatoxin G2 (AFG2) emerged as the most prevalent regulated mycotoxins, while enniatin B (ENNB) and sterigmatocystin (STG) were the most frequently detected emerging mycotoxins.

Keywords: cereal-based products, children´s nutrition, food safety, UPLC-MS/MS analysis

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Authors: P. Asiabi, M. Shahhoseini, R. Favaedi, F. Hassani, N. Nassiri, B. Movaghar, L. Karimian, P. Eftekhariyazdi

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Introduction: Polycystic Ovary Syndrome is a common gynecologic disorder. Many factors including environment, metabolism, hormones and genetics are involved in etiopathogenesis of PCOS. Of genes that have altered expression in human reproductive system disorders are HOX family genes which act as transcription factors in regulation of cell proliferation, differentiation, adhesion and migration. Since recent evidences consider epigenetic factors as causative mechanisms of PCOS, evaluation of association between known epigenetic marks of acetylation/methylation of histone 3 (H3K9ac/me) with regulatory regions of these genes can represent better insight about PCOS. In the current study, cumulus cells (CCs) which have critical roles during folliculogenesis, oocyte maturation, ovulation and fertilization were aimed to monitor epigenetic alterations of HOX genes. Material and methods: CCs were collected from 20 PCOS patients and 20 fertile women (18-36 year) with male infertility problems referred to the Royan Institute to have ICSI under GnRH antagonist protocol. Informed consents were obtained from the participants. Thirty six hours after hCG injection, ovaries were punctured and cumulus oocyte complexes were dissected. Soluble chromatin were extracted from CCs and Chromatin Immune precipitation (ChIP) coupled with Real Time PCR was performed to quantify the epigenetic marks of histone H3K9 acetylation/methylation (H3K9ac/me) on regulatory regions of 15 members of HOX genes from A-D subfamily. Results: Obtained data showed significant increase of H3K9ac epigenetic mark on regulatory regions of HOXA1, HOXB2, HOXC4, HOXD1, HOXD3 and HOXD4 (P < 0.01) and HOXC5 (P < 0.05) and also significant decrease of H3K9ac into regulatory regions of HOXA2, HOXA4, HOXA5, HOXB1 and HOXB5 (P < 0.01) and HOXB3 (P<0.05) in PCOS patients vs. control group. On the other side, there was a significant decrease in incorporation of H3K9me level on regulatory region of HOXA2, HOXA3, HOXA4, HOXA5, HOXB3 and HOXC4 (P≤0.01) and HOXB5 (P < 0.05) in PCOS patients vs. control group. This epigenetic mark (H3K9me2) has significant increase on regulatory region of HOXB1, HOXB2, HOXC5, HOXD1, HOXD3 and HOXD4 (P ≤ 0.01) and HOXB4 (P < 0.05) in patients vs. control group. There were no significant changes in acetylation/methylation levels of H3K9 on regulatory regions of the other studied genes. Conclusion: Current study suggests that epigenetic alterations of HOX genes can be correlated with PCOS and consequently female infertility. This finding might offer additional definitions of PCOS, and eventually provides insight for novel treatments with epidrugs for this disease.

Keywords: epigenetic, HOX genes, PCOS, female infertility

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Authors: Itzel Amaro-Estrada, Eduardo Vergara-Rivera, Virginia Juarez-Flores, Mayra Cobaxin-Cardenas, Rosa Estela Quiroz, Jesus F. Preciado, Sergio Rodriguez-Camarillo

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Bovine anaplasmosis is an infectious, tick-borne disease caused mainly by Anaplasma marginale; typical signs include anemia, fever, abortion, weight loss, decreased milk production, jaundice, and potentially death. Sick bovine can recover when antibiotics are administered; however, it usually remains as carrier for life, being a risk of infection for susceptible cattle. Anaplasma marginale is an obligate intracellular Gram-negative bacterium with genetic composition highly diverse among geographical isolates. There are currently no vaccines fully effective against bovine anaplasmosis; therefore, the economic losses due to disease are present. Vaccine formulation became a hard task for several pathogens as Anaplasma marginale, but peptide-based vaccines are an interesting proposal way to induce specific responses. Phage-displayed peptide libraries have been proved one of the most powerful technologies for identifying specific ligands. Screening of these peptides libraries is also a tool for studying interactions between proteins or peptides. Thus, it has allowed the identification of ligands recognized by polyclonal antiserums, and it has been successful for the identification of relevant epitopes in chronic diseases and toxicological conditions. Protective immune response to bovine anaplasmosis includes high levels of immunoglobulins subclass G2 (IgG2) but not subclass IgG1. Therefore, IgG2 from the serum of protected bovine can be useful to identify ligands, which can be part of an immunogen for cattle. In this work, phage display random peptide library Ph.D. ™ -12 was incubating with IgG2 or blood sera of immunized bovines against A. marginale as targets. After three rounds of biopanning, several candidates were selected for additional analysis. Subsequently, their reactivity with sera immunized against A. marginale, as well as with positive and negative sera to A. marginale was evaluated by immunoassays. A collection of recognized peptides tested by ELISA was generated. More than three hundred phage-peptides were separately evaluated against molecules which were used during panning. At least ten different peptides sequences were determined from their nucleotide composition. In this approach, three phage-peptides were selected by their binding and affinity properties. In the case of the development of vaccines or diagnostic reagents, it is important to evaluate the immunogenic and antigenic properties of the peptides. Immunogenic in vitro and in vivo behavior of peptides will be assayed as synthetic and as phage-peptide for to determinate their vaccine potential. Acknowledgment: This work was supported by grant SEP-CONACYT 252577 given to I. Amaro-Estrada.

Keywords: bovine anaplasmosis, peptides, phage display, veterinary vaccines

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Authors: Mudasir Ahmad Syed, Raashid Ahmd Wani, Mashooq Ahmad Dar, Uneeb Urwat, Riaz Ahmad Shah, Nazir Ahmad Ganai

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Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) is a primary avian pathogen responsible for severe intestinal pathology in younger chickens and economic losses. However, the Salmonella Typhimurium is also able to cause infection in humans, described by typhoid fever and acute gastro-intestinal disease. A study was conducted at days to investigate pathological, histopathological, haemato-biochemical, immunological and expression kinetics of NRAMP (natural resistance associated macrophage protein) gene family (NRAMP1 and NRAMP2) in broiler chickens following experimental infection of Salmonella Typhimurium at 0,1,3,5,7,9,11,13 and 15 days respectively. Infection was developed in birds through oral route at 2×108 CFU/ml. Clinical symptoms appeared 4 days post infection (dpi) and after one-week birds showed progressive weakness, anorexia, diarrhea and lowering of head. On postmortem examination, liver showed congestion, hemorrhage and necrotic foci on surface, while as spleen, lungs and intestines revealed congestion and hemorrhages. Histopathological alterations were principally observed in liver in second week post infection. Changes in liver comprised of congestion, areas of necrosis, reticular endothelial hyperplasia in association with mononuclear cell and heterophilic infiltration. Hematological studies confirm a significant decrease (P<0.05) in RBC count, Hb concentration and PCV. White blood cell count showed significant increase throughout the experimental study. An increase in heterophils was found up to 7dpi and a decreased pattern was observed afterwards. Initial lymphopenia followed by lymphocytosis was found in infected chicks. Biochemical studies showed a significant increase in glucose, AST and ALT concentration and a significant decrease (P<0.05) in total protein and albumin level in the infected group. Immunological studies showed higher titers of IgG in infected group as compared to control group. The real time gene expression of NRAMPI and NRAMP2 genes increased significantly (P<0.05) in infected group as compared to controls. The peak expression of NRAMP1 gene was seen in liver, spleen and caecum of infected birds at 3dpi, 5dpi and 7dpi respectively, while as peak expression of NRAMP2 gene in liver, spleen and caecum of infected chicken was seen at 9dpi, 5dpi and 9dpi respectively. This study has role in diagnostics and prognostics in the poultry industry for the detection of salmonella infections at early stages of poultry development.

Keywords: biochemistry, histopathology, NRAMP, poultry, real time expression, Salmonella Typhimurium

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Authors: M. I. Tyletc, O. I. Podgornya, T. G. Shaposhnikova, S. V. Shabelnikov, A. G. Mittenberg, M. A. Daugavet

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Ascidiacea is the most numerous class of the Tunicata subtype. These chordates' distinctive feature of the anatomical structure is a tunic consisting of cellulose fibrils, protein molecules, and single cells. The mechanisms of the tunic formation are not known in detail; tunic formation could be used as the model system for studying the interaction of cells with the extracellular matrix. Our model species is the ascidian Styela rustica, which is prevalent in benthic communities of the White Sea. As previously shown, the tunic formation involves morula blood cells, which contain the major 48 kDa protein p48. P48 participation in the tunic formation was proved using antibodies against the protein. The nature of the protein and its function remains unknown. The current research aims to determine the amino acid sequence of p48, as well as to clarify its role in the tunic formation. The peptides that make up the p48 amino acid sequence were determined by mass spectrometry. A search for peptides in protein sequence databases identified sequences homologous to p48 in Styela clava, Styela plicata, and Styela canopus. Based on sequence alignment, their level of similarity was determined as 81-87%. The correspondent sequence of ascidian Styela canopus was used for further analysis. The Styela rustica p48 sequence begins with a signal peptide, which could indicate that the protein is secretory. This is consistent with experimentally obtained data: the contents of morula cells secreted in the tunic matrix. The isoelectric point of p48 is 9.77, which is consistent with the experimental results of acid electrophoresis of morula cell proteins. However, the molecular weight of the amino acid sequence of ascidian Styela canopus is 103 kDa, so p48 of Styela rustica is a shorter homolog. The search for conservative functional domains revealed the presence of two Ca-binding EGF-like domains, thrombospondin (TSP1) and tyrosinase domains. The p48 peptides determined by mass spectrometry fall into the region of the sequence corresponding to the last two domains and have amino acid substitutions as compared to Styela canopus homolog. The tyrosinase domain (pfam00264) is known to be part of the phenoloxidase enzyme, which participates in melanization processes and the immune response. The thrombospondin domain (smart00209) interacts with a wide range of proteins, and is involved in several biological processes, including coagulation, cell adhesion, modulation of intercellular and cell-matrix interactions, angiogenesis, wound healing and tissue remodeling. It can be assumed that the tyrosinase domain in p48 plays the role of the phenoloxidase enzyme, and TSP1 provides a link between the extracellular matrix and cell surface receptors, and may also be responsible for the repair of the tunic. The results obtained are consistent with experimental data on p48. The domain organization of protein suggests that p48 is an enzyme involved in the tunic tunning and is an important regulator of the organization of the extracellular matrix.

Keywords: ascidian, p48, thrombospondin, tyrosinase, tunic, tunning

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Authors: Marco Frieslaar, Bing Chu, Eric Rogers

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Stroke is a devastating illness that is the second biggest cause of death in the world (after heart disease). Where it does not kill, it leaves survivors with debilitating sensory and physical impairments that not only seriously harm their quality of life, but also cause a high incidence of severe depression. It is widely accepted that early intervention is essential for recovery, but current rehabilitation techniques largely favor hospital-based therapies which have restricted access, expensive and specialist equipment and tend to side-step the emotional challenges. In addition, there is insufficient funding available to provide the long-term assistance that is required. As a consequence, recovery rates are poor. The relatively unexplored solution is to develop therapies that can be harnessed in the home and are formulated from technologies that already exist in everyday life. This would empower individuals to take control of their own improvement and provide choice in terms of when and where they feel best able to undertake their own healing. This research seeks to identify how effective post-stroke, rehabilitation therapy can be applied to upper limb mobility, within the physical context of a home rather than a hospital. This is being achieved through the design and construction of an automation scheme, based on iterative learning control and the Riener muscle model, that has the ability to adapt to the user and react to their level of fatigue and provide tangible physical recovery. It utilizes a SMART Phone and laptop to construct an iterative learning control (ILC) system, that monitors upper arm movement in three dimensions, as a series of exercises are undertaken. The equipment generates functional electrical stimulation to assist in muscle activation and thus improve directional accuracy. In addition, it monitors speed, accuracy, areas of motion weakness and similar parameters to create a performance index that can be compared over time and extrapolated to establish an independent and objective assessment scheme, plus an approximate estimation of predicted final outcome. To further extend its assessment capabilities, nerve conduction velocity readings are taken by the software, between the shoulder and hand muscles. This is utilized to measure the speed of response of neuron signal transfer along the arm and over time, an online indication of regeneration levels can be obtained. This will prove whether or not sufficient training intensity is being achieved even before perceivable movement dexterity is observed. The device also provides the option to connect to other users, via the internet, so that the patient can avoid feelings of isolation and can undertake movement exercises together with others in a similar position. This should create benefits not only for the encouragement of rehabilitation participation, but also an emotional support network potential. It is intended that this approach will extend the availability of stroke recovery options, enable ease of access at a low cost, reduce susceptibility to depression and through these endeavors, enhance the overall recovery success rate.

Keywords: home-based therapy, iterative learning control, Riener muscle model, SMART phone, stroke rehabilitation

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Authors: Thaminda Liyanage, Chamila Shamika Kurukulasuriya

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Introduction: Morbid obesity has been successfully treated with bariatric surgery for over 60 years. Although operative procedures have improved and associated complications have reduced substantially, surgery still carries the risk of post-operative malabsorption, malnutrition and a range of gastrointestinal disorders. Overweight by itself can impair libido in both sexes and cause erectile dysfunction in males by inducing a state of hypogonadotropic hypogonadism, proportional to the degree of obesity. Impact of weight reduction on libido and sexual activity remains controversial, however it is broadly accepted that weight loss improves sexual drive. Zinc deficiency, subsequent to malabsorption, may lead to impaired testosterone synthesis in men while excessive and/or rapid weight loss in females may result in reversible amenorrhoea leading to sub-fertility. Methods: We describe a 37 year old male, 6 years post Roux-en-Y gastric bypass surgery, who presented with erectile dysfunction, loss of libido, worsening fatigue and generalized weakness for 4 months. He also complained of constipation and frequent muscle cramps but denied having headache, vomiting or visual disturbances. Patient had lost 38 kg of body weight post gastric bypass surgery over four years {135kg (BMI 42.6 kg/m2) to 97 kg (BMI 30.6 kg/m2)} and the weight had been stable for past two years. He had no recognised co-morbidities at the time of the surgery and noted marked improvement in general wellbeing, physical fitness and psychological confident post surgery, up until four months before presentation. Clinical examination revealed dry pale skin with normal body hair distribution, no thyroid nodules or goitre, normal size testicles and normal neurological examination with no visual field defects or diplopia. He had low serum testosterone, follicular stimulating hormone (FSH), luteinizing hormone (LH), T3, T4, thyroid stimulating hormone (TSH), insulin like growth factor 1 (IGF-1) and 24-hour urine cortisol levels. Serum cortisol demonstrated an appropriate rise to ACTH stimulation test but growth hormone (GH) failed increase on insulin tolerance test. Other biochemical and haematological studies were normal, except for low zinc and folate with minimally raised liver enzymes. MRI scan of the head confirmed a solid pituitary mass with no mass effect on optic chiasm. Results: In this patient clinical, biochemical and radiological findings were consistent with anterior pituitary dysfunction. However, there were no features of raised intracranial pressure or neurological compromise. He was commenced on appropriate home replacement therapy and referred for neurosurgical evaluation. Patient reported marked improvement in his symptoms, specially libido and erectile dysfunction, on subsequent follow up visits. Conclusion: Sexual dysfunction coupled with non specific constitutional symptoms has multiple aetiologies. Clinical symptoms out of proportion to nutritional deficiencies post bariatric surgery should be thoroughly investigated. Close long term follow up is crucial for overall success.

Keywords: obesity, bariatric surgery, erectile dysfunction, loss of libido

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Authors: Lydia Tan, Philippe Lemey, Lieselot Houspie, Marco Viveen, Darren Martin, Frank Coenjaerts

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Introduction: Human respiratory syncytial virus (hRSV) is the leading cause of severe respiratory tract infections in infants under the age of two. Genomic substitutions and related evolutionary dynamics of hRSV are of great influence on virus transmission behavior. The evolutionary patterns formed are due to a precarious interplay between the host immune response and RSV, thereby selecting the most viable and less immunogenic strains. Studying genomic profiles can teach us which genes and consequent proteins play an important role in RSV survival and transmission dynamics. Study design: In this study, genetic diversity and evolutionary rate analysis were conducted on 36 RSV subgroup B whole genome sequences and 37 subgroup A genome sequences. Clinical RSV isolates were obtained from nasopharyngeal aspirates and swabs of children between 2 weeks and 5 years old of age. These strains, collected during epidemic seasons from 2001 to 2011 in the Netherlands and Belgium by either conventional or 454-sequencing. Sequences were analyzed for genetic diversity, recombination events, synonymous/non-synonymous substitution ratios, epistasis, and translational consequences of mutations were mapped to known 3D protein structures. We used Bayesian statistical inference to estimate the rate of RSV genome evolution and the rate of variability across the genome. Results: The A and B profiles were described in detail and compared to each other. Overall, the majority of the whole RSV genome is highly conserved among all strains. The attachment protein G was the most variable protein and its gene had, similar to the non-coding regions in RSV, more elevated (two-fold) substitution rates than other genes. In addition, the G gene has been identified as the major target for diversifying selection. Overall, less gene and protein variability was found within RSV-B compared to RSV-A and most protein variation between the subgroups was found in the F, G, SH and M2-2 proteins. For the F protein mutations and correlated amino acid changes are largely located in the F2 ligand-binding domain. The small hydrophobic phosphoprotein and nucleoprotein are the most conserved proteins. The evolutionary rates were similar in both subgroups (A: 6.47E-04, B: 7.76E-04 substitution/site/yr), but estimates of the time to the most recent common ancestor were much lower for RSV-B (B: 19, A: 46.8 yrs), indicating that there is more turnover in this subgroup. Conclusion: This study provides a detailed description of whole RSV genome mutations, the effect on translation products and the first estimate of the RSV genome evolution tempo. The immunogenic G protein seems to require high substitution rates in order to select less immunogenic strains and other conserved proteins are most likely essential to preserve RSV viability. The resulting G gene variability makes its protein a less interesting target for RSV intervention methods. The more conserved RSV F protein with less antigenic epitope shedding is, therefore, more suitable for developing therapeutic strategies or vaccines.

Keywords: drug target selection, epidemiology, respiratory syncytial virus, RSV

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Authors: Kennedy Zinn, Chris Anderson

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Chronic Covid syndrome (CCS) is a condition in which individuals who test positive for Covid-19 experience persistent symptoms after recovering from the virus. CCS affects every organ system, including the central nervous system. Neurological “long-haul” symptoms last from a few weeks to several months and include brain fog, chronic fatigue, dyspnea, mood dysregulation, and headaches. Data suggest that 10-30% of individuals testing positive for Covid-19 develop CCS. Current literature indicates a decreased quality of life in persistent symptoms. CCS is a pervasive and pernicious COVID-19 sequelae. More research is needed to understand risk factors, impact, and possible interventions. Research frequently cites cytokine storming as noteworthy etiology in CCS. Cytokine storming is a malfunctional immune response and facilitates multidimensional interconnected physiological responses. The most prominent responses include abnormal blood flow, hypoxia/hypoxemia, inflammation, and endothelial damage. Neurological impairments and pathogenesis in CCS parallel that of traumatic brain injury (TBI). Both exhibit impairments in memory, cognition, mood, sustained attention, and chronic fatigue. Evidence suggests abnormal blood flow, inflammation, and hypoxemia as shared causal factors. Cytokine storming is also typical in mTBI. The shared characteristics in symptoms and etiology suggest potential parallel routes of investigation that allow for better understanding of CCS. Research on the effect of altitude in mTBI varies. Literature finds decreased rates of concussions at higher altitudes. Other studies suggest that at a higher altitude, pre-existing mTBI symptoms are exacerbated. This may mean that in CCS, the geographical location where individuals live and the location where individuals experienced acute Covid-19 symptoms may influence the severity and risk of developing CCS. It also suggests that clinics which treat mTBI patients could also provide benefits for those with CCS. This study aims to examine the relationships between altitude and CCS as a risk factor and investigate the longevity and severity of symptoms in different altitudes. Existing patient data from a concussion clinic using fMRI scans and self-reported symptoms will be used for approximately 30 individuals with CCS symptoms. The association between acclimated altitude and CCS severity will be analyzed. Patients will be classified into low, medium, and high altitude groups and compared for differences on fMRI severity scores and self-reported measures. It is anticipated that individuals living in lower altitudes are at higher risk of developing more severe neuropsychological symptoms in CCS. It is also anticipated that a treatment approach for mTBI will also be beneficial to those with CCS.

Keywords: altitude, chronic covid syndrome, concussion, covid brain, EPIC treatment, fMRI, traumatic brain injury

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Authors: Alexander Vandesompele, Joni Dambre

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The diversity in dendritic arborization, as first illustrated by Santiago Ramon y Cajal, has always suggested a role for dendrites in the functionality of neurons. In the past decades, thanks to new recording techniques and optical stimulation methods, it has become clear that dendrites are not merely passive electrical components. They are observed to integrate inputs in a non-linear fashion and actively participate in computations. Regardless, in simulations of neural networks dendritic structure and functionality are often overlooked. Especially in a machine learning context, when designing artificial neural networks, point neuron models such as the leaky-integrate-and-fire (LIF) model are dominant. These models mimic the integration of inputs at the neuron soma, and ignore the existence of dendrites. In this work, the LIF point neuron model is extended with a simple form of dendritic computation. This gives the LIF neuron increased capacity to discriminate spatiotemporal input sequences, a dendritic functionality as observed in another study. Simulations of the spiking neurons are performed using the Bindsnet framework. In the common LIF model, incoming synapses are independent. Here, we introduce a dependency between incoming synapses such that the post-synaptic impact of a spike is not only determined by the weight of the synapse, but also by the activity of other synapses. This is a form of short term plasticity where synapses are potentiated or depressed by the preceding activity of neighbouring synapses. This is a straightforward way to prevent inputs from simply summing linearly at the soma. To implement this, each pair of synapses on a neuron is assigned a variable,representing the synaptic relation. This variable determines the magnitude ofthe short term plasticity. These variables can be chosen randomly or, more interestingly, can be learned using a form of Hebbian learning. We use Spike-Time-Dependent-Plasticity (STDP), commonly used to learn synaptic strength magnitudes. If all neurons in a layer receive the same input, they tend to learn the same through STDP. Adding inhibitory connections between the neurons creates a winner-take-all (WTA) network. This causes the different neurons to learn different input sequences. To illustrate the impact of the proposed dendritic mechanism, even without learning, we attach five input neurons to two output neurons. One output neuron isa regular LIF neuron, the other output neuron is a LIF neuron with dendritic relationships. Then, the five input neurons are allowed to fire in a particular order. The membrane potentials are reset and subsequently the five input neurons are fired in the reversed order. As the regular LIF neuron linearly integrates its inputs at the soma, the membrane potential response to both sequences is similar in magnitude. In the other output neuron, due to the dendritic mechanism, the membrane potential response is different for both sequences. Hence, the dendritic mechanism improves the neuron’s capacity for discriminating spa-tiotemporal sequences. Dendritic computations improve LIF neurons even if the relationships between synapses are established randomly. Ideally however, a learning rule is used to improve the dendritic relationships based on input data. It is possible to learn synaptic strength with STDP, to make a neuron more sensitive to its input. Similarly, it is possible to learn dendritic relationships with STDP, to make the neuron more sensitive to spatiotemporal input sequences. Feeding structured data to a WTA network with dendritic computation leads to a significantly higher number of discriminated input patterns. Without the dendritic computation, output neurons are less specific and may, for instance, be activated by a sequence in reverse order.

Keywords: dendritic computation, spiking neural networks, point neuron model

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Authors: Elena Bellini, Daniele Mugnaini, Michele Boschetto

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People with an Autistic Spectrum Disorder and an Intellectual Disability who need to attend a Hospital Emergency Waiting Room frequently present high levels of discomfort and challenging behaviors due to stress-related hyperarousal, sensory sensitivity, novelty-anxiety, communication and self-regulation difficulties. Increased agitation and acting out also disturb the diagnostic and therapeutic processes, and the emergency room climate. Architectural design disciplines aimed at reducing distress in hospitals or creating autism-friendly environments are called for to find effective answers to this particular need. A growing number of researchers are considering the physical environment as an important point of intervention for people with autism. It has been shown that providing the right setting can help enhance confidence and self-esteem and can have a profound impact on their health and wellbeing. Environmental psychology has evaluated the perceived quality of care, looking at the design of hospital rooms, paths and circulation, waiting rooms, services and devices. Furthermore, many studies have investigated the influence of the hospital environment on patients, in terms of stress-reduction and therapeutic intervention’ speed, but also on health professionals and their work. Several services around the world are organizing autism-friendly hospital environments which involve the architecture and the specific staff training. In Italy, the association Spes contra spem has promoted and published, in 2013, the ‘Chart of disabled people in the hospital’. It stipulates that disabled people should have equal rights to accessible and high-quality care. There are a few Italian examples of therapeutic programmes for autistic people as the Dama project in Milan and the recent experience of Children and Autism Foundation in Pordenone. Careggi’s Emergency Waiting Room in Florence has been built to satisfy this challenge. This project of research comes from a collaboration between the technical staff of Careggi Hospital, the Center for autism PAMAPI and some architects expert in the sensory environment. The methodology of focus group involved architects, psychologists and professionals through a transdisciplinary research, centered on the links between the spatial characteristics and clinical state of people with ASD. The relationship between architectural space and quality of life is studied to pay maximum attention to users’ needs and to support the medical staff in their work by a specific program of training. The result of this research is a sum of criteria used to design the emergency waiting room, that will be illustrated. A protected room, with a clear space design, maximizes comprehension and predictability. The multisensory environment is thought to help sensory integration and relaxation. Visual communication through Ipad allows an anticipated understanding of medical procedures, and a specific technological system supports requests, choices and self-determination in order to fit sensory stimulation to personal preferences, especially for hypo and hypersensitive people. All these characteristics should ensure a better regulation of the arousal, less behavior problems, improving treatment accessibility, safety, and effectiveness. First results about patient-satisfaction levels will be presented.

Keywords: accessibility of care, autism-friendly architecture, personalized therapeutic process, sensory environment

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Authors: Maia Kharadze, Indira Djaparidze, Maia Vanidze, Aleko Kalandia

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Modern scientific world studies chemical components and antioxidant activity of different kinds of vines according to their breed purity and location. To our knowledge, this kind of research has not been conducted in Georgia yet. The object of our research was to study Chkhaveri vine, which is included in the oldest varieties of the Black Sea basin vine. We have studied different-altitude Chkaveri grapes, juice, and wine (half dry rose-colored produced with European technologies) and their technical markers, qualitative and quantitive composition of their biologically active compounds and their antioxidant activity. We were determining the amount of phenols using Folin-Ciocalteu reagent, Flavonoids, Catechins and Anthocyanins using Spectral method and antioxidant activity using DPPH method. Several compounds were identified using –HPLC-UV-Vis, UPLC-MS methods. Six samples of Chkhaveri species– 5, 300, 360, 380, 400, 780 meter altitudes were taken and analyzed. The sample taken from 360 m altitude is distinguished by its cluster mass (383.6 grams) and high amount of sugar (20.1%). The sample taken from the five-meter altitude is distinguished by having high acidity (0.95%). Unlike other grapes varieties, such concentration of sugar and relatively low levels of citric acid ultimately leads to Chkhaveri wine individuality. Biologically active compounds of Chkhaveri were researched in 2014, 2015, 2016. The amount of total phenols in samples of 2016 fruit varies from 976.7 to 1767.0 mg/kg. Amount of Anthocians is 721.2-1630.2 mg/kg, and the amount of Flavanoids varies from 300.6 to 825.5 mg/kg. Relatively high amount of anthocyanins was found in the Chkhaveri at 780-meter altitude - 1630.2 mg/kg. Accordingly, the amount of Phenols and Flavanoids is high- 1767.9 mg/kg and 825.5 mg/kg. These characteristics are low in samples gathered from 5 meters above sea level, Anthocyanins-721.2 mg/ kg, total Phenols-976.7 mg/ kg, and Flavanoids-300.6 mg/kg. The highest amount of bioactive compounds can be found in the Chkhaveri samples of high altitudes because with rising height environment becomes harsh, the plant has to develop a better immune system using Phenolic compounds. The technology that is used for the production of wine also plays a huge role in the composition of the final product. Optimal techniques of maceration and ageing were worked out. While squeezing Chkhaveri, there are no anthocyanins in the juice. However, the amount of Anthocyanins rises during maceration. After the fermentation of dregs, the amount of anthocyanins is 55%, 521.3 gm/l, total Phenols 80% 1057.7 mg/l and Flavanoids 23.5 mg/l. Antioxidant activity of samples was also determined using the effect of 50% inhibition of the samples. All samples have high antioxidant activity. For instance, in samples at 780 meters above the sea-level antioxidant activity was 53.5%. It is relatively high compared to the sample at 5 m above sea-level with the antioxidant activity of 30.5%. Thus, there is a correlation between the amount Anthocyanins and antioxidant activity. The designated project has been fulfilled by financial support of the Georgia National Science Foundation (Grant AP/96/13, Grant 216816), Any idea in this publication is possessed by the author and may not represent the opinion of the Georgia National Science Foundation.

Keywords: antioxidants, bioactive content, wine, chkhaveri

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Authors: K. K. Balavenkatraman, B. Bertschi, K. Bigot, A. Grevot, A. Doelemeyer, S. D. Chibout, A. Wolf, F. Pognan, N. Manevski, O. Kretz, P. Swart, K. Litherland, J. Ashton-Chess, B. Ling, R. Wettstein, D. J. Schaefer

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Skin toxicity is poorly detected during preclinical studies, and drug-induced side effects in humans such as rashes, hyperplasia or more serious events like bullous pemphigus or toxic epidermal necrolysis represent an important hurdle for clinical development. In vitro keratinocyte-based epidermal skin models are suitable for the detection of chemical-induced irritancy, but do not recapitulate the biological complexity of full skin and fail to detect potential serious side-effects. Normal healthy skin explants may represent a valuable complementary tool, having the advantage of retaining the full skin architecture and the resident immune cell diversity. This study investigated several conditions for the maintenance of good morphological structure after several days of culture and the retention of phase II metabolism for 24 hours in skin explants in vitro. Human skin samples were collected with informed consent from patients undergoing plastic surgery and immediately transferred and processed in our laboratory by removing the underlying dermal fat. Punch biopsies of 4 mm diameter were cultured in an air-liquid interface using transwell filters. Different cultural conditions such as the effect of calcium, temperature and cultivation media were tested for a period of 14 days and explants were histologically examined after Hematoxylin and Eosin staining. Our results demonstrated that the use of Williams E Medium at 32°C maintained the physiological integrity of the skin for approximately one week. Upon prolonged incubation, the upper layers of the epidermis become thickened and some dead cells are present. Interestingly, these effects were prevented by addition of EGFR inhibitors such as Afatinib or Erlotinib. Phase II metabolism of the skin such as glucuronidation (4-methyl umbeliferone), sulfation (minoxidil), N-acetyltransferase (p-toluidene), catechol methylation (2,3-dehydroxy naphthalene), and glutathione conjugation (chlorodinitro benzene) were analyzed by using LCMS. Our results demonstrated that the human skin explants possess metabolic activity for a period of at least 24 hours for all the substrates tested. A time course for glucuronidation with 4-methyl umbeliferone was performed and a linear correlation was obtained over a period of 24 hours. Longer-term culture studies will indicate the possible evolution of such metabolic activities. In summary, these results demonstrate that human skin explants maintain a normal structure for several days in vitro and are metabolically active for at least the first 24 hours. Hence, with further characterisation, this model may be suitable for the study of drug-induced toxicity.

Keywords: human skin explant, phase II metabolism, epidermal growth factor receptor, toxicity

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Authors: N. Manjunatha, K. T. Rangswamy, N. Nagaraju, H. A. Prameela, P. Rudraswamy, M. Krishnareddy

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The identification of virus in cowpea especially potyviruses is confusing. Even though there are several studies on viruses causing diseases in cowpea, difficult to distinguish based on symptoms and serological detection. The differentiation of potyviruses considering as a constraint, the present study is initiated for molecular characterization, host plant resistance and epidemiology of the BCMV infecting cowpea. The etiological agent causing cowpea mosaic was identified as Bean Common Mosaic Virus (BCMV) on the basis of RT-PCR and electron microscopy. An approximately 750bp PCR product corresponding to coat protein (CP) region of the virus and the presence of long flexuous filamentous particles measuring about 952 nm in size typical to genus potyvirus were observed under electron microscope. The characterized virus isolate genome had 10054 nucleotides, excluding the 3’ terminal poly (A) tail. Comparison of polyprotein of the virus with other potyviruses showed similar genome organization with 9 cleavage sites resulted in 10 functional proteins. The pairwise sequence comparison of individual genes, P1 showed most divergent, but CP gene was less divergent at nucleotide and amino acid level. A phylogenetic tree constructed based on multiple sequence alignments of the polyprotein nucleotide and amino acid sequences of cowpea BCMV and potyviruses showed virus is closely related to BCMV-HB. Whereas, Soybean variant of china (KJ807806) and NL1 isolate (AY112735) showed 93.8 % (5’UTR) and 94.9 % (3’UTR) homology respectively with other BCMV isolates. This virus transmitted to different leguminous plant species and produced systemic symptoms under greenhouse conditions. Out of 100 cowpea genotypes screened, three genotypes viz., IC 8966, V 5 and IC 202806 showed immune reaction in both field and greenhouse conditions. Single marker analysis (SMA) was revealed out of 4 SSR markers linked to BCMV resistance, M135 marker explains 28.2 % of phenotypic variation (R2) and Polymorphic information content (PIC) value of these markers was ranged from 0.23 to 0.37. The correlation and regression analysis showed rainfall, and minimum temperature had significant negative impact and strong relationship with aphid population, whereas weak correlation was observed with disease incidence. Path coefficient analysis revealed most of the weather parameters exerted their indirect contributions to the aphid population and disease incidence except minimum temperature. This study helps to identify specific gaps in knowledge for researchers who may wish to further analyse the science behind complex interactions between vector-virus and host in relation to the environment. The resistant genotypes identified are could be effectively used in resistance breeding programme.

Keywords: cowpea, epidemiology, genotypes, virus

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Authors: Anita Bajpai, Sarah Duan, Ashlee Erskine, Shehzein Khan, Raymond Kramer

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Introduction: This research focuses on exploring the beneficial effects if any, of Vitamin-D in reducing the need for supplemental oxygen among hospitalized COVID-19 patients. Two questions are investigated – Q1)Doeshaving a healthy level of baselineVitamin-D 25-OH (≥ 30ng/ml) help,andQ2) does administering Vitamin-D therapy after-the-factduring inpatient hospitalization help? Methods/Study Design: This is a comprehensive, retrospective, observational study of all inpatients at RUHS from March through December 2020 who tested positive for COVID-19 based on real-time reverse transcriptase–polymerase chain reaction assay of nasal and pharyngeal swabs and rapid assay antigen test. To address Q1, we looked atall N1=182 patients whose baseline plasma Vitamin-D 25-OH was known and who needed supplemental oxygen. Of this, a total of 121 patients had a healthy Vitamin-D level of ≥30 ng/mlwhile the remaining 61 patients had low or borderline (≤ 29.9ng/ml)level. Similarly, for Q2, we looked at a total of N2=893 patients who were given supplemental oxygen, of which713 were not given Vitamin-D and 180 were given Vitamin-D therapy. The numerical value of the maximum amount of oxygen flow rate(dependent variable) administered was recorded for each patient. The mean values and associated standard deviations for each group were calculated. Thesetwo sets of independent data served as the basis for independent, two-sample t-Test statistical analysis. To be accommodative of any reasonable benefitof Vitamin-D, ap-value of 0.10(α< 10%) was set as the cutoff point for statistical significance. Results: Given the large sample sizes, the calculated statistical power for both our studies exceeded the customary norm of 80% or better (β< 0.2). For Q1, the mean value for maximumoxygen flow rate for the group with healthybaseline level of Vitamin-D was 8.6 L/min vs.12.6L/min for those with low or borderline levels, yielding a p-value of 0.07 (p < 0.10) with the conclusion that those with a healthy level of baseline Vitamin-D needed statistically significant lower levels of supplemental oxygen. ForQ2, the mean value for a maximum oxygen flow rate for those not administered Vitamin-Dwas 12.5 L/min vs.12.8L/min for those given Vitamin-D, yielding a p-valueof 0.87 (p > 0.10). We thereforeconcludedthat there was no statistically significant difference in the use of oxygen therapy between those who were or were not administered Vitamin-D after-the-fact in the hospital. Discussion/Conclusion: We found that patients who had healthy levels of Vitamin-D at baseline needed statistically significant lower levels of supplemental oxygen. Vitamin-D is well documented, including in a recent article in the Lancet, for its anti-inflammatory role as an adjuvant in the regulation of cytokines and immune cells. Interestingly, we found no statistically significant advantage for giving Vitamin-D to hospitalized patients. It may be a case of “too little too late”. A randomized clinical trial reported in JAMA also did not find any reduction in hospital stay of patients given Vitamin-D. Such conclusions come with a caveat that any delayed marginal benefits may not have materialized promptly in the presence of a significant inflammatory condition. Since Vitamin-D is a low-cost, low-risk option, it may still be useful on an inpatient basis until more definitive findings are established.

Keywords: COVID-19, vitamin-D, supplemental oxygen, vitamin-D in primary care

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Authors: Tristan R. Fraser, Christopher D. Steadman, Christopher J. Boos

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Myopericarditis is an inflammation syndrome characterised by clinical diagnostic criteria for pericarditis, such as chest pain, combined with evidence of myocardial involvement, such as elevation of biomarkers of myocardial damage, e.g., troponins. It can rarely be a complication of therapeutics used for dysregulated immune-mediated diseases such as inflammatory bowel disease (IBD), for example, mesalazine. The infrequency of mesalazine-induced myopericarditis adds to the challenge in its recognition. Rapid diagnosis and the early introduction of treatment are crucial. This case report follows a 24-year-old professional footballer with a past medical history of ulcerative colitis, recently started on mesalazine for disease control. Three weeks after mesalazine was initiated, he was admitted with fever, shortness of breath, and chest pain worse whilst supine and on deep inspiration, as well as elevated venous blood cardiac troponin T level (cTnT, 288ng/L; normal: <13ng/L). Myocarditis was confirmed on initial inpatient cardiac MRI, revealing the presence of florid myocarditis with preserved left ventricular systolic function and an ejection fraction of 67%. This was a longitudinal case study following the progress of a single individual with myopericarditis over four acute hospital admissions over nine weeks, with admissions ranging from two to five days. Parameters examined included clinical signs and symptoms, serum troponin, transthoracic echocardiogram, and cardiac MRI. Serial measurements of cardiac function, including cardiac MRI and transthoracic echocardiogram, showed progressive deterioration of cardiac function whilst mesalazine was continued. Prior to cessation of mesalazine, transthoracic echocardiography revealed a small global pericardial effusion of < 1cm and worsening left ventricular systolic function with an ejection fraction of 45%. After recognition of mesalazine as a potential cause and consequent cessation of the drug, symptoms resolved, with cardiac MRI performed as an outpatient showing resolution of myocardial oedema. The patient plans to make a return to competitive sport. Patients suffering from myopericarditis are advised to refrain from competitive sport for at least six months in order to reduce the risk of cardiac remodelling and sudden cardiac death. Additional considerations must be taken in individuals for whom competitive sport is an essential component of their livelihood, such as professional athletes. Myopericarditis is an uncommon, however potentially serious medical condition with a wide variety of aetiologies, including viral, autoimmune, and drug-related causes. Management is mainly supportive and relies on prompt recognition and removal of the aetiological process. Mesalazine-induced myopericarditis is a rare condition; as such increasing awareness of mesalazine as a precipitant of myopericarditis is vital for optimising the management of these patients.

Keywords: myopericarditis, mesalazine, inflammatory bowel disease, professional athlete

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Authors: Archana Sharma, Vijayashree Nayak, Ashok Kumar

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Three-dimensional matrices were fabricated from blend of natural-natural polymers like carrageenan-gelatin and synthetic -natural polymers such as PEG- gelatin (PEG of different molecular weights (2,000 and 6,000) using two different crosslinkers; glutaraldehyde and EDC-NHS by cryogelation technique. Blends represented a feasible approach to design 3-D scaffolds with controllable mechanical, physical and biochemical properties without compromising biocompatibility and biodegradability. These matrices possessed interconnected porous structure, good mechanical strength, biodegradable nature, constant swelling kinetics, ability to withstand high temperature and visco-elastic behavior. Hemocompatibility of cryogel matrices was determined by coagulation assays and hemolytic activity assay which demonstrated that these cryogels have negligible effects on coagulation time and have excellent blood compatibility. In vitro biocompatibility (cell-matrix interaction) inferred good cell adhesion, proliferation, and secretion of ECM on matrices. These matrices provide a microenvironment for the growth, proliferation, differentiation and secretion of ECM of different cell types such as IMR-32, C2C12, Cos-7, rat bone marrow derived MSCs and human bone marrow MSCs. Hoechst 33342 and PI staining also confirmed that the cells were uniformly distributed, adhered and proliferated properly on the cryogel matrix. An ideal scaffold used for tissue engineering application should allow the cells to adhere, proliferate and maintain their functionality. Neurotransmitter analysis has been done which indicated that IMR-32 cells adhered, proliferated and secreted neurotransmitters when they interacted with these matrices which showed restoration of their functionality. The cell-matrix interaction up to molecular level was also evaluated so to check genotoxicity and protein expression profile which indicated that these cryogel matrices are non-genotoxic and maintained biofunctionality of cells growing on these matrices. All these cryogels, when implanted subcutaneously in balb/c mice, showed no adverse systemic or local toxicity effects at implantation site. There was no significant increase in inflammatory cell count has otherwise been observed after scaffold implantation. These cryogels are supermacroporous and this porous structure allows cell infiltration and proliferation of host cells. This showed the integration and presence of infiltrated cells into the cryogel implants. Histological analysis confirmed that the implanted cryogels do not have any adverse effect in spite of host immune system recognition at the site of implantation, on its surrounding tissues and other vital host organs. In vivo biocompatibility study after in vitro biocompatibility analysis has also concluded that these synthesized cryogels act as important biological substitutes, more adaptable and appropriate for transplantation. Thus, these cryogels showed their potential for soft tissue engineering applications.

Keywords: cryogelation, hemocompatibility, in vitro biocompatibility, in vivo biocompatibility, soft tissue engineering applications

Procedia PDF Downloads 224

Authors: Aleksandra Chałupnik, Zuzanna Chilimoniuk, Joanna Borowik, Aleksandra Borkowska, Anna Torres

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Background: Precocious puberty is the occurrence of secondary sexual characteristics in girls before the age of 8. The diverse etiology of premature puberty is crucial to determine whether it is true precocious puberty, depending on the activation of the hypothalamic-pituitary-gonadal axis, or pseudo-precocious, which is independent of the activation of this axis. Whatever the cause, premature action of the sex hormones leads to the common symptoms of various forms of puberty. These include the development of sexual characteristics, acne, acceleration of growth rate and acceleration of skeletal maturation. Due to the possible genetic basis of the disorders, an interdisciplinary search for the cause is needed. Case report: The case report concerns a patient of a pediatric gynecology clinic who, at the age of two years, developed advanced thelarhe (M3) and started recurrent vaginal bleeding. In August 2019, gonadotropin suppression initially and after LHRH stimulation and high estradiol levels were reported at the Endocrinology Department. Imaging examinations showed a cyst in the right ovary projection. The bone age was six years. The entire clinical picture indicated pseudo- (peripheral) precocious in the course of ovarian autonomic cyst. In the follow-up ultrasound performed in September, the image of the cyst was stationary and normalization of estradiol levels and clinical symptoms was noted. In December 2019, cyst regression and normal gonadotropin and estradiol concentrations were found. In June 2020, white mucus tinged with blood on the underwear, without any other disturbing symptoms, was observed for several days. Two consecutive USG examinations carried out in the same month confirmed the change in the right ovary, the diameter of which was 25 mm with a very high level of estradiol. Germinal tumor markers were normal. On the Tanner scale, the patient scored M2P1. The labia and hymen had puberty features. The correct vaginal entrance was visible. Another active vaginal bleeding occurred in the first week of July 2020. The considered laparoscopic treatment was abandoned due to the lack of oncological indications. Treatment with Tamoxifen was recommended in July 2020. In the initiating period of treatment, no maturation progression, and even reduction of symptoms, no acceleration of growth and a marked reduction in the size of the cysts were noted. There was no bleeding. After the size of the cyst and hormonal activity increased again, the treatment was changed to Anastrozole, the effect of which led to a reduction in the size of the cyst. Conclusions: The entire clinical picture indicates alleged (peripheral) puberty. Premature puberty in girls, which is manifested as enlarged mammary glands with high levels of estrogens secreted by autonomic ovarian cysts and prepubertal levels of gonadotropins, may indicate McCune-Albright syndrome. Vaginal bleeding may also occur in this syndrome. Cancellation of surgical treatment of the cyst made it impossible to perform a molecular test that would allow to confirm the diagnosis. Taking into account the fact that cysts are often one of the first symptoms of McCune-Albrigt syndrome, it is important to remember about multidisciplinary care for the patient and careful search for skin and bone changes or other hormonal disorders.

Keywords: McCune Albrigth's syndrome, ovarian cyst, pediatric gynaecology, precocious puberty

Procedia PDF Downloads 190

Authors: Pauline Nyssen, Ange Mouithys-Mickalad, Maryse Hoebeke

Abstract:

Inflammation is a complex physiological phenomenon involving chemical and enzymatic mechanisms. Polymorphonuclear neutrophil leukocytes (PMNs) play an important role by producing reactive oxygen species (ROS) and releasing myeloperoxidase (MPO), a pro-oxidant enzyme. Released both in the phagolysosome and the extracellular medium, MPO produces during its peroxidase and halogenation cycles oxidant species, including hypochlorous acid, involved in the destruction of pathogen agents, like bacteria or viruses. Inflammatory pathologies, like rheumatoid arthritis, atherosclerosis induce an excessive stimulation of the PMNs and, therefore, an uncontrolled release of ROS and MPO in the extracellular medium, causing severe damages to the surrounding tissues and biomolecules such as proteins, lipids, and DNA. The treatment of chronic inflammatory pathologies remains a challenge. For many years, MPO has been used as a target for the development of effective treatments. Numerous studies have been focused on the design of new drugs presenting more efficient MPO inhibitory properties. However, some designed inhibitors can be toxic. An alternative consists of assessing the potential inhibitory action of clinically-known molecules, having antioxidant activity. Propofol, 2,6-diisopropyl phenol, which is used as an intravenous anesthetic agent, meets these requirements. Besides its anesthetic action employed to induce a sedative state during surgery or in intensive care units, propofol and its injectable form Diprivan indeed present antioxidant properties and act as ROS and free radical scavengers. A study has also evidenced the ability of propofol to inhibit the formation of the neutrophil extracellular traps fibers, which are important to trap pathogen microorganisms during the inflammation process. The aim of this study was to investigate the potential inhibitory action mechanism of propofol and Diprivan on MPO activity. To go into the anti-inflammatory action of propofol in-depth, two of its oxidative derivatives, 2,6-diisopropyl-1,4-p-benzoquinone (PPFQ) and 3,5,3’,5’-tetra isopropyl-(4,4’)-diphenoquinone (PPFDQ), were studied regarding their inhibitory action. Specific immunological extraction followed by enzyme detection (SIEFED) and molecular modeling have evidenced the low anti-catalytic action of propofol. Stopped-flow absorption spectroscopy and direct MPO activity analysis have proved that propofol acts as a reversible MPO inhibitor by interacting as a reductive substrate in the peroxidase cycle and promoting the accumulation of redox compound II. Overall, Diprivan exhibited a weaker inhibitory action than the active molecule propofol. In contrast, PPFQ seemed to bind and obstruct the enzyme active site, preventing the trigger of the MPO oxidant cycles. PPFQ induced a better chlorination cycle inhibition at basic and neutral pH in comparison to propofol. PPFDQ did not show any MPO inhibition activity. The three interest molecules have also demonstrated their inhibition ability on an important step of the inflammation pathway, the PMNs superoxide anions production, thanks to EPR spectroscopy and chemiluminescence. In conclusion, propofol presents an interesting immunomodulatory activity by acting as a reductive substrate in the peroxidase cycle of MPO, slowing down its activity, whereas PPFQ acts more as an anti-catalytic substrate. Although PPFDQ has no impact on MPO, it can act on the inflammation process by inhibiting the superoxide anions production by PMNs.

Keywords: Diprivan, inhibitor, myeloperoxidase, propofol, spectroscopy

Procedia PDF Downloads 148

Authors: D. Dixon, J. Nicol, J. A. Coulter, E. Harrison

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The ease with which they can be functionalized, combined with their excellent biocompatibility, make gold nanoparticles (AuNPs) ideal candidates for various applications in nanomedicine. Indeed several promising treatments are currently undergoing human clinical trials (CYT-6091 and Auroshell). A successful nanoparticle treatment must first evade the immune system, then accumulate within the target tissue, before enter the diseased cells and delivering the payload. In order to create a clinically relevant drug delivery system, contrast agent or radiosensitizer, it is generally necessary to functionalize the AuNP surface with multiple groups; e.g. Polyethylene Glycol (PEG) for enhanced stability, targeting groups such as antibodies, peptides for enhanced internalization, and therapeutic agents. Creating and characterizing the biological response of such complex systems remains a challenge. The two commonly used methods to attach multiple groups to the surface of AuNPs are the creation of a mixed monolayer, or by binding groups to the AuNP surface using a bi-functional PEG linker. While some excellent in-vitro and animal results have been reported for both approaches further work is necessary to directly compare the two methods. In this study AuNPs capped with both PEG and a Receptor Mediated Endocytosis (RME) peptide were prepared using both mixed monolayer and PEG linker approaches. The PEG linker used was SH-PEG-SGA which has a thiol at one end for AuNP attachment, and an NHS ester at the other to bind to the peptide. The work builds upon previous studies carried out at the University of Ulster which have investigated AuNP synthesis, the influence of PEG on stability in a range of media and investigated intracellular payload release. 18-19nm citrate capped AuNPs were prepared using the Turkevich method via the sodium citrate reduction of boiling 0.01wt% Chloroauric acid. To produce PEG capped AuNPs, the required amount of PEG-SH (5000Mw) or SH-PEG-SGA (3000Mw Jenkem Technologies) was added, and the solution stirred overnight at room temperature. The RME (sequence: CKKKKKKSEDEYPYVPN, Biomatik) co-functionalised samples were prepared by adding the required amount of peptide to the PEG capped samples and stirring overnight. The appropriate amounts of PEG-SH and RME peptide were added to the AuNP to produce a mixed monolayer consisting of approximately 50% PEG and 50% RME. The PEG linker samples were first fully capped with bi-functional PEG before being capped with RME peptide. An increase in diameter from 18-19mm for the ‘as synthesized’ AuNPs to 40-42nm after PEG capping was observed via DLS. The presence of PEG and RME peptide on both the mixed monolayer and PEG linker co-functionalized samples was confirmed by both FTIR and TGA. Bi-functional PEG linkers allow the entire AuNP surface to be capped with PEG, enabling in-vitro stability to be achieved using a lower molecular weight PEG. The approach also allows the entire outer surface to be coated with peptide or other biologically active groups, whilst also offering the promise of enhanced biological availability. The effect of mixed monolayer versus PEG linker attachment on both stability and non-specific protein corona interactions was also studied.

Keywords: nanomedicine, gold nanoparticles, PEG, biocompatibility

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Authors: Ripon Sarkar, Kabita Chaterjee, Ananya Barui

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Smoking is one of the leading causes of oral cancer. Cigarette smoke affects various cellular parameters and alters molecular metabolism of cells. Epithelial cells losses their cytoskeleton structure, membrane integrity, cellular polarity that subsequently initiates the process of epithelial cells to mesenchymal transition due to long exposure of cigarette smoking. It changes the normal cellular metabolic activity which induces oxidative stress and enhances the reactive oxygen spices (ROS) formation. Excessive ROS and associated oxidative stress are considered to be a driving force in alteration in cellular phenotypes, polarity distribution and mitochondrial metabolism. Noninvasive assessment of such parameters plays essential role in development of routine screening system for early diagnosis of oral cancer. Electrical cell-substrate impedance sensing (ECIS) is one of such method applied for detection of cellular membrane impedance which can be correlated to cell membrane integrity. Present study intends to explore the alteration in cellular impedance along with the expression of cellular polarity molecules and cytoskeleton distributions in oral epithelial cells of habitual smokers and to correlate the outcome to that of clinically diagnosed oral leukoplakia and oral squamous cell carcinoma patients. Total 80 subjects were categorized into four study groups: nonsmoker (NS), cigarette smoker (CS), oral leukoplakia (OLPK) and oral squamous cell carcinoma (OSCC). Cytoskeleton distribution was analyzed by staining of actin filament and generation of ROS was measured using assay kit using standard protocol. Cell impedance was measured through ECIS method at different frequencies. Expression of E-cadherin and protease-activated receptor (PAR) proteins were observed through immune-fluorescence method. Distribution of actin filament is well organized in NS group however; distribution pattern was grossly varied in CS, OLPK and OSCC. Generation of ROS was low in NS which subsequently increased towards OSCC. Expressions of E-cadherin and change in cellular electrical impedance in different study groups indicated the hallmark of cancer progression from NS to OSCC. Expressions of E-cadherin, PAR protein, and cell impedance were decreased from NS to CS and farther OSCC. Generally, the oral epithelial cells exhibit apico-basal polarity however with cancer progression these cells lose their characteristic polarity distribution. In this study expression of polarity molecule and ECIS observation indicates such altered pattern of polarity among smoker group. Overall the present study monitored the alterations in intracellular ROS generation and cell metabolic function, membrane integrity in oral epithelial cells in cigarette smokers. Present study thus has clinical significance, and it may help in developing a noninvasive technique for early diagnosis of oral cancer amongst susceptible individuals.

Keywords: cigarette smoking, early oral cancer detection, electric cell-substrate impedance sensing, noninvasive screening

Procedia PDF Downloads 176

Authors: Anja I. Petrov, Milica B. Veljković, Marija M. Ćorović, Ana D. Milivojević, Milica B. Simović, Katarina M. Banjanac, Dejan I. Bezbradica

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One of the fundamental requirements for overall human well-being is a stable and balanced microbiome. Aside from the microorganisms that reside within the body, a large number of microorganisms, especially bacteria, swarming the human skin is in homeostasis with the host and represents a skin microbiota. Even though the immune system of the skin is capable of distinguishing between commensal and potentially harmful transient bacteria, the cutaneous microbial balance can be disrupted under certain circumstances. In that case, a reduction in the skin microbiota diversity, as well as changes in metabolic activity, results in dermal infections and inflammation. Probiotics and prebiotics have the potential to play a significant role in the treatment of these skin disorders. The most common resident bacteria found on the skin, Staphylococcus epidermidis, can act as a potential skin probiotic, contributing to the protection of healthy skin from pathogen colonization, such as Staphylococcus aureus, which is related to atopic dermatitis exacerbation. However, as it is difficult to meet regulations in cosmetic products, another therapy approach could be topical prebiotic supplementation of the skin microbiota. In recent research, polyphenols are attracting scientists' interest as biomolecules with possible prebiotic effects on the skin microbiota. This research aimed to determine how herbal extracts rich in different polyphenolic compounds (lemon balm, St. John's wort, coltsfoot, pine needle, and yarrow) affected the growth of S. epidermidis and S. aureus. The first part of the study involved screening plants to determine if they could be regarded as probable candidates to be skin prebiotics. The effect of each plant on bacterial growth was examined by supplementing the nutrient medium with their extracts and comparing it with control samples (without extract). The results obtained after 24 h of incubation showed that all tested extracts influenced the growth of the examined bacteria to some extent. Since lemon balm and St. John's wort extracts displayed bactericidal activity against S. epidermidis, whereas coltsfoot inhibited both bacteria equally, they were not explored further. On the other hand, pine needles and yarrow extract led to an increase in S. epidermidis/S. aureus ratio, making them prospective candidates to be used as skin prebiotics. By examining the prebiotic effect of two extracts at different concentrations, it was revealed that, in the case of yarrow, 0.1% of extract dry matter in the fermentation medium was optimal, while for the pine needle extract, a concentration of 0.05% was preferred, since it selectively stimulated S. epidermidis growth and inhibited S. aureus proliferation. Additionally, the total polyphenols and flavonoid content of the two extracts were determined, revealing different concentrations and polyphenol profiles. Since yarrow and pine extracts affected the growth of skin bacteria in a dose-dependent manner, by carefully selecting the quantities of these extracts, and thus polyphenols content, it is possible to achieve desirable alterations of skin microbiota composition, which may be suitable for the treatment of atopic dermatitis.

Keywords: herbal extracts, polyphenols, skin microbiota, skin prebiotics

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Authors: Dmitriy Yu. Korulkin, Raissa A. Muzychkina

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The last decade the growth of severe and disseminated forms of inflammatory diseases is observed in Kazakhstan, in particular, septic shock, which progresses on 3-15% of patients with infectious complications of postnatal period. In terms of the rate of occurrence septic shock takes third place after hemorrhagic and cardiovascular shock, in terms of lethality it takes first place. The structure of obstetric sepsis has significantly changed. Currently the first place is taken by postabortive sepsis (40%) that is connected with usage of imperfect methods of artificial termination of pregnancy in late periods (intraamnial injection of sodium chloride, glucose). The second place is taken by postnatal sepsis (32%); the last place is taken by septic complications of caesarean section (28%). In this connection, search for and assessment of effectiveness of new medicines for treatment of postoperative infectious complications, having biostimulating effect and speeding up regeneration processes, is very promising and topical. Essential oil was obtained by the method hydrodistillation air-dry aerial part of Sedum L. plants using Clevenger apparatus. Pilot batch of plant medicinal product based on Sedum essential oils was produced by Chimpharm JSC, Santo Member of Polpharma Group (Kazakhstan). During clinical test of the plant medicinal product based on Sedum L. essential oils 37 female patients at the age from 35 to 57 with clinical signs of complicated postoperative processes and 12 new mothers with clinical signs of inflammatory process on sutures on anterior abdominal wall after caesarean section and partial disruption of surgical suture line on perineum were examined. Medicine usage methods - surgical wound treatment 2 times a day, treatment with other medicines of local action was not performed. Before and after treatment general clinical test, determination of immune status, bacterioscopic test of wound fluid was performed to all women, medical history data was taken into account, wound cleansing and healing time, full granulations, side effects and complications, satisfaction with the used medicine was assessed. On female patients with inflammatory infiltration and partial disruption of surgical suture line anesthetic wound healing effect of plant medicinal product based on Sedum L. essential oils was observed as early as on the second day after beginning of using it, wound cleansing took place, as a rule, within the first row days. Hyperemia in the area of suture line also was not observed for 2-3-d day of usage of medicine, good constant course was observed. The absence of clinical effect on this group of patients was not registered. The represented data give evidence of that clinical effect was accompanied with normalization of changed laboratory findings. No allergic responses or side effects were observed during usage of the plant medicinal products based on Sedum L. essential oils.

Keywords: antiinflammatory, bioactive substances, essential oils, isolation, sedum L., wound healing

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Authors: Maria Ines Azambuja

Abstract:

Graphic displays of Age-Period-Cohort (APC) mortality trends generally uses data aggregated within 5 or 10-year intervals. Technology allows one to increase the amount of processed data. Displaying occurrences by 1-year intervals is a logic first step in the direction of attaining higher quality landscapes of variations in temporal occurrences. Method: 1) Comparison of UK mortality trends plotted by 10-, 5- and 1-year intervals; 2) Comparison of UK and US mortality trends (period X age and cohort X age) displayed by 1-year intervals. Source: Mortality data (period, 1x1, males, 1933-1912) uploaded from the Human Mortality Database to Excel files, where Period X Age and Cohort X Age graphics were produced. The choice of transforming age-specific trends from calendar to birth-cohort years (cohort = period – age) (instead of using cohort 1x1 data available at the HMD resource) was taken to facilitate the comparison of age-specific trends when looking across calendar-years and birth-cohorts. Yearly live births, males, 1933 to 1912 (UK) were uploaded from the HFD. Influenza references are from the literature. Results: 1) The use of 1-year intervals unveiled previously unsuspected period, cohort and interacting period x cohort effects upon all-causes mortality. 2) The UK and US figures showed variations associated with particular calendar years (1936, 1940, 1951, 1957-68, 72) and, most surprisingly, with particular birth-cohorts (1889-90 in the US, and 1900, 1918-19, 1940-41 and 1946-47, in both countries. Also, the figures showed ups and downs in age-specific trends initiated at particular birth-cohorts (1900, 1918-19 and 1947-48) or a particular calendar-year (1968, 1972, 1977-78 in the US), variations at times restricted to just a range of ages (cohort x period interacting effects). Importantly, most of the identified “scars” (period and cohort) correlates with the record of occurrences of Influenza A epidemics since the late 19th Century. Conclusions: The use of 1-year intervals to describe APC mortality trends both increases the amount of information available, thus enhancing the opportunities for patterns’ recognition, and increases our capability of interpreting those patterns by describing trends across smaller intervals of time (period or birth-cohort). The US and the UK mortality landscapes share many but not all 'scars' and distortions suggested here to be associated with influenza epidemics. Different size-effects of wars are evident, both in mortality and in fertility. But it would also be realistic to suppose that the preponderant influenza A viruses circulating in UK and US at the beginning of the 20th Century might be different and the difference to have intergenerational long-term consequences. Compared with the live births trend (UK data), birth-cohort scars clearly depend on birth-cohort sizes relatives to neighbor ones, which, if causally associated with influenza, would result from influenza-related fetal outcomes/selection. Fetal selection could introduce continuing modifications on population patterns of immune-inflammatory phenotypes that might give rise to 'epidemic constitutions' favoring the occurrence of particular diseases. Comparative analysis of mortality landscapes may help us to straight our record of past circulation of Influenza viruses and document associations between influenza recycling and fertility changes.

Keywords: age-period-cohort trends, epidemic constitution, fertility, influenza, mortality

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Authors: Meitham Amereh, Mohsen Akbari, Ben Nadler

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Cancer has been recognized as one of the most challenging problems in biology and medicine. Aggressive tumors are a lethal type of cancers characterized by high genomic instability, rapid progression, invasiveness, and therapeutic resistance. Their behavior involves complicated molecular biology and consequential dynamics. Although tremendous effort has been devoted to developing therapeutic approaches, there is still a huge need for new insights into the dark aspects of tumors. As one of the key requirements in better understanding the complex behavior of tumors, mathematical modeling and continuum physics, in particular, play a pivotal role. Mathematical modeling can provide a quantitative prediction on biological processes and help interpret complicated physiological interactions in tumors microenvironment. The pathophysiology of aggressive tumors is strongly affected by the extracellular cues such as stresses produced by mechanical forces between the tumor and the host tissue. During the tumor progression, the growing mass displaces the surrounding extracellular matrix (ECM), and due to the level of tissue stiffness, stress accumulates inside the tumor. The produced stress can influence the tumor by breaking adherent junctions. During this process, the tumor stops the rapid proliferation and begins to remodel its shape to preserve the homeostatic equilibrium state. To reach this, the tumor, in turn, upregulates epithelial to mesenchymal transit-inducing transcription factors (EMT-TFs). These EMT-TFs are involved in various signaling cascades, which are often associated with tumor invasiveness and malignancy. In this work, we modeled the tumor as a growing hyperplastic mass and investigated the effects of mechanical stress from surrounding ECM on tumor invasion. The invasion is modeled as volume-preserving inelastic evolution. In this framework, principal balance laws are considered for tumor mass, linear momentum, and diffusion of nutrients. Also, mechanical interactions between the tumor and ECM is modeled using Ciarlet constitutive strain energy function, and dissipation inequality is utilized to model the volumetric growth rate. System parameters, such as rate of nutrient uptake and cell proliferation, are obtained experimentally. To validate the model, human Glioblastoma multiforme (hGBM) tumor spheroids were incorporated inside Matrigel/Alginate composite hydrogel and was injected into a microfluidic chip to mimic the tumor’s natural microenvironment. The invasion structure was analyzed by imaging the spheroid over time. Also, the expression of transcriptional factors involved in invasion was measured by immune-staining the tumor. The volumetric growth, stress distribution, and inelastic evolution of tumors were predicted by the model. Results showed that the level of invasion is in direct correlation with the level of predicted stress within the tumor. Moreover, the invasion length measured by fluorescent imaging was shown to be related to the inelastic evolution of tumors obtained by the model.

Keywords: cancer, invasion, mathematical modeling, microfluidic chip, tumor spheroids

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Authors: Leo Nnamdi Ozurumba-Dwight

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Messenger ribooxynucleic acid (mRNA) molecules are compositional, protein-based. These proteins, encoding mRNA molecules (which collectively connote the transcriptome), when analyzed by RNA sequencing (RNAseq), unveils the nature of gene expression in the RNA. The obtained gene expression provides clues of cellular traits and their dynamics in presentations. These can be studied in relation to function and responses. RNAseq is a practical concept in Genomics as it enables detection and quantitative analysis of mRNA molecules. Single cell and spatial transcriptomics both present varying avenues for expositions in genomic characteristics of single cells and pooled cells in disease conditions such as cancer, auto-immune diseases, hematopoietic based diseases, among others, from investigated biological tissue samples. Single cell transcriptomics helps conduct a direct assessment of each building unit of tissues (the cell) during diagnosis and molecular gene expressional studies. A typical technique to achieve this is through the use of a single-cell RNA sequencer (scRNAseq), which helps in conducting high throughput genomic expressional studies. However, this technique generates expressional gene data for several cells which lack presentations on the cells’ positional coordinates within the tissue. As science is developmental, the use of complimentary pre-established tissue reference maps using molecular and bioinformatics techniques has innovatively sprung-forth and is now used to resolve this set back to produce both levels of data in one shot of scRNAseq analysis. This is an emerging conceptual approach in methodology for integrative and progressively dependable transcriptomics analysis. This can support in-situ fashioned analysis for better understanding of tissue functional organization, unveil new biomarkers for early-stage detection of diseases, biomarkers for therapeutic targets in drug development, and exposit nature of cell-to-cell interactions. Also, these are vital genomic signatures and characterizations of clinical applications. Over the past decades, RNAseq has generated a wide array of information that is igniting bespoke breakthroughs and innovations in Biomedicine. On the other side, spatial transcriptomics is tissue level based and utilized to study biological specimens having heterogeneous features. It exposits the gross identity of investigated mammalian tissues, which can then be used to study cell differentiation, track cell line trajectory patterns and behavior, and regulatory homeostasis in disease states. Also, it requires referenced positional analysis to make up of genomic signatures that will be sassed from the single cells in the tissue sample. Given these two presented approaches to RNA transcriptomics study in varying quantities of cell lines, with avenues for appropriate resolutions, both approaches have made the study of gene expression from mRNA molecules interesting, progressive, developmental, and helping to tackle health challenges head-on.

Keywords: transcriptomics, RNA sequencing, single cell, spatial, gene expression.

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

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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

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Authors: Antonia Egli, Theo Lynn, Pierangelo Rosati, Gary Sinclair

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The World Health Organization (WHO) defines vaccine hesitancy as the postponement or complete denial of vaccines and estimates a direct linkage to approximately 1.5 million avoidable deaths annually. This figure is not immune to public health developments, as has become evident since the global spread of COVID-19 from Wuhan, China in early 2020. Since then, the proliferation of influential, but oftentimes inaccurate, outdated, incomplete, or false vaccine-related information on social media has impacted hesitancy levels to a degree described by the WHO as an infodemic. The COVID-19 pandemic and related vaccine hesitancy levels have in 2022 resulted in the largest drop in childhood vaccinations of the 21st century, while the prevalence of online stigma towards vaccine hesitant consumers continues to grow. Simultaneously, a second disease has risen to global importance: Monkeypox is an infection originating from west and central Africa and, due to racially motivated online hate, was in August 2022 set to be renamed by the WHO. To better understand public reactions towards two viral infections that became global threats to public health no two years apart, this research examines user replies to threads published by the WHO on Twitter. Replies to two Tweets from the @WHO account declaring COVID-19 and Monkeypox as ‘public health emergencies of international concern’ on January 30, 2020, and July 23, 2022, are gathered using the Twitter application programming interface and user mention timeline endpoint. Research methodology is unique in its analysis of stigmatizing, racist, and hateful content shared on social media within the vaccine discourse over the course of two disease outbreaks. Three distinct analyses are conducted to provide insight into (i) the most prevalent topics and sub-topics among user reactions, (ii) changes in sentiment towards the spread of the two diseases, and (iii) the presence of stigma, racism, and online hate. Findings indicate an increase in hesitancy to accept further vaccines and social distancing measures, the presence of stigmatizing content aimed primarily at anti-vaccine cohorts and racially motivated abusive messages, and a prevalent fatigue towards disease-related news overall. This research provides value to non-profit organizations or government agencies associated with vaccines and vaccination programs in emphasizing the need for public health communication fitted to consumers' vaccine sentiments, levels of health information literacy, and degrees of trust towards public health institutions. Considering the importance of addressing fears among the vaccine hesitant, findings also illustrate the risk of alienation through stigmatization, lead future research in probing the relatively underexamined field of online, vaccine-related stigma, and discuss the potential effects of stigma towards vaccine hesitant Twitter users in their decisions to vaccinate.

Keywords: social marketing, social media, public health communication, vaccines

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Authors: Lijuan Li

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Nitric oxide (NO) has become a fascinating entity in biological chemistry over the past few years. It is a gaseous lipophilic radical molecule that plays important roles in several physiological and pathophysiological processes in mammals, including activating the immune response, serving as a neurotransmitter, regulating the cardiovascular system, and acting as an endothelium-derived relaxing factor. NO functions in eukaryotes both as a signal molecule at nanomolar concentrations and as a cytotoxic agent at micromolar concentrations. The latter arises from the ability of NO to react readily with a variety of cellular targets leading to thiol S-nitrosation, amino acid N-nitrosation, and nitrosative DNA damage. Nitric oxide can readily bind to metals to give metal-nitrosyl (M-NO) complexes. Some of these species are known to play roles in biological NO storage and transport. These complexes have different biological, photochemical, or spectroscopic properties due to distinctive structural features. These recent discoveries have spawned a great interest in the development of transition metal complexes containing NO, particularly its iron complexes that are central to the role of nitric oxide in the body. Spectroscopic evidence would appear to implicate species of “Fe(NO)2+” type in a variety of processes ranging from polymerization, carcinogenesis, to nitric oxide stores. Our research focuses on isolation and structural studies of non-heme iron nitrosyls that mimic biologically active compounds and can potentially be used for anticancer drug therapy. We have shown that reactions between Fe(NO)2(CO)2 and a series of imidazoles generated new non-heme iron nitrosyls of the form Fe(NO)2(L)2 [L = imidazole, 1-methylimidazole, 4-methylimidazole, benzimidazole, 5,6-dimethylbenzimidazole, and L-histidine] and a tetrameric cluster of [Fe(NO)2(L)]4 (L=Im, 4-MeIm, BzIm, and Me2BzIm), resulted from the interactions of Fe(NO)2 with a series of substituted imidazoles was prepared. Recently, a series of sulfur bridged iron di nitrosyl complexes with the general formula of [Fe(µ-RS)(NO)2]2 (R = n-Pr, t-Bu, 6-methyl-2-pyridyl, and 4,6-dimethyl-2-pyrimidyl), were synthesized by the reaction of Fe(NO)2(CO)2 with thiols or thiolates. Their structures and properties were studied by IR, UV-vis, 1H-NMR, EPR, electrochemistry, X-ray diffraction analysis and DFT calculations. IR spectra of these complexes display one weak and two strong NO stretching frequencies (νNO) in solution, but only two strong νNO in solid. DFT calculations suggest that two spatial isomers of these complexes bear 3 Kcal energy difference in solution. The paramagnetic complexes [Fe2(µ-RS)2(NO)4]-, have also been investigated by EPR spectroscopy. Interestingly, the EPR spectra of complexes exhibit an isotropic signal of g = 1.998 - 2.004 without hyperfine splitting. The observations are consistent with the results of calculations, which reveal that the unpaired electron dominantly delocalize over the two sulfur and two iron atoms. The difference of the g values between the reduced form of iron-sulfur clusters and the typical monomeric di nitrosyl iron complexes is explained, for the first time, by of the difference in unpaired electron distributions between the two types of complexes, which provides the theoretical basis for the use of g value as a spectroscopic tool to differentiate these biologically active complexes.

Keywords: di nitrosyl iron complex, metal nitrosyl, non-heme iron, nitric oxide

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Authors: S. F. Afzali, W. L. Wong

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The epizootic ulcerative syndrome (EUS) causes by the oomycete fungus, Aphanomyces invadans; known to be one of the infectious fish diseases for farmed and wild fishes in fresh and brackish-water from the Asia-pacific region, America and Africa. Although, EUS had been documented by the Office International des Epizooties (OIE) since 1995, hitherto, there is neither standard chemical agents that can be used for successful treatment of this destructive infection in the time of outbreak; nor available vaccine for prevention. Plant-based remedies in controlling fish diseases are gaining much attention recently as an alternative to chemical treatments, which possess negative effects to the environment and human. In present study, Sonneratia alba, a mangrove plant belongs to the Sonneratiaceae family, was screened in vitro and in vivo for its antifungal activity against A. invadans mycelium growth and its effects on fish innate immune system and disease resistant. The in vitro tests was performed using the disc diffusion methods with measurements of minimum inhibitory concentration (MIC) and inhibition zone. For in vivo study, the S. alba extract supplemented diets were administrated at 0.0, 1.0%, 3.0%, and 5.0% on healthy goldfish, Carassius auratus, which challenged with A. invadans zoospores (100 spores/ml). To compare the significant differences in the hematological and immunological parameters obtained from the experiments, the data were analysed using the SPSS. The methanol extract of S. alba effectively inhibited the mycelial growth of A. invadans at a minimum concentration of 1000 ppm for agar and filter paper diffusion experiments. In the agar diffusion test, 500 ppm of the extract inhibited the fungus mycelial growth up to 96 hours after exposure. The mycelial growth from the edge of the pre-inoculated A. invadans agar discs treated with S. alba extracts at concentrations of 100, 500 and 1000 ppm were 15, 8 and 0 mm respectively. The results of the filter paper disc test showed that the S. alba extract at its minimal inhibitory concentration (1000 ppm) has similar qualitative inhibitory effect as malachite green at 1 ppm and formalin at 250 ppm. According to the in vivo tests findings, in the infected fish fed with 3.0% and 5.0% supplementation diet, the numbers of white blood cell and myeloperoxidase activity significantly increased after the second week of treatment. Whilst the numbers of red blood cell significantly decreased in the infected fish fed with 0.0 and 1.0% supplementation diet. After the third week of feeding, significant increases in the total protein, albumin level, lysozyme activity were recorded in the infected fish fed with 3.0% and 5.0% supplementation diet. Also, the enriched diets increased the survival rate as compared to the untreated group that suffered from 90% mortality. The present study indicated that S. alba extract may inhibit the mycelial growth of A. invadans effectively, suggesting an alternative to other chemotherapeutic agents, which brought much environmental and health concerns to the public, for EUS treatment.

Keywords: fungal pathogen, goldfish, organic extract, treatment

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