Search results for: virus mutation

Authors: Mastaneh Safarnejad Shad, Wim Dehaen, Steven De Jonghe

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Since CXCR4 is the main coreceptor of HIV-1 and plays an important role in human immunodeficiency virus (HIV) entry, numerous efforts were directed towards the discovery of new classes of small molecules that act as CXCR4 antagonists. In addition, CXCR4 antagonists are potentially useful in the treatment of several other disorders, such as cancer cell metastasis, leukemia cell proliferation, rheumatoid arthritis, and pulmonary fibrosis. Since AMD3100 (plerixafor) is the only CXCR4 antagonist which obtained approval by the Food and Drug Administration (FDA), we were motivated to investigate a new category of molecules as CXCR4 antagonists. Most of the scaffolds which have been studied so far as CXCR4 antagonists are based on the tetrahydroquinoline (THQ) moiety in which AMD11070 (mavorixafor), GSK-812394, and TIQ15 displayed the most potent CXCR4 antagonism. Due to the high potency of these scaffolds, two different series of compounds were prepared in this work. In the first set, the THQ moiety is coupled to an amine chain and various isoquinoline derivatives (prepared by an in-house developed triazolization strategy), of which the upper part of molecules is identical to AMD11070 and TIQ15. In the second category of compounds, the THQ moiety was simplified by the synthesis of a substituted pyridine moiety. In order to investigate if CXCR4 antagonism requires the presence of an isoquinoline moiety, the corresponding pyridine analogues were also prepared. In both series of compounds, potent CXCR4 antagonism was noticed.

Keywords: CXCR4 coreceptor, CXCR4 antagonists, HIV inhibitor, tetrahydroquinoline

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Authors: Sareh Rajabi, Salwa Bheiry

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In general, Covid-19 created many financial and non-financial damages to the economy and community. Level and severity of covid-19 as pandemic case varies over the region and due to different types of the projects. Covid-19 virus emerged as one of the most imperative risk management factors word-wide recently. Therefore, as part of portfolio management assessment, it is essential to evaluate severity of such risk on the project and program in portfolio management level to avoid any risky portfolio. Covid-19 appeared very effectively in South America, part of Europe and Middle East. Such pandemic infection affected the whole universe, due to lock down, interruption in supply chain management, health and safety requirements, transportations and commercial impacts. Therefore, this research proposes Analytical Hierarchy Process (AHP) to analyze and assess such pandemic case like Covid-19 and its impacts on the construction projects. The AHP technique uses four sub-criteria: Health and safety, commercial risk, completion risk and contractual risk to evaluate the project and program. The result will provide the decision makers with information which project has higher or lower risk in case of Covid-19 and pandemic scenario. Therefore, the decision makers can have most feasible solution based on effective weighted criteria for project selection within their portfolio to match with the organization’s strategies.

Keywords: portfolio management, risk management, COVID-19, analytical hierarchy process technique

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Authors: Saroj Bala Grover, Al Munther Alhasawi, Prem N. Sharma, P. S. N. Menon

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Background: Prisoners are considered one of the high-risk populations for the transmission of human immunodeficiency virus (HIV) infection. Targeting this group is one of the strategies to reduce the incidence of acquired immune deficiency syndrome (AIDS) in the community. Subjects and Methods: A cross-sectional study was conducted among male inmates in Kuwait’s prison by administering three sets of questionnaires to assess the level of their knowledge and awareness about the mode of transmission of HIV/AIDS, their risky personal behavior that may lead to HIV infection, and the presence of any negative attitudes and stigmatization towards HIV infected individuals. Results: The study included 123 male inmates, with a mean ± SD age of 30.9 ± 8.4 years. Most participants had good general knowledge (90%) about the mode of transmission of HIV/AIDS, including sharing contaminated syringes, risky personal behaviors such as having unprotected sex and increased number of extramarital relationships (66%), and the avoidance of the regular use of condoms. The younger age group (< 35 years) had more extramarital relationships than those > 35 years (71.4% Vs. 46.4%; p=0.016). There was a perceived attitude of stigmatization among inmates towards HIV-infected persons. Conclusions: This vulnerable group of prisoners, especially young adults, need educational programs to improve knowledge about the transmission of HIV and to correct and change their risky personal behaviors to protect themselves and the community against HIV transmission.

Keywords: HIV/AIDS, Kuwait, prisoners, knowledge, awareness, personal behavior, extramarital relationships, safe sex, discrimination, stigmatization

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Authors: Nishal Parbhoo, John B. Dewar, Samantha Gildenhuys

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Rotavirus is the major cause of severe gastroenteritis worldwide in children aged 5 and younger. Death rates are high particularly in developing countries. The mature rotavirus is a non-enveloped triple-layered nucleocapsid containing 11 double-stranded RNA segments. Here a global view on the sequence and structure of the three main capsid proteins, VP7, VP6, and VP2 is taken by generating a consensus sequence for each of these rotavirus proteins, for each species obtained from published data of representative rotavirus genotypes from across the world and across species. The degree of conservation between species was represented on homology models for each of the proteins. VP7 shows the highest level of variation with 14 - 45 amino acids showing conservation of less than 60%. These changes are localized to the outer surface which is exposed to antibodies alluding to a possible mechanism in evading the immune system. The middle layer, VP6 shows lower variability with only 14-32 sites having lower than 70% conservation. The inner structural layer made up of VP2 showed the lowest variability with only 1-16 sites having less than 70% conservation across species. The results correlate with proteins’ multiple structural roles. Although the nucleotide sequences vary due to an error-prone replication and lack of proofreading, the corresponding amino acid sequence of VP2, 6 and 7 remains conserved. Sequence conservation maintained for the virus results in stable protein structures, fit for function. This can be exploited in drug design, molecular studies and biotechnological applications.

Keywords: amino acid sequence conservation, capsid protein, protein structure, vaccine candidate

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Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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Authors: Asm Habibullah Choudhury

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Background: This study is an investigation into medical care, ethics, and human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) in the context of Bangladesh. The low prevalence of HIV and high prevalence of STDs in Bangladesh, in common with the global experience of HIV epidemics, has been characterized by tremendous stigmatization of those affected. Stigmatization has resulted in an extraordinary degree of unjust discrimination and in numerous human rights violations of PLWHA. Methodology: This will be a cross-sectional descriptive study and will be conducted at different points of Bangladesh. Result: PLWHA will be identified as many as possible and will be interviewed. Medical care providers will be interviewed to assess their attitude and will be observed for stigma while providing medical services. Some of the religious leaders, local influential people will be interviewed to assess their attitude towards PLWHA. Conclusion: If effective responses to HIV/AIDS-related stigma and discrimination are to be promoted in the region, work has to occur simultaneously on several fronts: Legal challenge, where necessary, to bring to account governments, employers, institutions and individuals. To create enabling environment in which PLWHA and their families, women, boys, and girls are able to access prevention and care services. Access to quality and comprehensive care. The fundamental objective, however, is to strive for action based on this understanding—action that will promote egalitarian and gender-progressive role models, and that will help guide the manner in which we interact with one another.

Keywords: HIV, AIDS, Bangladesh, human rights

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Authors: Maciej Sobczak, Julita Pietrzak, Tomasz Płoszaj, Agnieszka Robaszkiewicz

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Brg1, a member of SWI/SNF complex, plays a role in chromatin remodeling, therefore, regulates expression of many genes. Brg1 is an ATPase of SWI/SNF complex, thus its activity requires ATP. Through its bromodomain recognizes acetylated histone residues and evicts them, thus promoting transcriptionally active state of chromatin. One of the enzymes that is responsible for acetylation of histone residues is Ep300. It was previously shown in the literature that cooperation of Brg1 and Ep300 occurs at the promoter regions that have binding sites for E2F-family transcription factors as well as CpG islands. According to literature, approximately 20% of human cancer possess mutation in Brg1 or any other crucial SWI/SNF subunit. That phenomenon makes Brg1-Ep300 a very promising target for anti-cancer therapy. Therefore in our study, we investigated if physical interaction between Brg1 and Ep300 exists and what impact those two proteins have on key for breast cancer cells processes such as DNA damage repair and cell proliferation. Bioinformatical analysis pointed out, that genes involved in cell proliferation and DNA damage repair are overexpressed in MCF7 and MDA-MB-231 cells. Moreover, promoter regions of these genes are highly acetylated, which suggests high transcriptional activity of those sites. Notably, many of those gene possess within their promoters an E2F, Brg1 motives, as well as CpG islands and acetylated histones. Our data show that Brg1 physically interacts with Ep300, and together they regulate expression of genes involved in DNA damage repair and cell proliferation. Upon inhibiting Brg1 or Ep300, expression of vital for cancer cell survival genes such as CDK2/4, BRCA1/2, PCNA, and XRCC1 is decreased in MDA-MB-231 and MCF7 cells. Moreover, inhibition or silencing of either Brg1 or Ep300 leads to cell cycle arrest in G1. After inhibition of BRG1 or Ep300 on tested gene promoters, the repressor complex including Rb, HDAC1, and EZH2 is formed, which inhibits gene expression. These results highlight potentially significant target for targeted anticancer therapy to be introduced as a supportive therapy.

Keywords: brg1, ep300, breast cancer, epigenetics

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Authors: Lydia Foucan, Laurent Larifla, Emmanuelle Durand, Christine Rambhojan, Veronique Dhennin, Jean-Marc Lacorte, Philippe Froguel, Amelie Bonnefond

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In the population of Guadeloupe Island (472,124 inhabitants and 80% of subjects of African descent), overweight and obesity were estimated at 23% and 9% respectively among children. High prevalence of diabetes has been reported (~10%) in the adult population. Nevertheless, no study has investigated the contribution of gene mutations to childhood obesity in this population. We aimed to investigate rare genetic mutations in genes involved in monogenic obesity or diabetes in obese Afro-Caribbean children from Guadeloupe Island using next-generation sequencing. The present investigation included unrelated obese children, from a previous study on overweight conducted in Guadeloupe Island in 2013. We sequenced coding regions of 59 genes involved in monogenic obesity or diabetes. A total of 25 obese schoolchildren (with Z-score of body mass index [BMI]: 2.0 to 2.8) were screened for rare mutations (non-synonymous, splice-site, or insertion/deletion) in 59 genes. Mean age of the study population was 12.4 ± 1.1 years. Seventeen children (68%) had insulin-resistance (HOMA-IR > 3.16). A family history of obesity (mother or father) was observed in eight children and three of the accompanying parent presented with type 2 diabetes. None of the children had gonadotrophic abnormality or mental retardation. We detected five rare heterozygous mutations, in four genes involved in monogenic obesity, in five different obese children: MC4R p.Ile301Thr and SIM1 p.Val326Thrfs*43 mutations which were pathogenic; SIM1 p.Ser343Pro and SH2B1 p.Pro90His mutations which were likely pathogenic; and NTRK2 p.Leu140Phe that was of uncertain significance. In parallel, we identified seven carriers of mutation in ABCC8 or KCNJ11 (involved in monogenic diabetes), which were of uncertain significance (KCNJ11 p.Val13Met, KCNJ11 p.Val151Met, ABCC8 p.Lys1521Asn and ABCC8 p.Ala625Val). Rare pathogenic or likely pathogenic mutations, linked to severe obesity were detected in more than 15% of this Afro-Caribbean population at high risk of obesity and type 2 diabetes.

Keywords: childhood obesity, MC4R, monogenic obesity, SIM1

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Authors: Ian Campbell, Gillian Mitchell, Paul James, Na Li, Ella Thompson

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The genetic cause of the majority of multiple-case breast cancer families remains unresolved. Next generation sequencing has emerged as an efficient strategy for identifying predisposing mutations in individuals with inherited cancer. We are conducting whole exome sequence analysis of germ line DNA from multiple affected relatives from breast cancer families, with the aim of identifying rare protein truncating and non-synonymous variants that are likely to include novel cancer predisposing mutations. Data from more than 200 exomes show that on average each individual carries 30-50 protein truncating mutations and 300-400 rare non-synonymous variants. Heterogeneity among our exome data strongly suggest that numerous moderate penetrance genes remain to be discovered, with each gene individually accounting for only a small fraction of families (~0.5%). This scenario marks validation of candidate breast cancer predisposing genes in large case-control studies as the rate-limiting step in resolving the missing heritability of breast cancer. The aim of this study is to screen genes that are recurrently mutated among our exome data in a larger cohort of cases and controls to assess the prevalence of inactivating mutations that may be associated with breast cancer risk. We are using the Agilent HaloPlex Target Enrichment System to screen the coding regions of 168 genes in 1,000 BRCA1/2 mutation-negative familial breast cancer cases and 1,000 cancer-naive controls. To date, our interim analysis has identified 21 genes which carry an excess of truncating mutations in multiple breast cancer families versus controls. Established breast cancer susceptibility gene PALB2 is the most frequently mutated gene (13/998 cases versus 0/1009 controls), but other interesting candidates include NPSR1, GSN, POLD2, and TOX3. These and other genes are being validated in a second cohort of 1,000 cases and controls. Our experience demonstrates that beyond PALB2, the prevalence of mutations in the remaining breast cancer predisposition genes is likely to be very low making definitive validation exceptionally challenging.

Keywords: predisposition, familial, exome sequencing, breast cancer

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Authors: Simon Arunga, Teddy Kwaga, Rita Kageni, Michael Gichangi, Nyawira Mwangi, Fred Kagwa, Rogers Mwavu, Amos Baryashaba, Luis F. Nakayama, Katharine Morley, Michael Morley, Leo A. Celi, Jessica Haberer, Celestino Obua

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Purpose: The main aim for creating the Multimodal Database of Retinal Images for Africa (MoDRIA) was to provide a publicly available repository of retinal images for responsible researchers to conduct algorithm development in a bid to curb the challenges of ophthalmic artificial intelligence (AI) in Africa. Methods: Data and retina images were ethically sourced from sites in Uganda and Kenya. Data on medical history, visual acuity, ocular examination, blood pressure, and blood sugar were collected. Retina images were captured using fundus cameras (Foru3-nethra and Canon CR-Mark-1). Images were stored on a secure online database. Results: The database consists of 7,859 retinal images in portable network graphics format from 1,988 participants. Images from patients with human immunodeficiency virus were 18.9%, 18.2% of images were from hypertensive patients, 12.8% from diabetic patients, and the rest from normal’ participants. Conclusion: Publicly available data repositories are a valuable asset in the development of AI technology. Therefore, is a need for the expansion of MoDRIA so as to provide larger datasets that are more representative of Sub-Saharan data.

Keywords: retina images, MoDRIA, image repository, African database

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Authors: Pablo Reche

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Since 1980’s aquaculture has become the biggest economic activity in southern Chile, being Salmo salar and Oncorhynchus mykiss the main finfish species. High fish density makes both species prone to contract diseases, what drives the industry to big losses, affecting greatly the local economy. Three are the most concerning infective agents, the infectious salmon anemia virus (ISAv), the bacteria Piscirickettsia salmonis and the copepod Caligus rogercresseyi. To regulate the industry the government arranged the salmon farms within management areas named as barrios, which coordinate the fallowing periods and antibiotics treatments of their salmon farms. In turn, barrios are gathered into larger management areas, named as macrozonas whose purpose is to minimize the risk of disease transmission between them and to enclose the outbreaks within their boundaries. However, disease outbreaks still happen and transmission to neighbor sites enlarges the initial event. Salmon disease agents are mostly transported passively by local currents. Thus, to understand how transmission occurs it must be firstly studied the physical environment. In Chile, salmon farming takes place in the inner seas of the southernmost regions of western Patagonia, between 41.5ºS-55ºS. This coastal marine system is characterised by western winds, latitudinally modulated by the position of the South-Eats Pacific high-pressure centre, high precipitation rates and freshwater inflows from the numerous glaciers (including the largest ice cap out of Antarctic and Greenland). All of these forcings meet in a complex bathymetry and coastline system - deep fjords, shallow sills, narrow straits, channels, archipelagos, inlets, and isolated inner seas- driving an estuarine circulation (fast outflows westwards on surface and slow deeper inflows eastwards). Such a complex system is modelled on the numerical model MIKE3, upon whose 3D current fields particle-track-biological models (one for each infective agent) are decoupled. Each agent biology is parameterized by functions for maturation and mortality (reproduction not included). Such parameterizations are depending upon environmental factors, like temperature and salinity, so their lifespan will depend upon the environmental conditions those virtual agents encounter on their way while passively transported. CLIC (Connectivity-Langrangian–IFOP-Chile) is a service platform that supports the graphical visualization of the connectivity matrices calculated from the particle trajectories files resultant of the particle-track-biological models. On CLIC users can select, from a high-resolution grid (~1km), the areas the connectivity will be calculated between them. These areas can be barrios and macrozonas. Users also can select what nodes of these areas are allowed to release and scatter particles from, depth and frequency of the initial particle release, climatic scenario (winter/summer) and type of particle (ISAv, Piscirickettsia salmonis, Caligus rogercresseyi plus an option for lifeless particles). Results include probabilities downstream (where the particles go) and upstream (where the particles come from), particle age and vertical distribution, all of them aiming to understand how currently connectivity works to eventually propose a minimum risk zonation for aquaculture purpose. Preliminary results in Chiloe inner sea shows that the risk depends not only upon dynamic conditions but upon barrios location with respect to their neighbors.

Keywords: aquaculture zonation, Caligus rogercresseyi, Chilean Patagonia, coastal oceanography, connectivity, infectious salmon anemia virus, Piscirickettsia salmonis

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Authors: Mark Bezner, Shani Deri, Tom Trigano, Kfir Ben-Harush

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Intermediate filament (IF) proteins-based fibers are among the toughest fibers in nature, as was shown by native hagfish slime threads and by synthetic fibers that are based on type V IF-proteins, the nuclear lamins. It is assumed that their mechanical performance stems from two major factors: (1) the transition from elastic -helices to stiff-sheets during tensile load; and (2) the specific organization of the coiled-coil proteins into a hierarchical network of nano-filaments. Here, we investigated the interrelationship between these two factors by using wet-spun fibers based on C. elegans (Ce) lamin. We found that Ce-lamin fibers, whether assembled in aqueous or alcoholic solutions, had the same nonlinear mechanical behavior, with the elastic region ending at ~5%. The pattern of the transition was, however, different: the ratio between -helices and -sheets/random coils was relatively constant until a 20% strain for fibers assembled in an aqueous solution, whereas for fibers assembled in 70% ethanol, the transition ended at a 6% strain. This structural phenomenon in alcoholic solution probably occurred through the transition between compacted and extended conformation of the random coil, and not between -helix and -sheets, as cycle analyses had suggested. The different transition pattern can also be explained by the different higher order organization of Ce-lamins in aqueous or alcoholic solutions, as demonstrated by introducing a point mutation in conserved residue in Ce-lamin gene that alter the structure of the Ce-lamins’ nano-fibrils. In addition, biomimicking the layered structure of silk and hair fibers by coating the Ce-lamin fiber with a hydrophobic layer enhanced fiber toughness and lead to a reversible transition between -helix and the extended conformation. This work suggests that different hierarchical structures, which are formed by specific assembly conditions, lead to diverse secondary structure transitions patterns, which in turn affect the fibers’ mechanical properties.

Keywords: protein-based fibers, intermediate filaments (IF) assembly, toughness, structure-property relationships

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Authors: Mohammad Mehdizadeh, Sara Miri

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Due to the recent events surrounding the global health crisis and the spread of the coronavirus (COVID-19), the activities of many businesses and start-up companies have been disrupted. It solves many economic problems and can reduce unemployment in countries because governments can take advantage of their potential without direct investment. However, with the help of their innovative ideas and new technologies, these companies can develop and grow the economy. But it is essential to consider that there will be no guarantee of their success in the event of unforeseen events, as the coronavirus outbreak in the last two years has seriously damaged these companies and, like other businesses, challenges and stagnation have started. The startup companies' challenge in the face of coronavirus begins with its impact on customers. Changing customer behavior can affect their products and distribution channels. On the other hand, to prevent countless losses in this crisis, startup companies require creative solutions to address challenges in various areas of human capital, supply chain management, sales and marketing, and so on. Therefore, all business leaders must consider and plan for the current crisis and the future; after overcoming these conditions and returning to regular business routines, it will no longer be an option, and new situations will prevail in a competitive environment. The essential strategies for developing and growing startups during the Coronavirus outbreak can be connecting with the global startup ecosystem, hosting webinars, providing podcasts and free question and answer sessions, mentoring services to growing teams, and consulting pointed out this to firms for digitalization.

Keywords: business, COVID-19, digitalization, startups

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Authors: K. R. Padma, K. R. Don

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Background and aims: A balanced nutritional diet is essential in maintaining immunity and for deterrence as well as desisting of viral infections. Nevertheless, currently, very less information is available online regarding nutrition consumption during the period of coronavirus infection, i.e. (COVID-19). In our systematic review article, we portrayed and aimed to evaluate evidence from various previous clinical trials, which was based on nutritional interventions for viral diseases and given a concise overview. Methods: A systematic search was carried out employing 3 key medical databases: PubMed®, Web of Science®, and SciVerse Scopus®. Studies were performed and evaluated suitable if clinical trials in humans, appropriate immunological parameters on viral and respiratory infections, need to perform. Basic Clinical trials on nutritional vitamins, minerals, nutraceuticals as well as probiotics were included. Results: We have explored 10 review articles and extracted data for our study. A total of > 2000 participants were included and excluded several other trace elements as well as various vitamins, but in inclusion criteria mainly concentrated on those who have shown propitious immune-modulatory effects against viral respiratory infections. Conclusions: We have encapsulated the potential health benefits of some minerals, vitamins, as well as certain designer foods, nutraceuticals, and probiotics in viral infections. Based on this nutritional interventional strategy available from our present data, it could be promising to abstain and reduce the COVID-19 infection replication and boost our immunity to fight against the virus.

Keywords: COVID-19, immunity, vitamins, nutritional intervention strategy

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Authors: Dar-Bin Shieh, Gwo-Bin Lee, Chen-Ming Chang, Chen Sheng Yeh, Chih-Chia Huang, Tsung-Ju Li

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Mitochondrial defects have a significant impact in many human diseases and aging associated phenotypes. The pathogenic mitochondrial DNA (mtDNA) mutations are diverse and usually present as heteroplasmic. mtDNA 4977bps deletion is one of the common mtDNA defects, and the ratio of mutated versus normal copy is significantly associated with clinical symptoms thus their quantitative detection has become an important unmet needs for advanced disease diagnosis and therapeutic guidelines. This study revealed a Micro-electro-mechanical-system (MEMS) enabled automatic microfluidic chip that only required minimal sample. The system integrated multiple laboratory operation steps into a Lab-on-a-Chip for high-sensitive and prompt measurement. The entire process including magnetic nanoparticle based mtDNA extraction in chip, mutation selective photonic DNA cleavage, and nanoparticle accelerated photonic quantitative polymerase chain reaction (qPCR). All subsystems were packed inside a miniature three-dimensional micro structured system and operated in an automatic manner. Integration of magnetic beads with microfluidic transportation could promptly extract and enrich the specific mtDNA. The near infrared responsive magnetic nanoparticles enabled micro-PCR to be operated by pulse-width-modulation controlled laser pulsing to amplify the desired mtDNA while quantified by fluorescence intensity captured by a complementary metal oxide system array detector. The proportions of pathogenic mtDNA in total DNA were thus obtained. Micro capillary electrophoresis module was used to analyze the amplicone products. In conclusion, this study demonstrated a new magnetophotonic based qPCR MEMS system that successfully detects and quantify specific disease related DNA mutations thus provides a promising future for rapid diagnosis of mitochondria diseases.

Keywords: mitochondrial DNA, micro-electro-mechanical-system, magnetophotonics, PCR

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Authors: Nadia Naseem, Farwa Batool, Nasir Mehmood, AbdulHannan Nagi

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Background: The incidence and mortality of breast cancer vary significantly in geographically distinct populations. In Pakistan, breast cancer has shown an increase in incidence in young females and is characterized by more aggressive behavior. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. This study investigated the TP53 mutations in molecular subtypes of both nodes negative and positive breast cancer in young Pakistani patients. Material and Methods: p53, Estrogen Receptor (ER), Progesterone Receptor (PR), Her-2 neu and Ki 67 expressions were analyzed immunohistochemically in a series of 75 node negative (A) and 75 node positive (B) young (aged: 19-40 years) breast cancer patients diagnosed between 2014 to 2017 at two leading hospitals of Punjab, Pakistan. Tumor tissue specimens and peripheral blood samples were examined for TP53 mutations by direct sequencing of the gene (exons 4-9). The relation of TP53 mutations to these markers and clinicopathological data was investigated. Results: Mean age of the patients was 32.4 + 9.1 SD. Invasive breast carcinoma was the most frequent histological variant (A=92%, B=94.6%). Grade 3 carcinoma was the commonest grade (A=72%, B=81.3%). Triple negative cases (ER-, PR-, Her-2) formed most of the molecular subtypes (A=44%, B=50.6%). A total of 17.2% (A: 6.6%, B: 10.6%) patients showed TP53 mutations. Mutations were significantly more frequent in triple negative cases (A: 74.8%, B: 62.2%) compared to HER2-positive patients (P < 0.0001). In the multivariate analysis of the whole patient group, the independent prognosticator were triple negative cases (P=0.021), TP53 overexpression by IHC (P=0.001) and advanced-stage disease (P=0.007). No statistically significant correlation between TP53 mutations and clinicopathological parameters was found (P < 0.05). Conclusions: It is concluded that TP53 mutations are infrequently present in breast carcinoma of young Pakistani population and there was no significant correlation between p53 mutation and early onset disease. Immunohistochemically detected TP53 expression in our resource-constrained to set up can be beneficial in predicting mutations at the younger age in our population.

Keywords: immunohistochemistry (IHC), invasive breast carcinoma (IBC), Pakistan, TP53

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Authors: Marie-Therese Claes, Anett Hermann

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With the advent of the web and information technology since the end of the 20ᵗʰ century, digitalization has revolutionized our everyday life, from shopping and dating to education and transportation. The world of work is one of the areas that has been highly transformed by changing the time and spatial limits of the work. The expansion of the internet, wireless, and easily portable devices such as laptop computers and mobile phones has enabled us to work almost from any place at any time. As a result, telework, which started in the 1950s and elevated in the 1970s, steeply raised to a new level in 21ˢᵗ century. Telework consists of various forms of work done from outside the traditional workplace by using information technologies. The social distancing and lockdown measures that have been taken to reduce the spread of the virus in many countries worldwide resulted in an increasing number of teleworkers and made “working from home’’ synonymous with telework. Post-COVID-19, the number of teleworkers is still higher than before the pandemic period, and the interest in expanding teleworking has been growing too. Notwithstanding the advantages ushered by telework, it also has a number of drawbacks that negatively affect organizations and employees. The intention of this piece of work is not to indicate a causational relationship between telework and discrimination. Our aim is to indicate some unintended and/or unnoticed deleterious effects of telework in reinforcing discrimination and to instigate discussion on how to mitigate the effects. To do so, this insight indicates how telework reinforces traditional gender roles and how organizational culture towards telework and its access to employees at different levels of the organizational hierarchy opens the room for discrimination.

Keywords: mobile work, discrimination, gender roles, organizational culture

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Authors: Swarkar Sharma, Ekta Rai, Ankit Mahajan, Parvinder Kumar, Manoj K Dhar, Sushil Razdan, Kumarasamy Thangaraj, Carol Wise, Shiro Ikegawa M.D., K.K. Pandita M.D.

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Rare disorders are poorly understood hence, remain uncharacterized or patients are misdiagnosed and get poor medical attention. A rare mysterious skeletal disorder that remained unidentified for decades and rendered many people physically challenged and disabled for life has been reported in an isolated remote village ‘Arai’ of Poonch district of Jammu and Kashmir. This village is located deep in mountains and the population residing in the region is highly consanguineous. In our survey of the region, 70 affected people were reported, showing similar phenotype, in the village with a population of approximately 5000 individuals. We were able to collect samples from two multi generational extended families from the village. Through Whole Exome sequencing (WES), we identified a rare variation NM_003880.3:c.156C>A NP_003871.1:p.Cys52Ter, which results in introduction of premature stop codon in WISP3 gene. We found this variation perfectly segregating with the disease in one of the family. However, this variation was absent in other family. Interestingly, a novel splice site mutation at position c.643+1G>A of WISP3 gene, perfectly segregating with the disease was observed in the second family. Thus, exploiting WES and putting different evidences together (familial histories and genetic data, clinical features, radiological and biochemical tests and findings), the disease has finally been diagnosed as a very rare recessive hereditary skeletal disease “Progressive Pseudorheumatoid Arthropathy of Childhood” (PPAC) also known as “Spondyloepiphyseal Dysplasia Tarda with Progressive Arthropathy” (SEDT-PA). This genetic characterization and identification of the disease causing mutations will aid in genetic counseling, critically required to curb this rare disorder and to prevent its appearance in future generations in the population. Further, understanding of the role of WISP3 gene the biological pathways should help in developing treatment for the disorder.

Keywords: whole exome sequencing, Next Generation Sequencing, rare disorders

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Authors: Shanna Su, Kathleen Vincent

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Introduction: A non-hormonal prescription vaginal pH modulator (VPM) gel (Phexxi®), with active ingredients lactic acid, citric acid, and potassium bitartrate, has recently been approved for the prevention of pregnancy in the United States. The objective of this review is to compile the evidence available from published preclinical and clinical trials to support its use. Areas covered: PubMed was searched for published literature on VPM gel. Two Phase III trials were found on the clinicaltrials.gov database. The results demonstrated that VPM gel is safe, with minimal side effects, and effective (cumulative 6-7 cycle pregnancy rate of 4.1-13.65%, (Pearl Index 27.5) as a contraceptive. Microbicidal effects suggest the potential for the prevention of sexually transmitted infections (STIs); currently, a Phase III clinical trial is being conducted to evaluate the prevention of chlamydia and gonorrhea. Expert opinion: Non-hormonal reversible contraceptive options have been limited to the highly effective copper-releasing intrauterine device that requires insertion by a trained clinician and less effective coitally-associated barrier and spermicide options which are typically available over-the-counter. Spermicides, which improve the efficacy of barrier devices, may increase the risk of Human Immunodeficiency Virus (HIV)/STIs. VPM gel provides a new safe, effective non-hormonal contraceptive option with the potential for prevention of STIs.

Keywords: citric acid, lactic acid, non-hormonal contraception, potassium bitartrate, topical vaginal contraceptive, vaginal pH modulator gel

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Authors: William Mahony, L. Jacqueline Hirth, Richard Rupp, Sandra Gonzalez, Roger Zoorob

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Background: The impact of the COVID-19 pandemic on physicians has been considered by many researchers, but less is known about non-physician healthcare workers. The aim of this study is to examine the association of COVID-19 safety training and communication with stress. Methods: A 91-item online survey was distributed, starting January 2, 2021, to non-physician healthcare workers, including physician assistants, nurse practitioners, and medical assistants (MAs) in the United States through email and social media. A $1 donation was made to the Red Cross for each completed survey. The survey consisted of demographics, occupational questions, and perceived stress (perceived stress scale, PSS). Items on the PSS were combined for an overall score and categorized according to the severity of perceived stress. Chi-square tests were performed for bivariate analyses of categorical variables. Results: Of the 284 participants consenting to complete the survey, 197 participants completed the full survey. MAs made up most of the sample at 79%. Among all respondents, 47% had moderate PSS scores (scored between 14 and 26), and 51% had severe PSS scores (scored between 27 and 40). Unvaccinated participants reported statistically significantly lower levels of perceived stress (p = 0.002). Performing tasks outside of typical job responsibilities was not associated with PSS scores (p = .667). Discussion: Non-physician healthcare workers demonstrated a high level of perceived stress overall. The association between vaccination status and perceived stress should be examined in order to evaluate whether vaccination levels could be improved with further education about the virus and associated risks.

Keywords: COVID-19, SARS-Cov-2, nursing, public health

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Authors: S. Abera, T. Gidey, W. Terefe

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Introduction: Testing for HIV is the key entry point to HIV prevention, treatment, and care and support services. Hence, predictive data mining techniques can greatly benefit to analyze and discover new patterns from huge datasets like that of EDHS 2011 data. Objectives: The objective of this study is to build a predictive modeling for HIV testing and identify determinants of HIV testing for adults with age above fourteen years using data mining techniques. Methods: Cross-Industry Standard Process for Data Mining (CRISP-DM) was used to predict the model for HIV testing and explore association rules between HIV testing and the selected attributes among adult Ethiopians. Decision tree, Naïve-Bayes, logistic regression and artificial neural networks of data mining techniques were used to build the predictive models. Results: The target dataset contained 30,625 study participants; of which 16, 515 (53.9%) were women. Nearly two-fifth; 17,719 (58%), have never been tested for HIV while the rest 12,906 (42%) had been tested. Ethiopians with higher wealth index, higher educational level, belonging 20 to 29 years old, having no stigmatizing attitude towards HIV positive person, urban residents, having HIV related knowledge, information about family planning on mass media and knowing a place where to get testing for HIV showed an increased patterns with respect to HIV testing. Conclusion and Recommendation: Public health interventions should consider the identified determinants to promote people to get testing for HIV.

Keywords: data mining, HIV, testing, ethiopia

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Authors: Kkochorong Park, Keun Cheon Kim, Hyoban Lee, Eun Ju Lee, Bongsoo Kim

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Introduction of biomaterials such as DNA, RNA, proteins is important for many research areas. There are many methods to introduce biomaterials into living organisms like tissue and cells. To introduce biomaterials, several indirect methods including virus‐mediated delivery, chemical reagent (i.e., lipofectamine), electrophoresis have been used. Such methods are passive delivery using an endocytosis process of cell, reducing an efficiency of delivery. Unlike the indirect delivery method, it has been reported that a direct delivery of exogenous biomolecules into nucleus have been more efficient to expression or integration of biomolecules. Nano-sized material is beneficial for detect signal from cell or deliver stimuli/materials into the cell at cellular and molecular levels, due to its similar physical scale. Especially, because 1 dimensional (1D) nanomaterials such as nanotube, nanorod and nanowire with high‐aspect ratio have nanoscale geometry and excellent mechanical, electrical, and chemical properties, they could play an important role in molecular and cellular biology. In this study, by using single crystalline 1D noble metal nanowire, we fabricated nano-sized 1D injector which can successfully interface with living cells and directly deliver biomolecules into several types of cell line (i.e., stem cell, mammalian embryo) without inducing detrimental damages on living cell. This nano-bio technology could be a promising and robust tool for introducing exogenous biomaterials into living organism.

Keywords: DNA, gene delivery, nanoinjector, nanowire

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Authors: Ofosuhene O. Apenteng, Noor Azina Ismail

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The human immunodeficiency virus (HIV) that causes acquired immune deficiency syndrome (AIDS) remains a global cause of morbidity and mortality. It has caused panic since its emergence. Relationships between migration and HIV/AIDS have become complex. In the absence of prospectively designed studies, dynamic mathematical models that take into account the migration movement which will give very useful information. We have explored the utility of mathematical models in understanding transmission dynamics of HIV and AIDS and in assessing the magnitude of how migration has impact on the disease. The model was calibrated to HIV and AIDS incidence data from Malaysia Ministry of Health from the period of 1986 to 2011 using Bayesian analysis with combination of Markov chain Monte Carlo method (MCMC) approach to estimate the model parameters. From the estimated parameters, the estimated basic reproduction number was 22.5812. The rate at which the susceptible individual moved to HIV compartment has the highest sensitivity value which is more significant as compared to the remaining parameters. Thus, the disease becomes unstable. This is a big concern and not good indicator from the public health point of view since the aim is to stabilize the epidemic at the disease-free equilibrium. However, these results suggest that the government as a policy maker should make further efforts to curb illegal activities performed by migrants. It is shown that our models reflect considerably the dynamic behavior of the HIV/AIDS epidemic in Malaysia and eventually could be used strategically for other countries.

Keywords: epidemic model, reproduction number, HIV, MCMC, parameter estimation

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Authors: John Angelo Labuguen, Sarah Joy Salvio

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Despite the low prevalence rate of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) in the Philippines, the country is one of the seven countries in the world and the only country in Southeast Asia which reported an increasing trend in the number of people infected with HIV. Furthermore, people getting infected with HIV are becoming younger every year. Eighty-five percent (7,103) of the total number of youth (15-24 years old) with HIV were recorded in the past five years. The rising rates of HIV infection suggest the need to understand HIV knowledge, attitudes, and sexual behaviors among the youth in the Philippines. The University of the Philippines (UP), having a population that represents all regions of the country, can be reflective of the current situation of the Filipino youth in the issue of HIV/AIDS. This paper attempted to: (1) assess the level of knowledge on HIV/AIDS; (2) describe the attitude towards people living with HIV/AIDS; (3) identify socio-demographic and sexual behaviors associated with the level of HIV/AIDS knowledge; and (4) determine how knowledge on HIV/AIDS is related with attitude towards people living with HIV/AIDS among tertiary students of the UP Diliman. Self-administered survey was used to collect data from 308 randomly selected respondents. Data was encoded using CS Pro 6.2 and it was exported to SPSS v23 for further analysis. Findings of the study revealed that comprehensive correct knowledge on HIV/AIDS is associated with a somewhat accepting attitude towards PLWHA. Sociodemographic and sexual behavior characteristics do not contribute to the association between level of knowledge about HIV/AIDS and attitude towards PLWHA.

Keywords: attitude towards people living with HIV/AIDS, comprehensive HIV/AIDS knowledge, Philippines, university students

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Authors: Ilya B. Tsyrlov, Dmitry Y. Oshchepkov

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A computational search for dioxin response elements (DREs) in genes of proteins comprising the Ah receptor (AhR) cytosolic core complex was performed by highly efficient tool SITECON. Eventually, the following number of new DREs in 5’flanking region was detected by SITECON: one in AHR gene, five in XAP2, eight in HSP90AA1, and three in HSP90AB1 genes. Numerous DREs found in genes of AhR and AhR cytosolic complex members would shed a light on potential mechanisms of expression, the stoichiometry of unliganded AhR core complex, and its degradation vs biosynthesis dynamics resulted from treatment of target cells with the AhR most potent ligand, 2,3,7,8-TCDD. With human viruses, reduced susceptibility to TCDD of geneencoding HIV-1 P247 was justified by the only potential DRE determined in gag gene encoding HIV-1 P24 protein, whereas the regulatory region of CMV genes encoding IE gp/UL37 has five potent DRE, 1.65 kb/UL36 – six DRE, pp65 and pp71 – each has seven DRE, and pp150 – ten DRE. Also, from six to eight DRE were determined with SITECON in the regulatory region of HSV-1 IE genes encoding tegument proteins, UL36 and UL37, and of UL19 gene encoding bindingglycoprotein C (gC). So, TCDD in the low picomolar range may activate in human cells AhR: Arnt transcription pathway that triggers CMV and HSV-1 reactivation by binding to numerous promoter DRE within immediate-early (IE) genes UL37 and UL36, thus committing virus to the lytic cycle.

Keywords: dioxin response elements, Ah receptor, AhR: Arnt transcription pathway, human and viral genes

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Authors: Diya Kohli, Amalia Ardeljan, Lexi Frankel, Jose Garcia, Lokesh Manjani, Omar Rashid

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Gonorrhea is the second most common sexually transmitted disease (STDs) in the United States of America. Gonorrhea affects the urethra, rectum, or throat and the cervix in females. Lymphoma is a cancer of the immune network called the lymphatic system that includes the lymph nodes/glands, spleen, thymus gland, and bone marrow. Lymphoma can affect many organs in the body. When a lymphocyte develops a genetic mutation, it signals other cells into rapid proliferation that causes many mutated lymphocytes. Multiple studies have explored the incidence of cancer in people infected with STDs such as Gonorrhea. For instance, the studies conducted by Wang Y-C and Co., as well as Caini, S and Co. established a direct co-relationship between Gonorrhea infection and incidence of prostate cancer. We hypothesize that Gonorrhea infection also increases the incidence of Lymphoma in patients. This research study aimed to evaluate the correlation between Gonorrhea infection and the incidence of Lymphoma. The data for the research was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database. This database was utilized to evaluate patients infected with Gonorrhea versus the ones who were not infected to establish a correlation with the prevalence of Lymphoma using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale for academic research. Standard statistical methods were applied throughout. Between January 2010 and December 2019, the query was analyzed and resulted in 254 and 808 patients in both the infected and control group, respectively. The two groups were matched by Age Range and CCI score. The incidence of Lymphoma was 0.998% (254 patients out of 25455) in the Gonorrhea group (patients infected with Gonorrhea that was Lymphoma Positive) compared to 3.174% and 808 patients in the control group (Patients negative for Gonorrhea but with Lymphoma). This was statistically significant by a p-value < 2.210-16 with an OR= 0.431 (95% CI 0.381-0.487). The patients were then matched by antibiotic treatment to avoid treatment bias. The incidence of Lymphoma was 1.215% (82 patients out of 6,748) in the Gonorrhea group compared to 2.949% (199 patients out of 6748) in the control group. This was statistically significant by a p-value <5.410-10 with an OR= 0.468 (95% CI 0.367-0.596). The study shows a statistically significant correlation between Gonorrhea and a reduced incidence of Lymphoma. Further evaluation is recommended to assess the potential of Gonorrhea in reducing Lymphoma.

Keywords: gonorrhea, lymphoma, STDs, cancer, ICD

Procedia PDF Downloads 173

Authors: Marine Kobalava

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Introduction. The paper substantiates the crucial role of anti-crisis PR in managing the image and reputation of companies. The critical situation caused by the Covid-19 virus in various countries of the world and the actions taken have had a significant negative impact on the image of companies and public groups. The mentioned circumstance has caused some problems for companies’ products in terms of customer demand. Accordingly, the main goal of PR has become to achieve the optimal relationship between companies and society with effective management. It should also be taken into account that the range of action of PR in crisis situations is much wider than that of advertising. In the paper, Public Relations is evaluated as a determining factor of the companies' prestige, its reliability, which has a decisive effect on the goodwill, trust, and general reputation of the public towards the company. The purpose of the study is to reveal the challenges of anti-crisis PR in Georgian companies and to develop recommendations on effective management mechanisms. Methodologies. Analysis, induction, synthesis, and other methods are used in the paper; Matrix and SWOT analysis are constructed. Ways of establishing and implementing an anti-crisis PR system in companies are proposed. The main aspects of anti-crisis management are identified by using the matrix of the choice of diversification strategy of the companies' activities, the possibilities of making adequate decisions using PR are studied according to the characteristics of the companies' activities and priority directions. Conclusion. The paper draws conclusions on modern problems of anti-crisis PR, offers recommendations on ways to solve it through PR strategies.

Keywords: anti-crisis PR, effective management, company, PR strategy

Procedia PDF Downloads 56

Authors: Lucia Salvioni, Pietro Giorgio Lovaglio, Valerio Leoni, Miriam Colombo, Luisa Fiandra

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The involvement of plasmatic surfactant protein-D (SP-D) in pulmonary diseases has been long investigated, and over the last two years, more interest has been directed to determine its role as a marker of COVID-19. In this direction, several studies aimed to correlate pulmonary surfactant proteins with the clinical manifestations of the virus indicated SP-D as a prognostic biomarker of COVID-19 pneumonia severity. The present work has performed a retrospective study on a relatively large cohort of patients of Hospital Pio XI of Desio (Lombardia, Italy) with the aim to assess differences in the hematic SP-D concentrations among COVID-19 patients and healthy donors and the role of SP-D as a prognostic marker of severity and/or of mortality risk. The obtained results showed a significant difference in the mean of log SP-D levels between COVID-19 patients and healthy donors, so as between dead and survived patients. SP-D values were significantly higher for both hospitalized COVID-19 and dead patients, with threshold values of 150 and 250 ng/mL, respectively. SP-D levels at admission and increasing differences among follow-up and admission values resulted in the strongest significant risk factors of mortality. Therefore, this study demonstrated the role of SP-D as a predictive marker of SARS-CoV-2 infection and its outcome. A significant correlation of SP-D with patient mortality indicated that it is also a prognostic factor in terms of mortality, and its early detection should be considered to design adequate preventive treatments for COVID-19 patients.

Keywords: SARS-CoV-2 infection, COVID-19, surfactant protein-D (SP-D), mortality, biomarker

Procedia PDF Downloads 54

Authors: Roel Guinto Jr, John Peter Dacanay, Edison Ramos

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The Philippines now has the fastest-growing HIV epidemic in the entire Asia-Pacific region. According to the January 2023 HIV/AIDS Registry of the Philippines of the Department of Health (DOH), there were 86 newly reported HIV cases involving 19 years old and below. A cure for HIV is not yet readily available but effective preventive measures to prevent its transmission. Pre-Exposure Prophylaxis is a biomedical intervention for HIV infection in the form of a pill. Students play a significant role in identifying solutions to preventing the transmission of HIV Infection, making it critical to assess their Knowledge, Attitude, and Practice of Pre-Exposure Prophylaxis on HIV Infection. A study was conducted among 390 regular students from different college departments at National University – Manila. A structured questionnaire was used to collect data and other statistical tools were used to analyze data. The findings reveal that most students had no knowledge or idea about PreExposure Prophylaxis before being interviewed. It also shows that students have a positive attitude toward the practice of Pre-Exposure Prophylaxis. The study revealed that there is also a significant relationship between the Knowledge and the Socio-demographic profile of the respondents. Knowledge, Attitude, and Practices on PrEP of students were overall identified, and areas of improvement were also recognized. Sex Education and Sexual Health Awareness should be implemented to enhance students’ knowledge of practicing safe sex to help prevent HIV Transmission.

Keywords: HIV, cure, biomedical intervention, pre-exposure prophylaxis, pill, knowledge, attitude, practice, sex education, sexual health awareness

Procedia PDF Downloads 43

Authors: Anne Mastamet-Mason, Oluwatosin Onakoya, Karla Tissiman

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The COVID-19 pandemic that ravaged the world in 2020 brought about the need for handmade fabric face masks in South Africa and beyond. These masks showcased individuality and environmental responsibility and effectively aided our battle against the virus. These practical masks held significant meaning, representing human creativity, resilience, and commitment to sustainability in adversity. This paper examines how aesthetics, sustainability, and safety were achieved in the Handmade Fabric Face Masks. It analyses how their integration signified human agility and resilience to the pandemic while promoting dignity and environmental welfare. The research conducted a qualitative analysis to choose handmade fabric face masks and assess their aesthetic, sustainable, and safety features. The study involved interviewing a group of mask designers and users who evaluated the masks' efficacy in providing protection, aesthetics, and environmental sustainability. Although the designers demonstrated a high level of knowledge in the design aspects, the results indicated a need for more information regarding the functional safety measures and some environmental factors in mask selection and production. The mask analysis also revealed that the masks available in the market combined aesthetics and environmental protection but had limited safety measures. Despite the lack of balance of aesthetics, sustainability, and safety among the designers and the users of hand-fabric masks, functional aspects of fabrics and sustainability literacy are essential

Keywords: sustainable fashion, fabric mask, aesthetics, safety measures

Procedia PDF Downloads 38