A cyanobacterial LPS antagonist prevents endotoxin shock and blocks sustained TLR4 stimulation required for cytokine expression

Toll-like receptors (TLRs) function as primary sensors that elicit coordinated innate immune defenses through recognition of microbial products and induction of immune and proinflammatory genes. Here we report the identification and biological characterization of a lipopolysaccharide (LPS)-like molecule extracted from the cyanobacterium Oscillatoria Planktothrix FP1 (cyanobacterial product [CyP]) that is not stimulatory per se but acts as a potent and selective antagonist of bacterial LPS. CyP binds to MD-2 and efficiently competes with LPS for binding to the TLR4–MD-2 receptor complex. The addition of CyP together with LPS completely inhibited both MyD88- and TRIF-dependent pathways and suppressed the whole LPS-induced gene transcription program in human dendritic cells (DCs). CyP protected mice from endotoxin shock in spite of a lower capacity to inhibit LPS stimulation of mouse DCs. Interestingly, the delayed addition of CyP to DCs responding to LPS strongly inhibited signaling and cytokine production by immediate down-regulation of inflammatory cytokine mRNAs while not affecting other aspects of DC maturation, such as expression of major histocompatibility complex molecules, costimulatory molecules, and CCR7. Collectively, these results indicate that CyP is a potent competitive inhibitor of LPS in vitro and in vivo and reveal the requirement of sustained TLR4 stimulation for induction of cytokine genes in human DCs

Evaluation of vestibular function in patients affected by obstructive sleep apnea performing functional head impulse test (fHIT)

Purpose: Obstructive sleep apnoea (OSA) is a common disease with significantly related complications. Since a connection between the vestibular nucleus and sleep regulator pathways has been demonstrated, vestibular evaluation in OSA patients was partially studied and none used functional head impulse test (fHIT) for this purpose. This paper aimed at evaluating the vestibular function in patients affected by OSA using fHIT, selecting patients who did not present any other related to cardiovascular, neurological, or metabolic diseases. Patients and Methods: Patients enrolled had a diagnosis of OSA by polysomnography type III and were cataloged according to American Association of Sleep Medicine criteria. Each patient underwent fHIT. Statistical significance was set at 0.05. Results: A total of 85 patients were enrolled in the study of which 50 had a diagnosis of OSA and were included in the case group, while 35 belonged to the control group. In 88.6% of subjects of the case group was evidenced a vestibular impairment with a substantial difference between the two study groups (p<0.05). Conclusion: The results show that the incidence of vestibular lesions in patients with obstructive sleep apnoea is underestimated and that fHIT can identify these lesions early

Discovering the most elusive radio relic in the sky: Diffuse Shock Acceleration caught in the act?

The origin of radio relics is usually explained via diffusive shock acceleration (DSA) or re-acceleration of electrons at/from merger shocks in galaxy clusters. The case of acceleration is challenged by the low predicted efficiency of low-Mach number merger shocks, unable to explain the power observed in most radio relics. In this Letter we present the discovery of a new giant radio relic around the galaxy cluster Abell 2249 ($z=0.0838$) using LOFAR. It is special since it has the lowest surface brightness of all known radio relics. We study its radio and X-ray properties combinig LOFAR data with uGMRT, JVLA and XMM. This object has a total power of $L_{1.4\rm GHz}=4.1\pm 0.8 \times 10^{23}$ W Hz$^{-1}$ and integrated spectral index $\alpha = 1.15\pm 0.23$. We infer for this radio relic a lower bound on the magnetisation of $B\geq 0.4\, \mu$G, a shock Mach number of $\mathcal{M}\approx 3.79$, and a low acceleration efficiency consistent with DSA. This result suggests that a missing population of relics may become visible thanks to the unprecedented sensitivity of the new generation of radio telescopes.Comment: Letter, 5 pages, 4 figures, accepted for publication on MNRAS Letter

B cell response after SARS-CoV-2 mRNA vaccination in people living with HIV

Background: Limited longitudinal data are available on immune response to mRNA SARS-CoV-2 vaccination in people living with HIV (PLWHIV); therefore, new evidence on induction and persistence of spike-specific antibodies and B cells is needed. Methods: In this pilot study we investigated the spike-specific humoral and B cell responses up to six months after vaccination with two doses of mRNA vaccines in 84 PLWHIV under antiretroviral therapy compared to 79 healthy controls (HCs). Results: Spike-specific IgG persisted six months in PLWHIV with no significant differences compared to HCs, even though a significantly lower IgG response was observed in patients with CD4+ T cells < 350/mmc. The frequency of subjects with antibodies capable of inhibiting ACE2/RBD binding was comparable between PLWHIV and HCs a month after the second vaccine dose, then a higher drop was observed in PLWHIV. A comparable percentage of spike-specific memory B cells was observed at month six in PLWHIV and HCs. However, PLWHIV showed a higher frequency of spike-specific IgD- CD27- double-negative memory B cells and a significantly lower rate of IgD- CD27+ Ig-switched memory B cells compared to HCs, suggesting a reduced functionality of the antigen-specific memory B population. Conclusions: The mRNA vaccination against SARS-CoV-2 elicits humoral and B cell responses quantitatively similar between PLWHIV and HCs, but there are important differences in terms of antibody functionality and phenotypes of memory B cells, reinforcing the notion that tailored vaccination policies should be considered for these patients

Thiersch graft follow-up with narrow band imaging for acquired atresia of the external auditory canal: Canaloplasty with Thiersch graft versus vascularization evaluated with narrow band imaging

Acquired atresia of the external ear canal is a narrowing of the external ear canal (EAC) that appears obstructed by fibrous tissue or bone tissue. Acquired atresia has two different phases: wet and dry stage. Computed tomography (CT) scan may show a scan where soft tissue fills EAC. Treatment may be medical and/or surgical. The surgical treatment of choice is represented by canaloplasty with a skin-free flap. To our knowledge, no article has reported data on the analysis of vascularization of acquired atresia of the external ear canal and vascularization of skin flap during follow-up with narrow-band imaging. This study evaluated patients suffering from acquired atresia of the external auditory duct, treated surgically in our Department of Organi di Senso of Sapienza University, from 2017 to 2020. All patients underwent: anamnestic collection, physical examination, CT. Preoperative and postoperative otoendoscopic evaluation (1,3,6 and12 months) was performed with both cold white light endoscopic vision (CWL) and narrowband imaging (NBI). 17 patients were enrolled in the study. Preoperative otoendoscopic examination of WL showed stenosis with a diameter <75% and a tympanic membrane not viewable in all patients. At 12 months of follow-up, 94% of patients had no recurrence of external ear canal stenosis. 88% of patients had normal NBI light vascularization. Our study evaluated how NBI can be a superior method, compared to CWL, to assess the state of the flap and can be relevant in the decision-making process of a re-intervention

Integral use of immunopeptidomics and immunoinformatics for the characterization of antigen presentation and rational identification of BoLA-DR- presented peptides and epitopes

MHC peptide binding and presentation is the most selective event defining the landscape of T cell epitopes. Consequently, understanding the diversity of MHC alleles in a given population and the parameters that define the set of ligands that can be bound and presented by each of these alleles (the immunopeptidome) has an enormous impact on our capacity to predict and manipulate the potential of protein Ags to elicit functional T cell responses. Liquid chromatography–mass spectrometry analysis of MHC-eluted ligand data has proven to be a powerful technique for identifying such peptidomes, and methods integrating such data for prediction of Ag presentation have reached a high level of accuracy for both MHC class I and class II. In this study, we demonstrate how these techniques and prediction methods can be readily extended to the bovine leukocyte Ag class II DR locus (BoLA-DR). BoLA-DR binding motifs were characterized by eluted ligand data derived from bovine cell lines expressing a range of DRB3 alleles prevalent in Holstein–Friesian populations. The model generated (NetBoLAIIpan, available as a Web server at www.cbs.dtu.dk/services/NetBoLAIIpan) was shown to have unprecedented predictive power to identify known BoLA-DR–restricted CD4 epitopes. In summary, the results demonstrate the power of an integrated approach combining advanced mass spectrometry peptidomics with immunoinformatics for characterization of the BoLA-DR Ag presentation system and provide a prediction tool that can be used to assist in rational evaluation and selection of bovine CD4 T cell epitopes

C reactive protein in healthy term newborns during the first 48 hours of life

Background Early-onset neonatal sepsis (EOS) is a serious and potentially life-threatening disease in newborns. C reactive protein (CRP) is the most used laboratory biomarker for the detection of EOS. Little is known about normal reference values of CRP during the perinatal period as several factors are able to influence it. Objectives To identify an appropriate range of CRP values in healthy term newborns during the first 48 hours of life. Design CRP determination was performed in 859 term newborns at 12, 24 and 48 hours of life. Mode of delivery, maternal vaginal culture results, intrapartum antimicrobial prophylaxis (IAP) and other perinatal variables were recorded. Results CRP mean values were significantly higher at 48 hours (4.10 mg/L) than at both 24 (2.30 mg/L) and 12 hours of life (0.80 mg/L). CRP levels were affected by a number of perinatal proinflammatory variables. In particular, CRP mean values were significantly higher in babies born by vaginal delivery (3.80 mg/L) and emergency caesarean section (3.60 mg/L) than in babies born by elective caesarean section (2.10 mg/L). Completed course of IAP led to lower CRP mean values (2.90 mg/L) than IAP not completed (3.80 mg/L) or not performed (4.70 mg/L). Conclusions Postnatal age and mode of delivery significantly influence CRP values. Reliable reference values are crucial in order to obtain an adequate diagnostic accuracy

Acquired atresia of the external auditory canal and canaloplasty with Thiersch graft reconstruction: Outcomes and complications

Acquired atresia of the external auditory canal (EAC) is a rare disease characterized by otorrhea and progressive hearing loss. Clinically, it is differentiated into two stages: the wet stage and the dry stage. The dry stage does not respond to pharmacological treatment and has to be treated surgically. One surgical option is canaloplasty of the EAC with Thiersch graft reconstruction. This study aimed to report the follow-up outcomes (otomicroscopic signs and pure tone audiometry [PTA]) in patients with acquired atresia treated with this technique. Eighteen adult patients surgically treated for acquired atresia of the EAC between 2010 and 2020 were enrolled. All underwent canaloplasty with Thiersch graft reconstruction by one senior surgeon. Otomicroscopy and PTA results were evaluated before and after surgery. Postsurgical follow-up was performed at 1-3-6-12 months and then annually. Presurgical otomicroscopic examination revealed stenosis that occluded more than 75% of the EAC in all patients, and preoperative PTA showed conductive hearing loss in 89% of patients. However, postsurgical otomicroscopic examination showed that 94% of patients had a normal EAC diameter after one year, and only one patient had anterior blunting and recurrent atresia. In addition, postsurgical PTA evidenced a normal range in 89% of patients after one year. In conclusion, acquired atresia of the EAC is a troublesome disease usually associated with hearing loss. Therefore, treatment is chosen to resolve its symptoms. The results demonstrate evidence that canaloplasty with Thirsch graft may be a suitable surgical method considering the lower incidence of recurrence and the excellent hearing outcomes

Switch to raltegravir-based regimens and HIV DNA decrease in patients with suppressed HIV RNA

Raltegravir intensification is associated with an increase in 2-LTR episomal HIV DNA= circles, indicating a persistent low-level replication, in some individuals in ART with suppressed HIV RNA. We aimed at monitoring residual plasma HIV RNA and cellular HIV DNA in virologically suppressed patients switching to a raltegravir-based regimen

Fast magnetic field amplification in distant galaxyclusters

In the present-day Universe, magnetic fields pervade galaxy clusters, with strengths of a few microGauss obtained from Faraday Rotation. Evidence for cluster magnetic fields is also provided by Megaparsec-scale radio emission, namely radio halos and relics. These are commonly found in merging systems and are characterized by a steep radio spectrum. It is widely believed that magneto-hydrodynamical turbulence and shock-waves (re-)accelerate cosmic rays, producing halos and relics. The origin and the amplification of magnetic fields in clusters is not well understood. It has been proposed that turbulence drives a small-scaledynamo that amplifies seed magnetic fields (primordial and/or injected by galactic outflows, as active galactic nuclei, starbursts, or winds). At high redshift, radio halos are expected to be faint, due to the Inverse Compton losses and dimming effect with distance. Moreover, Faraday Rotation measurements are difficult to obtain. If detected, distant radio halosprovide an alternative tool to investigate magnetic field amplification. Here, we report LOFAR observations which reveal diffuse radio emission in massive clusters when the Universe was only half of its present age, with a sample occurrence fraction of about 50%. The high radio luminosities indicate that these clusters have similar magnetic field strengths to those in nearby clusters, and suggest that magnetic field amplification is fast during the first phases ofcluster formation.Comment: Published in Nature Astronomy on 2 November 2020. The published version is available at this URL https://www.nature.com/articles/s41550-020-01244-5#citea