The constant domain of CRTAM is essential for high-affinity interaction with Nectin-like 2.

CRTAM (Class-I MHC restricted T cell-associated molecule) is a member of the Nectin-like family, composed of two extracellular domains, one constant domain (IgC) and another variable domain (IgV), expressed in activated CD8 T cells, epithelial cells, natural killer (NK) cells, and in a subpopulation of CD4 T cells. CRTAM recognizes the ligand Nectin-like 2 (Necl2) through the IgV domain. However, the role of the IgC domain during this ligand recognition has yet to be understood. In this study, we show the purification of soluble-folded Ig domains of CRTAM, and we demonstrate that the IgC domain forms a homodimer in solution via hydrophobic interactions. By surface plasmon resonance (SPR) analysis, we also demonstrate that CRTAM binds to Necl2 with an affinity of 2.16 nM. In conclusion, CRTAM's IgC is essential for a high-affinity interaction with Necl-2.

The value of immature granulocyte percentage united with D-Dimer in the evaluation of severe pancreatitis and its prognosis.

OBJECTIVE: The study aimed at analyzing the serum expression of Immature Granulocyte percentage (IG %) and D-Dimer (D-D) in patients with severe pancreatitis and exploring their clinical diagnostic value. METHODS: Eighty-four cases with severe pancreatitis received in Shengjing Hospital, China Medical University from July 2020 to July 2023 were regarded as the study group and conducted for retrospective analysis. They were divided into a survival group (n = 62) and a death group (n = 22) based on the prognosis. Another 80 patients diagnosed with mild and moderate pancreatitis were selected as the control group. Serum IG % and D-D levels of all subjects were analyzed and the value of IG % and D-D in the evaluation of severe pancreatitis and its prognosis was conducted by Receiver Operating Characteristic (ROC) curve. RESULTS: The IG % and D-D levels in the study group were markedly higher than the control group (p < 0.05). The IG % and D-D level in the death group were observably higher than the survival group (p < 0.05). The Area Under the Curve (AUC) of IG % and D-D combined assessment for severe pancreatitis was 0.963, and the sensitivity and specificity were 98.75 %, 82.14 %, respectively. The AUC of IG % and D-D combined assessment for prognosis of severe pancreatitis was 0.814 with a sensitivity of 79.03 % and a specificity of 77.27 %. The efficiency of joint evaluation of the two indicators is superior to the individual evaluation. CONCLUSION: Serum IG % and D-D are highly expressed in patients with severe pancreatitis, which has important clinical value for the evaluation of severe pancreatitis and its prognosis.

Extended states in random dimer gated graphene superlattices.

Ordered and disordered semiconductor superlattices represent structures with completely opposed properties. For instance, ordered superlattices exhibit extended Bloch-like states, while disordered superlattices present localized states. These characteristics lead to higher conductance in ordered superlattices compared to disordered ones. Surprisingly, disordered dimer superlattices, which consist of two types of quantum wells with one type always appearing in pairs, exhibit extended states. The percentage of dissimilar wells does not need to be large to have extended states. Furthermore, the conductance is intermediate between ordered and disordered superlattices. In this work, we explore disordered dimer superlattices in graphene. We calculate the transmission and transport properties using the transfer matrix method and the Landauer-Büttiker formalism, respectively. We identify and discuss the main energy regions where the conductance of random dimer superlattices in graphene is intermediate to that of ordered and disordered superlattices. We also analyze the resonant energies of the double quantum well cavity and the electronic structure of the host gated graphene superlattice (GGSL), finding that the coupling between the resonant energies and the superlattice energy minibands gives rise to the extended states in random dimer GGSLs.

Entamoeba histolytica: In Silico and In Vitro Oligomerization of EhHSTF5 Enhances Its Binding to the HSE of the EhPgp5 Gene Promoter.

Throughout its lifecycle, Entamoeba histolytica encounters a variety of stressful conditions. This parasite possesses Heat Shock Response Elements (HSEs) which are crucial for regulating the expression of various genes, aiding in its adaptation and survival. These HSEs are regulated by Heat Shock Transcription Factors (EhHSTFs). Our research has identified seven such factors in the parasite, designated as EhHSTF1 through to EhHSTF7. Significantly, under heat shock conditions and in the presence of the antiamoebic compound emetine, EhHSTF5, EhHSTF6, and EhHSTF7 show overexpression, highlighting their essential role in gene response to these stressors. Currently, only EhHSTF7 has been confirmed to recognize the HSE as a promoter of the EhPgp5 gene (HSE_EhPgp5), leaving the binding potential of the other EhHSTFs to HSEs yet to be explored. Consequently, our study aimed to examine, both in vitro and in silico, the oligomerization, and binding capabilities of the recombinant EhHSTF5 protein (rEhHSTF5) to HSE_EhPgp5. The in vitro results indicate that the oligomerization of rEhHSTF5 is concentration-dependent, with its dimeric conformation showing a higher affinity for HSE_EhPgp5 than its monomeric state. In silico analysis suggests that the alpha 3 α-helix (α3-helix) of the DNA-binding domain (DBD5) of EhHSTF5 is crucial in binding to the major groove of HSE, primarily through hydrogen bonding and salt-bridge interactions. In summary, our results highlight the importance of oligomerization in enhancing the affinity of rEhHSTF5 for HSE_EhPgp5 and demonstrate its ability to specifically recognize structural motifs within HSE_EhPgp5. These insights significantly contribute to our understanding of one of the potential molecular mechanisms employed by this parasite to efficiently respond to various stressors, thereby enabling successful adaptation and survival within its host environment.

Spin-valley polarization and tunneling magnetoresistance in monomer, dimer, and trimer magnetic silicene superlattices.

Monomer, dimer and trimer semiconductor superlattices are an alternative for bandgap engineering due to the possibility of duplicate, triplicate, and in general multiply the number of minibands and minigaps in a specific energy region. Here, we show that monomer, dimer, and trimer magnetic silicene superlattices (MSSLs) can be the basis for tunable magnetoresistive devices due to the multiplication of the peaks of the tunneling magnetoresistance (TMR). In addition, these structures can serve as spin-valleytronic devices due to the formation of two well-defined spin-valley polarization states by appropriately adjusting the superlattice structural parameters. We obtain these conclusions by studying the spin-valley polarization and TMR of monomer, dimer, and trimer MSSLs. The magnetic unit cell is structured with one seed A with positive magnetization, and one, two, or three seeds B with variable magnetization. The number of B seeds defines the monomer, dimer, and trimer superlattice, while its magnetic orientation positive or negative the parallel (PM) or antiparallel magnetization (AM) superlattice configuration. The transfer matrix method and the Landauer-Büttiker formalism are employed to obtain the transmission and transport properties, respectively. We find multiplication of TMR peaks in staircase fashion according to the number of B seeds in the superlattice unit cell. This multiplication is related to the multiplication of the minibands which reflects as multiplication of the descending envelopes of the conductance. We also find well-defined polarization states for both PM and AM by adjusting asymmetrically the width and height of the barrier-well in seeds A and B.

Prostaglandin E2/Leukotriene B4 balance and viral load in distinct clinical stages of COVID-19: A cross-sectional study.

BACKGROUND: Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) are eicosanoids involved in modulation of the antiviral immune response. Recent studies have identified increased levels of several eicosanoids in the plasma and bronchoalveolar lavage of patients with coronavirus disease (COVID-19). This study investigated correlations between plasma levels of PGE2 and LTB4 and clinical severity of COVID-19. METHODS: This cross-sectional study involved non-infected (n = 10) individuals and COVID-19 patients classified as cured (n = 13), oligosymptomatic (n = 29), severe (n = 15) or deceased (n = 11). Levels of D-dimer a, known COVID-19 severity marker, PGE2 and LTB4 were measured by ELISAs and data were analysed with respect to viral load. RESULTS: PGE2 plasma levels were decreased in COVID-19 patients compared to the non-infected group. Changes in PGE2 and LTB4 levels did not correlate with any particular clinical presentations of COVID-19. However, LTB4 was related to decreased SARS-CoV-2 burden in patients, suggesting that only LTB4 is associated with control of viral load. CONCLUSIONS: Our data indicate that PGE2/LTB4 plasma levels are not associated with COVID-19 clinical severity. Hospitalized patients with COVID-19 are treated with corticosteroids, which may influence the observed eicosanoid imbalance. Additional analyses are required to fully understand the participation of PGE2 receptors in the pathophysiology of COVID-19.

Myristoylated GRASP55 dimerizes in the presence of model membranes.

The Golgi Reassembly and Stacking Proteins (GRASPs) are engaged in various functions within the cell, both in unconventional secretion mechanisms and structuring and organizing the Golgi apparatus. Understanding their specific role in each situation still requires more structural and functional data at the molecular level. GRASP55 is one of the GRASP members in mammals, anchored to the membrane via the myristoylation of a Gly residue at its N-terminus. Therefore, co-translational modifications, such as myristoylation, are fundamental when considering a strategy to obtain detailed information on the interactions between GRASP55 and membranes. Despite its functional relevance, the N-terminal myristoylation has been underappreciated in the studies reported to date, compromising the previously proposed models for GRASP-membrane interactions. Here, we investigated the synergy between the presence of the membrane and the formation of oligomeric structures of myristoylated GRASP55, using a series of biophysical techniques to perform the structural characterization of the lipidated GRASP55 and its interaction with biological lipid model membranes. Our data fulfill an unexplored gap: the adequate evaluation of the presence of lipidations and lipid membranes on the structure-function dyad of GRASPs.Communicated by Ramaswamy H. Sarma.

Fast screening using attenuated total reflectance- fourier transform infrared (ATR-FTIR) spectroscopy of patients based on D-dimer threshold value.

Attenuated Total Reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy is an emerging technology in the medical field. Blood D-dimer was initially studied as a marker of the activation of coagulation and fibrinolysis. It is mainly used as a potential diagnosis screening test for pulmonary embolism or deep vein thrombosis but was recently associated with COVID-19 severity. This study aimed to evaluate the use of ATR-FTIR spectroscopy with machine learning to classify plasma D-dimer concentrations. The plasma ATR-FTIR spectra from 100 patients were studied through principal component analysis (PCA) and two supervised approaches: genetic algorithm with linear discriminant analysis (GA-LDA) and partial least squares with linear discriminant (PLS-DA). The spectra were truncated to the fingerprint region (1800-1000 cm-1). The GA-LDA method effectively classified patients according to D-dimer cutoff (≤0.5 µg/mL and >0.5 µg/mL) with 87.5 % specificity and 100 % sensitivity on the training set, and 85.7 % specificity, and 95.6 % sensitivity on the test set. Thus, we demonstrate that ATR-FTIR spectroscopy might be an important additional tool for classifying patients according to D-dimer values. ATR-FTIR spectral analyses associated with clinical evidence can contribute to a faster and more accurate medical diagnosis, reduce patient morbidity, and save resources and demand for professionals.

D-dimer and HbA1c levels findings in COVID-19 Iraqi patients / Descobertas dos níveis de D-dímero e HbA1c em pacientes iraquianos com COVID-19

On March 11, 2020, the World Health Organization (WHO) declared a new coronavirus infection caused by the SARS-CoV-2 virus as a pandemic, making it the 11th pandemic of the 20th and 21st centuries. This study investigated the clinical and laboratory results (D-dimer, conventional coagulation, and HbA1c biomarker concentrations) of 150 patients (75 male and 75 female) with confirmed COVID-19 pneumonia and 50 controls (25 male and 25 female). For disease diagnosis, all COVID-19 patients were given a Real-Time Reverse Transcription Polymerase Chain Reaction Assay (RT-PCR). The findings revealed that D-dimer and HbA1c levels in COVID-19 patients were significantly higher (P 0.001) at the time of admission; In COVID-19 patients, there was also a strong correlation between D-dimer levels and HbA1c levels (P 0.001). In conclusion, COVID-19 patients are more likely to have a poor prognosis if their D-dimer and HbA1c levels remain uncontrolled over a lengthy period. To lower the likelihood of a bad prognosis in COVID-19, patients with higher levels of D-dimer and HbA1c should be continuously monitored.

Em 11 de março de 2020, a Organização Mundial da Saúde (OMS) declarou uma nova infecção por coronavírus causada pelo vírus SARS-CoV-2 como uma pandemia, tornando-a a 11ª pandemia dos séculos XX e XXI. Este estudo investigou os resultados clínicos e laboratoriais (D-dímero, coagulação convencional e concentrações de biomarcadores HbA1c) de 150 pacientes (75 homens e 75 mulheres) com pneumonia por COVID-19 confirmada e 50 controles (25 homens e 25 mulheres). Para o diagnóstico da doença, todos os pacientes com COVID-19 receberam um Ensaio de Reação em Cadeia da Polimerase com Transcrição Reversa em Tempo Real (RT-PCR). Os achados revelaram que os níveis de D-dímero e HbA1c em pacientes com COVID-19 foram significativamente maiores (P 0,001) no momento da admissão. Em pacientes com COVID-19, também houve uma forte correlação entre os níveis de D-dímero e os níveis de HbA1c (P 0,001). Em conclusão, os pacientes com COVID-19 têm maior probabilidade de ter um prognóstico ruim se seus níveis de D-dímero e HbA1c permanecerem descontrolados por um longo período. Para diminuir a probabilidade de um mau prognóstico na COVID-19, os pacientes com níveis mais altos de D-dímero e HbA1c devem ser monitorados continuamente.

Cxcl1 monomer-dimer equilibrium controls neutrophil extravasation.

The chemokine Cxcl1 plays a crucial role in recruiting neutrophils in response to infection. The early events in chemokine-mediated neutrophil extravasation involve a sequence of highly orchestrated steps including rolling, adhesion, arrest, and diapedesis. Cxcl1 function is determined by its properties of reversible monomer-dimer equilibrium and binding to Cxcr2 and glycosaminoglycans. Here, we characterized how these properties orchestrate extravasation using intravital microscopy of the cremaster. Compared to WT Cxcl1, which exists as both a monomer and a dimer, the trapped dimer caused faster rolling, less adhesion, and less extravasation. Whole-mount immunofluorescence of the cremaster and arrest assays confirmed these data. Moreover, the Cxcl1 dimer showed impaired LFA-1-mediated neutrophil arrest that could be attributed to impaired Cxcr2-mediated ERK signaling. We conclude that Cxcl1 monomer-dimer equilibrium and potent Cxcr2 activity of the monomer together coordinate the early events in neutrophil recruitment.

The value of immature granulocyte percentage united with D-Dimer in the evaluation of severe pancreatitis and its prognosis

ABSTRACT Objective: The study aimed at analyzing the serum expression of Immature Granulocyte percentage (IG %) and D-Dimer (D-D) in patients with severe pancreatitis and exploring their clinical diagnostic value. Methods: Eighty-four cases with severe pancreatitis received in Shengjing Hospital, China Medical University from July 2020 to July 2023 were regarded as the study group and conducted for retrospective analysis. They were divided into a survival group (n = 62) and a death group (n = 22) based on the prognosis. Another 80 patients diagnosed with mild and moderate pancreatitis were selected as the control group. Serum IG % and D-D levels of all subjects were analyzed and the value of IG % and D-D in the evaluation of severe pancreatitis and its prognosis was conducted by Receiver Operating Characteristic (ROC) curve. Results: The IG % and D-D levels in the study group were markedly higher than the control group (p < 0.05). The IG % and D-D level in the death group were observably higher than the survival group (p < 0.05). The Area Under the Curve (AUC) of IG % and D-D combined assessment for severe pancreatitis was 0.963, and the sensitivity and specificity were 98.75 %, 82.14 %, respectively. The AUC of IG % and D-D combined assessment for prognosis of severe pancreatitis was 0.814 with a sensitivity of 79.03 % and a specificity of 77.27 %. The efficiency of joint evaluation of the two indicators is superior to the individual evaluation. Conclusion: Serum IG % and D-D are highly expressed in patients with severe pancreatitis, which has important clinical value for the evaluation of severe pancreatitis and its prognosis.

Evaluation of d-dimer as outcome biomarker in COVID-19 acute respiratory distress patients

ABSTRACT Acute respiratory distress syndrome is a significant complication in critical care patients. COVID-19 (C19)-associated severe respiratory failure is related to it, and d-dimer rise predicts a worse outcome. To investigate the association between d-dimer and the severity of this respiratory syndrome, we conducted a study in C19 intubated patients. A retrospective, single-center observational study was conducted with 64 C19 adult intubated patients. Strata of d-dimer results between patients was evaluated using survival analysis. Survival was higher in mild respiratory distress patients. D-dimer showed poor sensitivity and specificity in predicting respiratory failure severity. Risk assessment for death showed a higher prevalence of admission d-dimer results (HR 1.335; 95% CI 0.695-2.564). Our sample confidently represented the medical profile of C19 severe patients. Sepsis development in C19 is associated with the inflammatory storm in respiratory distress syndrome. As the receiver operating curves show, the increase in d-dimer results is consistent with inflammation rather than a prognostic biomarker. As expected, severe respiratory distress patients presented higher mortality. In summary, d-dimer results are not associated with the prognosis of C19 respiratory distress syndrome patients.

Dímero D, ferritina y proteína C reactiva. Valor en la estratificación de pacientes con COVID-19 / D-dimer, ferritin and C-reactive protein. Value in the stratification of patients with COVID-19

Introducción: La pandemia de COVID-19 continúa desafiando a los sistemas de salud. La estratificación de los pacientes afectados a partir de biomarcadores, estrategia menos invasiva, aún es controversial. Objetivo: Comprobar la capacidad discriminante de la ferritina, proteína C reactiva y dímero D entre pacientes con COVID-19 moderados y severos. Métodos: Se aplicó un diseño transversal entre junio y noviembre de 2021. Las variables cualitativas y la edad fueron registradas por revisión de la historia clínica. La determinación de los biomarcadores mencionados fue realizada en el momento de inclusión en el estudio con el empleo de reactivos Roche en el analizador Hitachi cobas c 311. Se empleó el programa estadístico SSPS para el análisis de datos. Resultados: Existió predominio de hipertensos en ambos grupos. La vacunación y el sexo femenino prevalecieron entre los moderados, mientras los hombres y las enfermedades crónicas entre los graves. Se manifestaron mayores niveles de los tres biomarcadores analizados en el grupo grave (Mann-Whitney p 0,5; p < 0,05). Conclusiones: La presencia de comorbilidades crónicas y de individuos no vacunados predominó entre los pacientes graves. Se demostró una estrecha correlación entre los biomarcadores analizados en ambos grupos de pacientes. Los biomarcadores mostraron capacidad discriminante entre la enfermedad COVID-19 moderada y grave(AU)

Introduction: The COVID-19 pandemic continues to challenge healthcare systems. The stratification of affected patients from biomarkers, a less invasive strategy, is still controversial. Objective: To check the discriminating capacity of ferritin, C-reactive protein and D-dimer in patients with moderate and severe COVID-19. Methods: A cross-sectional design was applied from June to November 2021. The qualitative variables and age were recorded by review of the patient's clinical records. The determination of the aforementioned biomarkers was carried out at the time of inclusion in the study using the Roche reagents in the HITACHI Cobas C 311 analyzer. The SPSS statistical program was used for analyzing dates. Results: There was a predominance of hypertensive patients in both groups. Vaccination and female sex prevailed among the moderate ones, while men and chronic diseases among the severe ones. Higher levels of the three analyzed biomarkers were observed in the severe group (Mann-Whitney test p < 0.05). The association between these was significant in both groups (Spearman correlation, p < 0.05). 366 μg/L of ferritin; 36.25 mg/L of C- reactive protein and 1.02 μg/mL of D-dimer, acceptably distinguished between severe and moderate (area under the curve ˃ 0.5; p < 0.05). Conclusions: The presence of chronic comorbidities and unvaccinated individuals predominated among severe patients. A close correlation was shown between the biomarkers analyzed in both patient groups. Biomarkers showed discriminating capacity between moderate and severe COVID-19 disease(AU)

Evaluation of oxidative stress level: reactive oxygen species, reduced glutathione, and D-dimer in patients hospitalized due to COVID-19.

Elevated D-dimer levels at hospital admission may also indicate a higher likelihood of progressing to a severe or critical state. This study aimed to assess reactive oxygen species (ROS), non-enzymatic antioxidant reduced glutathione (GSH), and D-dimer levels in COVID-19 patients upon admission, examining their association with mortality outcomes. Data was collected from the medical records of 170 patients hospitalized in a referral hospital unit between March 2020 and December 2021. Patients were divided into two groups: the ward bed group (n = 87), comprising 51% with moderate clinical conditions, and the intensive care unit (ICU) group (n = 83), comprising 49% with severe conditions. The mean age was 59.4 years, with a male predominance of 52.4%. The overall death rate was 43%, with 30.6% in the moderate group and 69.4% in the severe group. The average time from symptom onset to hospitalization was 6.42 days. Results showed that non-survivors had high D-dimer and ROS counts, longer ICU stays, and worse saturation levels at admission. In conclusion, elevated ROS and D-dimer levels may contribute to worse outcomes in critically ill patients, potentially serving as specific and sensitive predictors of poor outcomes upon admission.

Estudio de marcadores de coagulación e inflamación y variantes genéticas de trombofilia al momento de la admisión hospitalaria para predecir mortalidad en una cohorte de la primera ola de COVID-19 en Argentina / Study of coagulation and inflammation biomarkers and thrombophilic genetic variants at hospital admission to predict mortality in a cohort from the first wave of COVID-19 in Argentina

Resumen Introducción: los cuadros clínicos más graves y los desenlaces fatales resultantes de la infección por SARS-CoV-2 han sido asociados con una hiperactivación del sistema inmune con inmunotrombosis, proceso caracterizado por una respuesta inflamatoria exacerbada y de hipercoagulabilidad. Diferentes comorbilidades y factores genéticos de cada individuo podrían estar involucrados en un peor pronóstico. El objetivo de este estudio fue analizar si distintos biomarcadores relacionados con inflamación y coagulación, así como ciertas variables clínicas, identificadas al momento de la admisiónhospitalaria, podrían ser factores de riesgo asociados con una evolución clínica desfavorable. Asimismo, investigar la posible asociación entre la portación de las variantes genéticas factor V Leiden, la variante G20210A del gen del factor II y las variantes alélicas 10034C/T del gen del fibrinógeno gamma y 7872C/T del gen del factor XI con el desenlace clínico de pacientes COVID-19. Materiales y métodos: se incluyeron 204 pacientes adultos con diagnóstico confirmado de COVID-19+, hospitalizados durante la primera ola de la pandemia. Se registraron variables demográficas y clínicas incluyendo comorbilidades y se midieron diversos parámetros bioquímicos plasmáticos. Los pacientes se dividieron en dos grupos (sobrevida: n=141 y muerte: n=63) para comparar su evolución clínica. Resultados: se observó que los pacientes fallecidos eran de mayor edad y presentaban un índice de masa corporal más alto. Además, tenían recuentos de plaquetas y linfocitos más bajos, recuentos totales de leucocitos y neutrófilos más altos, una mayor relación neutrófilos/linfocitos y niveles más elevados de dímero D, ferritina y LDH en comparación con los supervivientes (p<0.05). Estableciendo puntos de corte, se encontró que un recuento de plaquetas <200.103/ul [OR=2.81, IC 95% (1.51-5.23)], un recuento de leucocitos >10.103/ul [OR=2.54, IC 95% (1.32-5.23)], un porcentaje de linfocitos <10% [OR=3.48, IC 95% (1.85-6.54]), un porcentaje de neutrófilos >70% [OR=2.82, IC 95% (1.43-5.59)], una relación neutrófilos/linfocitos >4 [OR=2.77, IC 95% (1.40-5.40)], niveles de dímero D >1500 ng/ml FEU [OR=2.67 IC 95% (1.33-5.37)] y ferritina >1000 ng/ml [OR=2.33, IC 95%(1.214.49)] al momento de la admisión hospitalaria estarían asociados con mayores posibilidades de sufrir un desenlace fatal. No se encontraron diferencias significativas en las distribuciones genotípicas de las variantes genéticas estudiadas entre ambos grupos. Discusión: acorde a investigaciones previas, se encontró que la edad, la obesidad y los niveles de marcadores hematológicos/plasmáticos medidos al momento de la admisión hospitalaria serían predictores de mal pronóstico en pacientes no inmunizados. Pese a la típica exacerbación de los mecanismos de coagulación en casos de COVID-19 severo, la portación de las variantes genéticas protrombóticas estudiadas no estaría asociada a un peor pronóstico.

Abstract Introduction: the most severe clinical presentations and the fatal outcomes resulting from SARS-CoV-2 infection have been associated with hyperactivation of the immune system with immunothrombosis, a process characterized by an exacerbated inflammatory response and hypercoagulability. Different comorbidities and genetic factors of each individual could be involved in a worse prognosis. The objective of this study was to analyze whether different biomarkers related to inflammation and coagulation, as well as certain clinical variables, addressed at the time of hospital admission, could be risk factors associated with an adverse clinical outcome. Likewise, to investigate the possible association between the carriage of the genetic variants factor V Leiden, G20210A variant in the factor II gene and the allelic variants 10034C/T in the fibrinogen gamma gene and 7872C/T in the factor XI gene and the clinical outcome of COVID-19 patients. Materials and methods: 204 adult patients with a confirmed diagnosis of COVID-19+, hospitalized during the first wave of the pandemic, were included. Demographic and clinical variables including comorbidities were recorded and various plasma biochemical parameters were measured. The patients were divided into two groups (survival: n=141 and death: n=63) to compare their clinical evolution. Results: it was found that the deceased patients were older and had a higher body mass index. They also had lower platelet and lymphocyte counts, higher total leukocyte and neutrophil counts, higher neutrophil/lymphocyte ratio, and higher levels of D-dimer, ferritin, and LDH compared to survivors (p<0.05). Establishing cut-off points, it was found that a platelet count <200.103/ul [OR=2.81, IC 95% (1.515.23)], a leukocyte count >10.103/ul [OR=2.54, IC 95% (1.32-5.23)], a percentage of lymphocytes <10% [OR=3.48, IC 95% (1.85-6.54]), a percentage of neutrophils >70% [OR=2.82, IC 95% (1.43-5.59)] a relationship neutrophils/lymphocytes >4 [OR=2.77, IC 95% (1.40-5.40)], D-dimer levels >1500 ng/ml FEU [OR=2.67 IC 95% (1.33-5.37)] and ferritin >1000 ng/ml [OR=2.33, IC 95%(1.21-4.49)] at the time of hospital admission would be associated with greater chances of suffering a fatal outcome. No significant differences were found in the genotypic distributions of the genetic variants studied between both groups. Discussion: according to previous investigations, it was found that age, obesity and the levels of hematological/plasma markers measured at the time of hospital admission, would be predictors of poor prognosis in non-immunized patients. Despite the typical exacerbation of coagulation mechanisms in cases of severe COVID-19, the carriage of the prothrombotic genetic variants studied would not be associated with a worse prognosis.

Association of D-Dimer, C-Reactive Protein, and Ferritin with COVID-19 Severity in Pregnant Women: Important Findings of a Cross-Sectional Study in Northern Brazil.

BACKGROUND: The COVID-19 pandemic has had a great impact on pregnant women due to the broad clinical spectrum of the disease. The present study investigated the profile of three biomarkers during hospital admission of pregnant women-D-dimer, C-reactive protein (CRP), and ferritin-and their correlation with the severity and outcome of COVID-19. METHODS: The cross-sectional study included 226 pregnant women hospitalized in the city of Belém, Pará, Northern Brazil, from April 2020 to July 2021. Epidemiological and laboratory data were obtained from medical records, and all pregnant women underwent RT-PCR molecular testing for the detection of SARS-CoV-2. RESULTS: In total, 121 (53.5%) were positive and 105 (46.5%) were negative for SARS-CoV-2 using RT-PCR. Most pregnant women (49.5%) with COVID-19 were between 26 and 34 years old, were residing in the interior of the state of Pará (51.2%), and were in the third gestational trimester (71.9%). In addition, 71.1% of them were admitted to the ward and 28.9% were admitted to the intensive care unit (ICU), with 90.9% surviving COVID-19. The concentrations of D-dimer (p = 0.0122) and ferritin (p ≤ 0.0001) were significantly higher among pregnant women with COVID-19, especially among those hospitalized in the ICU. CONCLUSION: Ferritin and D-dimer seem to serve as important biomarkers for the prognosis of COVID-19 in pregnant women, which was not observed for CRP.

Microvascular lung vessels obstructive thromboinflammatory syndrome in patients with COVID-19: Insights from lung intravascular optical coherence tomography.

Background: Microvascular lung vessels obstructive thromboinflammatory syndrome has been proposed as a possible mechanism of respiratory failure in COVID-19 patients. However, it has only been observed in post-mortem studies and has never been documented in vivo, probably because of a lack of CT scan sensitivity in small pulmonary arteries. The aim of the present study was to assess the safety, tolerability, and diagnostic value of optical coherence tomography (OCT) for the assessment of patients with COVID-19 pneumonia for pulmonary microvascular thromboinflammatory syndrome. Methods: The COVID-OCT trial was a multicenter, open-label, prospective, interventional clinical study. Two cohorts of patients were included in the study and underwent pulmonary OCT evaluation. Cohort A consisted of patients with COVID-19 with a negative CT scan for pulmonary thrombosis and elevated thromboinflammatory markers (D-dimer > 10,000 ng/mL or 5,000 < D-dimer < 10,000 ng/mL and one of: C-reactive Protein > 100 mg/dL, IL-6 > 6 pg/mL, or ferritin > 900 ng/L). Cohort B consisted of patients with COVID-19 and a CT scan positive for pulmonary thrombosis. The primary endpoints of the study were: (i) to evaluate the overall safety of OCT investigation in patients with COVID-19 pneumonia, and (ii) to report on the potential value of OCT as a novel diagnostic tool for the diagnosis of microvascular pulmonary thrombosis in COVID-19 patients. Results: A total of 13 patients were enrolled. The mean number of OCT runs performed in each patient was 6.1 ± 2.0, both in ground glass and healthy lung areas, achieving a good evaluation of the distal pulmonary arteries. Overall, OCT runs identified microvascular thrombosis in 8 patients (61.5%): 5 cases of red thrombus, 1 case of white thrombus, and 2 cases of mixed thrombus. In Cohort A, the minimal lumen area was 3.5 ± 4.6 mm2, with stenosis of 60.9 ± 35.9% of the area, and the mean length of thrombus-containing lesions was 5.4 ± 3.0 mm. In Cohort B, the percentage area obstruction was 92.6 ± 2.6, and the mean thrombus-containing lesion length was 14.1 ± 13.9 mm. No peri-procedural complications occurred in any of the 13 patients. Conclusion: OCT appears to be a safe and accurate method of evaluating the distal pulmonary arteries in hospitalized COVID-19 patients. Here, it enabled the first in vivo documentation of distal pulmonary arterial thrombosis in patients with elevated thromboinflammatory markers, even when their CT angiogram was negative for pulmonary thrombosis. Clinical trial registration: ClinicalTrial.gov, identifier NCT04410549.

Deletion of the ATP20 gene in Ustilago maydis produces an unstable dimer of F1FO-ATP synthase associated with a decrease in mitochondrial ATP synthesis and a high H2O2 production.

The F1FO-ATP synthase uses the energy stored in the electrochemical proton gradient to synthesize ATP. This complex is found in the inner mitochondrial membrane as a monomer and dimer. The dimer shows higher ATPase activity than the monomer and is essential for cristae folding. The monomer-monomer interface is constituted by subunits a, i/j, e, g, and k. The role of the subunit g in a strict respiratory organism is unknown. A gene knockout was generated in Ustilago maydis to study the role of subunit g on mitochondrial metabolism and cristae architecture. Deletion of the ATP20 gene, encoding the g subunit, did not affect cell growth or glucose consumption, but biomass production was lower in the mutant strain (gΔ strain). Ultrastructure observations showed that mitochondrial size and cristae shape were similar in wild-type and gΔ strains. The mitochondrial membrane potential in both strains had a similar magnitude, but oxygen consumption was higher in the WT strain. ATP synthesis was 20 % lower in the gΔ strain. Additionally, the mutant strain expressed the alternative oxidase in the early stages of growth (exponential phase), probably as a response to ROS stress. Dimer from mutant strain was unstable to digitonin solubilization, avoiding its isolation and kinetic characterization. The isolated monomeric state activated by n-dodecyl-ß-D-maltopyranoside showed similar kinetic constants to the monomer from the WT strain. A decrease in mitochondrial ATP synthesis and the presence of the AOX during the exponential growth phase suggests that deletion of the g gene induces ROS stress.

Trombocitopenia inducida por heparina y síndrome de trombo blanco en paciente con SARS-CoV-2 / SARS-CoV-2 patient with heparin-induced thrombocytopenia and white thrombi syndrome / Trombocitopenia induzida por heparina e síndrome de trombo branco em paciente com SARS-CoV-2

Resumen: La trombocitopenia inducida por heparina es una entidad clínica infrecuente; sin embargo, la amplia y masiva utilización de anticoagulantes en épocas de pandemia por COVID-19 pone de manifiesto una realidad evidente a la cual no podemos escapar. Presentamos el caso de un paciente masculino en la sexta década de vida con SARS-CoV-2, quien luego de la administración de heparina en el escenario de una enfermedad pulmonar tromboembólica desarrolló consumo plaquetario asociado a presencia de anticuerpos antifactor de agregación plaquetaria 4.

Abstract: Heparin-induced thrombocytopenia is an uncommon clinical entity, however the wide and massive use of anticoagulants in times of pandemic by COVID-19 reveals an evident reality and we can not escape. we present the case of a male patient in sixth decade of life with SARS-CoV-2 who after the administration of heparin in the clinical setting of thromboembolic lung disease development platelet consumption associated with the presence of antibodies anti platelet activating factor 4.

Resumo: A trombocitopenia induzida por heparina é uma entidade clínica rara, no entanto, a ampla e massiva utilização de anticoagulantes em tempos de pandemia de COVID-19 revela uma realidade óbvia à qual não podemos fugir. Apresentamos o caso de um doente do sexo masculino na sexta década de vida com SARS-CoV-2 que, após administração de heparina no contexto de doença pulmonar tromboembólica, desenvolveu consumo de plaquetas associado à presença de anticorpos anti-fator de agregação plaquetária 4.

Dynamic inflammatory response among routine laboratory biomarkers and their predictive ability for mortality in patients with severe COVID-19.

Background: The severity of coronavirus disease 2019 (COVID-19) is related to several factors, including age, sex, and comorbidities (obesity, type 2 diabetes, and hypertension). However, systemic inflammation plays a fundamental role in COVID-19 pathophysiology. Several studies have described this association employing specific biomarkers that are not routinely used in clinical practice. On the other hand, very few reports in the literature focused on the analysis of the routine laboratory biomarkers to predict the outcome of severe COVID-19 patients. Objective: We aimed to analyze the dynamic inflammatory response using routine laboratory biomarkers to predict in-hospital mortality in Mexican patients with severe COVID-19. Methods: This is a cohort study including patients with severe COVID-19. Demographic characteristics were retrieved from medical charts and biochemical parameters were measured at hospital admission and subsequently on days 3, 5, 7, 10, 14, and 21 during the hospital stay; measurements were stopped when patients were discharged from the hospital (alive or death). Results: A total of 250 patients were included in the study, 40.8% of patients died. The analyzed routine laboratory parameters, such as serum levels of neutrophil-to-lymphocyte ratio, C-reactive protein, and D-dimer remained elevated in hospitalized patients who did not survive, whereas eosinophil and platelets were maintained at lower levels. In the multivariate analysis, leukocytes, and neutrophils were the best biomarkers for predicting mortality risk and were independent of age, gender, or comorbidities. Conclusion: Our results support the use of routine laboratory biomarkers as predictors of mortality in Mexican hospitalized patients with severe COVID-19.