Search results for: lung transplantation

Authors: Mohammadjavad Sotoudeheian

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COVID-19, which began in December 2019, uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter and spread through the cells. ACE2 mRNA is present in almost every organ, including nasopharynx, lung, as well as the brain. Ports of entry of SARS-CoV-2 into the central nervous system (CNS) may include arterial circulation, while viremia is remarkable. However, it is imperious to develop neurological symptoms evaluation CSF analysis in patients with COVID-19, but theoretically, ACE2 receptors are expressed in cerebellar cells and may be a target for SARS-CoV-2 infection in the brain. Recent evidence agrees that SARS-CoV-2 can impact the brain through direct and indirect injury. Two biomarkers for CNS injury, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NFL) detected in the plasma of patients with COVID-19. NFL, an axonal protein expressed in neurons, is related to axonal neurodegeneration, and GFAP is over-expressed in CNS inflammation. GFAP cytoplasmic accumulation causes Schwan cells to misfunction, so affects myelin generation, reduces neuroskeletal support over NfLs during CNS inflammation, and leads to axonal degeneration. Interleukin-6 (IL-6), which extensively over-express due to interleukin storm during COVID-19 inflammation, regulates gene expression, as well as GFAP through STAT molecular pathway. IL-6 also impresses the phosphoinositide 3-kinase (PI3K)/STAT/smads pathway. The PI3K/ protein kinase B (Akt) pathway is the main modulator upstream of the mammalian target of rapamycin (mTOR), and alterations in this pathway are common in neurodegenerative diseases. Most neurodegenerative diseases show a disruption of autophagic function and display an abnormal increase in protein aggregation that promotes cellular death. Therefore, induction of autophagy has been recommended as a rational approach to help neurons clear abnormal protein aggregates and survive. The mTOR is a major regulator of the autophagic process and is regulated by cellular stressors. The mTORC1 pathway and mTORC2, as complementary and important elements in mTORC1 signaling, have become relevant in the regulation of the autophagic process and cellular survival through the extracellular signal-regulated kinase (ERK) pathway.

Keywords: mTORC1, COVID-19, PI3K, autophagy, neurodegeneration

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Authors: Mohamad Ammar Ayass, Natalya Griko, Victor Pashkov, Wanying Cao, Kevin Zhu, Jin Zhang, Lina Abi Mosleh

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Respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for coronavirus disease 2019 (COVID-19). Early evidence pointed at the angiotensin-converting enzyme 2 (ACE-2) expressed on the epithelial cells of the lung as the main entry point of SARS-CoV-2 into the cells. The viral entry is mediated by the binding of the Receptor Binding Domain (RBD) of the spike protein that is expressed on the surface of the virus to the ACE-2 receptor. As the number of SARS-CoV-2 variants continues to increase, mutations arising in the RBD of SARS-CoV-2 may lead to the ineffectiveness of RBD targeted neutralizing antibodies. To address this limitation, the objective of this study is to develop a combination of aptamers that target different regions of the RBD, preventing the binding of the spike protein to ACE-2 receptor and subsequent viral entry and replication. A safe and innovative biomedical tool was developed to inhibit viral infection and reduce the harms of COVID-19. In the present study, DNA aptamers were developed against a recombinant trimer S protein using the Systematic Evolution of Ligands by Exponential enrichment (SELEX). Negative selection was introduced at round number 7 to select for aptamers that bind specifically to the RBD domain. A series of 9 aptamers (ADI2010, ADI2011, ADI201L, ADI203L, ADI205L, ADIR68, ADIR74, ADIR80, ADIR83) were selected and characterized with high binding affinity and specificity to the RBD of the spike protein. Aptamers (ADI25, ADI2009, ADI203L) were able to bind and pull down endogenous spike protein expressed on the surface of SARS-CoV-2 virus in COVID-19 positive patient samples and determined by liquid chromatography- tandem mass spectrometry analysis (LC-MS/MS). LC-MS/MS data confirmed that aptamers can bind to the RBD of the spike protein. Furthermore, results indicated that the combination of the 9 best aptamers inhibited the binding of the purified trimer spike protein to the ACE-2 receptor found on the surface of Vero E6 cells. In the same experiment, the combined aptamers displayed a better neutralizing effect than antibodies. The data suggests that the selected aptamers could be used in therapy to neutralize the effect of the SARS-CoV-2 virus by inhibiting the interaction between the RBD and ACE-2 receptor, preventing viral entry into target cells and therefore blocking viral replication.

Keywords: aptamer, ACE-2 receptor, binding inhibitor, COVID-19, spike protein, SARS-CoV-2, treatment

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Authors: Karen Boaz, C. R. Charan

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Background: The infiltration of tumour stroma by eosinophils, Tumor-Associated Tissue Eosinophilia (TATE), is known to modulate the progression of Oral Squamous Cell Carcinoma (OSCC). Eosinophils have direct tumoricidal activity by release of cytotoxic proteins and indirectly they enhance permeability into tumor cells enabling penetration of tumoricidal cytokines. Also, eosinophils may promote tumor angiogenesis by production of several angiogenic factors. Identification of eosinophils in the inflammatory stroma has been proven to be an important prognosticator in cancers of mouth, oesophagus, larynx, pharynx, breast, lung, and intestine. Therefore, the study aimed to correlate TATE with clinical and histopathological variables, and blood eosinophil count to assess the role of TATE as a prognosticator in Oral Squamous Cell Carcinoma (OSCC). Methods: Seventy two biopsy-proven cases of OSCC formed the study cohort. Blood eosinophil counts and TNM stage were obtained from the medical records. Tissue sections (5µm thick) were stained with Haematoxylin and Eosin. The eosinophils were quantified at invasive tumour front (ITF) in 10HPF (40x magnification) with an ocular grid. Bryne’s grading of ITF was also performed. A subset of thirty cases was also assessed for association of TATE with recurrence, involvement of lymph nodes and surgical margins. Results: 1) No statistically significant correlation was found between TATE and TNM stage, blood eosinophil counts and most parameters of Bryne’s grading system. 2) Statistically significant relation of intense degree of TATE was associated with the absence of distant metastasis, increased lympho-plasmacytic response and increased survival (diseasefree and overall) of OSCC patients. 3) In the subset of 30 cases, tissue eosinophil counts were higher in cases with lymph node involvement, decreased survival, without margin involvement and in cases that did not recur. Conclusion: While the role of eosinophils in mediating immune responses seems ambiguous as eosinophils support cell-mediated tumour immunity in early stages while inhibiting the same in advanced stages, TATE may be used as a surrogate marker for determination of prognosis in oral squamous cell carcinoma.

Keywords: tumour-associated tissue eosinophilia, oral squamous cell carcinoma, prognosticator, tumoral immunity

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Authors: R. L. Shirole, N. L. Shirole, R. B. Patil, M. N. Saraf

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The present investigation aimed to elucidate the probable mechanism of antiasthmatic action of essential oil of Pistacia integerrima J.L. Stewart ex Brandis galls (EOPI). EOPI was investigated for its potential antiasthmatic action using in vitro antiallergic assays mast cell degranulation and soyabean lipoxidase enzyme activit, and spasmolytic action using isolated guinea pig ileum preparation. In vivo studies included lipopolysaccharide-induced bronchial inflammation in rats and airway hyperresponsiveness in ovalbumin in sensitized guinea pigs using spirometry. Data was analysed by GraphPad Prism 5.01 and results were expressed as means ± SEM. P < 0.05 was considered to be significant. EOPI inhibits 5-lipoxidase enzyme activity, DPPH scavenging activity and erythropoietin- induced angiogenesis. It showed dose dependent anti-allergic activity by inhibiting compound 48/80 induced mast cell degranulation. The finding that essential oil induced inhibition of transient contraction of acetylcholine in calcium free medium, and relaxation of S-(-)-Bay 8644-precontracted isolated guinea pig ileum jointly suggest that suggesting that the L-subtype Cav channel is involved in spasmolytic action of EOPI. Treatment with EOPI dose dependently (7.5, 15 and 30 mg/kg i.p.) inhibited lipopolysaccharide- induced increased in total cell count, neutrophil count, nitrate-nitrite, total protein, albumin levels in bronchoalveolar fluid and myeloperoxidase levels in lung homogenates. Mild diffused lesions involving focal interalveolar septal, intraluminal infiltration of neutrophils were observed in EOPI (7.5 &15 mg/kg) pretreated while no abnormality was detected in EOPI (30 mg/kg) and roflumilast (1mg/kg) pretreated rats. Roflumilast was used as standard. EOPI reduced the respiratory flow due to gasping in ovalbumin sensitized guinea pigs. The study demonstrates the effectiveness of EOPI in bronchial asthma possibly related to its ability to inhibit L-subtype Cav channel, mast cell stabilization, antioxidant, angiostatic and through inhibition of 5-lipoxygenase enzyme.

Keywords: asthma, lipopolysaccharide, spirometry, Pistacia integerrima J.L. Stewart ex Brandis, essential oil

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Authors: Walid Al-Qerem, Ruba Zumot

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Background: The rise of obesity among children and adolescents remains a primary challenge for healthcare providers globally and in the Middle East. The aim of the present study is to determine the prevalence of obesity among 5-20 years old Jordanians based on CDC criteria. Method: A total of 5722 Jordanians (37% males; 63% females) aged 5-20 years data were retrieved from the Jordanian Ministry of Health electronic database (Hakeem). As per the CDC selection criteria, the chosen data pertains exclusively to healthy Jordanian children and adolescents who are medically sound, not suffering from health conditions, and not undergoing any treatments that could hinder normal growth patterns, such as severe infection, chronic kidney disease (CKD), Down’s syndrome, attention deficit hyperactivity disorder, cancer, heart disease, lung disease, cystic fibrosis, Crohn’s disease, type 1 diabetes, hormonal disturbances, any stress-related conditions, hormonal therapy such as corticosteroids, Growth hormones (GHS) or gonadotropin-releasing hormone agonists, insulin, and amphetamines or any other stimulants. In addition, participants with missing or invalid data values for anthropometric measurements were excluded from the study. Weight for age and body mass index for age were analyzed comparatively for Jordanian children and adolescents against the international growth standards. The Z-score for each record was computed based on CDC equations. As per CDC classifications, BMI for age percentiles, values ≥85th and < 95th are classified as overweight, and value at ≥ 95th is classified as obesity. Results: The average age of the evaluated sample was 12.33 ±4.39 years (10.79 ±3.39 for males and 13.23 ± 4.66 for females). The mean weight for males and females were 33.16±14.17 Kg and 133.54±17.17 cm for males, 43.86 ±18.82 Kg, and 142.19±18.35 for females, while for BMI the mean was for boys and girls 17.81±3.88 and 20.52±5.03 respectively. The results indicated that based on CDC criteria, 8.9% of males were classified as children/adolescents with overweight, and 9.7% were classified as children/adolescents with obesity, while in females, 17.8% were classified as children/adolescents with overweight and 10.2% were classified as children/adolescents with obesity. Discussion: The high prevalence of obesity reported in the present study emphasizes the importance of applying different strategies to prevent childhood obesity, including encouraging physical activity, promoting healthier food options, and behavioral changes. Conclusion: The results presented in this study indicated the high prevalence of overweight/obesity among Jordanian adolescents and children, which must be tagged by healthcare planners and providers.

Keywords: CDC, obesity, childhood, Jordan

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Authors: Sung-Hee Nam, Kwang-Gill Lee, You-Young Jo, HaeYong Kweon

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Entomopathogenic fungi is a Cordyceps species that is isolated from dead silkworm and cicada. Fungi on cicadas were described in old Chinese medicinal books and From ancient times, vegetable wasps and plant worms were widely known to have active substance and have been studied for pharmacological use. Among many fungi belonging to the genus Cordyceps, Cordyceps sinensis have been demonstrated to yield natural products possessing various biological activities and many bioactive components. Generally, It is commonly used to replenish the kidney and soothe the lung, and for the treatment of fatigue. Due to their commercial and economic importance, the demand for Cordyceps has been rapidly increased. However, a supply of Cordyceps specimen could not meet the increasing demand because of their sole dependence on field collection and habitat destruction. Because it is difficult to obtain many insect hosts in nature and the edibility of host insect needs to be verified in a pharmacological aspect. Recently, this setback was overcome that P. tenuipes was able to be cultivated in a large scale using silkworm as host. Pharmacological effects of P. tenuipes cultured on silkworm such as strengthening immune function, anti-fatigue, anti-tumor activity and controlling liver etc have been proved. They are widely commercialized. In this study, we attempted to establish a method for stable growth inhibition of P. tenuipes on silkworm hosts and an optimal condition for synnemata formation. To determine optimum culturing conditions, temperature and light conditions were varied. The length and number of synnemata was highest at 25℃ temperature and 100~300 lux illumination. On an average, the synnemata of wild P. tenuipes measures 70 ㎜ in length and 20 in number; those of the cultured strain were relatively shorter and more in number. The number of synnemata may have increased as a result of inoculating the host with highly concentrated conidia, while the length may have decreased due to limited nutrition per individual. It is not able that changes in light illumination cause morphological variations in the synnemata. However, regulation of only light and temperature could not produce stromata like perithecia, asci, and ascospores. Yamanaka reported that although a complete fruiting body can be produced under optimal culture conditions, it should be regarded as synnemata because it does not develop into an ascoma bearing ascospores.

Keywords: paecilomyces tenuipes, entomopathogenic fungi, silkworm larva, bombyx mori

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Authors: Eva de Mingo-Fernández, Lourdes Rubio Rico, Carmen Ortega-Segura, Montserrat Querol-García, Raúl González-Jauregui

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Today, one of the great challenges that the university faces is to get closer to society and transfer knowledge. The competency-based training approach favours a continuous interaction between practice and theory, which is why it is essential to establish real experiences with reflection and debate and to contrast them with personal and professional knowledge. Service-learning (SL) consists of an integration of academic learning with service in the community, which enables teachers to transfer knowledge with social value and students to be trained on the basis of experience of real needs and problems with the aim of solving them. SLE combines research, teaching, and social value knowledge transfer with the real social needs and problems of a community. Goal: The objective of this study was to design, implement, and evaluate a service-learning program in the subject of adult nursing for second-year nursing students. Methodology: After establishing collaboration with eight associations of people with different pathologies, the students were divided into eight groups, and each group was assigned an association. The groups were made up of 10-12 students. The associations willing to participate were for the following conditions: diabetes, multiple sclerosis, cancer, inflammatory bowel disease, fibromyalgia, heart, lung, and kidney diseases. The methodological design consisting of 5 activities was then applied. Three activities address personal and individual reflections, where the student initially describes what they think it is like to live with a certain disease. They then express their reflections resulting from an interview conducted by peers, in person or online, with a person living with this particular condition, and after sharing the results of their reflections with the rest of the group, they make an oral presentation in which they present their findings to the other students. This is followed by a service task in which the students collaborate in different activities of the association, and finally, a third individual reflection is carried out in which the students express their experience of collaboration. The evaluation of this activity is carried out by means of a rubric for both the reflections and the presentation. It should be noted that the oral presentation is evaluated both by the rest of the classmates and by the teachers. Results: The evaluation of the activity, given by the students, is 7.80/10, commenting that the experience is positive and brings them closer to the reality of the people and the area.

Keywords: academic learning integration, knowledge transfer, service-learning, teaching methodology

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Authors: Urvi Panwar, Kanchan Mishra, Kanjaksha Ghosh, ShankerLal Kothari

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Background: Day-by-day the increasing prevalence of neurodegenerative diseases have become a global issue to manage them by medical sciences. The adult neural stem cells are rare and require an invasive and painful procedure to obtain it from central nervous system. Mesenchymal stem cell (MSCs) therapies have shown remarkable application in treatment of various cell injuries and cell loss. MSCs can be derived from various sources like adult tissues, human bone marrow, umbilical cord blood and cord tissue. MSCs have similar proliferation and differentiation capability, but the human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are proved to be more beneficial with respect to cell procurement, differentiation to other cells, preservation, and transplantation. Material and method: Human umbilical cord is easily obtainable and non-controversial comparative to bone marrow and other adult tissues. The umbilical cord can be collected after delivery of baby, and its tissue can be cultured using explant culture method. Cell culture medium such as DMEMF12+10% FBS and DMEMF12+Neural growth factors (bFGF, human noggin, B27) with antibiotics (Streptomycin/Gentamycin) were used to culture and differentiate mesenchymal stem cells into neural cells, respectively. The characterisations of MSCs were done with Flow Cytometer for surface markers CD90, CD73 and CD105 and colony forming unit assay. The differentiated various neural cells will be characterised by fluorescence markers for neurons, astrocytes, and oligodendrocytes; quantitative PCR for genes Nestin and NeuroD1 and Western blotting technique for gap43 protein. Result and discussion: The high quality and number of MSCs were isolated from human umbilical cord via explant culture method. The obtained MSCs were differentiated into neural cells like neurons, astrocytes and oligodendrocytes. The differentiated neural cells can be used to treat neural injuries and neural cell loss by delivering cells by non-invasive administration via cerebrospinal fluid (CSF) or blood. Moreover, the MSCs can also be directly delivered to different injured sites where they differentiate into neural cells. Therefore, human umbilical cord is demonstrated to be an inexpensive and easily available source for MSCs. Moreover, the hUCMSCs can be a potential source for neural cell therapies and neural cell regeneration for neural cell injuries and neural cell loss. This new way of research will be helpful to treat and manage neural cell damages and neurodegenerative diseases like Alzheimer and Parkinson. Still the study has a long way to go but it is a promising approach for many neural disorders for which at present no satisfactory management is available.

Keywords: bone marrow, cell therapy, explant culture method, flow cytometer, human umbilical cord, mesenchymal stem cells, neurodegenerative diseases, neuroprotective, regeneration

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Authors: Drago Bratkovic, Curtis Gravance, David Ketteridge, Ravi Krishnan, Michael Imperiale

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The mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases that have a common defect in the catabolism of glycosaminoglycans (GAGs). MPS I is the most common of the MPS diseases. Manifestations of MPS I include coarsening of facial features, corneal clouding, developmental delay, short stature, skeletal manifestations, hearing loss, cardiac valve disease, hepatosplenomegaly, and umbilical and inguinal hernias. Treatments for MPS I restore or activate the missing or deficient enzyme in the case of enzyme replacement therapy (ERT) and haematopoietic stem cell transplantation (HSCT). Pentosan polysulfate sodium (PPS) is a potential treatment to improve bone and joint manifestations of MPS I. The mechanisms of action of PPS that are relevant to the treatment of MPS I are the ability to: (i) Reduce systemic and accumulated GAG, (ii) Reduce inflammatory effects via the inhibition of NF-kB, resulting in the reduction in pro-inflammatory mediators. (iii) Reduce the expression of the pain mediator nerve growth factor in osteocytes from degenerating joints. (iv) Inhibit the cartilage degrading enzymes related to joint dysfunction in MPS I. PPS is being evaluated as an adjunctive therapy to ERT and/or HSCT in an open-label, single-centre, phase 2 study. Patients are ≥ 5 years of age with a diagnosis of MPS I and previously received HSCT and/or ERT. Three white, female, patients with MPS I-Hurler, ages 14, 15, and 19 years, and one, white male patient aged 15 years are enrolled. All were diagnosed at ≤2 years of age. All patients received HSCT ≤ 6 months after diagnosis. Two of the patients were treated with ERT prior to HSCT, and 1 patient received ERT commencing 3 months prior to HSCT. Two patients received 0.75mg/kg and 2 patients received 1.5mg/kg of PPS. PPS was well tolerated at doses of 0.75 and 1.5 mg/kg to 47 weeks of continuous dosing. Of the 19 adverse events (AEs), 2 were related to PPS. One AE was moderate (pre-syncope) and 1 was mild (injection site bruising), experienced in the same patient. All AEs were reported as mild or moderate. There have been no SAEs. One subject experienced a COVID-19 infection and PPS was interrupted. The MPS I signature GAG fragments, sulfated disaccharide and UA-HNAc S, tended to decrease in 3 patients from baseline through Week 25. Week 25 GAG data are pending for the 4th patient. Overall, most biomarkers (inflammatory, cartilage degeneration, and bone turnover) evaluated in the 3 patients with 25-week assessments have indicated either no change or a reduction in levels compared to baseline. In 3 patients, there was a trend toward improvement in the 2MWT from baseline to Week 48 with > 100% increase in 1 patient (01-201). In the 3 patients that had Week 48 assessments, patients and proxies reported improvement in PGIC, including “worthwhile difference” (n=1), or “made all the difference” (n=2).

Keywords: MPS I, pentosan polysulfate sodium, clinical study, 2MWT, QoL

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Authors: Paresh Patel, Priya Patel, Vaidehi Sorathiya, Navin Sheth

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The aim of present work was to fabricate Salmeterol Xinafoate (SX) metered dose inhaler (MDI) for asthma and to evaluate the SX loaded solid lipid nanoparticles (SLNs) for pulmonary delivery. Solid lipid nanoparticles can be used to deliver particles to the lungs via MDI. A modified solvent emulsification diffusion technique was used to prepare Salmeterol Xinafoate loaded solid lipid nanoparticles by using compritol 888 ATO as lipid, tween 80 as surfactant, D-mannitol as cryoprotecting agent and L-leucine was used to improve aerosolization behaviour. Box-Behnken design was applied with 17 runs. 3-D surface response plots and contour plots were drawn and optimized formulation was selected based on minimum particle size and maximum % EE. % yield, in vitro diffusion study, scanning electron microscopy, X-ray diffraction, DSC, FTIR also characterized. Particle size, zeta potential analyzed by Zetatrac particle size analyzer and aerodynamic properties was carried out by cascade impactor. Pre convulsion time was examined for control group, treatment group and compare with marketed group. MDI was evaluated for leakage test, flammability test, spray test and content per puff. By experimental design, particle size and % EE found to be in range between 119-337 nm and 62.04-76.77% by solvent emulsification diffusion technique. Morphologically, particles have spherical shape and uniform distribution. DSC & FTIR study showed that no interaction between drug and excipients. Zeta potential shows good stability of SLNs. % respirable fraction found to be 52.78% indicating reach to the deep part of lung such as alveoli. Animal study showed that fabricated MDI protect the lungs against histamine induced bronchospasm in guinea pigs. MDI showed sphericity of particle in spray pattern, 96.34% content per puff and non-flammable. SLNs prepared by Solvent emulsification diffusion technique provide desirable size for deposition into the alveoli. This delivery platform opens up a wide range of treatment application of pulmonary disease like asthma via solid lipid nanoparticles.

Keywords: salmeterol xinafoate, solid lipid nanoparticles, box-behnken design, solvent emulsification diffusion technique, pulmonary delivery

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Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

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Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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Authors: Hani M. Alothaid, Louise Robson, Richmond Muimo

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Cystic fibrosis (CF) is a disease that affects respiratory function and in EU it affects about 1 in 2,500 live births with an average 40-year life expectancy. This disease caused by mutations within the gene encoding the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel leading to dysregulation of epithelial fluid transport and chronic lung inflammation, suggesting functional alterations of immune cells. In airways, CFTR been found to form a functional complex with S100A10 and AnxA2 in a cAMP/PKA dependent manner. The multiprotein complex of AnxA2-S100A10 and CFTR is also regulated by calcineurin. The aim of this study was i) to investigate whether chloride ion (Cl−) channels are activated by Pseudomonas aeruginosa lipopolysaccharide (LPS from PA), ii) if this activation is regulated by cAMP/PKA/calcineurin pathway and iii) to investigate the role of LPS-activated Cl− channels in the release of pro-inflammatory cytokines by immune cells. Human peripheral blood monocytes were used in the study. Whole-cell patch records showed that LPS from PA can activate Cl− channels, including CFTR and outwardly-rectifying Cl− channel (ORCC). This activation appears to require an intact PKA/calcineurin signalling pathway. The Gout in the presence of LPS was significantly inhibited by diisothiocyanatostilbene-disulfonic acid (DIDS), an ORCC blocker (p<0.001). The Gout was further suppressed by CFTR(inh)-172, a specific inhibitor for CFTR channels (p<0.001). Monocytes pre-incubated with PKA inhibitor or calcineurin inhibitor before stimulated with LPS from PA that were resulted in DIDS and CFTR(inh)-172 insensitive currents. Activation of both ORCC and CFTR was however, observed in response to monocytes exposure to LPS. Additionally, ELISA showed that the CFTR and ORCC play a role in mediating the release of pro-inflammatory cytokines such as IL-1β upon exposure of monocytes to LPS. However, this secretion was significantly inhibited due to CFTR and ORCC inhibition. However, Cl− may play a role in IL-1β release independent of cAMP/PKA/calcineurin signalling due to the enhancement of IL-1β secretion even when cAMP/PKA/calcineurin pathway was inhibited. In conclusion, our data confirmed that LPS from PA activates Cl− channels in human peripheral blood monocytes. Our data also confirmed that Cl− channels were involved in IL-1β release in monocytes upon exposure to LPS. However, it has been found that PKA and calcineurin does not seem to influence the Cl− dependent cytokine release.

Keywords: cystic fibrosis, CFTR, Annexin A2, S100A10, PP2B, PKA, outwardly-rectifying Cl− channel, Pseudomonas aeruginosa

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Authors: B. B. S. Pereira, M. O. Souza, L. P. Zanetti, L. C. S. Oliveira, J. R. P. Moreno, M. P. Souza, V. R. Colturato, C. M. Machado

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Background: The introduction of prophylactic or preemptive therapies has effectively decreased the CMV mortality rates after hematopoietic stem cell transplantation (HSCT). CMV antigenemia (pp65) or quantitative PCR are methods currently approved for CMV surveillance in pre-emptive strategies. Commercial assays are preferred as cut-off levels defined by in-house assays may vary among different protocols and in general show low reproducibility. Moreover, comparison of published data among different centers is only possible if international standards of quantification are included in the assays. Recently, the World Health Organization (WHO) established the first international standard for CMV detection. The real time PCR COBAS Ampliprep/ CobasTaqMan (CAP/CTM) (Roche®) was developed using the WHO standard for CMV quantification. However, the cut-off for the introduction of antiviral has not been determined yet. Methods: We conducted a retrospective study to determine: 1) the sensitivity and specificity of the new CMV CAP/CTM test in comparison with pp65 antigenemia to detect episodes of CMV infection/reactivation, and 2) the cut-off of viral load for introduction of ganciclovir (GCV). Pp65 antigenemia was performed and the corresponding plasma samples were stored at -20°C for further CMV detection by CAP/CTM. Comparison of tests was performed by kappa index. The appearance of positive antigenemia was considered the state variable to determine the cut-off of CMV viral load by ROC curve. Statistical analysis was performed using SPSS software version 19 (SPSS, Chicago, IL, USA.). Results: Thirty-eight patients were included and followed from August 2014 through May 2015. The antigenemia test detected 53 episodes of CMV infection in 34 patients (89.5%), while CAP/CTM detected 37 episodes in 33 patients (86.8%). AG and PCR results were compared in 431 samples and Kappa index was 30.9%. The median time for first AG detection was 42 (28-140) days, while CAP/CTM detected at a median of 7 days earlier (34 days, ranging from 7 to 110 days). The optimum cut-off value of CMV DNA was 34.25 IU/mL to detect positive antigenemia with 88.2% of sensibility, 100% of specificity and AUC of 0.91. This cut-off value is below the limit of detection and quantification of the equipment which is 56 IU/mL. According to CMV recurrence definition, 16 episodes of CMV recurrence were detected by antigenemia (47.1%) and 4 (12.1%) by CAP/CTM. The duration of viremia as detected by antigenemia was shorter (60.5% of the episodes lasted ≤ 7 days) in comparison to CAP/CTM (57.9% of the episodes lasting 15 days or more). This data suggests that the use of antigenemia to define the duration of GCV therapy might prompt early interruption of antiviral, which may favor CMV reactivation. The CAP/CTM PCR could possibly provide a safer information concerning the duration of GCV therapy. As prolonged treatment may increase the risk of toxicity, this hypothesis should be confirmed in prospective trials. Conclusions: Even though CAP/CTM by ROCHE showed great qualitative correlation with the antigenemia technique, the fully automated CAP/CTM did not demonstrate increased sensitivity. The cut-off value below the limit of detection and quantification may result in delayed introduction of pre-emptive therapy.

Keywords: antigenemia, CMV COBAS/TAQMAN, cytomegalovirus, antiviral cut-off

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Authors: Federico Herrera, Valle Gomez García de Soria, Itxaso Portero Sainz, Carlos Fernández Arandojo, Mercedes Royg, Ana Marcos Jimenez, Anna Kreutzman, Cecilia MuñozCalleja

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Introduction: Graft-versus-host disease (GVHD) still remains the major complication associated with allogeneic stem cell transplantation (SCT). The pathogenesis involves migration of donor naïve T-cells into recipient secondary lymphoid organs. Two molecules are important in this process: CD62L and CCR7, which are characteristically expressed in naïve/central memory T-cells. With this background, we aimed to study the influence of CCR7 and CD62L on donor lymphocytes in the development and severity of GVHD. Material and methods: This single center study included 98 donor-recipient pairs. Samples were collected prospectively from the apheresis product and phenotyped by flow cytometry. CCR7 and CD62L expression in CD4+ and CD8+ T-cells were compared between patients who developed acute (n=40) or chronic GVHD (n=33) and those who did not (n=38). Results: The patients who developed acute GVHD were transplanted with a higher percentage of CCR7+CD4+ T-cells (p = 0.05) compared to the no GVHD group. These results were confirmed when these patients were divided in degrees according to the severity of the disease; the more severe disease, the higher percentage of CCR7+CD4+ T-cells. Conversely, chronic GVHD patients received a higher percentage of CCR7+CD8+ T-cells (p=0.02) in comparison to those who did not develop the complication. These data were also confirmed when patients were subdivided in degrees of the disease severity. A multivariable analysis confirmed that percentage of CCR7+CD4+ T-cells is a predictive factor of acute GVHD whereas the percentage of CCR7+CD8+ T-cells is a predictive factor of chronic GVHD. In vitro functional assays (migration and activation assays) supported the idea of CCR7+ T-cells were involved in the development of GVHD. As low levels of CD62L expression were detected in all apheresis products, we tested the hypothesis that CD62L was shed during apheresis procedure. Comparing CD62L surface levels in T-cells from the same donor immediately before collecting the apheresis product, and the final apheresis product we found that this process down-regulated CD62L in both CD4+ and CD8+ T cells (p=0.008). Interestingly, when CD62L levels were analysed in days 30 or 60 after engraftment, they recovered to baseline (p=0.008). However, to investigate the relation between CD62L expression and the development of GVHD in the recipient samples after the engraftment, no differences were observed comparing patients with GVHD to those who did not develop the disease. Discussion: Our prospective study indicates that the CCR7+ T-cells from the donor, which include naïve and central memory T-cells, contain the alloreactive cells with a high ability to mediate GVHD (in the case of both migration and activation). Therefore we suggest that the proportion and functional properties of CCR7+CD4+ and CCR7+CD8+ T-cells in the apheresis could act as a predictive biomarker to both acute and chronic GVHD respectively. Importantly, our study precludes that CD62L is lost in the apheresis and therefore it is not a reliable biomarker for the development of GVHD.

Keywords: CCR7, CD62L, GVHD, SCT

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Authors: Alexander Heckman, Rohan Goswami, Zachi Attia, Paul Friedman, Peter Noseworthy, Demilade Adedinsewo, Pablo Moreno-Franco, Rickey Carter, Tathagat Narula

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Background: Postoperative atrial fibrillation (POAF) is associated with adverse health consequences, higher costs, and longer hospital stays. Utilizing existing predictive models that rely on clinical variables and circulating biomarkers, multiple societies have published recommendations on the treatment and prevention of POAF. Although reasonably practical, there is room for improvement and automation to help individualize treatment strategies and reduce associated complications. Methods and Results: In this retrospective cohort study of solid organ transplant recipients, we evaluated the diagnostic utility of a previously developed AI-based ECG prediction for silent AF on the development of POAF within 30 days of transplant. A total of 2261 non-cardiac transplant patients without a preexisting diagnosis of AF were found to have a 5.8% (133/2261) incidence of POAF. While there were no apparent sex differences in POAF incidence (5.8% males vs. 6.0% females, p=.80), there were differences by race and ethnicity (p<0.001 and 0.035, respectively). The incidence in white transplanted patients was 7.2% (117/1628), whereas the incidence in black patients was 1.4% (6/430). Lung transplant recipients had the highest incidence of postoperative AF (17.4%, 37/213), followed by liver (5.6%, 56/1002) and kidney (3.6%, 32/895) recipients. The AUROC in the sample was 0.62 (95% CI: 0.58-0.67). The relatively low discrimination may result from undiagnosed AF in the sample. In particular, 1,177 patients had at least 1 AI-ECG screen for AF pre-transplant above .10, a value slightly higher than the published threshold of 0.08. The incidence of POAF in the 1104 patients without an elevated prediction pre-transplant was lower (3.7% vs. 8.0%; p<0.001). While this supported the hypothesis that potentially undiagnosed AF may have contributed to the diagnosis of POAF, the utility of the existing AI-ECG screening algorithm remained modest. When the prediction for POAF was made using the first postoperative ECG in the sample without an elevated screen pre-transplant (n=1084 on account of n=20 missing postoperative ECG), the AUROC was 0.66 (95% CI: 0.57-0.75). While this discrimination is relatively low, at a threshold of 0.08, the AI-ECG algorithm had a 98% (95% CI: 97 – 99%) negative predictive value at a sensitivity of 66% (95% CI: 49-80%). Conclusions: This study's principal finding is that the incidence of POAF is rare, and a considerable fraction of the POAF cases may be latent and undiagnosed. The high negative predictive value of AI-ECG screening suggests utility for prioritizing monitoring and evaluation on transplant patients with a positive AI-ECG screening. Further development and refinement of a post-transplant-specific algorithm may be warranted further to enhance the diagnostic yield of the ECG-based screening.

Keywords: artificial intelligence, atrial fibrillation, cardiology, transplant, medicine, ECG, machine learning

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Authors: Yulistiani Yulistiani, Wenny Nilamsari, Laurin Winarso, Rizkiya Rizkiya, Zamrotul Izzah, Budi Suprapti, Arif Bachtiar

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Approximately, a million new cases of TB have been found out per year, making Indonesia as the second greatest country with TBC after India. Nevertheless, until now, there are still many patients failure to conventional therapy with oral anti tuberculosis. Thus, the discovery of supplement therapy is urgently needed. Many studies showed that probiotic had the positive impact in lung diseases, diarrhea, pneumonia and it was attributed to its capability to balance the level of cytokine pro-inflammatory and anti-inflammatory. It was demonstrated in active disease the production of IFN-γ is strongly depressed and IL-10 level increases. This study aimed to investigate the effect of probiotic (multi strains) and vitamin B complex supplementation on IFN-γ and IL-10 level in patients with TB infection during intensive phase therapy. A randomized controlled trial, open labeled was conducted in TB patients with the following criteria: 1) age 18-55 years old 2) receiving oral antituberculosis during intensive therapy 3) not using probiotic, vitamin B1, B6, B12 2 weeks before enrollment 4) willing to participate in this study and signed an informed consent. While, patients with HIV, pregnant, had the history of diabetes mellitus, using corticosteroid or other immunosuppressants were excluded. IFN-γ and IL-10 levels were drawn before observation and after a month observation. The assay was performed by ELISA. There were seven patients in treated group and five patients in controlled group obtained in this study. Between groups, there was no statistical difference in comorbid, age, and disease duration. The mean level of IFN-γ after a month observation increased in treated group and controlled group, which were 31.47 ± 105.46 pg/ml and 15.09 ± 24.23 pg/ml, respectively (p> 0.005). Although, there were not statistically different, treated group showed a greater increase of IFN-γ level than that of the controlled group. IFN-γ plays an important role in immune response to Mycobacterium Tuberculosis, by activating macrofag, monosit and furthermore killing Mycobacterium Tuberculosis. Thus the level was expected to increase after supplementation with probiotic and Vitamin B complex. While the mean level of IL-10 also increased after one month observation in the treated group and controlled group (4.28 ± 12.29 pg/ml and 5.77± 6.21 pg/ml, respectively) (p>0.005). To be compared, the increased level of IL-10 in the treated group were lower than the controlled group, although it was not statistically different. IL-10 is a cytokine anti-inflammatory, thus, the level after the observation was expected to decrease. In this study, a month therapy of probiotic and vitamin B complex was not able to demonstrate the decrease of the IL-10 level. It is suggested to prolong observation up to 2 months, because, in intensive phase, the level of cytokine anti-inflammatory is very high, so the longer therapy is needed. It is indicated that supplementation therapy with probiotic and vitamin B complex to Oral Anti-Tuberculosis may have a positive effect on increasing IFN-γ level and slowing the progression of IL-10.

Keywords: TB Infection, IFN-γ, IL-10, probiotic, vitamin B complex

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Authors: Kyung Jin Kim, Jiwon Kwak, Jae-Hoon Lee, Soo Suk Lee

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MicroRNAs (miRNA) are a class of endogenous, single-stranded, small, and non-protein coding RNA molecules typically 20-25 nucleotides long. They are thought to regulate the expression of other genes in a broad range by binding to 3’- untranslated regions (3’-UTRs) of specific mRNAs. The detection of miRNAs is very important for understanding of the function of these molecules and in the diagnosis of variety of human diseases. However, detection of miRNAs is very challenging because of their short length and high sequence similarities within miRNA families. So, a simple-to-use, low-cost, and highly sensitive method for the detection of miRNAs is desirable. In this study, we demonstrate a novel bi-directional extension (BDE) assay. In the first step, a specific linear RT primer is hybridized to 6-10 base pairs from the 3’-end of a target miRNA molecule and then reverse transcribed to generate a cDNA strand. After reverse transcription, the cDNA was hybridized to the 3’-end which is BDE sequence; it played role as the PCR template. The PCR template was amplified in an SYBR green-based quantitative real-time PCR. To prove the concept, we used human brain total RNA. It could be detected quantitatively in the range of seven orders of magnitude with excellent linearity and reproducibility. To evaluate the performance of BDE assay, we contrasted sensitivity and specificity of the BDE assay against a commercially available poly (A) tailing method using miRNAs for let-7e extracted from A549 human epithelial lung cancer cells. The BDE assay displayed good performance compared with a poly (A) tailing method in terms of specificity and sensitivity; the CT values differed by 2.5 and the melting curve showed a sharper than poly (A) tailing methods. We have demonstrated an innovative, cost-effective BDE assay that allows improved sensitivity and specificity in detection of miRNAs. Dynamic range of the SYBR green-based RT-qPCR for miR-145 could be represented quantitatively over a range of 7 orders of magnitude from 0.1 pg to 1.0 μg of human brain total RNA. Finally, the BDE assay for detection of miRNA species such as let-7e shows good performance compared with a poly (A) tailing method in terms of specificity and sensitivity. Thus BDE proves a simple, low cost, and highly sensitive assay for various miRNAs and should provide significant contributions in research on miRNA biology and application of disease diagnostics with miRNAs as targets.

Keywords: bi-directional extension (BDE), microRNA (miRNA), poly (A) tailing assay, reverse transcription, RT-qPCR

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Authors: Olatokunbo Yakeem

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Human trafficking is a crime against gross violations of human rights. Trafficking in persons is a severe socio-economic dilemma that affects the national and international dimensions. Human trafficking or modern-day-slavery emanated from slavery, and it has been in existence before the 6ᵗʰ century. Today, no country is exempted from dehumanizing human beings, and as a result, it has been an international issue. The United Nations (UN) presented the International Protocol to fight human trafficking worldwide, which brought about the international definition of human trafficking. The protocol is to prevent, suppress, and punish trafficking in persons, especially women and children. The trafficking protocol has a link with transnational organised crime rather than migration. Over a hundred and fifty countries nationwide have enacted their criminal and panel code trafficking legislation from the UN trafficking protocol. Sex trafficking is the most common type of exploitation of women and children. Other forms of this crime involve exploiting vulnerable victims through forced labour, child involvement in warfare, domestic servitude, debt bondage, and organ removal for transplantation. Trafficking of women and children into sexual exploitation represents the highest form of human trafficking than other types of exploitation. Trafficking of women and children can either happen internally or across the border. It affects all kinds of people, regardless of their race, social class, culture, religion, and education levels. However, it is more of a gender-based issue against females. Furthermore, human trafficking can lead to life-threatening infections, mental disorders, lifetime trauma, and even the victim's death. The study's significance is to explore why the root causes of women and children trafficking in Nigeria are based around poverty, entrusting children in the hands of relatives and friends, corruption, globalization, weak legislation, and ignorance. The importance of this study is to establish how the national, regional, and international organisations are using the 3P’s Protection, Prevention, and Prosecution) to tackle human trafficking. The methodology approach for this study will be a qualitative paradigm. The rationale behind this selection is that the qualitative method will identify the phenomenon and interpret the findings comprehensively. The data collection will take the form of semi-structured in-depth interviews through telephone and email. The researcher will use a descriptive thematic analysis to analyse the data by using complete coding. In summary, this study aims to recommend to the Nigerian federal government to include human trafficking as a subject in their educational curriculum for early intervention to prevent children from been coerced by criminal gangs. And the research aims to find the root causes of women and children trafficking. Also, to look into the effectiveness of the strategies in place to eradicate human trafficking globally. In the same vein, the research objective is to investigate how the anti-trafficking bodies such as law enforcement and NGOs collaborate to tackle the upsurge in human trafficking.

Keywords: children, Nigeria, trafficking, women

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Authors: Jayshree P. Zend, Ashatai B. Pawar

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The study was carried out in Parbhani district of Maharashtra state, India with the objectives to study environmental problems faced by flour mill workers, prevalence of work-related health hazards and the physiological cost of workers while performing work in flour mill in traditional method as well as improved method. The use of flour presser, dust controlling bag and noise and dust controlling mask developed by AICRP College of Home Science, VNMKV, Parbhani was considered as an improved method. This investigation consisted survey and experiment which was conducted in the respective locations of flour mills. Healthy, non-smoking 30 flour mill workers ranged between the age group of 20-50 yrs comprising 16 female and 14 male working at flour mill for 4-8 hrs/ day and 6 days/ week and had minimum five years experience of work in flour mill were selected for the study. Pulmonary function test of flour mill workers was carried out by trained technician at Dr. ShankarraoChavan Government Medical College, Nanded by using Electronic Spirometer. The data regarding heart rate (resting, working and recovery), energy expenditure, musculoskeletal problems and occupational health hazards and accidents were recorded by using pretested questionnaire. Scientific equipment used in the experiment were polar sport test heart rate monitor, Hygrometer, Goniometer, Dialed Thermometer, Sound Level Meter, Lux Meter, Ambient Air Sampler and Air Quality Monitor. The collected data were subjected to appropriate statistical analysis such as 't' test and correlation coefficient test. Results indicated that improved method i.e. use of noise and dust controlling mask, flour presser and dust controlling bag were effective in reducing physiological cost of work of flour mill workers. Lung function test of flour mill workers showed decreased values of all parameters, hence the results of present study support paying attention to use of personal protective noise and dust controlling mask by flour mill workers and also to the working conditions in flour mill especially ventilation and illumination level needs to be enhanced in flour mill. The study also emphasizes the need to develop some mechanism for lifting load of grains and unloading in the hopper. It is also suggested that the flour mill workers should use flour presser suitable to their height to avoid frequent bending and should use dust controlling bag to flour outlet of machine to reduce inhalable flour dust level in the flour mill.

Keywords: physiological cost, energy expenditure, musculoskeletal problems

Procedia PDF Downloads 377

Authors: Suang K. Lau, Ismail Goolam, Rafid Al-Asady

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Background: The majority of patients with hepatocellular carcinoma (HCC) are not suitable for curative treatment, in the form of surgical resection or transplantation, due to tumour extent and underlying liver dysfunction. In these non-resectable cases, a variety of non-surgical therapies are available, including microwave ablation (MWA), which has shown increasing popularity due to its low morbidity, low reported complication rate, and the ability to perform multiple ablations simultaneously. Objective: The aim of this study was to evaluate the validity of MWA as a viable treatment option in the management of HCC and hepatic metastatic disease, by assessing its efficacy and complication rate at a tertiary hospital situated in Westmead (Australia). Methods: A retrospective observational study was performed evaluating patients that underwent MWA between 1/1/2017–31/12/2018 at Westmead Hospital, NSW, Australia. Outcome measures, including residual disease, recurrence rates, as well as major and minor complication rates, were retrospectively analysed over a 12-months period following MWA treatment. Excluded patients included those whose lesions were treated on the basis of residual or recurrent disease from previous treatment, which occurred prior to the study window (11 patients) and those who were lost to follow up (2 patients). Results: Following treatment of 106 new hepatic lesions, the complete response rate (CR) was 86% (91/106) at 12 months follow up. 10 patients had the residual disease at post-treatment follow up imaging, corresponding to an incomplete response (ICR) rate of 9.4% (10/106). The local recurrence rate (LRR) was 4.6% (5/106) with follow-up period up to 12 months. The minor complication rate was 9.4% (10/106) including asymptomatic pneumothorax (n=2), asymptomatic pleural effusions (n=2), right lower lobe pneumonia (n=3), pain requiring admission (n=1), hypotension (n=1), cellulitis (n=1) and intraparenchymal hematoma (n=1). There was 1 major complication reported, with pleuro-peritoneal fistula causing recurrent large pleural effusion necessitating repeated thoracocentesis (n=1). There was no statistically significant association between tumour size, location or ablation factors, and risk of recurrence or residual disease. A subset analysis identified 6 segment VIII lesions, which were treated via a trans-pleural approach. This cohort demonstrated an overall complication rate of 33% (2/6), including 1 minor complication of asymptomatic pneumothorax and 1 major complication of pleuro-peritoneal fistula. Conclusions: Microwave ablation therapy is an effective and safe treatment option in cases of non-resectable hepatocellular carcinoma and liver metastases, with good local tumour control and low complication rates. A trans-pleural approach for high segment VIII lesions is associated with a higher complication rate and warrants greater caution.

Keywords: hepatocellular carcinoma, liver metastases, microwave ablation, trans-pleural approach

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Authors: Chrislaura Carmo, Luca Deiana, Mafalda Laranjo, Abilio Sobral, Armando Cordova

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Photodynamic therapy (PDT) is currently used for the treatment of malignancies and premalignant tumors. It is based on the capture of a photosensitizing molecule (PS) which, when excited by light at a certain wavelength, reacts with oxygen and generates oxidizing species (radicals, singlet oxygen, triplet species) in target tissues, leading to cell death. BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indaceno) derivatives are emerging as important candidates for photosensitizer in photodynamic therapy of cancer cells due to their high triplet quantum yield. Today these dyes are relevant molecules in photovoltaic materials and fluorescent sensors. In this study, it will be demonstrated the possibility that BODIPY can be covalently linked to thioglycolic acid through the click reaction. Thiol−ene click chemistry has become a powerful synthesis method in materials science and surface modification. The design of biobased allyl-terminated precursors with high renewable carbon content for the construction of the thiol-ene polymer networks is essential for sustainable development and green chemistry. The work aims to synthesize the BODIPY (10-(4-(allyloxy) phenyl)-2,8-diethyl-5,5-difluoro-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f] [1,3,2] diazaborinin-4-ium-5-uide) and to click reaction with Thioglycolic acid. BODIPY was synthesized by the condensation reaction between aldehyde and pyrrole in dichloromethane, followed by in situ complexation with BF3·OEt2 in the presence of the base. Then it was functionalized with allyl bromide to achieve the double bond and thus be able to carry out the click reaction. The thiol−ene click was performed using DMPA (2,2-Dimethoxy-2-phenylacetophenone) as a photo-initiator in the presence of UV light (320–500 nm) in DMF at room temperature for 24 hours. Compounds were characterized by standard analytical techniques, including UV-Vis Spectroscopy, 1H, 13C, 19F NMR and mass spectroscopy. The results of this study will be important to link BODIPY to polymers through the thiol group offering a diversity of applications and functionalization. This new molecule can be tested as third-generation photosensitizers, in which the dye is targeted by antibodies or nanocarriers by cells, mainly in cancer cells, PDT and Photodynamic Antimicrobial Chemotherapy (PACT). According to our studies, it was possible to visualize a click reaction between allyl BODIPY and thioglycolic acid. Our team will also test the reaction with other thiol groups for comparison. Further, we will do the click reaction of BODIPY with a natural polymer linked with a thiol group. The results of the above compounds will be tested in PDT assays on various lung cancer cell lines.

Keywords: bodipy, click reaction, thioglycolic acid, allyl, thiol-ene click

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Authors: Pakize Ozlem Kurt Polat

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GMO (genetically modified organism) is the result of a laboratory process where genes from the DNA of one species are extracted and artificially forced into the genes of an unrelated plant or animal. This technology includes; nucleic acid hybridization, recombinant DNA, RNA, PCR, cell culture and gene cloning techniques. The studies are divided into three groups of properties transferred to the transgenic plant. Up to 59% herbicide resistance characteristic of the transfer, 28% resistance to insects and the virus seems to be related to quality characteristics of 13%. Transgenic crops are not included in the commercial production of each product; mostly commercial plant is soybean, maize, canola, and cotton. Day by day increasing GMO interest can be listed as follows; Use in the health area (Organ transplantation, gene therapy, vaccines and drug), Use in the industrial area (vitamins, monoclonal antibodies, vaccines, anti-cancer compounds, anti -oxidants, plastics, fibers, polyethers, human blood proteins, and are used to produce carotenoids, emulsifiers, sweeteners, enzymes , food preservatives structure is used as a flavor enhancer or color changer),Use in agriculture (Herbicide resistance, Resistance to insects, Viruses, bacteria, fungi resistance to disease, Extend shelf life, Improving quality, Drought , salinity, resistance to extreme conditions such as frost, Improve the nutritional value and quality), we explain all this methods step by step in this research. GMO has advantages and disadvantages, which we explain all of them clearly in full text, because of this topic, worldwide researchers have divided into two. Some researchers thought that the GMO has lots of disadvantages and not to be in use, some of the researchers has opposite thought. If we look the countries law about GMO, we should know Biosafety law for each country and union. For this Biosecurity reasons, the problems caused by the transgenic plants, including Turkey, to minimize 130 countries on 24 May 2000, ‘the United Nations Biosafety Protocol’ signed nudes. This protocol has been prepared in addition to Cartagena Biosafety Protocol entered into force on September 11, 2003. This protocol GMOs in general use by addressing the risks to human health, biodiversity and sustainable transboundary movement of all GMOs that may affect the prevention, transit covers were dealt and used. Under this protocol we have to know the, ‘US Regulations GMO’, ‘European Union Regulations GMO’, ‘Turkey Regulations GMO’. These three different protocols have different applications and rules. World population increasing day by day and agricultural fields getting smaller for this reason feeding human and animal we should improve agricultural product yield and quality. Scientists trying to solve this problem and one solution way is molecular biotechnology which is including the methods of GMO too. Before decide to support or against the GMO, should know the GMO protocols and it effects.

Keywords: biotechnology, GMO (genetically modified organism), molecular marker

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Authors: Naima Jannat, Ariful Islam, Sharafat Hossain

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Due to the involvement of the large target volume, Craniospinal Irradiation makes it challenging to achieve a uniform dose, and it requires different isocenters. This isocentric junction needs to shift after every five fractions to overcome the possibility of hot and cold spots. This study aims to evaluate the Planning Target Volume coverage & sparing Organ at Risk between two techniques and shows that the Field Alignment Technique does not need replanning and resetting. Planning method for Craniospinal Irradiation by Eclipse treatment planning system Field Alignment and Extended Source to Surface Distance technique was developed where 36 Gy in 20 Fraction at the rate of 1.8 Gy was prescribed. The patient was immobilized in the prone position. In the Field Alignment technique, the plan consists of half beam blocked parallel opposed cranium and a single posterior cervicospine field was developed by sharing the same isocenter, which obviates divergence matching. Further, a single field was created to treat the remaining lumbosacral spine. Matching between the inferior diverging edge of the cervicospine field and the superior diverging edge of a lumbosacral field, the field alignment option was used, which automatically matches the field edge divergence as per the field alignment rule in Eclipse Treatment Planning System where the couch was set to 2700. In the Extended Source to Surface Distance technique, two parallel opposed fields were created for the cranium, and a single posterior cervicospine field was created where the Source to Surface Distance was from 120-140 cm. Dose Volume Histograms were obtained for each organ contoured and for each technique used. In all, the patient’s maximum dose to Planning Target Volume is higher for the Extended Source to Surface Distance technique to Field Alignment technique. The dose to all surrounding structures was increased with the use of a single Extended Source to Surface Distance when compared to the Field Alignment technique. The average mean dose to Eye, Brain Steam, Kidney, Oesophagus, Heart, Liver, Lung, and Ovaries were respectively (58% & 60 %), (103% & 98%), (13% & 15%), (10% & 63%), (12% & 16%), (33% & 30%), (14% & 18%), (69% & 61%) for Field Alignment and Extended Source to Surface Distance technique. However, the clinical target volume at the spine junction site received a less homogeneous dose with the Field Alignment technique as compared to Extended Source to Surface Distance. We conclude that, although the use of a single field Extended Source to Surface Distance delivered a more homogenous, but its maximum dose is higher than the Field Alignment technique. Also, a huge advantage of the Field Alignment technique for Craniospinal Irradiation is that it doesn’t need replanning and resetting up of patients after every five fractions and 95% prescribed dose was received by more than 95% of the Planning Target Volume in all the plane with the acceptable hot spot.

Keywords: craniospinalirradiation, cranium, cervicospine, immobilize, lumbosacral spine

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Authors: Leonard Tiong, Sonit Singh, Kevin Ho Shon, Sarah Lewis

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Investigation into the use of artificial intelligence in radiology continues to develop at a rapid rate. During the coronavirus pandemic, the combination of an exponential increase in chest x-rays and unpredictable staff shortages resulted in a huge strain on the department's workload. There is a World Health Organisation estimate that two-thirds of the global population does not have access to diagnostic radiology. Therefore, there could be demand for a program that could detect acute changes in imaging compatible with infection to assist with screening. We generated a conventional neural network and tested its efficacy in recognizing changes compatible with coronavirus infection. Following ethics approval, a deidentified set of 77 normal and 77 abnormal chest x-rays in patients with confirmed coronavirus infection were used to generate an algorithm that could train, validate and then test itself. DICOM and PNG image formats were selected due to their lossless file format. The model was trained with 100 images (50 positive, 50 negative), validated against 28 samples (14 positive, 14 negative), and tested against 26 samples (13 positive, 13 negative). The initial training of the model involved training a conventional neural network in what constituted a normal study and changes on the x-rays compatible with coronavirus infection. The weightings were then modified, and the model was executed again. The training samples were in batch sizes of 8 and underwent 25 epochs of training. The results trended towards an 85.71% true positive/true negative detection rate and an area under the curve trending towards 0.95, indicating approximately 95% accuracy in detecting changes on chest X-rays compatible with coronavirus infection. Study limitations include access to only a small dataset and no specificity in the diagnosis. Following a discussion with our programmer, there are areas where modifications in the weighting of the algorithm can be made in order to improve the detection rates. Given the high detection rate of the program, and the potential ease of implementation, this would be effective in assisting staff that is not trained in radiology in detecting otherwise subtle changes that might not be appreciated on imaging. Limitations include the lack of a differential diagnosis and application of the appropriate clinical history, although this may be less of a problem in day-to-day clinical practice. It is nonetheless our belief that implementing this program and widening its scope to detecting multiple pathologies such as lung masses will greatly assist both the radiology department and our colleagues in increasing workflow and detection rate.

Keywords: artificial intelligence, COVID, neural network, machine learning

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Authors: Ying-Chang Yu, Yuan-Lung Lo

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Building envelope design is one of the most popular design fields of architectural profession in nowadays. The main design trend of such system is to highlight the designer's aesthetic intention from the outlook of building project. Due to the trend of current façade design, the building envelope contains more and more layers of components, such as double skin façade, photovoltaic panels, solar control system, or even ornamental components. These exterior components are designed for various functional purposes. Most researchers focus on how these exterior elements should be structurally sound secured. However, not many researchers consider these elements would help to improve the performance of façade system. When the exterior elements are deployed in large scale, it creates an additional layer outside of original façade system and acts like a porous interface which would interfere with the aerodynamic of façade surface in micro-scale. A standard façade performance consists with 'water penetration, air infiltration rate, operation force, and component deflection ratio', and these key performances are majorly driven by the 'Design Wind Load' coded in local regulation. A design wind load is usually determined by the maximum wind pressure which occurs on the surface due to the geometry or location of building in extreme conditions. This research was designed to identify the air damping phenomenon of micro turbulence caused by porous exterior layer leading to surface wind load reduction for improvement of façade system performance. A series of wind tunnel test on dynamic pressure sensor array covered by various scale of porous exterior skin was conducted to verify the effect of wind pressure reduction. The testing specimens were designed to simulate the typical building with two-meter extension offsetting from building surface. Multiple porous exterior skins were prepared to replicate various opening ratio of surface which may cause different level of damping effect. This research adopted 'Pitot static tube', 'Thermal anemometers', and 'Hot film probe' to collect the data of surface dynamic pressure behind porous skin. Turbulence and distributed resistance are the two main factors of aerodynamic which would reduce the actual wind pressure. From initiative observation, the reading of surface wind pressure was effectively reduced behind porous media. In such case, an actual building envelope system may be benefited by porous skin from the reduction of surface wind pressure, which may improve the performance of envelope system consequently.

Keywords: multi-layer facade, porous media, facade performance, turbulence and distributed resistance, wind tunnel test

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Authors: Bistra Kunovska, Kremena Ivanova, Jana Djounova, Desislava Djunakova, Zdenka Stojanovska

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The carcinogenic effects of radon as a radioactive noble gas have been studied and show a strong correlation between radon exposure and lung cancer occurrence, even in the case of low radon levels. The major part of the natural radiation dose in humans is received by inhaling radon and its progenies, which originates from the decay chain of U-238. Indoor radon poses a substantial threat to human health when build-up occurs in confined spaces such as homes, mines and caves and the risk increases with the duration of radon exposure and is proportional to both the radon concentration and the time of exposure. Tourist caves are a case of special environmental conditions that may be affected by high radon concentration. Tourist caves are a recognized danger in terms of radon exposure to cave workers (guides, employees working in shops built above the cave entrances, etc.), but due to the sensitive nature of the cave environment, high concentrations cannot be easily removed. Forced ventilation of the air in the caves is considered unthinkable due to the possible harmful effects on the microclimate, flora and fauna. The risks to human health posed by exposure to elevated radon levels in caves are not well documented. Various studies around the world often detail very high concentrations of radon in caves and exposure of employees but without a follow-up assessment of the overall impact on human health. This study was developed in the implementation of a national project to assess the potential health effects caused by exposure to elevated levels of radon in buildings with public access under the National Science Fund of Bulgaria, in the framework of grant No КП-06-Н23/1/07.12.2018. The purpose of the work is to assess the radon level in Bulgarian caves and the exposure of the visitors and workers. The number of caves (sampling size) was calculated for simple random selection from total available caves 65 (sampling population) are 13 caves with confidence level 95 % and confidence interval (margin of error) approximately 25 %. A measurement of the radon concentration in air at specific locations in caves was done by using CR-39 type nuclear track-etch detectors that were placed by the participants in the research team. Despite the fact that all of the caves were formed in karst rocks, the radon levels were rather different from each other (97–7575 Bq/m3). An assessment of the influence of the orientation of the caves in the earth's surface (horizontal, inclined, vertical) on the radon concentration was performed. Evaluation of health hazards and radon risk exposure causing by inhaling the radon and its daughter products in each surveyed caves was done. Reducing the time spent in the cave has been recommended in order to decrease the exposure of workers.

Keywords: tourist caves, radon concentration, exposure, Bulgaria

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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 200

Authors: Cameron Wilson, Megan Hanrahan, Katie Brittain, Riona McArdle, Alison Keogh, Lynn Rochester

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Background: The loss of mobility and functional dependence is a significant marker in the progression of neurodegenerative diseases such as Parkinson’s Disease (PD). Pharmacological, surgical, and therapeutic treatments are available that can help in the management and amelioration of PD symptoms; however, these only prolong more severe symptoms. Accordingly, ensuring people with PD can maintain independence and a healthy wellbeing are essential in establishing an effective treatment option for those afflicted. Existing literature reviews have examined experiences in engaging with PD treatment options and the impact of PD on independence and wellbeing. Although, the literature fails to explore the influence of treatment options on independence and wellbeing and therefore misses what people value in their treatment. This review is the first that synthesises the impact of mobility-related treatments on independence and wellbeing in people with PD and their carers, offering recommendations to clinical practice and provides a conceptual framework (in development) for future research and practice. Objectives: To explore the impact of mobility-related treatment (both pharmacological and non-pharmacological) on the independence and wellbeing of people with PD and their carers. To propose a conceptual framework to patients, carers and clinicians which captures the qualities people with PD value as part of their treatment. Methods: We performed a critical interpretive synthesis of qualitative evidence, searching six databases for reports that explored the impact of mobility-related treatments (both drug and non-pharmacological) on independence and wellbeing in Parkinson’s Disease. The types of treatments included medication (Levodopa and Amantadine), dance classes, Deep-Brain Stimulation, aquatic therapies, physical rehabilitation, balance training and foetal transplantation. Data was extracted, and quality was assessed using an adapted version of the NICE Quality Appraisal Tool Appendix H before being synthesised according to the critical interpretive synthesis framework and meta-ethnography process. Results: From 2301 records, 28 were eligible. Experiences and impact of treatment pathway on independence and wellbeing was similar across all types of treatments and are described by five inter-related themes: (i) desire to maintain independence, (ii) treatment as a social experience during and after, (iii) medication to strengthen emotional health, (iv) recognising physical capacity and (v) emphasising the personal journey of Parkinson’s treatments. Conclusion: There is a complex and inter-related experience and effect of PD treatments common across all types of treatment. The proposed conceptual framework (in development) provides patients, carers, and clinicians recommendations to personalise the delivery of PD treatment, thereby potentially improving adherence and effectiveness. This work is vital to disseminate as PD treatment transitions from subjective and clinically captured assessments to a more personalised process supplemented using wearable technology.

Keywords: parkinson's disease, medication, treatment, dance, review, healthcare, delivery, levodopa, social, emotional, psychological, personalised healthcare

Procedia PDF Downloads 47

Authors: Sree Sanyal

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Research in ageing often highlights the age-related health dimension more than the psycho-social characteristics of the elderly, which also influences and challenges the health outcomes. Multimorbidity is defined as the person having more than one chronic non-communicable diseases and their prevalence increases with ageing. The study aims to evaluate the influence of social ties on self-reported prevalence of multimorbidity (selected chronic non-communicable diseases) among the selected states of elderly population in India. The data is accessed from Building Knowledge Base on Population Ageing in India (BKPAI), collected in 2011 covering the self-reported chronic non-communicable diseases like arthritis, heart disease, diabetes, lung disease with asthma, hypertension, cataract, depression, dementia, Alzheimer’s disease, and cancer. The data of the above diseases were taken together and categorized as: ‘no disease’, ‘one disease’ and ‘multimorbidity’. The predicted variables were demographic, socio-economic, residential types, and the variable of social ties includes social support, social engagement, perceived support, connectedness, and importance of the elderly. Predicted probability for multiple logistic regression was used to determine the background characteristics of the old in association with chronic morbidities showing multimorbidity. The finding suggests that 24.35% of the elderly are suffering from multimorbidity. Research shows that with reference to ‘no disease’, according to the socio-economic characteristics of the old, the female oldest old (80+) from others in caste and religion, widowed, never had any formal education, ever worked in their life, coming from the second wealth quintile standard, from rural Maharashtra are more prone with ‘one disease’. From the social ties background, the elderly who perceives they are important to the family, after getting older their decision-making status has been changed, prefer to stay with son and spouse only, satisfied with the communication from their children are more likely to have less single morbidity and the results are significant. Again, with respect to ‘no disease’, the female oldest old (80+), who are others in caste, Christian in religion, widowed, having less than 5 years of education completed, ever worked, from highest wealth quintile, residing in urban Kerala are more associated with multimorbidity. The elderly population who are more socially connected through family visits, public gatherings, gets support in decision making, who prefers to spend their later years with son and spouse only but stays alone shows lesser prevalence of multimorbidity. In conclusion, received and perceived social integration and support from associated neighborhood in the older days, knowing about their own needs in life facilitates better health and wellbeing of the elderly population in selected states of India.

Keywords: morbidity, multi-morbidity, prevalence, social ties

Procedia PDF Downloads 100

Authors: M. Roberts

Abstract:

We Are Undefeatable - is a mass marketing behaviour change campaign that aims to support the least active people living with long term health conditions to be more active. This is an important issue to address because people with long term conditions are an historically underserved community for the sport and physical activity sector and the least active of those with long term conditions have the most to gain in health and wellbeing benefits. The campaign has generated a significant change in the way physical activity is communicated and people with long term conditions are represented in the media and marketing. The goal is to create a social norm around being active. The campaign is led by a unique partnership of organisations: the Richmond Group of Charities (made up of Age UK, Alzheimer’s Society, Asthma + Lung UK, Breast Cancer Now, British Heart Foundation, British Red Cross, Diabetes UK, Macmillan Cancer Support, Rethink Mental Illness, Royal Voluntary Service, Stroke Association, Versus Arthritis) along with Mind, MS Society, Parkinson’s UK and Sport England, with National Lottery Funding. It is underpinned by the COM-B model of behaviour change. It draws on the lived experience of people with multiple long term conditions to shape the look and feel of the campaign and all the resources available. People with long term conditions are the campaign messengers, central to the ethos of the campaign by telling their individual stories of overcoming barriers to be active with their health conditions. The central messaging is about finding a way to be active that works for the individual. We Are Undefeatable is evaluated through a multi-modal approach, including regular qualitative focus groups and a quantitative evaluation tracker undertaken three times a year. The campaign has highlighted the significant barriers to physical activity for people with long term conditions. This has changed the way our partnership talks about physical activity but has also had an impact on the wider sport and physical activity sector, prompting an increasing departure from traditional messaging and marketing approaches for this audience of people with long term conditions. The campaign has reached millions of people since its launch in 2019, through multiple marketing and partnership channels including primetime TV advertising and promotion through health professionals and in health settings. Its diverse storytellers make it relatable to its target audience and the achievable activities highlighted and inclusive messaging inspire our audience to take action as a result of seeing the campaign. The We Are Undefeatable campaign is a blueprint for physical activity campaigns; it not only addresses individual behaviour change but plays a role in addressing systemic barriers to physical activity by sharing the lived experience insight to shape policy and professional practice.

Keywords: behaviour change, long term conditions, partnership, relatable

Procedia PDF Downloads 43