Search results for: Viral Nagori

Authors: S. Pathak, R. Lazarus

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A 25-year-old male HIV patient (CD4 cells 20/µL and HIV viral load 14200000 copies/ml) with a past medical history of duodenal ulcer, pneumocystis carinii pneumonia, oesophageal candidiasis presented with fever and a seizure to hospital. The only recent travel had been a religious pilgrimage from Singapore to Malaysia 5 days prior; during the trip he sustained skin abrasions. The patient had recently started highly active antiretroviral therapy 2 months prior. Clinical examination was unremarkable other than a temperature of 38.8°C and perianal warts. Laboratory tests showed a leukocyte count 12.5x109 cells/L, haemoglobin 9.4 g/dL, normal biochemistry and a C-reactive protein 121 mg/L. CT head and MRI head were unremarkable and cerebrospinal fluid analysis performed after a delay (due to technical difficulties) of 11 days was unremarkable. Blood cultures (three sets) taken on admission showed Gram-negative rods in the anaerobic bottles only at the end of incubation with culture result confirmed by molecular sequencing showing Helicobacter cinaedi. The patient was treated empirically with ceftriaxone for seven days and this was converted to oral co-amoxiclav for a further seven days after the blood cultures became positive. A Transthoracic echocardiogram was unremarkable. The patient made a full recovery. Helicobacter cinaedi is a gram-negative anaerobic fastidious organism affecting patients with comorbidity. Infection may manifest as cellulitius, colitis or as in this case as bloodstream infection – the latter is often attributed to faeco-oral infection. Laboratory identification requires prolonged culture. Therapeutic options may be limited by resistance to macrolides and fluoroquinolones. The likely pathogen inoculation routes in the case described include gastrointestinal translocation due to proctitis at the site of perianal warts, or breach of the skin via abrasions occurring during the pilgrimage. Such organisms are increasing in prevalence as our patient population ages and patients have multiple comorbidities including HIV. It may be necessary in patients with unexplained fever to prolong incubation of sterile sites including blood in order to identify this unusual fastidious organism.

Keywords: fastidious, Helicobacter cinaedi, HIV, immunocompromised

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Authors: Joyce K. Anastasi, Bernadette Capili

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Community Engagement Strategies to Assist with the Development of an RCT Among People Living with HIV Our research team focuses on developing and testing protocols to manage chronic symptoms. For many years, our team designed and implemented symptom management studies for people living with HIV (PLWH). We identify symptoms that are not curative and are not adequately controlled by conventional therapies. As an exemplar, we describe how we successfully engaged PLWH in developing and refining our research feasibility protocol for distal sensory peripheral neuropathy (DSP) associated with HIV. With input from PLWH with DSP, our research received National Institutes of Health (NIH) research funding support. Significance: DSP is one of the most common neurologic complications in HIV. It is estimated that DSP affects 21% to 50% of PLWH. The pathogenesis of DSP in HIV is complex and unclear. Proposed mechanisms include cytokine dysregulation, viral protein-produced neurotoxicity, and mitochondrial dysfunction associated with antiretroviral medications. There are no FDA-approved treatments for DSP in HIV. Purpose: Aims: 1) to explore the impact of DSP on the lives of PLWH, 2) to identify patients’ perspectives on successful treatments for DSP, 3) to identify interventions considered feasible and sensitive to the needs of PLWH with DSP, and 4) to obtain participant input for protocol/study design. Description of Process: We conducted a needs assessment with PLWH with DSP. From our needs assessment, we learned from the patients’ perspective detailed descriptions of their symptoms; physical functioning with DSP; self-care remedies tried, and desired interventions. We also asked about protocol scheduling, instrument clarity, study compensation, study-related burdens, and willingness to participate in a randomized controlled trial (RCT) with a placebo and a waitlist group. Implications: We incorporated many of the suggestions learned from the need assessment. We developed and completed a feasibility study that provided us with invaluable information that informed subsequent NIH-funded studies. In addition to our extensive clinical and research experience working with PLWH, learning from the patient perspective helped in developing our protocol and promoting a successful plan for recruitment and retention of study participants.

Keywords: clinical trial development, peripheral neuropathy, traditional medicine, HIV, AIDS

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Authors: A. K. Faizah, G. Vadamalai, S. K. Balasundram, W. L. Lim

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Pineapple (Ananas comosus) is a common crop in tropical and subtropical areas of the world. Malaysia once ranked as one of the top 3 pineapple producers in the world in the 60's and early 70's, after Hawaii and Brazil. Moreover, government’s recognition of the pineapple crop as one of priority commodities to be developed for the domestics and international markets in the National Agriculture Policy. However, pineapple industry in Malaysia still faces numerous challenges, one of which is the management of disease and pest. Red tip disease on pineapple was first recognized about 20 years ago in a commercial pineapple stand located in Simpang Renggam, Johor, Peninsular Malaysia. Since its discovery, there has been no confirmation on its causal agent of this disease. The epidemiology of red tip disease is still not fully understood. Nevertheless, the disease symptoms and the spread within the field seem to point toward viral infection. Bioassay test on nucleic acid extracted from the red tip-affected pineapple was done on Nicotiana tabacum cv. Coker by rubbing the extracted sap. Localised lesions were observed 3 weeks after inoculation. Negative staining of the fresh inoculated Nicotiana tabacum cv. Coker showed the presence of membrane-bound spherical particles with an average diameter of 94.25nm under transmission electron microscope. The shape and size of the particles were similar to tospovirus. SDS-PAGE analysis of partial purified virions from inoculated N. tabacum produced a strong and a faint protein bands with molecular mass of approximately 29 kDa and 55 kDa. Partial purified virions of symptomatic pineapple leaves from field showed bands with molecular mass of approximately 29 kDa, 39 kDa and 55kDa. These bands may indicate the nucleocapsid protein identity of tospovirus. Furthermore, a handheld sensor, Greenseeker, was used to detect red tip symptoms on pineapple non-destructively based on spectral reflectance, measured as Normalized Difference Vegetation Index (NDVI). Red tip severity was estimated and correlated with NDVI. Linear regression models were calibrated and tested developed in order to estimate red tip disease severity based on NDVI. Results showed a strong positive relationship between red tip disease severity and NDVI (r= 0.84).

Keywords: pineapple, diagnosis, virus, NDVI

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Authors: Mahbuba Rahman, Sabri Boughorbel, Scott Presnell, Charlie Quinn, Darawan Rinchai, Damien Chaussabel, Nico Marr

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Collections of large-scale datasets made available in public repositories can be used to identify and fill gaps in biomedical knowledge. But first, these data need to be made readily accessible to researchers for analysis and interpretation. Here a collection of transcriptome datasets was made available to investigate the functional programming of human hematopoietic cells in early life. Thirty two datasets were retrieved from the NCBI Gene Expression Omnibus (GEO) and loaded in a custom, interactive web application called the Gene Expression browser (GXB), designed for visualization and query of integrated large-scale data. Multiple sample groupings and gene rank lists were created based on the study design and variables in each dataset. Web links to customized graphical views can be generated by users and subsequently be used to graphically present data in manuscripts for publication. The GXB tool also enables browsing of a single gene across datasets, which can provide information on the role of a given molecule across biological systems. The dataset collection is available online. As a proof-of-principle, one of the datasets (GSE25087) was re-analyzed to identify genes that are differentially expressed by regulatory T cells in early life. Re-analysis of this dataset and a cross-study comparison using multiple other datasets in the above mentioned collection revealed that PMCH, a gene encoding a precursor of melanin-concentrating hormone (MCH), a cyclic neuropeptide, is highly expressed in a variety of other hematopoietic cell types, including neonatal erythroid cells as well as plasmacytoid dendritic cells upon viral infection. Our findings suggest an as yet unrecognized role of MCH in immune regulation, thereby highlighting the unique potential of the curated dataset collection and systems biology approach to generate new hypotheses which can be tested in future mechanistic studies.

Keywords: early-life, GEO datasets, PMCH, interactive query, systems biology

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Authors: Manoj Kumar Reddy Pulim, Lakshmi Muthukrishnan, Geetha Jayapathy, Radhika Raman

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Introduction: In the past two decades, noninvasive positive pressure ventilation (NIPPV) emerged as one of the most important advances in the management of both acute and chronic respiratory failure in children. In the acute setting, it is an alternative to intubation with a goal to preserve normal physiologic functions, decrease airway injury, and prevent respiratory tract infections. There is a need to determine the clinical profile and parameters which point towards the need for NIV in the pediatric emergency setting. Objectives: i) To study the clinical profile of children who required non invasive ventilation and invasive ventilation, ii) To study the clinical parameters common to children who required non invasive ventilation. Methods: All children between one month to 18 years, who were intubated in the pediatric emergency department and those for whom decision to commence Non Invasive Ventilation was made in Emergency Room were included in the study. Children were transferred to the Paediatric Intensive Care Unit and started on Non Invasive Ventilation as per our hospital policy and followed up in the Paediatric Intensive Care Unit. Clinical profile of all children which included age, gender, diagnosis and indication for intubation were documented. Clinical parameters such as respiratory rate, heart rate, saturation, grunting were documented. Parameters obtained were subject to statistical analysis. Observations: Airway disease (Bronchiolitis 25%, Viral induced wheeze 22%) was a common diagnosis in 32 children who required Non Invasive Ventilation. Neuromuscular disorder was the common diagnosis in 27 children (78%) who were Intubated. 17 children commenced on Non Invasive Ventilation who later needed invasive ventilation had Neuromuscular disease. High frequency nasal cannula was used in 32, and mask ventilation in 17 children. Clinical parameters common to the Non Invasive Ventilation group were age < 1 year (17), tachycardia n = 7 (22%), tachypnea n = 23 (72%) and severe respiratory distress n = 9 (28%), grunt n = 7 (22%), SPO2 (80% to 90%) n = 16. Children in the Non Invasive Ventilation + INTUBATION group were > 3 years (9), had tachycardia 7 (41%), tachypnea 9(53%) with a male predominance n = 9. In statistical comparison among 3 groups,'p' value was significant for pH, saturation, and use of Ionotrope. Conclusion: Invasive ventilation can be avoided in the paediatric Emergency Department in children with airway disease, by commencing Non Invasive Ventilation early. Intubation in the pediatric emergency department has a higher association with neuromuscular disorders.

Keywords: clinical parameters, indications, non invasive ventilation, paediatric emergency room

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Authors: Emanuela Chiarella, Clelia Nisticò, Nicola Lombardo, Giovanna Lucia Piazzetta, Nadia Lobello, Maria Mesuraca

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Killian’s Antrochoanal Polyp is a benign lesion of the maxillary sinus characterized by unilateral nasal obstruction, pus discharge, and headache. It affects, more commonly children and young adults. Although its etiology still remains unclear, chronic inflammation, autoreactivity, allergies, and viral infections are strongly associated with its formation and development, resulting in nasal tissue remodeling. We aimed to investigate the stem cells components which reside in this pathological tissue. In particular, we adopted a protocol for the isolation and culturing of mesenchymal stem cells from surgical biopsies of three Killian nasal polyp patients (KNP-MSCs) as well as from their healthy nasal tissue (HNT-MSCs) that were used as controls. The immunophenotype profile of HNT-MSCs and KNP-MSCs was more similar, with a marked positivity for CD73, CD90, and CD105 expression, while being negative for CD34 and CD14 haematopoietic genes. Cell proliferation assay showed that KNP-MSCs had a replicative disadvantage compared to HNT-MSCs, as evidenced by the significantly lower number of cells in the S-phase of the cell cycle. KNP-MSCs also took longer to close a wound than HNT-MSCs, indicating a partial epithelial phenotype in which low levels of ICAM-1 mRNA and a significant increase in E-CAD transcript were detectable. Subsequently, the differentiation potential of both MSCs populations was analyzed by inducing osteoblastic or adipocyte differentiation for up to 20 days. KNP-MSCs showed the ability to differentiate into osteoblasts, although ALP activity as well as the number and size of calcium deposits were lower than osteogenic induced-HNT-MSCs. Also, mRNA levels of osteoblastic marker genes (OCN, OPN, OSX, RUNX2) resulted lower compared to control cell population. Instead, the analysis of the adipogenic differentiation potential showed a similar behavior between KNP-MSCs and HNT-MSCs considering that the amount of lipid droplets, the expression of adipocyte-specific genes (FABP4, AdipoQ, PPARγ2, LPL) and the content of triacylglycerols were almost overlapping. Taken together, these results first demonstrated that Killian's nasal polyp is a source of mesenchymal stem cells with self-renewal and multi-differentiative capabilities.

Keywords: Mesenchymal stem cells, adipogenic differentiation, osteogenic differentiation, EMT

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Authors: Reshu Saxena, R. K. Tripathi

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HIV-1 transmission and spread involves significant host-virus interaction. Potential targets for prevention of HIV-1 lies at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and lead their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. HIV-1 Nef is important for viral infectivity and pathogenicity. It promotes HIV-1 replication, facilitating immune evasion by interacting with various host factors and altering cellular pathways via multiple protein-protein interactions. In this study nef was sequenced from HIV-1 patients, and showed specific mutations revealing sequence variability in nef. To explore the difference in Nef functionality based on sequence variability we have studied the effects of HIV-1 Nef in human SupT1 T cell line and (THP-1) monocyte-macrophage cell lines through proteomics approach. 2D-Gel Electrophoresis in control and Nef-transfected SupT1 cells demonstrated several differentially expressed proteins with significant modulation of alpha-enolase. Through further studies, effects of Nef on alpha-enolase regulation were found to be cell lineage-specific, being stimulatory in macrophages/monocytes, inhibitory in T cells and without effect in HEK-293 cells. Cell migration and invasion studies were employed to determine biological function affected by Nef mediated regulation of alpha-enolase. Cell invasion was enhanced in THP-1 cells but was inhibited in SupT1 cells by wildtype nef. In addition, the modulation of enolase and cell invasion remained unaffected by a unique nef variant. These results indicated that regulation of alpha-enolase expression and invasive property of host cells by Nef is sequence specific, suggesting involvement of a particular motif of Nef. To precisely determine this site, we designed a heptapeptide including the suggested alpha-enolase regulating sequence of nef and a nef mutant with deletion of this site. Macrophages/monocytes being the major cells affected by HIV-1 at mucosal barriers, were particularly investigated by the nef mutant and peptide. Both the nef mutant and heptapeptide led to inhibition of enhanced enolase expression and increased invasiveness in THP-1 cells. Together, these findings suggest a possible mechanism of host invasion by HIV-1 through Nef mediated regulation of alpha-enolase and identifies a potential therapeutic target for HIV-1 entry at mucosal barriers.

Keywords: HIV-1 Nef, nef variants, host-virus interaction, tissue invasion

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Authors: Zsolt Szucs, Viktor Kelemen, Son Le Thai, Magdolna Csavas, Erzsebet Roth, Gyula Batta, Annelies Stevaert, Evelien Vanderlinden, Aniko Borbas, Lieve Naesens, Pal Herczegh

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The approval of modern glycopeptide antibiotics such as dalbavancin and oritavancin which have excellent activity against Gram-positive bacteria, encouraged our research group to prepare semisynthetic compounds from several members of glycopeptides by various chemical methods. Derivatives from the aglycone of ristocetin, eremomycin, vancomycin and a pseudoaglycon of teicoplanin have been synthesized in a systematic manner. Interestingly, some of the aglycoristocetin derivatives displayed noteworthy anti-influenza activity. More recently our group has been focusing on the modifications of one of the pseudoaglycons of teicoplanin. The reaction of N-ethoxycarbonyl maleimide derivatives with the primary amino function, the copper-catalysed azide-alkyne click reaction and the sulfonylation of the N-terminus were utilized to obtain systematic series of compounds. All substituents provide a more lipophilic character to the new molecules compared to the parent antibiotics, which is known to be favourable for activity against resistant bacteria. Lipoglycopeptides are also known to have antiviral properties, which has been predominantly studied on HIV by others. The structure-activity relationship study of our compounds revealed the influence of a few structural elements on biological activity. In many cases, minimal changes in lipophilicity and structure produced great differences in efficacy and cytotoxicity. In vitro experiments showed that these compounds are not only active against glycopeptide resistant Gram-positive bacteria but in several cases they prevent the infection of cell cultures by different strains of influenza viruses. This is probably related to the inhibition of the viral entry into the host cell nucleus, of which the exact mechanism is unknown. In some instances, reasonably low concentrations were sufficient to observe this effect. Several derivatives were highly cytotoxic at the same time, but some of them displayed a good selectivity index. The antiviral properties of the compounds are not restricted to influenza viruses e.g., some of them showed good activity against Human Coronavirus 229E. This work could potentially lead to the development of antiviral drugs which possess the crucial structural motifs that are needed for antiviral activity, while missing those which contribute to the antibacterial effect.

Keywords: antiviral, glycopeptide, semisynthetic, teicoplanin

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Authors: Amirreza Razzaghipour Sorkhab

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One of the most common disorders among humans is hearing impairment. This paper provides an evidence base that recovers understanding of Meniere’s disease and highlights the physical and mental health correlates of the disorder. Meniere's disease is more common in the elderly. The term idiopathic endolymphatic hydrops has been attributed to this disease by some in the previous. Meniere’s disease demonstrations a genetic tendency, and a family history is found in 10% of cases, with an autosomal dominant inheritance pattern. The COCH gene may be one of the hereditary factors contributing to Meniere’s disease, and the possibility of a COCH mutation should be considered in patients with Meniere’s disease symptoms. Should be considered Missense mutations in the COCH gene cause the autosomal dominant sensorineural hearing loss and vestibular disorder. Meniere’s disease is a complex, heterogeneous disorder of the inner ear and that is characterized by episodes of vertigo lasting from minutes to hours, fluctuating sensorineural hearing loss, tinnitus, and aural fullness. The existing evidence supports the suggestion that age and sleep disorder are risk factors for Meniere's disease. Many factors have been reported to precipitate the progress of Menier, including endolymphatic hydrops, immunology, viral infection, inheritance, vestibular migraine, and altered intra-labyrinthine fluid dynamics. Although there is currently no treatment that has a proven helpful effect on hearing levels or on the long-term evolution of the disease, however, in the primary stages, the hearing may improve among attacks, but a permanent hearing loss occurs in the majority of cases. Current publications have proposed a role for the intratympanic use of medicine, mostly aminoglycosides, for the control of vertigo. more than 85% of patients with Meniere's disease are helped by either changes in lifestyle and medical treatment or minimally aggressive surgical procedures such as intratympanic steroid therapy, intratympanic gentamicin therapy, and endolymphatic sac surgery. However, unilateral vestibular extirpation methods (intratympanic gentamicin, vestibular nerve section, or labyrinthectomy) are more predictable but invasive approaches to control the vertigo attacks. Medical therapy aimed at reducing endolymph volume, such as low-sodium diet, diuretic use, is the typical initial treatment.

Keywords: meniere's disease, endolymphatic hydrops, hearing loss, vertigo, tinnitus, COCH gene

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Authors: Yasser Ahmed Mahmoud Ali Helal

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The use of CAD (Computer Aided Design) technology is ubiquitous in the architecture, engineering and construction (AEC) industry. This has led to its inclusion in the curriculum of architecture schools in Nigeria as an important part of the training module. This article examines the ethical issues involved in implementing CAD (Computer Aided Design) content into the architectural education curriculum. Using existing literature, this study begins with the benefits of integrating CAD into architectural education and the responsibilities of different stakeholders in the implementation process. It also examines issues related to the negative use of information technology and the perceived negative impact of CAD use on design creativity. Using a survey method, data from the architecture department of University was collected to serve as a case study on how the issues raised were being addressed. The article draws conclusions on what ensures successful ethical implementation. Millions of people around the world suffer from hepatitis C, one of the world's deadliest diseases. Interferon (IFN) is treatment options for patients with hepatitis C, but these treatments have their side effects. Our research focused on developing an oral small molecule drug that targets hepatitis C virus (HCV) proteins and has fewer side effects. Our current study aims to develop a drug based on a small molecule antiviral drug specific for the hepatitis C virus (HCV). Drug development using laboratory experiments is not only expensive, but also time-consuming to conduct these experiments. Instead, in this in silicon study, we used computational techniques to propose a specific antiviral drug for the protein domains of found in the hepatitis C virus. This study used homology modeling and abs initio modeling to generate the 3D structure of the proteins, then identifying pockets in the proteins. Acceptable lagans for pocket drugs have been developed using the de novo drug design method. Pocket geometry is taken into account when designing ligands. Among the various lagans generated, a new specific for each of the HCV protein domains has been proposed.

Keywords: drug design, anti-viral drug, in-silicon drug design, hepatitis C virus (HCV) CAD (Computer Aided Design), CAD education, education improvement, small-size contractor automatic pharmacy, PLC, control system, management system, communication

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Authors: Sarah Holdren, Laura Crook, Anne Drapkin Lyerly

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Objective: The COVID-19 Pandemic has drawn new attention to long-existing bioethical questions around pregnancy, childbirth, and parenthood. Due to the increased risk of severe COVID-19, pregnant individuals may experience anxiety regarding medical decision-making. Especially in the case of hospital births, questions around the ethics of bringing healthy pregnant individuals into a high-risk environment for viral transmission illuminate gaps in the American maternal and child healthcare system. Limited research has sought to understand the experiences of those who gave birth outside hospitals during this time. This study aims to understand pregnant individuals’ conceptualization of risk during the COVID-19 pandemic. Methods: Individuals who gave birth after March 2020 were recruited through advertisements on social media. Participants completed a 1-hour semi-structured interview and a demographic questionnaire. Interviews were transcribed and coded by members of the research team using thematic narrative analysis. Results: A total of 18 participants were interviewed and completed the demographic questionnaire. The language of risk was utilized in birth narratives in three different ways, which highlighted the multileveled and nuanced ways in which risk is understood and mitigated by pregnant and birthing individuals. These included: 1. The risk of contracting COVID-19 before, during, and after birth, 2. The risk of birth complications requiring medical interventions dependent on selected birthing space (home, birthing center, hospital), and 3. The overall risk of creating life in the middle of a pandemic. The risk of contracting COVID-19 and risk of birth complications were often weighed in paradoxical ways throughout each individual’s pregnancy, while phrases such as “pandemic baby” and “apocalypse” appeared throughout narratives and highlighted the broader implications of pregnancy and childbirth during this momentous time. Conclusions: Healthcare professionals should consider the variety of ways that pregnant and birthing individuals understand the risk when counseling patients on healthcare decisions, especially during times of healthcare crisis such as COVID-19. Future work should look to understand how the language of risk fits into a broader understanding of the human experience of growing life in times of crisis.

Keywords: maternal and child health, thematic narrative analysis, COVID-19, risk mitigation

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Authors: Yori Gidron, Maartje Mol, Norbert Foudraine, Frits Van Osch, Joop Van Den Bergh, Moshe Farchi, Maud Straus

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Background: The worldwide pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-COV2), which began in 2019, also known as Covid-19, has infected over 136 million people and tragically took the lives of over 2.9 million people worldwide. Many of the complications and deaths are predicted by the inflammatory “cytokine storm.” One way to progress in the prevention of death is by finding a predictive and protective factor that inhibits inflammation, on the one hand, and which also increases anti-viral immunity on the other hand. The vagal nerve does precisely both actions. This study examined whether vagal nerve activity, indexed by heart-rate variability (HRV), predicts survival in patients with Covid-19. Method: We performed a pseudo-prospective study, where we retroactively obtained ECGs of 271 Covid-19 patients arriving at a large regional hospital in The Netherlands. HRV was indexed by the standard deviation of the intervals between normal heartbeats (SDNN). We examined patients’ survival at 3 weeks and took into account multiple confounders and known prognostic factors (e.g., age, heart disease, diabetes, hypertension). Results: Patients’ mean age was 68 (range: 25-95) and nearly 22% of the patients had died by 3 weeks. Their mean SDNN (17.47msec) was far below the norm (50msec). Importantly, relatively higher HRV significantly predicted a higher chance of survival, after statistically controlling for patients’ age, cardiac diseases, hypertension and diabetes (relative risk, H.R, and 95% confidence interval (95%CI): H.R = 0.49, 95%CI: 0.26 – 0.95, p < 0.05). However, since HRV declines rapidly with age and since age is a profound predictor in Covid-19, we split the sample by median age (40). Subsequently, we found that higher HRV significantly predicted greater survival in patients older than 70 (H.R = 0.35, 95%CI: 0.16 – 0.78, p = 0.01), but HRV did not predict survival in patients below age 70 years (H.R = 1.11, 95%CI: 0.37 – 3.28, p > 0.05). Conclusions: To the best of our knowledge, this is the first study showing that higher vagal nerve activity, as indexed by HRV, is an independent predictor of higher chances for survival in Covid-19. The results are in line with the protective role of the vagal nerve in diseases and extend this to a severe infectious illness. Studies should replicate these findings and then test in controlled trials whether activating the vagus nerve may prevent mortality in Covid-19.

Keywords: Covid-19, heart-rate Variability, prognosis, survival, vagal nerve

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Authors: Recep Kesli, Cengiz Demir, Riza Durmaz, Zekiye Bakkaloglu, Aysegul Bukulmez

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Objective: Acute diarrhea disease in children is a major cause of morbidity worldwide and is a leading cause of mortality, and it is the most common agent responsible for acute gastroenteritis in developing countries. With hospitalized children suffering from acute enteric disease up to 50% of the analyzed specimen were positive for rotavirus. Further molecular surveillance could provide a sound basis for improving the response to epidemic gastroenteritis and could provide data needed for the introduction of vaccination programmes in the country. The aim of this study was to investigate the prevalence of viral etiology of the gastroenteritis in children aged 0-6 years with acute gastroenteritis and to determine predominant genotypes of rotaviruses in the province of Afyonkarahisar, Turkey. Methods: An epidemiological study on rotavirus was carried out during 2016. Fecal samples obtained from the 144 rotavirus positive children with 0-6 years of ages and applied to the Pediatric Diseases Outpatient of ANS Research and Practice Hospital, Afyon Kocatepe University with the complaint of diarrhea. Bacterial agents causing gastroenteritis were excluded by using bacteriological culture methods and finally, no growth observed. Rotavirus antigen was examined by both the immunochromatographic (One Step Rotavirus and Adenovirus Combo Test, China) and ELISA (Premier Rotaclone, USA) methods in stool samples. Rotavirus RNA was detected by using one step real-time reverse transcription-polymerase chain reaction (RT-PCR). G and P genotypes were determined using RT-PCR with consensus primers of VP7 and VP4 genes, followed by semi nested type-specific multiplex PCR. Results: Of the total 144 rotavirus antigen-positive samples with RT-PCR, 4 (2,8%) were rejected, 95 (66%) were examined, and 45 (31,2%) have not been examined for PCR yet. Ninety-one (95,8%) of the 95 examined samples were found to be rotavirus positive with RT-PCR. Rotavirus subgenotyping distributions in G, P and G/P genotype groups were determined as; G1:45%, G2:27%, G3:13%, G9:13%, G4:1% and G12:1% for G genotype, and P[4]:33%, P[8]:66%, P[10]:1% for P genotype, and G1P[8]:%37, G2P[4]:%21, G3P[8]:%10, G4P[8]:%1, G9P[8]:%8, G2P[8]:%3 for G/P genotype . Not common genotype combination were %20 in G/P genotype. Conclusions: This study subscribes to the global agreement of the molecular epidemiology of rotavirus which will be useful in guiding the alternative and application of rotavirus vaccines or effective control and interception. Determining the diversity and rates of rotavirus genotypes will definitely provide guidelines for developing the most suitable vaccine.

Keywords: gastroenteritis, genotyping, rotavirus, RT-PCR

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Authors: Samuel E. Okere, Anthony E. Ataga

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Introduction: This paper evaluated the mineral compositions, disease resistance elicitors in Pleurotus ostratus (POWESMS), and Pleurotus tuber-regium water extract spent mushroom substrate (PTWESMS) on the growth, yield, and management of cassava mosaic disease. Materials and Methods: The cassava plantlet (tms 98/0505) were generated through meristem tip culture at the Tissue Culture Laboratory, National Root Crop Research Institute, Umudike before they were transferred to the screen house, University of Port Harcourt Research Farm. The minerals and elicitors contained in the two spent mushroom substrates were evaluated using standard procedures. The treatments for this investigation comprised cassava plants treated with POWESMS, PTWESMS, and untreated cassava as control, which were inoculated with viral inoculum seven days after treatment application. The experiment was laid out in a completely randomized block design with 3 replicates. The data generated were subjected to analysis of variance (ANOVA). Means were separated using Fishers Least Significant Difference at p=0.05. Results: The results obtained revealed that POWESMS contained 19.3, 0.52, and 0.1g/200g substrate of carbohydrate polymers, glycoproteins, and lipid molecules elicitors respectively while it also contained 3.17, 212.1, 17.9,21.8, 58.8 and 111.0 mg/100g substrate for N, P, K, Na, Mg and Ca respectively. Further, PTWESMS contain 1.6, 0.04, and 0.2g/200g of the substrate as carbohydrate polymers, glycoprotein, and lipid respectively; the minerals contained in this substrate were 3.4, 204.8, 8.9, 24.2, 32.2 and 105.5 mg respectively for N, P, K, Na, and Ca. There were also significant differences in the mean values of the number of storage roots, root length, fresh root weight, fresh weight plant biomass, root girth, and whole plant dry biomass, but no significant difference was recorded for harvest index. The result also revealed significant differences in mean values of disease severity index evaluated at 4, 8, 12, 16, 20, 24, and 28 weeks after inoculation (WAI). Conclusion: The aqueous extract of these spent mushrooms substrate have shown outstanding prospect in managing cassava mosaic disease and also improvement in growth and yield of cassava due to the high level of the minerals and elicitors they contain when compared with the control. However, more work is recommended, especially in understanding the mechanism of this induced resistance.

Keywords: characterization, elicitors, mosaic, mushroom

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Authors: Sabin Aslam, Sultan Habibullah Khan, James G. Thomson, Abhaya M. Dandekar

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Losses due to viral diseases are posing a serious threat to crop production. A quick breakdown of resistance to viruses like Cotton Leaf Curl Virus (CLCuV) demands the application of a proficient technology to engineer durable resistance. Gene stacking has recently emerged as a potential approach for integrating multiple genes in crop plants. In the present study, recombinase technology has been used for site-specific gene stacking. A target vector (pG-Rec) was designed for engineering a predetermined specific site in the plant genome whereby genes can be stacked repeatedly. Using Agrobacterium-mediated transformation, the pG-Rec was transformed into Coker-312 along with Nicotiana tabacum L. cv. Xanthi and Nicotiana benthamiana. The transgene analysis of target lines was conducted through junction PCR. The transgene positive target lines were used for further transformations to site-specifically stack two genes of interest using Bxb1 and PhiC31 recombinases. In the first instance, Cas9 driven by multiplex gRNAs (for Rep gene of CLCuV) was site-specifically integrated into the target lines and determined by the junction PCR and real-time PCR. The resulting plants were subsequently used to stack the second gene of interest (AVP3 gene from Arabidopsis for enhancing cotton plant growth). The addition of the genes is simultaneously achieved with the removal of marker genes for recycling with the next round of gene stacking. Consequently, transgenic marker-free plants were produced with two genes stacked at the specific site. These transgenic plants can be potential germplasm to introduce resistance against various strains of cotton leaf curl virus (CLCuV) and abiotic stresses. The results of the research demonstrate gene stacking in crop plants, a technology that can be used to introduce multiple genes sequentially at predefined genomic sites. The current climate change scenario highlights the use of such technologies so that gigantic environmental issues can be tackled by several traits in a single step. After evaluating virus resistance in the resulting plants, the lines can be a primer to initiate stacking of further genes in Cotton for other traits as well as molecular breeding with elite cotton lines.

Keywords: cotton, CRISPR/Cas9, gene stacking, genome editing, recombinases

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Authors: Marissa Dallara, Amalia Ardeljan, Lexi Frankel, Nadia Obaed, Naureen Rashid, Omar Rashid

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Human Cytomegalovirus (HCMV) is a ubiquitous virus that remains latent in approximately 60% of individuals in developed countries. Viral load is kept at a minimum due to a robust immune response that is produced in most individuals who remain asymptomatic. HCMV has been recently implicated in cancer research because it may impose oncomodulatory effects on tumor cells of which it infects, which could have an impact on the progression of cancer. HCMV has been implicated in increased pathogenicity of certain cancers such as gliomas, but in contrast, it can also exhibit anti-tumor activity. HCMV seropositivity has been recorded in tumor cells, but this may also have implications in decreased pathogenesis of certain forms of cancer such as leukemia as well as increased pathogenesis in others. This study aimed to investigate the correlation between cytomegalovirus and the incidence of breast cancer. Methods The data used in this project was extracted from a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to analyze the patients infected versus patients not infection with cytomegalovirus using ICD-10, ICD-9 codes. Permission to utilize the database was given by Holy Cross Health, Fort Lauderdale, for the purpose of academic research. Data analysis was conducted using standard statistical methods. Results The query was analyzed for dates ranging from January 2010 to December 2019, which resulted in 14,309 patients in both the infected and control groups, respectively. The two groups were matched by age range and CCI score. The incidence of breast cancer was 1.642% and 235 patients in the cytomegalovirus group compared to 4.752% and 680 patients in the control group. The difference was statistically significant by a p-value of less than 2.2x 10^-16 with an odds ratio of 0.43 (0.4 to 0.48) with a 95% confidence interval. Investigation into the effects of HCMV treatment modalities, including Valganciclovir, Cidofovir, and Foscarnet, on breast cancer in both groups was conducted, but the numbers were insufficient to yield any statistically significant correlations. Conclusion This study demonstrates a statistically significant correlation between cytomegalovirus and a reduced incidence of breast cancer. If HCMV can exert anti-tumor effects on breast cancer and inhibit growth, it could potentially be used to formulate immunotherapy that targets various types of breast cancer. Further evaluation is warranted to assess the implications of cytomegalovirus in reducing the incidence of breast cancer.

Keywords: human cytomegalovirus, breast cancer, immunotherapy, anti-tumor

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Authors: Josiane N. Muller, Allan K. R. Galardo, Tatiane A. Barbosa, Evan P. Ferro, Wellington M. Dos Santos, Ana Paula S. A. Correa, Edinaldo C. Rego, Jose B. P. Lima

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The susceptibility status of an insect population to any larvicide depends on several factors such includes genetic constitution, environmental conditions and others. The mosquito Aedes aegypti is the primary vector of three important viral diseases, Zika, Dengue, and Chikungunya. The frequent outbreaks of those diseases in different parts of Brazil demonstrate the importance of testing the susceptibility of vectors in different environments. Since the control of this mosquito leads to the control of disease, alternatives for vector control that value the different Brazilian environmental conditions are needed for effective actions. The aim of this study was to evaluate a new commercial formulation of Bacillus thuringiensis israelenses (DengueTech: Brazilian innovative technology) in the Brazilian Legal Amazon considering the climate conditions. Semi-field tests were conducted in the Institute of Scientific and Technological Research of the State of Amapa in two different environments, one in a shaded area and the other exposed to sunlight. The mosquito larvae were exposed to larvicide concentration and a control; each group was tested in three containers of 40 liters each. To assess persistence 50 third instar larvae of Aedes aegypti laboratory lineages (Rockefeller) and 50 larvae of Aedes aegypti collected in the municipality of Macapa, Brazil’s Amapa state, were added weekly and after 24 hours the mortality was assessed. In total 16 tests were performed, where 12 were done with replacement of water (1/5 of the volume, three times per week). The effectiveness of the product was determined through mortality of ≥ 80%, as recommend by the World Health Organization. The results demonstrated that high-water temperatures (26-35 °C) on the containers influenced the residual time of the product, where the maximum effect achieved was 21 days in the shaded area; and no effectiveness of 60 days was found in any of the tests, as expected according to the larvicide company. The test with and without water replacement did not present significant differences in the mortality rate. Considering the different environments and climate, these results stimulate the need to test larvicide and its effectiveness in specific environmental settings in order to identify the parameters required for better results. Thus, we see the importance of semi-field researches considering the local climate conditions for a successful control of Aedes aegypti.

Keywords: Aedes aegypti, bioassay, larvicida, vector control

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Authors: Samuel Munaf, Kevin Swingler, Franz Brülisauer, Anthony O’Hare, George Gunn, Aaron Reeves

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Background: Avian influenza, more commonly known as Bird flu, is a viral zoonotic respiratory disease stemming from various species of poultry, including pets and migratory birds. Researchers have purported that the accessibility of health information online, in addition to the low-cost data collection methods the internet provides, has revolutionized the methods in which epidemiological and disease surveillance data is utilized. This paper examines the feasibility of using internet data sources, such as Twitter and livestock forums, for the early detection of the avian flu outbreak, through the use of text mining algorithms and social network analysis. Methods: Social media mining was conducted on Twitter between the period of 01/01/2021 to 31/12/2021 via the Twitter API in Python. The results were filtered firstly by hashtags (#avianflu, #birdflu), word occurrences (avian flu, bird flu, H5N1), and then refined further by location to include only those results from within the UK. Analysis was conducted on this text in a time-series manner to determine keyword frequencies and topic modeling to uncover insights in the text prior to a confirmed outbreak. Further analysis was performed by examining clinical signs (e.g., swollen head, blue comb, dullness) within the time series prior to the confirmed avian flu outbreak by the Animal and Plant Health Agency (APHA). Results: The increased search results in Google and avian flu-related tweets showed a correlation in time with the confirmed cases. Topic modeling uncovered clusters of word occurrences relating to livestock biosecurity, disposal of dead birds, and prevention measures. Conclusions: Text mining social media data can prove to be useful in relation to analysing discussed topics for epidemiological surveillance purposes, especially given the lack of applied research in the veterinary domain. The small sample size of tweets for certain weekly time periods makes it difficult to provide statistically plausible results, in addition to a great amount of textual noise in the data.

Keywords: veterinary epidemiology, disease surveillance, infodemiology, infoveillance, avian influenza, social media

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Authors: Ashutosh Biswas, Poonam Coushic, Kalpana Baruah, Paras Singla, A. C. Dhariwal, Pawana Murthy

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Burden of Dengue in Northern India Ashutosh Biswas, Poonam Coushic, Kalpana Baruah, Paras Singla, AC Dhariwal, Pawana Murthy. All India Institute of Medical Sciences, NVBDCP,WHO New Delhi, India Aim: This study was conducted to estimate the burden of dengue in capital region of India. Methodology:Seropositivity of Dengue for IgM Ab, NS1 Ag and IgG Ab were performed among the blood donors’ samples from blood bank, those who were coming to donate blood for the requirement of blood for the admitted patients in hospital. Blood samplles were collected through out the year to estimate seroprevalance of dengue with or without outbreak season. All the subjects were asymptomatic at the time of blood donation. Results: A total of 1558 donors were screened for the study. On the basis of inclusion/ exclusion criteria, we enrolled 1531subjects for the study.Twenty seven donors were excluded from the study, out of which 6 were detected HIV +ve, 11 were positive for HBsAg and 10 were found positive for HCV.Mean age was 30.51 ± 7.75 years.Of 1531subjects, 18 (1.18%) had a past history of typhoid fever, 28 (1.83%) had chikungunya fever, 9 (0.59%) had malaria and 43 subjects (2.81%) had a past history of symptomatic dengue infection.About 2.22% (34) of subjects were found to have sero-positive for NS1 Ag with a peak point prevalence of 7.14% in the month of October and sero-positive of IgM Ab was observed about 5.49% (84)with a peak point prevalence of 14.29% in the month of October. Sero-prevalnce of IgGwas detected in about 64.21% (983) of subjects. Conclusion: Acute asymptomatic dengue (NS1 Ag+ve) was observed in 7.14%, as the subjects were having no symptoms at the time of sampling. This group of subjects poses a potential public health threat for transmitting dengue infection through blood transfusion (TTI) in the community as evident by presence of active viral infection due to NS1Ag +VE. Therefore a policy may be implemented in the blood bank for testing NS1 Ag to look for active dengue infection for preventing dengue transmission through blood transfusion (TTI). Acute or Subacute dengue infection ( IgM Ab+ve) was observed from 5.49% to 14.29% which is a peak point prevalence in the month of October. About 64.21% of the population were immunized by natural dengue infection ( IgG Ab+ve) in theNorthern province of India. This might be helpful for implementing the dengue vaccine in a region. Blood samples in blood banks should be tested for dengue before transfusion to any other person to prevent transfusion transmitted dengue infection as we estimated upto 7.14% positivity of NS1 Ag in our study which indicates presence of dengue virus in blood donors’ samples.

Keywords: Dengue Burden, Seroprevalance, Asymptomatic dengue, Dengue transmission through blood transfusion

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Authors: A. H. Taghdisi, M. Mirmohammadi, S. Kamali

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Evening primrose (Oenothera biennis L.) is a biennial and herbaceous and one of the most important species of medicinal plants in the world. due to the production of unsaturated fatty acids such as linoleic acid, alpha-linolenic acid, etc. in its seeds and roots, and compounds such as kaempferol in its leaves, Evening primrose has important medicinal efficiency such as reducing premenstrual problems, acceleration of wound healing, inhibiting platelet aggregation, sedation of cardiovascular diseases, and treatment of viral infections. The sap of the plant is used to treat warts, and the plant itself is used as a charm against mental and spiritual diseases and poisonous animals. Its leaves have significant antibacterial activity against yellow staphylococci. It is also used in the treatment of poisoning, especially the toxication caused by the consumption of alcoholic beverages, in the treatment of arteriosclerosis and diseases caused by liver cell insufficiency. Low germination and production speed are the problems of evening primrose growth and propagation. In the present study, extracts were obtained from four components (flowers, stems, seeds, leaves) of the evening primrose plant using the Soxhlet apparatus. To measure the antibacterial properties against MDR bacteria, microbial methods, including dilution, cultivation on a plate containing nutrient agar culture medium, and disc diffusion in agar, were performed using Staphylococcus aureus and Escherichia coli bacteria on all four extracts. The maximum antibacterial activity related to the dilution method was obtained in all extracts. In the plate culture method, antibacterial activity was obtained for all extracts in the nutrient agar medium. The maximum diameter of the non-growth halo was obtained in the disc diffusion method in agar in the leaf extract. The statistical analysis of the microbial part was done by one-way ANOVA test (SPSS). By comparing the amount of omega-3 in extracts of Iranian and foreign oils available in the market and the extracts extracted from evening primrose plant samples with gas chromatography, it is shown that the stem extract had the most omega-3 (oleic acid) and compared to the extract of the mentioned oils, it had the highest amount of omega-3 overall. Also, the amount of omega-3 in the extract of Iranian oils was much higher than in the extract of foreign oils. It should be noted that the extract of foreign oils had a more complete composition of omega-3 than the extract of Iranian oils.

Keywords: antibacterial activity, MDR bacteria, evening primrose, omega-3

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Authors: Esshili Awatef, Manitz Marie-Pierre, Eßlinger Manuela, Gerhardt Alexandra, Plümper Jennifer, Wachholz Simone, Friebe Astrid, Juckel Georg

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Maternal immune activation (MIA) resulting from maternal viral infection during pregnancy is a known risk factor for schizophrenia. The neural mechanisms by which maternal infections increase the risk for schizophrenia remain unknown, although the prevailing hypothesis argues that an activation of the maternal immune system induces changes in the maternal-fetal environment that might interact with fetal brain development. It may lead to an activation of fetal microglia inducing long-lasting functional changes of these cells. Based on post-mortem analysis showing an increased number of activated microglial cells in patients with schizophrenia, it can be hypothesized that these cells contribute to disease pathogenesis and may actively be involved in gray matter loss observed in such patients. In the present study, we hypothesize that prenatal treatment with the inflammatory agent Poly(I:C) during embryogenesis at contributes to microglial activation in the offspring, which may, therefore, represent a contributing factor to the pathogenesis of schizophrenia and underlines the need for new pharmacological treatment options. Pregnant rats were treated with intraperitoneal injections a single dose of Poly(I:C) or saline on gestation day 17. Brains of control and Poly(I:C) offspring, were removed and into 20-μm-thick coronal sections were cut by using a Cryostat. Brain slices were fixed and immunostained with ba1 antibody. Subsequently, Iba1-immunoreactivity was detected using a secondary antibody, goat anti-rabbit. The sections were viewed and photographed under microscope. The immunohistochemical analysis revealed increases in microglia cell number in the prefrontal cortex, in offspring of poly(I:C) treated-rats as compared to the controls injected with NaCl. However, no significant differences were observed in microglia activation in the cerebellum among the groups. Prenatal immune challenge with Poly(I:C) was able to induce long-lasting changes in the offspring brains. This lead to a higher activation of microglia cells in the prefrontal cortex, a brain region critical for many higher brain functions, including working memory and cognitive flexibility. which might be implicated in possible changes in cortical neuropil architecture in schizophrenia. Further studies will be needed to clarify the association between microglial cells activation and schizophrenia-related behavioral alterations.

Keywords: Microglia, neuroinflammation, PolyI:C, schizophrenia

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Authors: L. D. Upegui, Isabel Alvarez-Solorza, Karina Garduno-Ulloa, Maren Boecker

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Introduction: The increasing prevalence rate of resistant and multiresistant bacterial strains to antibiotics is a threat to public health and requires a rapid multifunctional answer. Individuals that are affected by resistant strains present a higher morbidity and mortality than individuals that are infected with the same species of bacteria but with sensitive strains. There have been identified risk factors that are related to the misuse and overuse of antibiotics, like socio-demographic characteristics and psychological aspects of the individuals that have not been explored objectively due to a lack of valid and reliable instruments for their measurement. Objective: To validate a questionnaire for the evaluation of the levels of knowledge related to the use of antibiotics in a Mexican population. Materials and Methods: Analytical cross-sectional observational study. The questionnaire consists of 12 items to evaluated knowledge (1=no, 2=not sure, 3=yes) regarding the use of antibiotics, with higher scores corresponding to a higher level of knowledge. Data are collected in a sample of students. Data collection is still ongoing. In this abstract preliminary results of 30 respondents are reported which were collected during pilot-testing. The validation of the instrument was done using the Rasch model. Fit to the Rasch model was tested checking overall fit to the model, unidimensionality, local independence and evaluating the presence of Differential Item Functioning (DIF) by age and gender. The software Rumm2030 and the SPSS were used for the analyses. Results: The participants of the pilot-testing presented an average age of 32 years ± 12.6 and 53% were women. The preliminary results indicated that the items showed good fit to the Rasch model (chi-squared=12.8 p=0.3795). Unidimensionality (number of significant t-tests of 3%) could be proven, the items were locally independent, and no DIF was observed. Knowledge was the smallest regarding statements on the role of antibiotics in treating infections, e.g., most of the respondents did not know that antibiotics would not work against viral infections (70%) and that they could also cause side effects (87%). The knowledge score ranged from 0 to 100 points with a transformed measurement (mean of knowledge 27.1 ± 4.8). Conclusions: The instrument showed good psychometric proprieties. The low scores of knowledge about antibiotics suggest that misinterpretations on the use of these medicaments were prevalent, which could influence the production of antibiotic resistance. The application of this questionnaire will allow the objective identification of 'Hight risk groups', which will be the target population for future educational campaigns, to reduce the knowledge gaps on the general population as an effort against antibiotic resistance.

Keywords: antibiotics, knowledge, misuse, overuse, questionnaire, Rasch model, validation

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Authors: Satendra Pal Singh, Dalip Kr. Kakru, Jyoti Mishra, Rajesh Thakur, Tarana Sarwat

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COVID-19 is still an intrigue as far as morbidity or mortality is concerned. The rate of recovery varies from person to person, & it depends upon the accessibility of the healthcare system and the roles played by the physicians and caregivers. It is envisaged that with the passage of time, people would become immune to this virus, and those who are vulnerable would sustain themselves with the help of vaccines. The proposed study deals with the severeness of COVID-19 is associated with some specific biomarkers linked to correlate age and gender. We will be assessing the overall homeostasis of the persons who were affected by the coronavirus infection and also of those who recovered from it. Some people show more severe effects, while others show very mild symptoms, however, they show low CT values. Thus far, it is unclear why the new strain of Covid has different effects on different people in terms of age, gender, and ABO blood typing. According to data, the fatality rate with heart disease was 10.5 percent, 7.3 percent were diabetic, and 6 percent who are already infected from other comorbidities. However, some COVID-19 cases are worse than others & it is not fully explainable as of date. Overall data show that the ABO blood group is effective or prone to the risk of SARS-COV2 infection, while another study also shows the phenotypic effects of the blood group related to covid. It is an accepted fact that females have more strong immune systems than males, which may be related to the fact that females have two ‘X’ chromosomes, which might contain a more effective immunity booster gene on the X chromosome, and are capable to protect the female. Also specific sex hormones also induce a better immune response in a specific gender. This calls for in-depth analysis to be able to gain insight into this dilemma. COVID-19 is still not fully characterized, and thus we are not very familiar with its biology, mode of infection, susceptibility, and overall viral load in the human body. How many virus particles are needed to infect a person? How, then, comorbidity contribute to coronavirus infection? Since the emergence of this virus in 2020, a large number of papers have been published, and seemingly, vaccines have been prepared. But still, a large number of questions remain unanswered. The proneness of humans for infection by covid-19 needs to be established to be able to develop a better strategy to fight this virus. Our study will be on the Impact of demography on the Severity of covid-19 infection & at the same time, will look into gender-specific sensitivity of Covid-19 and the Operational variation of different biochemical markers in Covid-19 positive patients. Besides, we will be studying the co-relation, if any, of COVID severity & ABO Blood group type and the occurrence of the most common blood group type amongst positive patience.

Keywords: coronavirus, ABO blood group, age, gender

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Authors: Ismail Bamidele Afolabi, Abdulmujeeb Babatunde Aremu, Lawal Abdurraheem Maidoki, Nnodimele Onuigbo Atulomah

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Background: Hepatitis B virus infection remains a significant global public health challenge with infectivity as well as the potential for transmission more than 50 to 100 times that of HIV. Annually, global HBV-related mortality is linked primarily to cirrhosis and liver carcinoma. The ever-increasing endemicity of HBV among children under-5-years, owing to vertical transmission and its lingering chronicity in developing countries, will hamper the global efforts concertedly endorsed towards eliminating viral hepatitis as a global public health threat by 2030. Objective: This study assessed information motivation behavioral skills model constructs as predictors of HBV infection prevention practices among consenting expectant mothers attending antenatal care in Central Uganda as a focal point of intervention towards breaking materno-foetal transmission of HBV. Methods: A cross-sectional study with a quantitative data collection approach based on the constructs of the IMB model was used to capture data on the study variables among 385 randomly selected pregnant women between September and October 2020. Data derived from the quantitative instrument were transformed into weighted aggregate scores using SPSS version 26. ANOVA and regression analysis were done to ascertain the study hypotheses with a significance level set as (p ≤ 0.05). Results: Relatively 60% of the respondents were aged between 18 and 28. Expectant mothers with secondary education (42.3%) were predominant. Furthermore, an average but inadequate knowledge (X ̅=5.97±6.61; B=0.57; p<.001), incorrect perception (X ̅=17.10±18.31; B=0.97; p=.014), and good behavioral skills (X ̅=12.39±13.37; B=0.56; p<.001) for adopting prevention practices all statistically predicted the unsatisfactory level of prevention practices (X ̅=15.03±16.20) among the study respondents as measured on rating scales of 12, 33, 21 and 30 respectively. Conclusion: Evidence from this study corroborates the imperativeness of IMB constructs in reducing the burden of HBV infection in developing countries. Therefore, the inadequate HBV knowledge and misperception among obstetric populations necessitate personalized health education during antenatal visits and subsequent health campaigns in order to inform better prevention practices and, in turn, reduce the lingering chronicity of HBV infection in developing countries.

Keywords: behavioral skills, HBV infection, knowledge, perception, pregnant women, prevention practices

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Authors: Steven G. Sclan

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Background: Since December 2019, the world has been afflicted by the spread of the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2), which is responsible for the condition referred to as Covid-19. The illness has had a cataclysmic impact on the political, social, economic, and overall well-being of the population of the entire globe. While Covid-19 has had a substantial universal fatality impact, it may have an even greater effect on the socioeconomic, medical well-being, and healthcare planning for remaining societies. Significance: As these numbers illustrate, many more persons survive the infection than die from it, and many of those patients have noted ongoing, persistent symptoms after successfully enduring the acute phase of the illness. Recognition and understanding of these symptoms are crucial for developing and arranging efficacious models of care for all patients (whether or not having been hospitalized) surviving acute covid illness and plagued by post-acute symptoms. Furthermore, regarding Covid infection in children (< 18 y/o), although it may be that Covid “+” children are not major vectors of infective transmission, it now appears that many more children than initially thought are carrying the virus without accompanying obvious symptomatic expression. It seems reasonable to wonder whether viral effects occur in children – those children who are Covid “+” and now asymptomatic – and if, over time, they might also experience similar symptoms. An even more significant question is whether Covid “+” asymptomatic children might manifest increased multiple health problems as they grow – i.e., developmental complications (e.g., physical/medical, metabolic, neurobehavioral, etc.) – in comparison to children who had been consistently Covid “ - ” during the pandemic. Topics Addressed and Theoretical Importance: This review is important because of the description of both quantitative and qualitative methods for clinical and biomedical research. Topics reviewed will consider the importance of well-designed, comprehensive (i.e., quantitative and qualitative methods) longitudinal studies of Post Covid-19 symptoms in both adults and children. Also reviewed will be general characteristics of longitudinal studies and a presentation of a model for a proposed study. Also discussed will be the benefit of longitudinal studies for the development of efficacious interventions and for the establishment of cogent, practical, and efficacious community healthcare service planning for post-acute covid patients. Conclusion: Results of multi-dimensional, longitudinal studies will have important theoretical implications. These studies will help to improve our understanding of the pathophysiology of long COVID and will aid in the identification of potential targets for treatment. Such studies can also provide valuable insights into the long-term impact of COVID-19 on public health and socioeconomics.

Keywords: COVID-19, post-COVID-19, long COVID, longitudinal research, quantitative research, qualitative research

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Authors: R. Pussinen, V. Jankovic, U. Herzberg, M. Cerrada-Gimenez, T. Huhtala, A. Nurmi, T. Ahtoniemi

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Targeted over-expression of human α-synuclein using viral-vector mediated gene delivery into the substantia nigra of rats and non-human primates has been reported to lead to dopaminergic cell loss and the formation of α-synuclein aggregates reminiscent of Lewy bodies. We have previously shown how AAV-mediated expression of α-synuclein is seen in the chronic phenotype of the rats over 16 week follow-up period. In the context of these findings, we attempted to further characterize this long term PD related functional and motor deficits as well as neurochemical and neuropathological changes in AAV-mediated α-synuclein transfection model in rats during chronic follow-up period. Different titers of recombinant AAV expressing human α-synuclein (A53T) were stereotaxically injected unilaterally into substantia nigra of Wistar rats. Rats were allowed to recover for 3 weeks prior to initial baseline behavioral testing with rotational asymmetry test, stepping test and cylinder test. A similar behavioral test battery was applied again at weeks 5, 9,12 and 15. In addition to traditionally used rat PD model tests, MotoRater test system, a high speed kinematic gait performance monitoring was applied during the follow-up period. Evaluation focused on animal gait between groups. Tremor analysis was performed on weeks 9, 12 and 15. In addition to behavioral end-points, neurochemical evaluation of dopamine and its metabolites were evaluated in striatum. Furthermore, integrity of the dopamine active transport (DAT) system was evaluated by using 123I- β-CIT and SPECT/CT imaging on weeks 3, 8 and 12 after AAV- α-synuclein transfection. Histopathology was examined from end-point samples at 3 or 12 weeks after AAV- α-synuclein transfection to evaluate dopaminergic cell viability and microglial (Iba-1) activation status in substantia nigra by using stereological analysis techniques. This study focused on the characterization and validation of previously published AAV- α-synuclein transfection model in rats but with the addition of novel end-points. We present the long term phenotype of AAV- α-synuclein transfected rats with traditionally used behavioral tests but also by using novel fine motor analysis techniques and tremor analysis which provide new insight to unilateral effects of AAV α-synuclein transfection. We also present data about neurochemical and neuropathological end-points for the dopaminergic system in the model and how well they correlate with behavioral phenotype.

Keywords: adeno-associated virus, alphasynuclein, animal model, Parkinson’s disease

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Authors: Christi Jackson, Chuka Onaga

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Introduction: We report a case of delayed diagnosis of extra-pulmonary INH-mono-resistant Tuberculosis (TB) in a South African patient with drug-resistant HIV. Case Presentation: A 36-year old male was initiated on 1st line (NNRTI-based) anti-retroviral therapy (ART) in September 2009 and switched to 2nd line (PI-based) ART in 2011, according to local guidelines. He was following up at the outpatient wellness unit of a public hospital, where he was diagnosed with Protease Inhibitor resistant HIV in March 2016. He had an HIV viral load (HIVVL) of 737000 copies/mL, CD4-count of 10 cells/µL and presented with complaints of productive cough, weight loss, chronic diarrhoea and a septic buttock wound. Several investigations were done on sputum, stool and pus samples but all were negative for TB. The patient was treated with antibiotics and the cough and the buttock wound improved. He was subsequently started on a 3rd-line ART regimen of Darunavir, Ritonavir, Etravirine, Raltegravir, Tenofovir and Emtricitabine in May 2016. He continued losing weight, became too weak to stand unsupported and started complaining of abdominal pain. Further investigations were done in September 2016, including a urine specimen for Line Probe Assay (LPA), which showed M. tuberculosis sensitive to Rifampicin but resistant to INH. A lymph node biopsy also showed histological confirmation of TB. Management and outcome: He was started on Rifabutin, Pyrazinamide and Ethambutol in September 2016, and Etravirine was discontinued. After 6 months on ART and 2 months on TB treatment, his HIVVL had dropped to 286 copies/mL, CD4 improved to 179 cells/µL and he showed clinical improvement. Pharmacy supply of his individualised drugs was unreliable and presented some challenges to continuity of treatment. He successfully completed his treatment in June 2017 while still maintaining virological suppression. Discussion: Several laboratory-related factors delayed the diagnosis of TB, including the unavailability of urine-lipoarabinomannan (LAM) and urine-GeneXpert (GXP) tests at this facility. Once the diagnosis was made, it presented a treatment dilemma due to the expected drug-drug interactions between his 3rd-line ART regimen and his INH-resistant TB regimen, and specialist input was required. Conclusion: TB is more difficult to diagnose in patients with severe immunosuppression, therefore additional tests like urine-LAM and urine-GXP can be helpful in expediting the diagnosis in these cases. Patients with non-standard drug regimens should always be discussed with a specialist in order to avoid potentially harmful drug-drug interactions.

Keywords: drug-resistance, HIV, line probe assay, tuberculosis

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Authors: David Tennison

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In the wake of the Covid-19 pandemic, a new chronic illness emerged onto the global stage: Long Covid. Long Covid presents with several symptoms commonly seen in other poorly-understood illnesses, such as fibromyalgia (FM) and myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). However, while Long Covid has swiftly become a recognised illness, FM and ME/CFS are still seen as contested, which impacts patient care and healthcare experiences. This study aims to examine what the differences are between Long Covid and FM; and if the Long Covid case can provide guidance for how to address the healthcare challenge of contested illnesses. To address this question, this study performed comprehensive research into the history of FM; our current biomedical understanding of it; and available healthcare interventions (within the context of the UK NHS). Analysis was undertaken of the stigma and stereotypes around FM, and a comparison made between FM and the emerging Long Covid literature, along with the healthcare response to Long Covid. This study finds that healthcare for chronic contested illnesses in the UK is vastly insufficient - in terms of pharmaceutical and holistic interventions, and the provision of secondary care options. Interestingly, for Long Covid, many of the treatment suggestions are pulled directly from those used for contested illnesses. The key difference is in terms of funding and momentum – Long Covid has generated exponentially more interest and research in a short time than there has been in the last few decades of contested illness research. This stands to help people with FM and ME/CFS – for example, research has recently been funded into “brain fog”, a previously elusive and misunderstood symptom. FM is culturally regarded as a “women’s disease” and FM stigma stems from notions of “hysteria”. A key finding is that the idea of FM affecting women disproportionally is not reflected in modern population studies. Emerging data on Long Covid also suggests a slight leaning towards more female patients, however it is less feminised, potentially due to it emerging in the global historical moment of the pandemic. Another key difference is that FM is rated as an extremely low-prestige illness by healthcare professionals, while it was in large part due to the advocacy of affected healthcare professionals that Long Covid was so quickly recognised by science and medicine. In conclusion, Long Covid (and the risk of future pandemics and post-viral illnesses) highlight a crucial need for implementing new, and reinforcing existing, care networks for chronic illnesses. The difference in how contested illnesses like FM, and new ones like Long Covid are treated have a lot to do with the historical moment in which they emerge – but cultural stereotypes, from within and without medicine, need updating. Particularly as they contribute to disease stigma that causes genuine harm to patients. However, widespread understanding and acceptance of Long Covid could help fight contested illness stigma, and the attention, funding and research into Long Covid may actually help raise the profile of contested illnesses and uncover answers about their symptomatology.

Keywords: long COVID, fibromyalgia, myalgic encephalomyelitis, chronic fatigue syndrome, NHS, healthcare, contested illnesses, chronic illnesses, COVID-19 pandemic

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Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava

Abstract:

The elaboration of effective drug delivery vehicles is still topical nowadays since targeted drug delivery is one of the most important challenges of the modern nanomedicine. The last decade has witnessed enormous research focused on synthetic cationic polymers (CPs) due to their flexible properties, in particular as non-viral gene delivery systems, facile synthesis, robustness, not oncogenic and proven gene delivery efficiency. However, the toxicity is still an obstacle to the application in pharmacotherapy. For overcoming the problem, creation of new cationic compounds including the polymeric nano-size particles – nano-containers (NCs) loading with different pharmaceuticals and biologicals is still relevant. In this regard, a variety of NCs-based drug delivery systems have been developed. We have found that amino acid-based biodegradable polymers called as pseudo-proteins (PPs), which can be cleared from the body after the fulfillment of their function are highly suitable for designing pharmaceutical NCs. Among them, one of the most promising are NCs made of biodegradable Cationic PPs (CPPs). For preparing new cationic NCs (CNCs), we used CPPs composed of positively charged amino acid L-arginine (R). The CNCs were fabricated by two approaches using: (1) R-based homo-CPPs; (2) Blends of R-based CPPs with regular (neutral) PPs. According to the first approach NCs we prepared from CPPs 8R3 (composed of R, sebacic acid and 1,3-propanediol) and 8R6 (composed of R, sebacic acid and 1,6-hexanediol). The NCs prepared from these CPPs were 72-101 nm in size with zeta potential within +30 ÷ +35 mV at a concentration 6 mg/mL. According to the second approach, CPPs 8R6 was blended in organic phase with neutral PPs 8L6 (composed of leucine, sebacic acid and 1,6-hexanediol). The NCs prepared from the blends were 130-140 nm in size with zeta potential within +20 ÷ +28 mV depending on 8R6/8L6 ratio. The stability studies of fabricated NCs showed that no substantial change of the particle size and distribution and no big particles’ formation is observed after three months storage. In vitro biocompatibility study of the obtained NPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed both type cathionic NCs are biocompatible. The obtained data allow concluding that the obtained CNCs are promising for the application as biodegradable drug delivery vehicles. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 'New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications'.

Keywords: biodegradable polymers, cationic pseudo-proteins, nano-containers, drug delivery vehicles

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Authors: Tatyana Savchuk, Yelena Grinvald, Mohamed Ali, Ramune Sepetiene, Dinara Sadvakassova, Saniya Saussakova, Kuralay Zhangazieva, Dulat Imashpayev

Abstract:

Introduction. The problem of viral hepatitis B (HBV) takes a vital place in the global health system. The existing risk of HBV transmission through blood transfusions is associated with transfusion of blood taken from infected individuals during the “serological window” period or from patients with latent HBV infection, the marker of which is anti-HBcore. In the absence of information about other markers of hepatitis B, the presence of anti-HBcore suggests that a person may be actively infected or has suffered hepatitis B in the past and has immunity. Aim. To study the risk factors influencing the positive anti-HBcore indicators among the donor population. Materials and Methods. The study was conducted in 2021 in the Scientific and Production Center of Transfusiology of the Ministry of Healthcare in Kazakhstan. The samples taken from blood donors were tested for anti-HBcore, by CLIA on the Architect i2000SR (ABBOTT). A special questionnaire was developed for the blood donors’ socio-demographic characteristics. Statistical analysis was conducted by the R software (version 4.1.1, USA, 2021). Results.5709 people aged 18 to 66 years were included in the study, the proportion of men and women was 68.17% and 31.83%, respectively. The average age of the participants was 35.7 years. A weighted multivariable mixed effects logistic regression analysis showed that age (p<0.001), ethnicity (p<0.05), and marital status (p<0.05) were statistically associated with anti-HBcore positivity. In particular, analysis adjusting for gender, nationality, education, marital status, family history of hepatitis, blood transfusion, injections, and surgical interventions, with a one-year increase in age (adjOR=1.06, 95%CI:1.05-1.07), showed an 6% growth in odds of having anti-HBcore positive results. Those who were russian ethnicity (adjOR=0.65, 95%CI:0.46-0.93) and representatives of other nationality groups (adjOR=0.56, 95%CI:0.37-0.85) had lower odds of having anti-HBcore when compared to Kazakhs when controlling for other covariant variables. Among singles, the odds of having a positive anti-HBcore were lower by 29% (adjOR = 0.71, 95%CI:0.57-0.89) compared to married participants when adjusting for other variables. Conclusions.Kazakhstan is one of the countries with medium endemicity of HBV prevalence (2%-7%). Results of the study demonstrated the possibility to form a profile of risk factors (age, nationality, marital status). Taking into account the data, it is recommended to increase attention to donor questionnaires by adding leading questions and to improve preventive measures to prevent HBV. Funding. This research was supported by a grant from Abbott Laboratories.

Keywords: anti-HBcore, blood donor, donation, hepatitis B virus, occult hepatitis

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