SARS-CoV-2 Neutralizing Antibodies in Mexican Population: A Five Vaccine Comparison

Neutralizing antibodies (NAs) are key immunological markers and are part of the humoral response of the adaptive immune system. NA assays determine the presence of functional antibodies to prevent SARS-CoV-2 infection. We performed a real-world evidence study to detect NAs that confer protection against SARS-CoV-2 after the application of five vaccines (Pfizer/BioNTech, AstraZeneca, Sinovac, Moderna, and CanSino) in the Mexican population. Side effects of COVID-19 vaccines and clinical and demographic factors associated with low immunogenicity were also evaluated. A total of 242 SARS-CoV-2-vaccinated subjects were recruited. Pfizer/BioNTech and Moderna proved the highest percentage of inhibition in a mono-vaccine scheme. Muscular pain, headache, and fatigue were the most common adverse events. None of the patients reported severe adverse events. We found an estimated contagion-free time of 207 (IQR: 182–231) and 187 (IQR: 184–189) days for Pfizer/BioNTech and CanSino in 12 cases in each group. On the basis of our results, we consider that the emerging vaccination strategy in Mexico is effective and safe

Integrating Lean Six Sigma and discrete-event simulation for shortening the appointment lead-time in gynecobstetrics departments: a case study

Long waiting time to appointment may be a worry for pregnant women, particularly those who need perinatology consultation since it could increase anxiety and, in a worst case scenario, lead to an increase in fetal, infant, and maternal mortality. Treatment costs may also increase since pregnant women with diverse pathologies can develop more severe complications. As a step towards improving this process, we propose a methodological approach to reduce the appointment lead-time in outpatient gynecobstetrics departments. This framework involves combining the Six Sigma method to identify defects in the appointment scheduling process with a discrete-event simulation (DES) to evaluate the potential success of removing such defects in simulation before we resort to changing the real-world healthcare system. To do these, we initially characterize the gynecobstetrics department using a SIPOC diagram. Then, six sigma performance metrics are calculated to evaluate how well the department meets the government target in relation to the appointment lead-time. Afterwards, a cause-and-effect analysis is undertaken to identify potential causes of appointment lead-time variation. These causes are later validated through ANOVA, regression analysis, and DES. Improvement scenarios are next designed and pretested through computer simulation models. Finally, control plans are deployed to maintain the results achieved through the implementation of the DES-Six sigma approach. The aforementioned framework was validated in a public gynecobstetrics outpatient department. The results revealed that mean waiting time decreased from 6.9 days to 4.1 days while variance passed from 2.46 days2 to 1.53 days2

Antibody recognition of the glycoprotein g of viral haemorrhagic septicemia virus (VHSV) purified in large amounts from insect larvae

<p>Abstract</p> <p>Background</p> <p>There are currently no purification methods capable of producing the large amounts of fish rhabdoviral glycoprotein G (gpG) required for diagnosis and immunisation purposes or for studying structure and molecular mechanisms of action of this molecule (ie. pH-dependent membrane fusion). As a result of the unavailability of large amounts of the gpG from viral haemorrhagic septicaemia rhabdovirus (VHSV), one of the most dangerous viruses affecting cultured salmonid species, research interests in this field are severely hampered. Previous purification methods to obtain recombinant gpG from VHSV in <it>E. coli</it>, yeast and baculovirus grown in insect cells have not produced soluble conformations or acceptable yields. The development of large-scale purification methods for gpGs will also further research into other fish rhabdoviruses, such as infectious haematopoietic necrosis virus (IHNV), spring carp viremia virus (SVCV), hirame rhabdovirus (HIRRV) and snakehead rhabdovirus (SHRV).</p> <p>Findings</p> <p>Here we designed a method to produce milligram amounts of soluble VHSV gpG. Only the transmembrane and carboxy terminal-deleted (amino acid 21 to 465) gpG was efficiently expressed in insect larvae. Recognition of G21-465 by ß-mercaptoethanol-dependent neutralizing monoclonal antibodies (N-MAbs) and pH-dependent recognition by sera from VHSV-hyperimmunized or VHSV-infected rainbow trout (<it>Oncorhynchus mykiss</it>) was demonstrated.</p> <p>Conclusions</p> <p>Given that the purified G21-465 conserved some of its most important properties, this method might be suitable for the large-scale production of fish rhabdoviral gpGs for use in diagnosis, fusion and antigenicity studies.</p

Applying multi-phase DES approach for modelling the patient journey through accident and emergency departments

Accident and Emergency departments (A&ED) are in charge of providing access to patients requiring urgent acute care. A&ED are difficult to model due to the presence of interactions, different pathways and the multiple outcomes that patients may undertake depending on their health status. In addition, public concern has focused on the presence of overcrowding, long waiting times, patient dissatisfaction and cost overruns associated with A&ED. There is then a need for tackling these problems through developing integrated and explicit models supporting healthcare planning. However, the studies directly concentrating on modelling the A&EDs are largely limited. Therefore, this paper presents the use of a multi-phase DES framework for modelling the A&ED and facilitating the assessment of potential improvement strategies. Initially, the main components, critical variables and different states of the A&ED are identified to correctly model the entire patient journey. In this step, it is also necessary to characterize the demand in order to categorize the patients into pipelines. After this, a discrete-event simulation (DES) model is developed. Then, validation is conducted through the 2-sample t test to demonstrate whether the model is statistically comparable with the real-world A&ED department. This is followed by the use of Markov phase-type models for calculating the total costs of the whole system. Finally, various scenarios are explored to assess their potential impact on multiple outcomes of interest. A case study of a mixed-patient environment in a private A&E department is provided to validate the effectiveness of the multi-phase DES approach

Determination of diquat by flow injection-chemiluminescence

A simple, economic, sensitive and rapid method for the determination of the pesticide diquat was described. This new method was based on the coupling of flow injection analysis methodology and direct chemiluminescent detection; to the authors' knowledge, this approach had not been used up to now with this pesticide. It was based on its oxidation with ferricyanide in alkaline medium; significant improvements in the analytical signal were achieved by using high temperatures and quinine as sensitiser. Its high throughput (144 h(-1)), together with its low limit of detection (2 ng mL(-1)), achieved without need of preconcentration steps, permitted the reliable quantification of diquat over the linear range of (0.01-0.6) mu g mL(-1) in samples from different origins (river, tap, mineral and ground waters), even in the presence of a 40-fold concentration of paraquat, a pesticide commonly present in the commercial formulations of diquat.López-Paz, JL.; Catalá-Icardo, M.; Antón Garrido, B. (2009). Determination of diquat by flow injection-chemiluminescence. Analytical and Bioanalytical Chemistry. 394(4):1073-1079. doi:10.1007/s00216-009-2609-zS107310793944Hayes WJ Jr, Laws ER Jr (1991) Handbook of pesticide toxicology, Academic Press, San DiegoUS Environmental Protection Agency. http://www.epa.gov/06WDW/contaminants/dw_contamfs/diquat.html (accessed in August 2008)Horwitz W (2000) Official methods of analysis of AOAC International 17th edition. AOAC International, Gaithersburg, MD, USAHara S, Sasaki N, Takase D, Shiotsuka S, Ogata K, Futagami K, Tamura K (2007) Anal Sci 23(5):523–531Rial Otero R, Cancho Grande B, Pérez Lamela C, Simal Gandara J, Aria Estevez M (2006) J Chromatogr Sci 44(9):539–542Aramendia MA, Borau V, Lafont F, Marinas JM, Moreno JM, Porras JM, Urbano FJ (2006) Food Chem 97(1):181–188Nuñez O, Moyano E, Galceran MT (2004) Anal Chim Acta 525(2):183–190Martinez Vidal JL, Belmonte Vega A, Sanchez Lopez FJ, Garrido Frenich AJ (2004) Chromatogr A 1050(2):179–184Lee XP, Kumazawa T, Fujishiro M, Hasegawa C, Arinobu T, Seno H, Sato K (2004) J Mass Spectrom 39(10):1147–1152De Almeida RM, Yonamine M (2007) J Chromatogr B 853(1–2):260–264De Souza D, Machado SAS (2006) Electroanalysis 18(9):862–872De Souza D, Da Silva MRC, Machado SAS (2006) Electroanalysis 18(23):2305–2313Picó Y, Rodriguez R, Manes J (2003) Trends Anal Chem 22(3):133–151Ishiwata T (2004) Bunseki Kagaku 53(8):863–864Carneiro MC, Puignou L, Galcerán MT (2000) Anal Chim Acta 408:263Luque M, Rios A, Valcarcel M (1998) Analyst 123(11):2383–2387Perez Ruiz T, Martínez Lozano C, Tomas V (1991) Int J Environ Anal Chem 44(4):243–252Perez Ruiz T, Martínez Lozano C, Tomas V (1991) Anal Chim Acta 244(1):99–104Townshend A (1990) Analyst 115:495–500López Paz JL, Catalá Icardo M (2008) Anal Chim Acta 625:173–179Pawlicová Z, Sahuquillo I, Catalá Icardo M, García Mateo JV, Martínez Calatayud J (2006) Anal Sci 22:29–34Albert García JR, Catalá Icardo M, Martínez Calatayud J (2006) Talanta 69:608–614Tomlin CDS (1997) The pesticide manual, 11th edn.The British Crop Protection CouncilUKCatalá-Icardo M, Martínez-Calatayud J (2008) Crit Rev Anal Chem 38:118–130Ministerio de Medio Ambiente y Medio Rural y Marino. http://www.marm.es/ (accessed in September 2008)US Environmental Protection Agency. http://www.epa.gov/OGWWDW/contaminants (accessed in October 2008

Unusual Dengue Virus 3 Epidemic in Nicaragua, 2009

The four dengue virus serotypes (DENV1–4) cause the most prevalent mosquito-borne viral disease affecting humans worldwide. In 2009, Nicaragua experienced the largest dengue epidemic in over a decade, marked by unusual clinical presentation, as observed in two prospective studies of pediatric dengue in Managua. From August 2009–January 2010, 212 dengue cases were confirmed among 396 study participants at the National Pediatric Reference Hospital. In our parallel community-based cohort study, 170 dengue cases were recorded in 2009–10, compared to 13–65 cases in 2004–9. In both studies, significantly more patients experienced “compensated shock” (poor capillary refill plus cold extremities, tachycardia, tachypnea, and/or weak pulse) in 2009–10 than in previous years (42.5% [90/212] vs. 24.7% [82/332] in the hospital study (p<0.001) and 17% [29/170] vs. 2.2% [4/181] in the cohort study (p<0.001). Signs of poor peripheral perfusion presented significantly earlier (1–2 days) in 2009–10 than in previous years according to Kaplan-Meier survival analysis. In the hospital study, 19.8% of subjects were transferred to intensive care, compared to 7.1% in previous years – similar to the cohort study. DENV-3 predominated in 2008–9, 2009–10, and 2010–11, and full-length sequencing revealed no major genetic changes from 2008–9 to 2010–11. In 2008–9 and 2010–11, typical dengue was observed; only in 2009–10 was unusual presentation noted. Multivariate analysis revealed only “2009–10” as a significant risk factor for Dengue Fever with Compensated Shock. Interestingly, circulation of pandemic influenza A-H1N1 2009 in Managua was shifted such that it overlapped with the dengue epidemic. We hypothesize that prior influenza A H1N1 2009 infection may have modulated subsequent DENV infection, and initial results of an ongoing study suggest increased risk of shock among children with anti-H1N1-2009 antibodies. This study demonstrates that parameters other than serotype, viral genomic sequence, immune status, and sequence of serotypes can play a role in modulating dengue disease outcome

β-Cyclodextrins as affordable antivirals to treat coronavirus infection

The SARS-CoV-2 pandemic made evident that there are only a few drugs against coronavirus. Here we aimed to identify a cost-effective antiviral with broad spectrum activity and high safety profile. Starting from a list of 116 drug candidates, we used molecular modelling tools to rank the 44 most promising inhibitors. Next, we tested their efficacy as antivirals against α and β coronaviruses, such as the HCoV-229E and SARS-CoV-2 variants. Four drugs, OSW-1, U18666A, hydroxypropyl-β-cyclodextrin (HβCD) and phytol, showed in vitro antiviral activity against HCoV-229E and SARS-CoV-2. The mechanism of action of these compounds was studied by transmission electron microscopy and by fusion assays measuring SARS-CoV-2 pseudoviral entry into target cells. Entry was inhibited by HβCD and U18666A, yet only HβCD inhibited SARS-CoV-2 replication in the pulmonary Calu-3 cells. Compared to the other cyclodextrins, β-cyclodextrins were the most potent inhibitors, which interfered with viral fusion via cholesterol depletion. β-cyclodextrins also prevented infection in a human nasal epithelium model ex vivo and had a prophylactic effect in the nasal epithelium of hamsters in vivo. All accumulated data point to β-cyclodextrins as promising broad-spectrum antivirals against different SARS-CoV-2 variants and distant alphacoronaviruses. Given the wide use of β-cyclodextrins for drug encapsulation and their high safety profile in humans, our results support their clinical testing as prophylactic antivirals

β-Cyclodextrins as affordable antivirals to treat coronavirus infection

The SARS-CoV-2 pandemic made evident that there are only a few drugs against coronavirus. Here we aimed to identify a cost-effective antiviral with broad spectrum activity and high safety profile. Starting from a list of 116 drug candidates, we used molecular modelling tools to rank the 44 most promising inhibitors. Next, we tested their efficacy as antivirals against α and β coronaviruses, such as the HCoV-229E and SARS-CoV-2 variants. Four drugs, OSW-1, U18666A, hydroxypropyl-β-cyclodextrin (HβCD) and phytol, showed in vitro antiviral activity against HCoV-229E and SARS-CoV-2. The mechanism of action of these compounds was studied by transmission electron microscopy and by fusion assays measuring SARS-CoV-2 pseudoviral entry into target cells. Entry was inhibited by HβCD and U18666A, yet only HβCD inhibited SARS-CoV-2 replication in the pulmonary Calu-3 cells. Compared to the other cyclodextrins, β-cyclodextrins were the most potent inhibitors, which interfered with viral fusion via cholesterol depletion. β-cyclodextrins also prevented infection in a human nasal epithelium model ex vivo and had a prophylactic effect in the nasal epithelium of hamsters in vivo. All accumulated data point to β-cyclodextrins as promising broad-spectrum antivirals against different SARS-CoV-2 variants and distant alphacoronaviruses. Given the wide use of β-cyclodextrins for drug encapsulation and their high safety profile in humans, our results support their clinical testing as prophylactic antivirals.This work has been funded by grant RTI2018-094445-B100 (MCIU/AEI/FEDER, UE) from the Ministry of Science and Innovation of Spain (C.R.), by Palex Medical S.A., Sika S.A.U. and 7 more companies, and by Ms. Raquel Casaus Alvarez, Mr. Miguel Pardo Gil, Mr. Jacques Noguès and a total of 2916 citizens through the Precipita crowdfunding platform of Fecyt (Fundación Española para la Ciencia y la Tecnología). NI-U is supported by the Spanish Ministry of Science and Innovation (grant PID2020-117145RB-I00), EU HORIZON-HLTH-2021-CORONA-01 (grant 101046118) and by institutional funding of Grifols, Pharma Mar, HIPRA, Amassence and Palobiofarma. This work used the computational resources of the Centro de Supercomputación de Galicia (CESGA) supported by the Partnership for Advanced Computing in Europe (PRACE) COVID-19 Fast Track Call for Proposals – Allocation Decision – Proposal COVID19-85.info:eu-repo/semantics/publishedVersio