Vaccine effectiveness against the B.1.617.2 in the intensive care unit.

Severe acute respiratory syndrome-coronavirus 2 and its variants are still a concern for the World. The effectiveness of the BioNTech and Sinovac vaccines against the B.1.617.2 variant, particularly in the intensive care unit, has been unclear. This study aimed to investigate the vaccine effectiveness of BioNTech and Sinovac vaccines in reducing severe disease, intubation, and mortality rates in B.1.617.2 infected patients followed in the intensive care unit. The data of 208 unvaccinated and 234 vaccinated B.1.617.2 variants were retrospectively reviewed. Severe disease status, complaints, the percent oxygen saturation in the blood at the first admission, and other clinical information during follow-up were recorded. With the BioNTech and Sinovac vaccines being the most common in the region, mortality rate, severe disease, and intubation were more frequent in the unvaccinated group. As for survival rates, 58.5 (137) of the vaccinated and 35.1 % (73) of the unvaccinated survived. In the vaccinated group, 64.3 % (27) of vaccinated with 3 Sinovac, 80 % (16) of 2 Sinovac and 1 BioNTech, and 71.7 % of 2 BioNTech survived. Vaccination with 2 doses of BioNTech and 3 doses of Sinovac reduces mortality. Furthermore, 2 doses of Sinovac and 1 dose of BioNTech are more protective.

Predicting acute pulmonary embolism in COVID-19.

Acute pulmonary embolism (PE) is a life-threatening condition in patients with Coronavirus disease-2019 (COVID-19). Computed tomography pulmonary angiography is the preferred test to confirm the diagnosis. However, computed tomography pulmonary angiography is expensive and is not available in every clinic. This study aimed to determine whether clinical findings, symptoms, and parameters that are cost-effective and available in many clinics such as C-reactive protein (CRP) lymphocyte ratio (CLR), and ferritin CRP ratio (FCR) can be used in the diagnosis of PE in patients with COVID-19. Out of the reviewed files, 127 patients were diagnosed with PE, whereas 105 patients had no PE. At the first admission, laboratory parameters, complaints, respiratory rate, and percent oxygen saturation in the blood (SpO2) with a pulse oximeter were recorded for each patient. Eosinophil levels remained lower, whereas ferritin lymphocyte ratio and CLR were higher in the PE group. Patients with more elevated ferritin, CRP, and CLR had an increased mortality risk. Shortness of breath and tiredness was more common in the PE group. A decrease in eosinophil levels, whereas an increase in CLR, D-dimer, and CRP may predict PE. Elevated CLR is highly predictive of PE and is associated with increased mortality risk. COVID-19 patients with a CLR level above 81 should be investigated for PE.

Diagnosis of COVID-19 in Patients with Acute Pulmonary Embolism.

Acute pulmonary embolism (PE) and coronavirus disease -2019 (COVID-19) are life-threatening diseases associated with significant morbidity and mortality. Yet little is known about their co-existence.This study explored clinical and laboratory differences between PE patients who tested positive with real-time reverse-transcription polymerase chain reaction (PCR+) and those who tested negative (PCR-) for SARS-CoV-2. Also, to determine whether ferritin D-dimer ratio (FDR) and platelet D-dimer ratio (PDR) can be used to predict COVID-19 in patients with PE. Files of 556 patients who underwent a computed tomography pulmonary angography (CTPA) examination were retrospectively investigated. Out of them, 197 were tested positive and 188 negative for SARS-CoV-2. One hundred thirteen patients (57.36%) in the PCR+ group and 113 (60.11%) in the PCR- group had a diagnosis of PE. Complaints, respiratory rate, and oxygen saturation level in the blood (SpO2) were recorded at the first admission. Monocyte and eosinophil levels remained low, whereas FDR and PDR were higher in the PCR+ group. No difference was detected in ferritin, D-dimer levels, comorbidities, SpO2, and death rates between the two groups. Cough, fever, joint pain, and higher respiratory rate were more common in the PCR+ group. A decrease in white blood cell, monocyte, and eosinophil levels, whereas an increase in FDR and PDR levels may predict COVID-19 in patients with PE. PE patients complaining of cough, fever, and fatigue should undergo PCR testing as common symptoms. COVID-19 does not seem to increase the risk of mortality in patients with PE.

Eosinophil Levels, Neutrophil-Lymphocyte Ratio, and Platelet-Lymphocyte Ratio in the Cytokine Storm Period of Patients with COVID-19.

Background: In the early stages of the COVID-19 pandemic, elevated inflammatory cytokine levels, particularly interleukin-6 (IL-6), were detected in patients with cytokine storm (CS). Aims: This study aimed to investigate levels, diagnostic usefulness, and optimal cutoff values of monocyte, eosinophil, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) in CS of patients with COVID-19 and also to identify risk factors for mortality. Methods: Seventy-six patients with COVID-19 who developed CS and randomly chosen 150 COVID-19 patients who had no CS during their stay in the hospital were included in the study. Results: Lymphocytes and eosinophil levels remained lower in the CS group. Patients with low lymphocyte levels had a higher risk for mortality (OR: 1.92). Neutrophil, D-dimer, ferritin, IL-6, NLR, and PLR were higher in the CS group. High levels of neutrophil, ferritin, D-dimer, and NLR and a history of coronary artery disease (CAD) and diabetes mellitus (DM) were identified as independent risk factors for mortality. Conclusion: In the light of the obtained results, COVID-19 patients with a decrease in lymphocyte levels and an increase in NLR and D-dimer levels and a history of CAD and DM have a higher risk of cytokine storm and mortality.

Clinical and Laboratory Differences between Delta and UK Variants of SARS-CoV-2: B.1.617.2 and B.1.1.7.

At the end of 2019, the world met with the coronavirus disease 2019 (COVID-19), which will affect all humanity. Later in the course, the genetic variants of SARS-CoV-2 have emerged, bringing new questions and concerns. This study investigated differences between patients infected with the B.1.1.7 (UK variant) and the B.1.617.2 (Delta variant) regarding patient complaints, intensive care unit (ICU) admission and stay time, intubation, severe disease, mortality rates, and laboratory parameters. Hospitalized 205 patients infected with B.1.1.7 and 207 patients infected with B.1.617.2 were included in the study. Laboratory parameters, admission complaints, and the percent saturation of oxygen in the blood (SpO2) were recorded on the same day as the diagnosis and clinical findings during their follow-up. Cough and fever were more common complaints in the B.1.1.7 infected group, whereas tiredness, joint pain, and gastrointestinal complaints were more frequent in patients infected with B.1.617.2. The B.1.617.2 infected group had higher severe disease, acute coronary syndrome (ACS), mortality rates, neutrophil, troponin, and ferritin levels. In conclusion, patients infected with B.1.617.2 had a higher risk of intubation, ACS, and mortality rates. Cough and fever were more common in B.1.1.7 infected group, whereas tiredness was more frequent in B.1.617.2 infected group. Vaccination with at least one dose of Pfizer-BioNTech or CoronaVac is independently associated with a decreased mortality risk caused by two variants (Odds Ratio 0.4).

Recruitment: A Problem of Entangled Temporal Parts.

Recruitment is a pervasive activity of life that is at the center of novelty generation and persistence. Without recruitment, novelties cannot spread and biological systems cannot maintain identity through time. Here we explore the problem of identity and change unfolding in space and time. We illustrate recruitment operating at different timescales with metabolic networks, protein domain makeup, the functionome, and the rise of viral 'variants of concern' during the coronavirus disease 2019 (COVID-19) pandemic. We define persistence within a framework of fluxes of matter-energy and information and signal processing in response to internal and external challenges. A 'triangle of persistence' describing reuse, innovation and stasis defines a useful polytope in a phase space of trade-offs between economy, flexibility and robustness. We illustrate how the concept of temporal parts embraced by the perdurantist school provides a processual 4-dimensional 'worm' view of biology that is historical and atemporal. This view is made explicit with chronologies and evolving networks inferred with phylogenomic methodologies. Exploring the origin and evolution of the ribosome reveals recruitment of helical segments and/or large fragments of interacting rRNA molecules in a unification process of accretion that is counteracted by diversification. A biphasic (bow-tie) theory of module generation models this frustrated dynamics. Finally, we further elaborate on a theory of entanglement that takes advantage of the dimensionality reduction offered by holographic principles to propose that short and long-distance interactions are responsible for the increasingly granular and tangled structure of biological systems.

Emergence of Hierarchical Modularity in Evolving Networks Uncovered by Phylogenomic Analysis.

Networks describe how parts associate with each other to form integrated systems which often have modular and hierarchical structure. In biology, network growth involves two processes, one that unifies and the other that diversifies. Here, we propose a biphasic (bow-tie) theory of module emergence. In the first phase, parts are at first weakly linked and associate variously. As they diversify, they compete with each other and are often selected for performance. The emerging interactions constrain their structure and associations. This causes parts to self-organize into modules with tight linkage. In the second phase, variants of the modules diversify and become new parts for a new generative cycle of higher level organization. The paradigm predicts the rise of hierarchical modularity in evolving networks at different timescales and complexity levels. Remarkably, phylogenomic analyses uncover this emergence in the rewiring of metabolomic and transcriptome-informed metabolic networks, the nanosecond dynamics of proteins, and evolving networks of metabolism, elementary functionomes, and protein domain organization.

Performance of a pilot-scale reverse osmosis process for water recovery from biologically-treated textile wastewater.

Textile industry generates a high volume of wastewater containing various type of pollutants. Although high color and chemical oxygen demand (COD) removals are achieved with the combination of biological and chemical treatment processes, reverse osmosis (RO) process is generally needed for water recovery due to high conductivity of the textile wastewater. In this study, a pilot scale RO process containing one spiral wound membrane element was operated under three different operational modes, i.e. concentrated, complete recycle and continuous, to collect more information for the prediction of a real-scale RO process performance. It was claimed that complete recycle mode of operation enabled mimicking the operational conditions exerted on the first membrane, whereas continuous mode of operation created conditions very similar to the ones exerted on the last membrane element in a real scale RO process train. In the concentrated and continuous mode of operation, water recovery and flux were around 70% and 19 L/m2/h (LMH). Permeate produced in the RO process can be safely reused in the dyeing process as the feed and permeate conductivities were around 5500 µS/cm and 150 µS/cm, respectively, at 70% water recovery. However, color concentration in the concentrate exceeded the discharge limits and would need further treatment. The RO performance was accurately predicted by ROSA simulations.

Metabolite-Centric Reporter Pathway and Tripartite Network Analysis of Arabidopsis Under Cold Stress.

The study of plant resistance to cold stress and the metabolic processes underlying its molecular mechanisms benefit crop improvement programs. Here we investigate the effects of cold stress on the metabolic pathways of Arabidopsis when directly inferred at system level from transcriptome data. A metabolite-centric reporter pathway analysis approach enabled the computation of metabolites associated with transcripts at four time points of cold treatment. Tripartite networks of gene-metabolite-pathway connectivity outlined the response of metabolites and pathways to cold stress. Our metabolome-independent analysis revealed stress-associated metabolites in pathway routes of the cold stress response, including amino acid, carbohydrate, lipid, hormone, energy, photosynthesis, and signaling pathways. Cold stress first triggered the mobilization of energy from glycolysis and ethanol degradation to enhance TCA cycle activity via acetyl-CoA. Interestingly, tripartite networks lacked power law behavior and scale free connectivity, favoring modularity. Network rewiring explicitly involved energetics, signal, carbon and redox metabolisms and membrane remodeling.

The natural history of molecular functions inferred from an extensive phylogenomic analysis of gene ontology data.

The origin and natural history of molecular functions hold the key to the emergence of cellular organization and modern biochemistry. Here we use a genomic census of Gene Ontology (GO) terms to reconstruct phylogenies at the three highest (1, 2 and 3) and the lowest (terminal) levels of the hierarchy of molecular functions, which reflect the broadest and the most specific GO definitions, respectively. These phylogenies define evolutionary timelines of functional innovation. We analyzed 249 free-living organisms comprising the three superkingdoms of life, Archaea, Bacteria, and Eukarya. Phylogenies indicate catalytic, binding and transport functions were the oldest, suggesting a 'metabolism-first' origin scenario for biochemistry. Metabolism made use of increasingly complicated organic chemistry. Primordial features of ancient molecular functions and functional recruitments were further distilled by studying the oldest child terms of the oldest level 1 GO definitions. Network analyses showed the existence of an hourglass pattern of enzyme recruitment in the molecular functions of the directed acyclic graph of molecular functions. Older high-level molecular functions were thoroughly recruited at younger lower levels, while very young high-level functions were used throughout the timeline. This pattern repeated in every one of the three mappings, which gave a criss-cross pattern. The timelines and their mappings were remarkable. They revealed the progressive evolutionary development of functional toolkits, starting with the early rise of metabolic activities, followed chronologically by the rise of macromolecular biosynthesis, the establishment of controlled interactions with the environment and self, adaptation to oxygen, and enzyme coordinated regulation, and ending with the rise of structural and cellular complexity. This historical account holds important clues for dissection of the emergence of biomcomplexity and life.

Genome-wide identification and expression analysis of sulfate transporter (SULTR) genes in potato (Solanum tuberosum L.).

MAIN CONCLUSION: Solanum tuberosum genome analysis revealed 12 StSULTR genes encoding 18 transcripts. Among genes annotated at group level ( StSULTR I-IV), group III members formed the largest SULTRs-cluster and were potentially involved in biotic/abiotic stress responses via various regulatory factors, and stress and signaling proteins. Employing bioinformatics tools, this study performed genome-wide identification and expression analysis of SULTR (StSULTR) genes in potato (Solanum tuberosum L.). Very strict homology search and subsequent domain verification with Hidden Markov Model revealed 12 StSULTR genes encoding 18 transcripts. StSULTR genes were mapped on seven S. tuberosum chromosomes. Annotation of StSULTR genes was also done as StSULTR I-IV at group level based mainly on the phylogenetic distribution with Arabidopsis SULTRs. Several tandem and segmental duplications were identified between StSULTR genes. Among these duplications, Ka/Ks ratios indicated neutral nature of mutations that might not be causing any selection. Two segmental and one-tandem duplications were calculated to occur around 147.69, 180.80 and 191.00 million years ago (MYA), approximately corresponding to the time of monocot/dicot divergence. Two other segmental duplications were found to occur around 61.23 and 67.83 MYA, which is very close to the origination of monocotyledons. Most cis-regulatory elements in StSULTRs were found associated with major hormones (such as abscisic acid and methyl jasmonate), and defense and stress responsiveness. The cis-element distribution in duplicated gene pairs indicated the contribution of duplication events in conferring the neofunctionalization/s in StSULTR genes. Notably, RNAseq data analyses unveiled expression profiles of StSULTR genes under different stress conditions. In particular, expression profiles of StSULTR III members suggested their involvement in plant stress responses. Additionally, gene co-expression networks of these group members included various regulatory factors, stress and signaling proteins, and housekeeping and some other proteins with unknown functions.

Identification and Comparative Analysis of H2O2-Scavenging Enzymes (Ascorbate Peroxidase and Glutathione Peroxidase) in Selected Plants Employing Bioinformatics Approaches.

Among major reactive oxygen species (ROS), hydrogen peroxide (H2O2) exhibits dual roles in plant metabolism. Low levels of H2O2 modulate many biological/physiological processes in plants; whereas, its high level can cause damage to cell structures, having severe consequences. Thus, steady-state level of cellular H2O2 must be tightly regulated. Glutathione peroxidases (GPX) and ascorbate peroxidase (APX) are two major ROS-scavenging enzymes which catalyze the reduction of H2O2 in order to prevent potential H2O2-derived cellular damage. Employing bioinformatics approaches, this study presents a comparative evaluation of both GPX and APX in 18 different plant species, and provides valuable insights into the nature and complex regulation of these enzymes. Herein, (a) potential GPX and APX genes/proteins from 18 different plant species were identified, (b) their exon/intron organization were analyzed, (c) detailed information about their physicochemical properties were provided, (d) conserved motif signatures of GPX and APX were identified, (e) their phylogenetic trees and 3D models were constructed, (f) protein-protein interaction networks were generated, and finally (g) GPX and APX gene expression profiles were analyzed. Study outcomes enlightened GPX and APX as major H2O2-scavenging enzymes at their structural and functional levels, which could be used in future studies in the current direction.

Comparative analysis of plant lycopene cyclases.

Carotenoids are essential isoprenoid pigments produced by plants, algae, fungi and bacteria. Lycopene cyclase (LYC) commonly cyclize carotenoids, which is an important branching step in the carotenogenesis, at one or both end of the backbone. Plants have two types of LYC (ß-LCY and ϵ-LCY). In this study, plant LYCs were analyzed. Based on domain analysis, all LYCs accommodate lycopene cyclase domain (Pf05834). Furthermore, motif analysis indicated that motifs were conserved among the plants. On the basis of phylogenetic analysis, ß-LCYs and ϵ-LCYs were classified in ß and ϵ groups. Monocot and dicot plants separated from each other in the phylogenetic tree. Subsequently, Oryza sativa Japonica Group and Zea mays of LYCs as monocot plants and Vitis vinifera and Solanum lycopersicum of LYCs as dicot plants were analyzed. According to nucleotide diversity analysis of ß-LCY and ϵ-LCY genes, nucleotide diversities were found to be π: 0.30 and π: 0.25, respectively. The result highlighted ß-LCY genes showed higher nucleotide diversity than ϵ-LCY genes. LYCs interacting genes and their co-expression partners were also predicted using String server. The obtained data suggested the importance of LYCs in carotenoid metabolism. 3D modeling revealed that depicted structures were similar in O. sativa, Z mays, S. lycopersicum, and V. vinifera ß-LCYs and ϵ-LCYs. Likewise, the predicted binding sites were highly similar between O. sativa, Z mays, S. lycopersicum, and V. vinifera LCYs. Most importantly, analysis elucidated the V/IXGXGXXGXXXA motif for both type of LYC (ß-LCY and ϵ-LCY). This motif related to Rossmann fold domain and probably provides a flat platform for binding of FAD in O. sativa, Z mays, S. lycopersicum, and V. vinifera ß-LCYs and ϵ-LCYs with conserved structure. In addition to lycopene cyclase domain, the V/IXGXGXXGXXXA motif can be used for exploring LYCs proteins and to annotate the function of unknown proteins containing lycopene cyclase domain. Overall results indicated that a high degree of conserved signature were observed in plant LYCs.

Comparative analysis and modeling of superoxide dismutases (SODs) in Brachypodium distachyon L.

Superoxide dismutase (SOD, EC 1.15.1.1) is an enzyme catalyzing the dismutation of superoxide radical to hydrogen peroxide and dioxygen. To date, four types of SODs--Cu/ZnSOD, MnSOD, FeSOD, and NiSOD--have been identified. In this study, SOD proteins of Brachypodium distachyon (L.) Beauv. were screened by utilization of bioinformatics approaches. According to our results, Mn/FeSODs and Cu/ZnSODs of B. distachyon were found to be in basic and acidic character, respectively. Domain analyzes of SOD proteins revealed that iron/manganese SOD and copper/zinc SOD were within studied SOD proteins. Based on the seconder structure analyzes, Mn/FeSODs and Cu/ZnSODs of B. distachyon were found as having similar sheets, turns and coils. Although helical structures were noticed in the types of Mn/FeSODs, no the type of Cu/ZnSODs were identified having helical structures. The predicted binding sites of Fe/MnSODs and Cu/ZnSODs were confirmed for having His-His-Asp-His and His-His-His-Asp-Ser residues with different positions, respectively. The 3D structure analyzes of SODs revealed that some structural divergences were observed in patterns of SODs domains. Based on phylogenetic analysis, Mn/FeSODs were found to have similarities whereas Cu/ZnSODs were clustered independently in phylogenetic tree.

Palosuran treatment effective as bosentan in the treatment model of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive and fatal disorder that any valuable advance in the management of diseases has crucial importance. The present study aimed to compare the Endothelin1 (ET1) inhibitor bosentan which is regarded as standard therapy with different dose regimens of palosuran which is urotensin-II (UII) inhibitor and explore the discrepancy for mean pulmonary arterial pressure (mPAP), UII, ET1 levels, and pulmonary vascular pathology. Seventy rats were randomly divided into seven groups of ten animals each: group 1 (control group) received the vehicle subcutaneously, instead of monocrotaline (MCT) and vehicle; group 2 (MCT group) received subcutaneous MCT and vehicle; and group 3 (MCT + palosuran 30 mg) received subcutaneous MCT and palosuran. Other groups consist of group 4 (MCT + palosuran 100 mg), group 5 (MCT + bosentan 30 mg), group 6 (MCT + bosentan 100 mg), and group 7 (combination therapy). Serum ET1, UII, mPAP levels, and pulmonary arteriolar pathology of different diameter vessels of all groups have been measured and recorded. The ET1 and UII levels of untreated rats (group 2) were significantly higher than the other groups (p < 0.05). Moreover, mPAP levels of group 2 were significantly higher than the other groups (p = 0.001). Finally, 50-125-µm diameter of arteriole wall thickness was found to be significantly thicker in monocrotaline group compared to groups 4 and 6 (p < 0.001). Statistical differences of wall thickness/diameter ratios of arteries and arterioles larger than 125 was found to be significant between group 5, group 6, and the control group (p < 0.001). UII inhibitor is at least as effective as standard therapy bosentan. Findings of this study consolidate that palosuran could be a new future promising therapeutic option in PAH.

Prognostic role of incidental pleural effusion diagnosed during echocardiographic evaluation.

BACKGROUND: The purpose of this study was to determine the long-term prognostic implications of incidental pleural effusion (PE) detected during echocardiographic examination and its relationship with concomitant diseases. HYPOTHESIS: The study hypothesis is to test whether incidental pleural PE detected during echocardiographic examination be used as a prognostic marker. METHODS: The study was performed by evaluating patient records (N = 251) in whom PE was incidentally detected during echocardiographic examination in a tertiary hospital between 1999 and 2012. The patients were classified into 4 major groups according to the concomitant primary disease: malignancy, and cardiovascular, renal, and pulmonary diseases. The total survival time was obtained from hospital records for patients who died during the hospital stay and social security institution records for patients with out-of-hospital death. RESULTS: One-year and 5-year life expectancies of PE cases concomitant with different disorders were as follows; heart failure (n = 151), 81% and 70%; malignancies (n = 45), 53% and 44%; pulmonary diseases (n = 37), 89% and 78%; renal diseases (n = 18), 100% and 83%; respectively. PE associated with heart failure, renal disease, and pulmonary disease had similar (P > 0.05 for all) and favorable outcomes compared to PE associated with malignancies (P < 0.001). CONCLUSIONS: The prognosis of incidental PE was the worst in patients with concomitant malignancies; however, PE associated with nonmalignant diseases including heart failure, pulmonary disease, and renal disease have similar and favorable outcomes.

Is Toxoplasma gondii a causal agent in migraine?

BACKGROUND: Many different tissues may be parasitized by Toxoplasma gondii, particularly, lung, heart, lymphoid organs, and the central nervous tissues. Tissue cysts of this parasite in the brain may spontaneously rupture, releasing parasites that cause antibody titers to rise. In immunocompetent subjects with acquired toxoplasmosis, the most frequent symptoms were lymphadenopathy and headache. In the neurogenic inflammation theory of the pathogenesis of migraine, the cause of initial release of ions and inflammatory agents has not been established. In this study, we aimed to investigate if T. gondii infection is a possible cause of neurogenic inflammation of migraines. METHODS: The anti-T. gondii antibody status of 104 patients with migraine were studied and compared with those of control groups, 50 healthy subjects and 50 subjects with headache due to rhinosinusitis, by using a micro-enzyme-linked immunosorbent assay technique. RESULTS: Forty-six (44.2%) patients with migraine, 13 (26.0%) healthy control subjects, and 12 (24%) control subjects with rhinosinusitis were positive for anti-T. gondii IgG antibody. The rate of positivity in the migraine patient group was statistically different from those of the control groups (P < 0.05). CONCLUSIONS: The results show the presence of chronic Toxoplasma infection in patients with migraine. Toxoplasma infection may contribute to neurogenic inflammation as the pathogenesis of migraine, as many studies in the literature have reported that Toxoplasma infection causes biochemical and immunologic changes.