Many aspects of the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), such as its role in protection after natural infection, are still unclear. We evaluated ...IgA and IgG response to spike subunits 1 and 2 (S1 and S2) and Nucleocapsid proteins of SARS‐COV‐2 in serum samples of 109 volunteers with viral RNA detected or seroconversion with different clinical evolution (asymptomatic, mild, moderate, and severe coronavirus disease 2019), using the ViraChip® Test Kit. We observed that the quantification of antibodies to all antigens had a positive correlation to disease severity, which was strongly associated with the presence of comorbidities. Seroreversion was not uncommon even during the short (median of 77 days) observation, occurring in 15% of mild‐asymptomatic cases at a median of 55 days for IgG and 46 days for IgA. The time to reach the maximal antibody response did not differ significantly among recovered and deceased volunteers. Our study illustrated the dynamic of anti‐S1, anti‐N, and anti‐S2 IgA and IgG antibodies, and suggests that high production of IgG and IgA does not guarantee protection to disease severity and that functional responses that have been studied by other groups, such as antibody avidity, need further attention.
Highlights
Symptomatic SARS‐CoV‐2 infection generally elicits strong humoral immune response.
IgA and IgG titers to three viral antigens (S1, S2 and N) correlate to severity of COVID‐19 disease.
Seroreversion is not uncommon and may occur few months after SARS‐CoV‐2 infection.
Elucidation of functional characteristics of antibodies are necessary to better understand disease pathogenesis and may guide vaccine boosting strategies.
Abstract Many studies have been dedicated to the development of scaffolds for improving post-traumatic nerve regeneration. The goal of this study was to develop and test hybrid chitosan membranes to ...use in peripheral nerve reconstruction, either alone or enriched with N1E-115 neural cells. Hybrid chitosan membranes were tested in vitro , to assess their ability in supporting N1E-115 cell survival and differentiation, and in vivo to assess biocompatibility as well as to evaluate their effects on nerve fiber regeneration and functional recovery after a standardized rat sciatic nerve crush injury. Functional recovery was evaluated using the sciatic functional index (SFI), the static sciatic index (SSI), the extensor postural thrust (EPT), the withdrawal reflex latency (WRL) and ankle kinematics. Nerve fiber regeneration was assessed by quantitative stereological analysis and electron microscopy. All chitosan membranes showed good biocompatibility and proved to be a suitable substrate for plating the N1E-115 cellular system. By contrast, in vivo nerve regeneration assessment after crush injury showed that the freeze-dried chitosan type III, without N1E-115 cell addition, was the only type of membrane that significantly improved posttraumatic axonal regrowth and functional recovery. It can be thus suggested that local enwrapping with this type of chitosan membrane may represent an effective approach for the improvement of the clinical outcome in patients receiving peripheral nerve surgery.
A choice experiment is undertaken to elicit preferences of scuba divers in the Marine Protected Area of Medes Islands (Spain). This is the first non-market valuation study of a typical Mediterranean ...habitat, the Coralligenous, which is characterized by high biodiversity, geomorphologic complexity and iconic species like gorgonians. This habitat is not only very attractive for scuba diving, but is also threatened by climate change and ocean acidification, which is our motivation for undertaking this valuation study. Choice attributes include the number of divers on a diving trip, underwater landscape, presence of jellyfish species, expected state of gorgonians, and price of a dive. Results of multinomial and random parameter logit models indicate a decrease in the attractiveness of Coralligenous areas for scuba diving as a result of both environmental pressures. Estimates of welfare values show that the local extinction of gorgonians had the highest negative effect on utility equivalent to a cost of €60 per dive, followed by abundance of stinging jellyfish with a cost of €26 per dive. Choice probabilities for the selection of different dive experiences indicate the highest rejection rates for the combined sea warming and acidification scenarios.
The impact of structural differentiation between phenylcarbazoles (
PhC
,
mCP
,
CBP
,
TCB
) and phenylamines (
TPA
,
BDB
,
TPB
,
TDAB
) on the phase equilibria, optical spectrum, band gap, and ...thin-film morphology is evaluated and discussed. The carbazolyl units lead to a lower electronic conjugation contributing to a wide band gap when compared with the diphenylamine analogs. The fusion and sublimation equilibria indicate that entropic contribution is the key factor for the distinguished melting behavior and solid-phase volatility between phenylcarbazole derivatives and phenylamine analogs. The molecular differentiation between the two classes of compounds is not reflected in the crystal packing and intermolecular interactions. However, compared with the diphenylamino groups, the incorporation of carbazolyl moieties contributes to a less flexible molecule. Moreover, the results evidence that intermolecular bonding disruption along the fusion transition is more extensive for phenylamine derivatives. Due to the asymmetric nonplanar structure,
mCP
is characterized by a ratio of {
T
g
/
T
m
3/4} while the more symmetric
CBP
and
TCB
molecules display ratios closer to {
T
g
/
T
m
2/3}. Vapor-deposited thin films of
mCP
,
CBP
, and
TCB
are amorphous and their morphology is highly dependent on the substrate roughness. The lower flexibility of nonplanar phenylcarbazoles induces the formation of a glassy state due to the harder packing mechanism leading to the lower ability of the crystallization process.
The phenyl-phenyl linkage in
N
-phenylcarbazoles contributes to several optical, structural, thermodynamic and morphological changes.
Metal homoenolates, produced via C–C bond cleavage of cyclopropanols, have been extensively investigated as nucleophiles for the synthesis of β-substituted carbonyl derivatives. Herein, we ...demonstrate that zinc homoenolates can react as carbonyl-electrophiles in the presence of nucleophilic amines to yield highly valuable trans-cyclopropylamines in good yields and high diastereoselectivities. GSK2879552, a lysine demethylase 1 inhibitor currently in clinical trials for the treatment of small cell lung carcinoma, was synthesized using this strategy.
Cystic fibrosis (CF) is a monogenetic disease resulting from mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene encoding an anion channel. Recent evidence indicates that ...CFTR plays a role in other cellular processes, namely in development, cellular differentiation and wound healing. Accordingly, CFTR has been proposed to function as a tumour suppressor in a wide range of cancers. Along these lines, CF was recently suggested to be associated with epithelial-mesenchymal transition (EMT), a latent developmental process, which can be re-activated in fibrosis and cancer. However, it is unknown whether EMT is indeed active in CF and if EMT is triggered by dysfunctional CFTR itself or a consequence of secondary complications of CF. In this study, we investigated the occurrence of EMT in airways native tissue, primary cells and cell lines expressing mutant CFTR through the expression of epithelial and mesenchymal markers as well as EMT-associated transcription factors. Transepithelial electrical resistance, proliferation and regeneration rates, and cell resistance to TGF-β1induced EMT were also measured. CF tissues/cells expressing mutant CFTR displayed several signs of active EMT, namely: destructured epithelial proteins, defective cell junctions, increased levels of mesenchymal markers and EMT-associated transcription factors, hyper-proliferation and impaired wound healing. Importantly, we found evidence that the mutant CFTR triggered EMT was mediated by EMT-associated transcription factor TWIST1. Further, our data show that CF cells are over-sensitive to EMT but the CF EMT phenotype can be reversed by CFTR modulator drugs. Altogether, these results identify for the first time that EMT is intrinsically triggered by the absence of functional CFTR through a TWIST1 dependent mechanism and indicate that CFTR plays a direct role in EMT protection. This mechanistic link is a plausible explanation for the high incidence of fibrosis and cancer in CF, as well as for the role of CFTR as tumour suppressor protein.
Contrast agents are important imaging probes in clinical MRI, allowing the identification of anatomic changes that otherwise would not be possible. Intensive research on the development of new ...contrast agents is being made to image specific pathological markers or sense local biochemical changes. The most widely used MRI contrast agents are based on gadolinium(III) complexes. Due to their very high charge density, they have low permeability through tight biological barriers such as the blood-brain barrier, hampering their application in the diagnosis of neurological disorders. In this study, we explore the interaction between the widely used contrast agent Gd(DOTA)− (Dotarem) and POPC lipid bilayers by means of molecular dynamics simulations. This metal complex is a standard reference where several chemical modifications have been introduced to improve key properties such as bioavailability and targeting. The simulations unveil detailed insights into the agent’s interaction with the lipid bilayer, offering perspectives beyond experimental methods. Various properties, including the impact on global and local bilayer properties, were analyzed. As expected, the results indicate a low partition coefficient (K P) and high permeation barrier for this reference compound. Nevertheless, favorable interactions are established with the membrane leading to moderately long residence times. While coordination of one inner-sphere water molecule is maintained for the membrane-associated chelate, the physical-chemical attributes of Gd(DOTA)− as a MRI contrast agent are affected. Namely, increases in the rotational correlation times and in the residence time of the inner-sphere water are observed, with the former expected to significantly increase the water proton relaxivity. This work establishes a reference framework for the use of simulations to guide the rational design of new contrast agents with improved relaxivity and bioavailability and for the development of liposome-based formulations for use as imaging probes or theranostic agents.
Lactic acid bacteria (LAB) are traditionally used in fermentation and food preservation processes and are recognized as safe for consumption. Recently, they have attracted attention due to their ...health-promoting properties; many species are already widely used as probiotics for treatment or prevention of various medical conditions, including inflammatory bowel diseases, infections, and autoimmune disorders. Some LAB, especially
Lactococcus lactis
, have been engineered as live vehicles for delivery of DNA vaccines and for production of therapeutic biomolecules. Here, we summarize work on engineering of LAB, with emphasis on the model LAB,
L. lactis
. We review the various expression systems for the production of heterologous proteins in
Lactococcus
spp. and its use as a live delivery system of DNA vaccines and for expression of biotherapeutics using the eukaryotic cell machinery. We have included examples of molecules produced by these expression platforms and their application in clinical disorders. We also present the CRISPR-Cas approach as a novel methodology for the development and optimization of food-grade expression of useful substances, and detail methods to improve DNA delivery by LAB to the gastrointestinal tract. Finally, we discuss perspectives for the development of medical applications of recombinant LABs involving animal model studies and human clinical trials, and we touch on the main safety issues that need to be taken into account so that bioengineered versions of these generally recognized as safe organisms will be considered acceptable for medical use.
Purpose
The purpose of this study was to study the relationship between the presence of a deep lateral femoral notch sign (DLFNS) in anterior cruciate ligament (ACL)‐injured patients and a higher ...posterior lateral tibial slope (LPTS), a reduced meniscal bone angle (MBA), a higher LPTS/MBA ratio and a higher incidence of concomitant injuries in primary ACL tears.
Methods
A retrospective case‐control study was performed in patients submitted to primary ACL reconstruction with an available preoperative magnetic resonance imaging (MRI) scan. Patients with ACL tears and a femoral impactation with a depth ≥2 mm were assorted to the DLFNS group and patients with ACL tear and without a DLFNS to the control group. LPTS and MBA were measured in MRI. The presence of concomitant injuries (meniscal, posterior cruciate ligament, medial collateral ligament, lateral collateral ligament and bone injuries) was assessed in MRI. Quantitative data are presented in the median ± interquartile range (IQR).
Results
There were 206 patients included in the study, with 46 patients assorted to the DLFNS group and 160 patients to the control group. In the DLFNS group, the median LPTS was 6.7° (IQR: 4.0–8.2) versus 4.0° in the control group (IQR: 2.2–6.5) (p = 0.003). The LPTS/MBA ratio was significantly higher in the DLFNS group, with a median of 0.32 (IQR: 0.19–0.44), in comparison to the control group, with a median of 0.19 (IQR: 0.11–0.31) (p < 0.001). The multivariable logistic regression analysis showed that the LPTS is an independent risk factor to having a DLFNS (odds ratio OR = 1.161; 95% confidence interval CI: 1.042–1.293, p = 0.007). There was a higher incidence of concomitant lateral meniscal injuries in the DLFNS group (67% vs. 48%, p = 0.017).
Conclusions
In patients with ACL tears, the presence of a DLFNS is associated with a steeper lateral posterior tibial slope, as well as a higher incidence of concomitant lateral meniscal injuries.
Level of Evidence
Level III.
This paper presents a communication network for a squadron of unmanned aerial vehicles (UAVs) to be used in the scanning rocket impact area for Barreira do Inferno Launch Center-CLBI (Rio Grande do ...Norte, Brazil), aiming at detecting intruder boats. The main features of communication networks associated with multi-UAV systems are presented. This system sends information through Wireless Sensor Networks (WSN). After comparing and analyzing area scanning strategies, it presents the specification of a data communication network architecture for a squadron of UAVs within a sensor network using XBee Pro 900HP S3B modules. A brief description is made about the initial information from the construction of the system. The embedded hardware and the design procedure of a dedicated communication antenna to the XBee modules are presented. In order to evaluate the performance of the proposed architecture in terms of robustness and reliability, a set of experimental tests in different communication scenarios is carried out. Network management software is employed to measure the throughput, packet loss and other performance indicators in the communication links between the different network nodes. Experimental results allow verifying the quality and performance of the network nodes, as well as the reliability of the communication links, assessing signal received quality, range and latency.
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