1,720,970 research outputs found
Study of antiviral activity of diazadispiroalkane compounds against alpha- and beta- coronaviruses.
Full text linkRNA viruses cause many human and animal infections characterized by worldwide spread, high mortality, and significant health costs. In the case of some RNA virus diseases, such as Polio, Measles, Yellow Fever, and others, there is the possibility of accessing effective immunoprophylaxis measures. Still, the incidence and severity of some viral diseases are to develop effective and selective therapies. This scenario is essential to develop and manufacture new and effective antiviral agents.Usually, existing antiviral agents target specific viral proteins, with a higher probability of developing drug-resistant, especially those with an RNA genome. The recent SARS-CoV-2 pandemic has moved the scientific world to pay particular attention to the Coronaviridae family, ssRNA (+) viruses that cause respiratory diseases.We focused our studies on Alphacoronavirus HCoV-229E and Betacoronavirus HCoV-OC43 andSARS-CoV-2.
These viruses use different cell receptors to enter the host cell. Recent studies have highlighted an additional mechanism of endocytosis upstream of the binding with the receptor, which involves the heparan sulfate (HS) present on the cell surface through an electrostatic interaction in which negative HS charges interact with the virus envelope, concentrating the virions and allowing the recognition of the secondary receptor.Therefore, this phase of the entry process is strategically interesting as it could be the target of broad-spectrum antivirals.Among the strategies used to block the HS-virus interaction, one particularly effective is the use of small cationic molecules that bind competitively to HS. Among these cationic molecules of particular interest are the
dispirotripiperazines and their diazadispiroalkane derivatives synthesized and kindly provided us by Prof. Vadim Makarov (Russian Academy of Sciences) and colleagues.
During my Ph.D. course, the main goal was to identify new antiviral compounds with broad- spectrum activity and study their mechanism of action. These objectives have been achieved through a multidisciplinary approach. We evaluated the toxicity and the antiviral activity of some diazadispiroalkanes, against HCoV-229E, -OC43, and SARS-CoV-2.
Subsequently, we then evaluated the selectivity and potency of these compounds, studied its mechanism of action, examined the kinetics of virus adsorption in the presence of the compound. After all, we verified whether our identified lead derivative could interfere with the penetration of the virus in the cells.
The lead compound was shown to be a SARS-COV-2 inhibitor and more robust against HCoV- OC43. The molecule acts during the pre-treatment and in the early stages of infection, causing a dose-dependent reduction in infectivity.
Therefore, the validated method for evaluating the antiviral activity of diazadispiroalkanes can be applied for the discovery and development of broad-spectrum antiviral drugs in vitroRNA viruses cause many human and animal infections characterized by worldwide spread, high mortality, and significant health costs. In the case of some RNA virus diseases, such as Polio, Measles, Yellow Fever, and others, there is the possibility of accessing effective immunoprophylaxis measures. Still, the incidence and severity of some viral diseases are to develop effective and selective therapies. This scenario is essential to develop and manufacture new and effective antiviral agents. Usually, existing antiviral agents target specific viral proteins, with a higher probability of developing drug-resistant, especially those with an RNA genome. The recent SARS-CoV-2 pandemic has moved the scientific world to pay particular attention to the Coronaviridae family, ssRNA (+) viruses that cause respiratory diseases. We focused our studies on Alphacoronavirus HCoV-229E and Betacoronavirus HCoV-OC43 and SARS-CoV-2.
These viruses use different cell receptors to enter the host cell. Recent studies have highlighted an additional mechanism of endocytosis upstream of the binding with the receptor, which involves the heparan sulfate (HS) present on the cell surface through an electrostatic interaction in which negative HS charges interact with the virus envelope, concentrating the virions and allowing the recognition of the secondary receptor. Therefore, this phase of the entry process is strategically interesting as it could be the target of broad-spectrum antivirals. Among the strategies used to block the HS-virus interaction, one particularly effective is the use of small cationic molecules that bind competitively to HS. Among these cationic molecules of particular interest are the dispirotripiperazines and their diazadispiroalkane derivatives synthesized and kindly provided us by Prof. Vadim Makarov (Russian Academy of Sciences) and colleagues. During my Ph.D. course, the main goal was to identify new antiviral compounds with broad-spectrum activity and study their mechanism of action. These objectives have been achieved through a multidisciplinary approach. We evaluated the toxicity and the antiviral activity of some diazadispiroalkanes, against HCoV-229E, -OC43, and SARS-CoV-2.
Subsequently, we then evaluated the selectivity and potency of these compounds, studied its mechanism of action, examined the kinetics of virus adsorption in the presence of the compound. After all, we verified whether our identified lead derivative could interfere with the penetration of the virus in the cells.
The lead compound was shown to be a SARS-COV-2 inhibitor and more robust against HCoV-OC43. The molecule acts during the pre-treatment and in the early stages of infection, causing a dose- dependent reduction in infectivity.
Therefore, the validated method for evaluating the antiviral activity of diazadispiroalkanes can be applied for the discovery and development of broad-spectrum antiviral drugs in vitro
1.5-T Field Intraoperative Magnetic Resonance Imaging Improves Extent of Resection and Survival in Glioblastoma Removal
No full textObjective Gross total resection (GTR) of glioblastoma may be achieved with the aid of intraoperative magnetic resonance imaging (Io-MRI), which detects residual tumor during surgery, with the aim of maximizing resection, therefore reducing the risk of recurrence. Moreover, intraoperative fiber tracking and neuronavigated electrophysiologic cortical and subcortical mapping may help prevent postoperative deficits. Methods There were 114 patients who underwent surgical removal of newly diagnosed supratentorial glioblastoma between January 2009 and January 2013: 78 (group A) were operated on with the aid of Io-MRI, and 36 were operated on without Io-MRI (group B). The protocol included preoperative magnetic resonance imaging and Io-MRI with diffusion tensor imaging in all the cases that presented eloquent areas of involvement. The extent of resection (EOR) was compared in the 2 groups 24–72 hours after surgery. Results The first Io-MRI detected a GTR in 31 patients (39.7%) and a residual tumor in 47 patients (60.3%) in group A. Twenty-one patients had residual tumor within eloquent areas: Io-MRI with fiber tracking permitted further resection, achieving GTR in 12 patients. GTR was radiologically detected in the remaining 26 patients (33.3% of group A) who had residual tumor in noneloquent areas after 1 or 2 further resection extensions. Io-MRI enhanced both EOR and 6-month progression-free survival (6-PFS): the overall GTR for group A amounted to 88.5% (n = 69), whereas for group B it was 44% (n = 16). 6-PFS accounted for 73% (n = 57) for group A and 38.9% (n = 14) for group B. Conclusions Our experience suggests that Io-MRI may lead to EOR optimization and associated 6-PFS improvement
Pannus regression after posterior decompression and occipito-cervical fixation in occipito-atlanto-axial instability due to rheumatoid arthritis: case report and literature review.
No full textObjectives: Several techniques have been proposed for treating cervical spine instability due to rheumatoid arthritis. The aim of this study was to screen the different treatment options used in this pathology to evaluate the best form of treatment when the progression of rheumatoid disease affected the cranio-vertebral junction (CVJ) stability. The most important purpose of this study was to achieve both the efficacy of occipito-cervical fusion (OCF) to stabilize the occipitocervical junction and stop pannus progression. The authors describe their case example and stress, in the light of a literature review, the hypothesis that a stable biomechanical system extended to all the spaces involved, has both direct and indirect effects on RA pannus progression and the condition responsible for its formation, such as inflammation and articular hypermobility. Hence, the aim of this study is to advance this thesis, which may be extended to a wider statistical sample, with the same characteristics. Method: A systematic literature research of case report articles, review articles, original articles, and prospective cohort studies, published from 1978 to 2011, was performed using PUBMED to analyze the different surgical strategies of RA involving CVJ and the role of OCF in these conditions. The key words used for the search the were: "inflammatory cervical pannus regression", "rheumatoid arthritis of the cranio-cervical junction", "occipito-cervical fusion", "treatment option in rheumatoid cervical instability", "altanto-axial dislocation", "craniovertebral junction" and "surgical technique". In addition, the authors reported their experience in a patient affected by erosive rheumatoid arthritis (ERA) with an anterior and posterior pannus involving C0-C1-C2. They decided to report this exemplative case to emphasize their own assumptions concerning the association between a posterior bony fusion, the arrest of anterior pannus progression and the improvement of functional outcome, without, however, a direct intervention on the anterior pannus. Result: Thirty-seven different studies were identified that reflected search criteria, five of which were literature reviews. The different surgical treatment options in cervical RA disease are described in relation to neurological outcome according to the Ranawat grading system, functional outcome or quality of life according to the Steinbrocker classification, and progression of cervical instability and radiographic index of cranial settling, focusing on the role of OCF. © 2012 Elsevier B.V
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Prevalence of double-stranded RNA virus in Trichomonas vaginalis isolated in Italy and association with the symbiont Mycoplasma hominis
No full textTrichomonas vaginalis and Mycoplasma hominis: New tales of two old friends
No full textTrichomonas vaginalis is an anaerobic protist, responsible for the most prevalent non-viral sexually transmitted infection in humans. One of the most intriguing aspects of T. vaginalis pathobiology is the complex relationship with intracellular microbial symbionts: a group of dsRNA viruses belonging to family of Totiviridae (T. vaginalis virus), and eubacteria belonging to the Mycoplasma genus, in particular Mycoplasma hominis. Both microorganisms seem to strongly influence the lifestyle of T. vaginalis, suggesting a role of the symbiosis in the high variability of clinical presentation and sequelae during trichomoniasis. In the last few years many aspects of this unique symbiotic relationship have been investigated: M. hominis resides and replicates in the protozoan cell, and T. vaginalis is able to pass the bacterial infection to both mycoplasma-free protozoan isolates and human epithelial cells; M. hominis synergistically upregulates the proinflammatory response of human monocytes to T. vaginalis. Furthermore, the influence of M. hominis over T. vaginalis metabolism and physiology has been characterized. The identification of a novel species belonging to the class of Mollicutes (Candidatus Mycoplasma girerdii) exclusively associated to T. vaginalis opens new perspectives in the research of the complex series of events taking place in the multifaceted world of the vaginal microbiota, both under normal and pathological conditions
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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