SARS-CoV-2 infection represents a global health problem that has affected millions of people. The fine host immune response and its association with the disease course have not yet been fully ...elucidated. Consequently, we analyze circulating B cell subsets and their possible relationship with COVID-19 features and severity.
Using a multiparametric flow cytometric approach, we determined B cell subsets frequencies from 52 COVID-19 patients, grouped them by hierarchical cluster analysis, and correlated their values with clinical data.
The frequency of CD19
B cells is increased in severe COVID-19 compared to mild cases. Specific subset frequencies such as transitional B cell subsets increase in mild/moderate cases but decrease with the severity of the disease. Memory B compartment decreased in severe and critical cases, and antibody-secreting cells are increased according to the severity of the disease. Other non-typical subsets such as double-negative B cells also showed significant changes according to disease severity. Globally, these differences allow us to identify severity-associated patient clusters with specific altered subsets. Finally, respiratory parameters, biomarkers of inflammation, and clinical scores exhibited correlations with some of these subpopulations.
The severity of COVID-19 is accompanied by changes in the B cell subpopulations, either immature or terminally differentiated. Furthermore, the existing relationship of B cell subset frequencies with clinical and laboratory parameters suggest that these lymphocytes could serve as potential biomarkers and even active participants in the adaptive antiviral response mounted against SARS-CoV-2.
Hepatitis E virus infection in equines in Spain García‐Bocanegra, Ignacio; Rivero, Antonio; Caballero‐Gómez, Javier ...
Transboundary and emerging diseases,
January 2019, 2019-Jan, 20190101, Letnik:
66, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Hepatitis E (HE) is an important emerging disease in European countries. To analyse the role of equids as potential reservoirs for HE virus (HEV), we determined the prevalence of HEV infection in 861 ...equines from 464 herds in Spain. HEV RNA in serum was detected in 0.4% (3/692) of horses, 1.2% (1/86) of donkeys and 3.6% (3/83) of mules. Phylogenetic analysis identified the zoonotic genotype 3 as being closely related to viral human and swine strains. In this first report on HEV in equids in Europe, we confirm the susceptibility of horses, donkeys and mules to HEV infection. The low prevalence detected indicates that equids may be considered spillover hosts rather than true reservoirs.
Purpose
To obtain initial data on the effect of different levels of targeted temperature management (TTM) in out-of-hospital cardiac arrest (OHCA).
Methods
We designed a multicentre pilot trial with ...1:1:1 randomization to either 32 °C (
n
= 52), 33 °C (
n
= 49) or 34 °C (
n
= 49), via endovascular cooling devices during a 24-h period in comatose survivors of witnessed OHCA and initial shockable rhythm. The primary endpoint was the percentage of subjects surviving with good neurologic outcome defined by a modified Rankin Scale (mRS) score of ≤ 3, blindly assessed at 90 days.
Results
At baseline, different proportions of patients who had received defibrillation administered by a bystander were assigned to groups of 32 °C (13.5%), 33 °C (34.7%) and 34 °C (28.6%;
p
= 0.03). The percentage of patients with an mRS ≤ 3 at 90 days (primary endpoint) was 65.3, 65.9 and 65.9% in patients assigned to 32, 33 and 34 °C, respectively, non-significant (NS). The multivariate Cox proportional hazards model identified two variables significantly related to the primary outcome: male gender and defibrillation by a bystander. Among the 43 patients who died before 90 days, 28 died following withdrawal of life-sustaining therapy, as follows: 7/16 (43.8%), 10/13 (76.9%) and 11/14 (78.6%) of patients assigned to 32, 33 and 34 °C, respectively (trend test
p
= 0.04). All levels of cooling were well tolerated.
Conclusions
There were no statistically significant differences in neurological outcomes among the different levels of TTM. However, future research should explore the efficacy of TTM at 32 °C.
Clinical trial registration
ClinicalTrials.gov unique identifier: NCT02035839 (
http://clinicaltrials.gov
).
A chabazite-type zeolite was prepared by the hydrothermal method. Before ion exchange, the chabazite was activated with ammonium chloride (NH
Cl). The ion exchange process was carried out at a ...controlled temperature and constant stirring to obtain ion-exchanged chabazites of Ti
chabazite (TiCHA), Zn
chabazite (ZnCHA), Cu
chabazite (CuCHA), Ag
chabazite (AgCHA) and Au
chabazite (AuCHA). Modified chabazite samples were characterized by X-ray diffraction (XRD), scanning electron microscope equipped with energy-dispersive spectroscopy (SEM-EDS), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), N
adsorption methods and UV-visible diffuse reflectance spectroscopy (DRS). XRD results revealed that the chabazite structure did not undergo any modification during the exchange treatments. The photocatalytic activity of chabazite samples was evaluated by the degradation of methylene blue (MB) in the presence of H
O
under ultraviolet (UV) light illumination. The photodegradation results showed a higher degradation efficiency of modified chabazites, compared to the synthesized chabazite. CuCHA showed an efficiency of 98.92% in MB degradation, with a constant of k = 0.0266 min
following a first-order kinetic mechanism. Then, it was demonstrated that the modified chabazites could be used for the photodegradation of dyes.
A second-generation tetrathiomolybdate analogue (ATN-224; choline tetrathiomolybdate), which selectively binds copper with high affinity, is currently completing two phase I clinical trials in ...patients with advanced solid and advanced hematologic malignancies. However, there is very little information about the mechanism of action of ATN-224 at the molecular level.
The effects of ATN-224 on endothelial and tumor cell growth were evaluated in cell culture experiments in vitro. The antiangiogenic activity of ATN-224 was investigated using the Matrigel plug model of angiogenesis.
ATN-224 inhibits superoxide dismutase 1 (SOD1) in tumor and endothelial cells. The inhibition of SOD1 leads to inhibition of endothelial cell proliferation in vitro and attenuation of angiogenesis in vivo. The inhibition of SOD1 activity in endothelial cells is dose and time dependent and leads to an increase in the steady-state levels of superoxide anions, resulting in the inhibition of extracellular signal-regulated kinase phosphorylation without apparent induction of apoptosis. In contrast, the inhibition of SOD1 in tumor cells leads to the induction of apoptosis. The effects of ATN-224 on endothelial and tumor cells could be substantially reversed using Mn(III)tetrakis(4-benzoic acid)porphyrin chloride, a catalytic small-molecule SOD mimetic.
These data provide a distinct molecular target for the activity of ATN-224 and provide validation for SOD1 as a target for the inhibition of angiogenesis and tumor growth.
The aim of our study was to evaluate HEV antibody kinetics in HIV/HCV‐coinfected patients with cirrhosis. A longitudinal retrospective study was designed. Patients were followed up every 6 months; ...anti‐HEV IgG and IgM antibodies levels and HEV‐RNA by qPCR were analysed. The prevalence and incidence of every HEV infection marker were calculated. The kinetics of anti‐HEV IgG and IgM during the follow‐up were evaluated. Seventy‐five patients comprised the study population. The seroprevalence observed was 17.3%. None showed IgM antibodies or HEV‐RNA at baseline. None showed detectable HEV viral load during the study period. After a median follow‐up of 5.1 years, two of 62 seronegative patients (3.2%) seroconverted to IgG antibody. The incidence for IgM was 2.7%. Of the 13 patients with IgG seropositivity at baseline, five (38.5%) seroreverted. Meanwhile, of the two patients who exhibited IgM positivity during the study, one (50%) showed intermittent positivity. We found that HEV seropositivity is common in HIV/HCV‐coinfected cirrhotic patients. A remarkable rate of IgG seroreversions and IgM intermittence was found, limiting the use of antibodies for the diagnosis of HEV infection in this population.
It has been shown that wildlife can serve as natural reservoirs of hepatitis E virus (HEV). The wild boar (Sus scrofa) is probably the main natural reservoir of HEV and could therefore represent an ...important route of transmission in Europe, especially in regions where game meat is widely consumed. We evaluated the prevalence of HEV infection in wild boar in the south of Spain, with the aim of identifying associated risk factors. A cross-sectional study that included hunted wild boar was carried out during the 2015/2016 hunting season (October 15 to February 15) in Andalusia (southern Spain). The outcome variable was HEV infection, defined as amplification of HEV RNA in serum by RT-PCR.
A total of 142 animals, selected from 12 hunting areas, were included and formed the study population. Thirty-three wild boars (23.2%; 95% CI: 16.8%-30.7%) were positive for HEV infection. Prevalence peaked in October and November, then gradually declined until the end of December. After multivariate analysis, only hunting date was independently associated with HEV infection across sex and age.
Our study found a relatively high prevalence of HEV infection in wild boar in the south of Spain, suggesting that prevalence may depend on the season when the animal is hunted. In consequence, the potential risk of zoonotic transmission could fluctuate.
HIV infection and HAART trigger genetic and functional mitochondrial alterations leading to cell death and adverse clinical manifestations. Mitochondrial dynamics enable mitochondrial turnover and ...degradation of damaged mitochondria, which may lead to apoptosis.
To evaluate markers of mitochondrial dynamics and apoptosis in pregnancies among HIV-infected women on HAART and determine their potential association with obstetric complications.
This controlled, single-site, observational study without intervention included 26 HIV-infected pregnant women on HAART and 18 control pregnancies and their newborns. Maternal PBMCs and neonatal cord blood mononuclear cells (CBMCs) were isolated at the first trimester of gestation and at delivery. The placenta was homogenized at 5% w/v. Mitochondrial dynamics, fusion events mitofusin 2 (Mfn2)/β-actin and fission events dynamin-related protein 1 (Drp1/β-actin) and apoptosis (caspase 3/β-actin) were assessed by western blot analysis.
Obstetric complications were significantly more frequent in pregnancies among HIV-infected women OR 5.00 (95% CI 1.21-20.70). Mfn2/β-actin levels in PBMCs from controls significantly decreased during pregnancy (202.13 ± 57.45%), whereas cases maintained reduced levels from the first trimester of pregnancy and no differences were observed in CBMCs. Mfn2/β-actin and Drp1/β-actin contents significantly decreased in the placenta of cases. Caspase 3/β-actin levels significantly increased during pregnancy in PBMCs of cases (50.00 ± 7.89%), remaining significantly higher than in controls. No significant differences in caspase 3/β-actin content of neonatal CBMCs were observed, but there was a slight increased trend in placenta from cases.
HIV- and HAART-mediated mitochondrial damage may be enhanced by decreased mitochondrial dynamics and increased apoptosis in maternal and placental compartments but not in the uninfected fetus. However, direct effects on mitochondrial dynamics and implication of apoptosis were not demonstrated in adverse obstetric outcomes.
Lung cancer represents a significant global health concern, often diagnosed in its advanced stages. The advent of massive DNA sequencing has revolutionized the landscape of cancer treatment by ...enabling the identification of target mutations and the development of tailored therapeutic approaches. Unfortunately, access to DNA sequencing technology remains limited in many developing countries. In this context, we emphasize the critical importance of integrating this advanced technology into healthcare systems in developing nations to improve treatment outcomes.
We conducted an analysis of electronic clinical records of patients with confirmed advanced non-small cell lung cancer (NSCLC) and a verified negative status for the epidermal growth factor receptor (
) mutation. These patients underwent next-generation sequencing (NGS) for molecular analysis. We performed descriptive statistical analyses for each variable and conducted both univariate and multivariate statistical analyses to assess their impact on progression-free survival (PFS) and overall survival (OS). Additionally, we classified genetic mutations as actionable or non-actionable based on the European Society for Medical Oncology Scale of Clinical Actionability of Molecular Targets (ESCAT) guidelines.
Our study included a total of 127 patients, revealing the presence of twenty-one distinct mutations. The most prevalent mutations were
(18.9%) and Kirsten rat sarcoma viral oncogene homolog (
) (15.7%). Notably, anaplastic lymphoma kinase (
) hazard ratio (HR): 0.258, P<0.001, tumor mutation burden (TMB) (HR: 2.073, P=0.042) and brain magnetic resonance imaging (MRI) (HR: 0.470, P=0.032) demonstrated statistical significance in both the univariate and multivariate analyses with respect to PFS. In terms of OS,
(HR: 0.285, P<0.001) and
(HR: 0.482, P=0.024) exhibited statistical significance in both analyses. Applying the ESCAT classification system, we identified actionable genomic variations (ESCAT level-1), including
,
, breast cancer (
) gene, c-ros oncogene 1 (
), and rearranged during transfection (
) gene, in 32.3% of the patients.
Our findings from massive DNA sequencing underscore that 32.3% of patients who test negative for the
mutation possess other targetable mutations, enabling them to receive personalized, targeted therapies at an earlier stage of their disease. Implementing massive DNA sequencing in developing countries is crucial to enhance survival rates among NSCLC patients and guide more effective treatment strategies.
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