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The risk of stroke and cerebrovascular disease complicating infection with SARS-CoV-2 has been extensively reported since the onset of the pandemic. The striking efforts of many scientists in cooperation with regulators and governments worldwide have rapidly brought the development of a large landscape of vaccines against SARS-CoV-2. The novel DNA and mRNA vaccines have offered great flexibility in terms of antigen production and led to an unprecedented rapidity in effective and safe vaccine production. However, as mass vaccination has progressed, rare but catastrophic cases of thrombosis have occurred in association with thrombocytopenia and antibodies against PF4 (platelet factor 4). This catastrophic syndrome has been named vaccine-induced immune thrombotic thrombocytopenia. Rarely, ischemic stroke can be the symptom onset of vaccine-induced immune thrombotic thrombocytopenia or can complicate the course of the disease. In this review, we provide an overview of stroke and cerebrovascular disease as a complication of the SARS-CoV-2 infection and outline the main clinical and radiological characteristics of cerebrovascular complications of vaccinations, with a focus on vaccine-induced immune thrombotic thrombocytopenia. Based on the available data from the literature and from our experience, we propose a therapeutic protocol to manage this challenging condition. Finally, we highlight the overlapping pathophysiologic mechanisms of SARS-CoV-2 infection and vaccination leading to thrombosis.

In 2020, the novel coronavirus, SARS-CoV-2, caused a pandemic, which is still raging at the time of writing this. Here, we present results from SpikeSeq, the first published Sanger sequencing-based method for the detection of Variants of Concern (VOC) and key mutations, using a 1 kb amplicon from the recognized ARTIC Network primers. The proposed setup relies entirely on materials and methods already in use in diagnostic RT-qPCR labs and on existing commercial infrastructure offering sequencing services. For data analysis, we provide an automated, open source, and browser-based mutation calling software (https://github.com/kblin/covid-spike-classification, https://ssi.biolib.com/covid-spike-classification). We validated the setup on 195 SARS-CoV-2 positive samples, and we were able to profile 85% of RT-qPCR positive samples, where the last 15% largely stemmed from samples with low viral count. We compared the SpikeSeq results to WGS results. SpikeSeq has been used as the primary variant identification tool on > 10.000 SARS-CoV-2 positive clinical samples during 2021. At approximately 4€ per sample in material cost, minimal hands-on time, little data handling, and a short turnaround time, the setup is simple enough to be implemented in any SARS-CoV-2 RT-qPCR diagnostic lab. Our protocol provides results that can be used to choose antibodies in a clinical setting and for the tracking and surveillance of all positive samples for new variants and known ones such as Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) Delta (B.1.617.2), Omicron BA.1(B.1.1.529), BA.2, BA.4/5, BA.2.75.x, and many more, as of October 2022.

Biodiesel has great potential as an alternative fuel for diesel engines. However, poor low-temperature flow property and high viscosity of biodiesel limit its use in engines. Therefore, alcohol comes into researchers’ eyes as a promising additive for diesel–biodiesel (DB) blends. In this study, the effects of lower and higher alcohol contents with different speeds on combustion and emissions characteristics were investigated in a modified single cylinder diesel engine. The results indicated that the maximum pressure rise rate (MPRR) maintained a consistent drop ratio as speed increased from 1500 rpm to 1800 rpm for the tested fuels. However, B10E10 (10% biodiesel and %10 ethanol by volume) had a big drop, which meant that engine’s power ability had a big loss at high speed. The declining rate with speed decreased for indicated thermal efficiency (ITE) when adding alcohol to diesel–biodiesel blends, especially n-pentanol. Moreover, compared with other tested fuels, B10P10 (10% biodiesel and 10% n-pentanol) had smaller cycle variation and more stable combustion state as speed changed, despite it had the highest coefficient of variation (COV) at 1000 rpm. It can be found that has advantages in combustion stability, and can well reduce the total hydrocarbon (THC) and carbon monoxide (CO) emissions under the condition of medium speed commonly used by vehicle. Overall consideration, using diesel/biodiesel/alcohol ternary fuels may be a better choice for diesel engines.

Los granos de cacao son altamente comercializados a nivel mundial, ya que es la materia prima en la industria del chocolate. Uno de los procesos más importantes por los que pasan los granos de cacao es la fermentación. En este proceso las levaduras, bacterias ácido lácticas y bacterias ácido acéticas son introducidas espontáneamente o no en la pulpa de cacao y son responsables de un conjunto de cambios fisicoquímicos que ocurre en los granos, generando compuestos orgánicos volátiles (COV) y no volátiles que confieren aromas y sabores característicos al chocolate. En la presente tesis de investigación se identificó y analizó la dinámica de los COV de dos variedades de granos de cacao, el cacao nativo fino de aroma (CFA) y el clon comercial Colección Castro Naranjal 51 (CCN-51), durante las 156 horas de fermentación espontánea. Las técnicas utilizadas para extraer, separar e identificar a los COV fueron: microextracción en fase sólida (SPME), cromatografía de gases acoplada a un espectrómetro de masas (GC-MS) y la base de datos de la biblioteca NIST 2017 (National Institute of Standards and Technology). Se identificó y semicuantificó a 122 COV entre ambas variedades durante la fermentación espontánea, se compararon las dinámicas de 20 COV con mayor presencia entre ambas variedades y se realizó análisis de componentes principales. Se concluyó que la variedad CFA contiene mayores concentraciones relativas de los compuestos aromáticos: afrutados, florales y dulces (2-heptanol, éster etílico del ácido benzoico, acetato de 2-heptanol, bencenoacetaldehído, 2-heptanona, acetofenona, 2-nonanona y trans-.beta.-ocimeno) que cumplen un rol importante en la calidad del chocolate. Cocoa is highly traded and consumed worldwide as the essential raw material for chocolate. One of the most important processes that cocoa beans go through is 12 fermentation. In this process, yeasts, lactic acid bacteria and acetic acid bacteria are introduced spontaneously or not in the cocoa pulp and are responsible for a set of physicochemical changes that occur in the beans, generating volatile organic compounds (VOC) and non-volatile organic compounds that confer characteristic aromas and flavors to chocolate. In the present research project, the dynamics of the VOCs of fine aroma cocoa (CFA) and the commercial clone CCN-51 were analyzed during the entire spontaneous fermentation process, which lasted 156 hours, and the VOCs were analyzed using solid phase microextraction (SPME) and gas chromatography coupled to mass spectrometer (GC-MS) techniques. A total of 122 VOCs were identified and semi-quantified between both varieties during spontaneous fermentation, the dynamics of 20 VOCs with the highest presence were compared between the two varieties and principal component analysis was performed. It was concluded that the CFA variety contains higher relative concentrations of the aromatic compounds: fruity, floral and sweet (2-heptanol, benzoic acid ethyl ester, 2-heptanol acetate, benzeneacetaldehyde, 2-heptanone, acetophenone, 2-nonanone and trans-.beta.ocimen) that play an important role in the quality of chocolate.

๋Journal of Current Science and Technology, 13, 1, 91-106

Coronaviruses (CoV) are a group of RNA viruses that have continuously posed risks to humans’ health and economy. Since the first recorded major CoV outbreak of SARS-CoV in 2001, using modern scientific methods, tremendous effort and resources have been devoted to better understanding the transmission of these viruses to humans and the associated disease manifestations. Like all known viruses, CoV require and utilize intracellular signaling pathways to replicate in the host cell. In doing so, CoV have apparently evolved diverse strategies to modulate these systems to initiate the formation of novel pathogenic intracellular structures, including so-called double membrane vesicles (DMVs), which collectively have been termed replicative organelles (ROs). DMVs and ROs are essential for successful CoV replication. Their formation, together with massively increased synthesis of viral protein and RNA components, leads to pronounced activation of affected cells. Among the cellular processes modulated early and most strongly during CoV infection are those related to the endoplasmic reticulum (ER) stress response and autophagy. Activation of ER signaling pathways by CoV results in ER stress and triggering of the unfolded protein response (UPR). The UPR is an adaptive process by which the cell attempts to restore normal ER function through activation of protein kinases, transcription factors, and downstream genetic programs. This involves a number of well-characterized molecular sensor and effector molecules anchored in the ER membrane, which include the protein kinases PERK and IRE1α and the chaperone BiP (GRP78, HSPA5). Autophagy refers to a highly dynamic process by which the cell can degrade larger molecular complexes, organelles, or invading pathogens and recycle or destroy the resulting macromolecules. As part of the autophagy process, a double membrane structure (the autophagosome) is formed, which interacts with the proteins LC3B and p62/SQSTM1 (sequestosome1) to coordinate basal, as well as selective, autophagy flux in response to various stressors, including viral infections. In this work, the central questions were investigated to what extent (i) CoV specifically modulate the ER stress and autophagy system and whether (ii) new starting points for antiviral strategies can be derived from this. To this end, a series of specific molecular but also proteome-wide analyses were performed in pharmacologically and genetically perturbed cellular model systems. Small molecule inhibitors were used to examine the effect of inhibiting PERK, IRE1α, or both protein kinases on CoV replication as well as on activation of the UPR and host response. One of the major findings of this approach was that inhibition of PERK resulted in a reduction in replication of HCoV-229E and MERS-CoV, but not SARS-CoV-2. HCoV-229E infection of Huh7 cells resulted in induction of the transcription factor ATF3 and suppression of BiP. PERK inhibition abolished both of these effects and led to a reduction in phosphorylation of serine 52 of the translation-inhibitory factor eIF2α. In contrast, inhibition of IRE1α resulted in only a small reduction in HCoV-229E replication but completely prevented virus-induced ATF3 induction. Arteficial, "chemical" activation of the UPR by the natural product thapsigargin resulted in strong inhibition of replication of all three CoV tested with a half-maximal effective concentration (EC50) in the low nanomolar range with concomitant low cytotoxicity. Furthermore, thapsigargin treatment of CoV-infected cells was associated with partial abrogation of global HCoV-229E-induced inhibition of protein biosynthesis and resulted in almost complete inhibition of CoV-induced selective and basal autophagy flux. Subsequently, a genetic approach based on the CRISPR-CAS-9 system was used to further investigate the roles of PERK, IRE1α, and ATF3 in CoV replication. Silencing of PERK resulted in a decrease in HCoV-229E replication, whereas suppression of IRE1α or ATF3 showed very little or no effect on virus replication. In addition, mass spectrometric techniques were used to comparatively examine changes in the proteome in CoV-infected and thapsigargin-treated cells. Bioinformatic analyses of the differentially expressed proteins resulted in the identification of a number of specific metabolic processes, signaling pathways, and factors that may be responsible for the antiviral effect of thapsigargin, including ER-associated degradation (ERAD) and ER quality control (ERQC) pathways. In the final part of the work, a proximity-based, proteome-wide interaction screen was performed to reveal the intracellular binding partners of ATF3 in the context of HCoV-229E infection. This led to the identification of a number of components of the immune system and mitochondrial homeostasis that are potential ATF3-dependent regulated effector molecules. In summary, the results obtained in this work provide insight into the CoV-specific activation patterns of the ER stress factors PERK, IRE1α, BiP, and ATF3 and their role in CoV replication and host response. The extensive evidence for antiviral efficacy of thapsigargin establishes chemical activation of the ER stress system as a novel antiviral therapeutic principle against enveloped RNA viruses such as HCoV-229E, MERS-CoV, and SARS-CoV-2 and identifies thapsigargin as a new prototype of compounds with multimodal host-directed antiviral activity based on molecular mechanisms of action.

The BIO-MAÏDO (Bio-physicochemistry of tropical clouds at Maïdo (Réunion Island): processes and impacts on secondary organic aerosols formation) campaign was conducted from the 13th of March to the 4th of April 2019 on the tropical Réunion Island and implied several scientific teams and state-of-the-art instrumentation. The campaign was part of the BIO-MAÏDO project with the main objective is to improve our understanding of cloud impacts on the formation of secondary organic aerosols (SOA) from biogenic volatile organic compounds (BVOC) precursors in a tropical environment. Instruments were deployed at five sites: a receptor site, the Maïdo observatory (MO) at 2165 m asl, and four sites along the slope of the Maïdo mountain. The obtained dataset includes measurements of the gas-phase mixings ratio of volatile organic compounds (VOC), the characterization of the physical, chemical, and biological (bacterial diversity) properties of aerosols and the characterization of the physical, chemical and biological (identification of viable bacteria through culture-based approaches) properties of the cloud water. In addition, the turbulent parameters of the boundary layer, radiative fluxes, and emissions fluxes of BVOC from the surrounding vegetation were measured to help with the interpretation of the observed chemical concentrations in the different phases. Dynamical analyses using back-trajectories show two preferred trajectories routes for air masses arriving at MO during the daytime both corresponding to the return branches of the trade winds associated with the up-slopes thermal breezes, and both influenced by marine boundary layer and endemic forest below the Maïdo observatory. Additional analysis based on a high-resolution Meso-NH simulation for a typical cloudy day indicates that air masses sampled at MO likely encountered cloud processing during its transport along the slope. The highest mixing ratio of oxygenated VOC (OVOC) were measured above the site located in the endemic forest and the highest contribution of OVOC to total VOC at MO. Chemical composition of particles during the daytime shows that organic aerosol is more oxidized at MO than at other sites along the slope. This is a signature of photochemical aerosols aging along the slope. A higher concentration of oxalic acid at a site below MO indicates this oxidation occurs potentially through cloud processing. Despite an in-depth analysis of organic compounds in cloud water, around 80% on average of dissolved organic compounds is undefined highlighting the complexity of the cloud organic matter. The BIO-MAÏDO project is focusing on the analysis of observations and processes using numerical simulations: a 0D cloud chemistry model including biodegradation by bacteria in cloud water and a high-resolution 3D model coupling dynamical, microphysical and chemical processes.

Allogeneic haematopoietic cell transplantation (allo-HCT) recipients show impaired antibody (Ab) response to a standard two-dose vaccination against severe acute respiratory syndrome coronavirus-2 and currently a third dose is recommended as part of the primary vaccination regimen. By assessing Ab titres 1 month after a third mRNA vaccine dose in 74 allo-HCT recipients we show sufficient neutralisation activity in 77% of the patients. Discontinuation of immunosuppression before the third vaccine led to serological responses in 50% of low responders to two vaccinations. Identifying factors that might contribute to better vaccine responses in allo-HCT recipients is critical to optimise current vaccination strategies.

The purpose of this project is to principally investigate the tacit activities of Chimpanzee individuals lead to detrimental health problems in nonhuman communities.

Context One risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is postulated to be vitamin D deficiency. To better understand the role of vitamin D deficiency in the disease course of COVID-19, we undertook a retrospective case-control study in North West England. Objective To examine whether hospitalization with COVID-19 is more prevalent in individuals with lower vitamin D levels. Methods The study included individuals with test results for serum 25-hydroxyvitamin D (25[OH]D) between April 1, 2020, and January 29, 2021, from 2 districts in North West England. The last 25(OH)D level in the previous 12 months was categorized as “deficient” if less than 25 nmol/L and “insufficient” if 25 to 50 nmol/L. Results The study included 80 670 participants. Of these, 1808 were admitted to the hospital with COVID-19, of whom 670 died. In a primary cohort, median serum 25(OH)D in nonhospitalized participants with COVID-19 was 50.0 nmol/L (interquartile range [IQR], 34.0-66.7) vs 35.0 nmol/L (IQR, 21.0-57.0) in those admitted with COVID-19 (P Conclusion Vitamin D deficiency is associated with higher risk of COVID-19 hospitalization. Widespread measurement of serum 25(OH)D and treatment of insufficiency or deficiency may reduce this risk.

Based on CoVs, the genomic structure is arranged in a +ssRNA with approximately 30kb in length which is the biggest known RNA viruses including a 5′-cap structure and 3′-poly-A tail. CoVs, (positive stranded RNA viruses), can infect humans and multiple species of animals, cause enteric, respiratory, and central nervous system diseases in many species. These viruses are important for anti-CoV drug delivery through a pivotal function in viral gene expression and replication through the proteolytic processing of replicase polyproteins. In this paper, it has been illustrated the linkage of 6 inhibitors of N-[[4-(4-methylpiperazin-1-yl)phenyl]methyl]-1,2-oxazole-5-carboxamide, “inh1”, NSC 158362, “inh2”,JMF 1586 ,”inh3”,(N-(2-aminoethyl)-1-1ziridine-ethanamine) , “inh4” ,[(Z)-1-thiophen-2-ylethylideneamino]thiourea, “inh5” and Vanillinbananin, “inh6”, to CoVs by forming the complexes of “inhibitor- CoV” in water phase through the H-bonding using some physico-chemical properties including heat of formation , Gibbs free energy , electronic energy , charge distribution of active parts in the hydrogen bonding ,NMR estimation of inhibitor jointed to the database amino acids fragment of Tyr-Met-His as the selective zone of the CoV, positive frequency and intensity of different normal modes of these structures.The theoretical calculations were done at various levels of theory in water simulated medium to gain the more accurate equilibrium geometrical results, and infrared spectral data for each of the complex proposed drugs of N-terminal or O-terminal auto-cleavage substrate were individually determined to elucidate the structural flexibility and substrate binding of six inhibitors including jointed to TMH, inh[ 1 – 6 ]-TMH. A comparison of these structures with two configurations provides new insights for the design of substrate-based inhibitors targeting CoV. This indicates a feasible model for designing wide-spectrum inhibitors against CoV-associated diseases.The structure-based optimization of these structures has yielded two more efficacious lead compounds, N and O atoms through forming the hydrogen bonding (hydrogen-bonding) with potent inhibition against CoV (Tyr160-Met161-His162) because of water polar medium which has been abbreviated as TMH in this paper.

Background: SARS-CoV virus infection results in a dysbalanced and severe inflammatory response with hypercytokinemia and immunodepression. Viral infection triggers systemic inflammation and the virus itself can potentially cause vascular damage, including blood-brain barrier (BBB) disruption and alterations in the coagulation system, which may result in cardiovascular and neurovascular events. Here, we review the literature and present a case of COVID-19 infection leading to an aneurysmal subarachnoid haemorrhage (aSAH). Case Description: A 61-year-old woman presented with dyspnea, cough, and fever. She had a history of hypertension and was overweight with a body mass-index of 34. There was no history of subarachnoid hemorrhage in the family. Due to low oxygen saturation (89%) she was admitted into ICU. A chest CT showed a typical picture of COVID-19 pneumonia. The PCR-based test of an oropharyngeal swab was COVID-19-positive. In addition to oxygen support she was prescribed with favipiravir and hydroxychloroquine. She experienced a sudden headache and lost consciousness on the second day. Computer tomography (CT) with CT-angiography revealed a subarachnoid haemorrhage in the basal cisterns from a ruptured anterior communicating artery aneurysm. The aneurysm was clipped microsurgically through a left-sided standard pterional approach and the patient was admitted again to the intensive care unit for further intensive medical treatment. Post-operatively, the patient showed slight motor dysphasia. No other neurological deficits. Conclusion: Systemic inflammation and ventilator support-associated blood pressure fluctuations may trigger aneurysmal subarachnoid haemorrhage secondary to COVID-19 infection. COVID-19 infection could be considered as one of the possible risk factors leading to instability and rupture of intracranial aneurysm.

En aquest treball s’ha realitzat un anàlisi estadístic de les concentracions d’un total de 62 contaminants atmosfèrics corresponents a compostos orgànics volàtils, recollides en un total de 12 localitats catalanes diferents durant l’any 2020. Després de situar les localitats segons les zones industrials properes, les dades de concentració han estat comparades amb les recollides durant l’any 2019, calculant l’evolució de les concentracions, realitzant test de Student i comparant gràficament mitjançant diagrames de caixa. S’ha estudiat quins són els compostos orgànics volàtils més abundants en les diferents localitats, individualment i en classificació per grups químics. Per últim, s’ha estudiat l’efecte que ha tingut l’etapa de confinament per la pandèmia ocasionada pel virus COVID-19 en els valors de concentració de compostos orgànics volàtils, quines substàncies s’han vist afectades en les diferents localitats, individualment i en classificació per grups químics. D’aquest s’ha pogut concloure que la majoria de substàncies estudiades ha disminuït la seva concentració durant l’etapa de confinament. En aquest treball s’ha realitzat un anàlisi estadístic de les concentracions d’un total de 62 contaminants atmosfèrics corresponents a compostos orgànics volàtils, recollides en un total de 12 localitats catalanes diferents durant l’any 2020. Després de situar les localitats segons les zones industrials properes, les dades de concentració han estat comparades amb les recollides durant l’any 2019, calculant l’evolució de les concentracions, realitzant test de Student i comparant gràficament mitjançant diagrames de caixa. S’ha estudiat quins són els compostos orgànics volàtils més abundants en les diferents localitats, individualment i en classificació per grups químics. Per últim, s’ha estudiat l’efecte que ha tingut l’etapa de confinament per la pandèmia ocasionada pel virus COVID-19 en els valors de concentració de compostos orgànics volàtils, quines substàncies s’han vist afectades en les diferents localitats, individualment i en classificació per grups químics. D’aquest s’ha pogut concloure que la majoria de substàncies estudiades ha disminuït la seva concentració durant l’etapa de confinament. In this paper, a statistical analysis of the concentrations of a total of 62 atmospheric pollutants corresponding to volatile organic compounds, collected in a total of 12 different Catalan locations during the year 2020, has been carried out. After locating the localities according to the nearby industrial zones, the concentration data have been compared with those collected during the year 2019, calculating the evolution of the concentrations, performing the Student test and comparing graphically using box plots. It has been studied which are the most abundant volatile organic compounds in the different localities, individually and in classification by chemical groups. Finally, the effect that the confinement stage caused by the COVID-19 virus has had on the concentration values of volatile organic compounds, which substances have been affected in different locations, individually and in chemical groups, has been studied. From this it has been possible to conclude that most of the substances studied have decreased their concentration during the confinement stage.

El present projecte té com a objectiu l’estudi d’aplicació i justificació de les Millors Tècniques Disponibles dels sistemes de tractament i gestió d’emissions de gasos i aigües residuals a una industria farmacèutica que es dedica a la fabricació de principis actius i productes farmacèutics. La part inicial del projecte es basa en la recerca bibliogràfica de la normativa vigent del sector per tal de comprendre la situació ambiental i determinar els límits que s’estableixen actualment per reduir els efectes del canvi climàtic. Per a l’anàlisi de minimització de l’impacte ambiental de l’establiment, s’han estudiat els diferents aspectes que afecten de manera negativa al medi ambient com són les emissions difuses de compostos orgànics volàtils (COV), emissions d’olors, emissions de sorolls, aigües residuals, contaminació de sòls i residus, i s’han determinat els focus principals de generació d’aquestes emissions. S’estudien els equips del procés de producció de la planta detectant un incorrecte funcionament en la neutralització de gasos de dos dels scrubbers degut a la corrosió al seu interior. Aquest fet provoca que les emissions entrin a la planta de tractament de gasos sense neutralitzar i que, per tant, s’emetin emissions contaminades a l’atmosfera. S’analitzen les possibles causes i es determinen diferents propostes de millora per a un correcte funcionament. Finalment, es proposa la incorporació d’equips de millora de processos com per exemple la instal·lació d’un nou sistema de neteja de tipus Clean in Place per optimitzar el consum energètic i el consum d’aigua, així com reduir el risc de contaminació, i la instal·lació de vàlvules de pressió al buit amb apagaflames als venteigs dels tancs d’emmagatzematges per reduir les emissions de COV a l’atmosfera. El presente proyecto tiene como objetivo el estudio de aplicación y justificación de las Mejores Técnicas Disponibles de los sistemas de tratamiento y gestión de gases y aguas residuales en una industria farmacéutica que se dedica a la fabricación de principios activos y productos farmacéuticos. La parte inicial del proyecto se basa en la búsqueda bibliográfica de la normativa vigente del sector con el fin de comprender la situación ambiental y determinar los límites establecidos actualmente para la reducción de los efectos del cambio climático. Para el análisis de minimización del impacto ambiental del establecimiento, se han estudiado los diferentes aspectos que afectan de manera negativa al medio ambiente como son las emisiones difusas de compuestos orgánicos volátiles (COV), emisiones de olores, emisiones de ruidos, aguas residuales, contaminación de suelos y residuos, y se han determinado los focos principales de generación de dichas emisiones. Se realiza un estudio de los equipos de proceso de producción de la planta detectando un incorrecto funcionamiento en la neutralización de gases de dos de los scrubbers debido a la corrosión en su interior. Este hecho provoca que las emisiones entren en la planta de tratamiento de gases sin neutralizar y que, por lo tanto, se emitan emisiones contaminadas en la atmosfera. Se analizan las posibles causas y se determinan diferentes propuestas de mejora para un correcto funcionamiento. Finalmente, se propone la incorporación de equipos de mejora de los procesos como por ejemplo la instalación de un nuevo sistema de limpieza de tipo Clean in Place para optimizar el consumo energético, el consumo de agua y reducir el riesgo de contaminación. También se propone la instalación de válvulas de presión al vacío con apagallamas en los venteos de los tanques de almacenamiento para reducir las emisiones de COV en la atmosfera. The aim of this project is to study the application and justification of the Best Available Techniques for gas and wastewater treatment and management Systems in a pharmaceutical industry dedicated to the manufacture of active ingredients and pharmaceutical products. The first part of the project is based on a bibliographic search of the sector’s current regulations in order to understand the environmental situation and determine the limits currently established for reducing the effects of climate change. For the analysis of the minimisation of the establishment environmental impact, the different aspects that negatively affect the environment were studied, such as diffuse emissions of volatile orgic compounds (VOC), odour emissions, noise emissions, waste water, soil contamination and waste, and also the main sources of these emissions were determinate. The plant’s production process equipment is studied, detecting an incorrect operation in the neutralisation of gases in two of the scrubbers due to corrosion inside them. This causes emissions to enter the gas treatment plant without being neutralised and, therefore, contaminated emissions are emitted into the atmosphere. The possible causes are analysed and different proposals for improvement for correct operation are determined. Finally, the incorporation of process improvement equipment is proposed, such as the installation of a new Clean in Place cleaning system to optimise energy consumption, water consumption and reduce the risk of contamination. It is also proposed to install vacuum pressure valves with flame arresters on the storage tank vents to reduce VOC emissions into the atmosphere. Objectius de Desenvolupament Sostenible::6 - Aigua Neta i Sanejament Objectius de Desenvolupament Sostenible::13 - Acció per al Clima

Background A notable feature of coronavirus disease 2019 (COVID-19) is that children are less susceptible to severe disease. Children are known to experience more infections with endemic human coronaviruses (HCoVs) compared to adults. Little is known whether HCoV infections lead to cross-reactive anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Methods We investigated the presence of cross-reactive anti–SARS-CoV-2 IgG antibodies to spike 1 (S1), S1-receptor-binding domain (S1-RBD), and nucleocapsid protein (NP) by enzyme-linked immunosorbent assays, and neutralizing activity by a SARS-CoV-2 pseudotyped virus neutralization assay, in prepandemic sera collected from children (n = 50) and adults (n = 45), and compared with serum samples from convalescent COVID-19 patients (n = 16). Results A significant proportion of children (up to 40%) had detectable cross-reactive antibodies to SARS-CoV-2 S1, S1-RBD, and NP antigens, and the anti-S1 and anti–S1-RBD antibody levels correlated with anti–HCoV-HKU1 and anti–HCoV-OC43 S1 antibody titers in prepandemic samples (P < .001). There were marked increases of anti–HCoV-HKU1 and - OC43 S1 (but not anti-NL63 and -229E S1-RBD) antibody titers in serum samples from convalescent COVID-19 patients (P < .001), indicating an activation of cross-reactive immunological memory to β-coronavirus spike. Conclusions We demonstrated cross-reactive anti–SARS-CoV-2 antibodies in prepandemic serum samples from children and young adults. Promoting this cross-reactive immunity and memory response derived from common HCoV may be an effective strategy against SARS-COV-2 and future novel coronaviruses., We demonstrated preexisting cross-reactive anti–SARS-CoV-2 antibodies in prepandemic serum samples from children and young adults, which were likely derived from previous infection with common endemic β-coronaviruses. Promoting this cross-reactive immunity may be an effective strategy against SARS-COV-2 and future novel coronaviruses.

Remdesivir (RDV) is a direct-acting antiviral agent that is used to treat patients with severe coronavirus disease 2019 (COVID-19). RDV targets the viral RNA-dependent RNA polymerase (RdRp) of severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2). We have previously shown that incorporation of the active triphosphate form of RDV (RDV-TP) at position i causes delayed chain termination at position i + 3. Here we demonstrate that the S861G mutation in RdRp eliminates chain termination, which confirms the existence of a steric clash between Ser-861 and the incorporated RDV-TP. With WT RdRp, increasing concentrations of NTP pools cause a gradual decrease in termination and the resulting read-through increases full-length product formation. Hence, RDV residues could be embedded in copies of the first RNA strand that is later used as a template. We show that the efficiency of incorporation of the complementary UTP opposite template RDV is compromised, providing a second opportunity to inhibit replication. A structural model suggests that RDV, when serving as the template for the incoming UTP, is not properly positioned because of a significant clash with Ala-558. The adjacent Val-557 is in direct contact with the template base, and the V557L mutation is implicated in low-level resistance to RDV. We further show that the V557L mutation in RdRp lowers the nucleotide concentration required to bypass this template-dependent inhibition. The collective data provide strong evidence to show that template-dependent inhibition of SARS–CoV-2 RdRp by RDV is biologically relevant.

Objective The novel coronavirus, SARS‐CoV‐2 is an international public health emergency. Until now, the intermediate host and mechanisms of interspecies jump of this virus are unknown. Methods Phylogenetic analysis of all available bat coronavirus (CoV) complete genomes was performed in order to analyze the relationships between bat CoV and SARS‐CoV‐2. In order to suggest a possible intermediate host, another phylogenetic reconstruction of CoV genomes obtained from animals which were hypothetically commercialized in the Chinese markets was also carried out. Moreover, mutation analysis was executed to suggest genomic regions which may have permitted the adaptation of SARS‐CoV‐2 to the human host. Results The phylogenetic analysis demonstrated that SARS‐CoV‐2 formed a cluster with the bat CoV isolate RaTG13. Possible CoV interspecies jumps among bat isolates were also observed. The phylogenetic tree reconstructed from CoV strains belonging to different animals demonstrated that SARS‐CoV‐2, bat RaTG13 and pangolin CoV genomes formed a monophyletic cluster, demonstrating that pangolins may be suggested as SARS‐CoV‐2 intermediate hosts. Three AA substitutions localized in the S1 portion of the S gene were observed, some of which have been correlated to structural modifications of the S protein which may facilitate SARS‐CoV‐2 tropism to human cells. Conclusions Our analysis shows the tight relationship between SARS‐CoV‐2 and bat SARS‐like strains. It also hypothesizes that pangolins might have been possible intermediate hosts of the infection. Some of the observed AA substitutions in the S binding protein may serve as possible adaptation mutations in humans but more studies are needed to elucidate their function. This article is protected by copyright. All rights reserved.

The growth of motor vehicles over the past five years has reached 8.63 % per year. The increasing number of vehicles has an impact on increasing fuel consumption. One alternative energy as another fuel currently being developed in motor vehicles is bioethanol. The addition of bioethanol will certainly change the fuel properties, the fuel will be more difficult to self-ignite so the pressure generated in the combustion chamber will be more consistent. The coefficient of variation (COV) represents the ratio of the standard deviation to the mean of a set of data, in this study in-cylinder pressure data (IMEP) is used. Based on previous research that discussed the analysis of emission gas and fuel consumption on SI engine fueled with low-grade bioethanol and oxygenated additive, the authors examined further to analyze the characteristic of gasoline-ethanol blend and oxygenated additive to COVIMEP and exhaust gas emissions of the various fuel mixture at variable engine speed were investigated. The results of the study show that gasoline-ethanol blend and oxygenated additive decrease variation in combustion pressure. It also reduces exhaust emissions; CO and HC are found to be reduced while CO_2 and O_2 increased as concentration increases.

The aim of the bachelor thesis is to identify the main representatives of a wide group of Pharmaceuticals and personal care products (PPCP for short) and to explain the reasons why they pose an increasing risk to aquatic ecosystems. In the theoretical part, the work is devoted to defining the concept of PPCP and explaining the main reasons why their concentration in the aquatic environment has been growing steadily in recent decades. It also deals with the division into the main groups of preparations found in the aquatic environment, their characteristics, documented impacts on aquatic organisms and currently detected concentrations in the world's rivers. In the following chapters, the thesis addresses the issue of the effectiveness of the removal of these substances and the mechanisms by which they can be improved. The work briefly summarizes the effects on the organisms caused by both bioaccumulation and endocrine disruption and at the end of the theoretical part deals with the properties of ten selected drugs, which are regularly detected in Czech rivers. The practical part evaluates the volume of sales of ten drugs in the Czech Republic during 2019, their detected concentrations in the rivers Vltava, Elbe, Morava and Dyje and processing these data to assess the risk of concentrations found for...

Individuals on immunosuppressive (IS) therapy have increased mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and delayed viral clearance may lead to new viral variants. IS therapy reduces antibody responses following coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccination; however, a comprehensive assessment of vaccine immunogenicity is lacking. Here we show that IS therapy reduced neutralizing, binding, and nonneutralizing antibody functions in addition to CD4 and CD8 T-cell interferon-γ responses following COVID-19 mRNA vaccination compared to immunocompetent individuals. Moreover, IS therapy reduced cross-reactivity against SARS-CoV-2 variants. These data suggest that the standard COVID-19 mRNA vaccine regimens will likely not provide optimal protection in immunocompromised individuals., Individuals on immunosuppression for various indications have impaired neutralizing, binding, and nonneutralizing antibody responses and reduced T-cell activity in response to COVID-19 mRNA vaccination compared to immunocompetent controls. This suggests that standard vaccination may not result in protective immunity in this population.