Detection and differentiation of Borrelia burgdorferi sensu lato in ticks collected from sheep and cattle in China

<p>Abstract</p> <p>Background</p> <p>Lyme disease caused by <it>Borrelia burgdorferi </it>sensu lato complex is an important endemic zoonosis whose distribution is closely related to the main ixodid tick vectors. In China, isolated cases of Lyme disease infection of humans have been reported in 29 provinces. Ticks, especially ixodid ticks are abundant and a wide arrange of <it>Borrelia </it>natural reservoirs are present. In this study, we developed a reverse line blot (RLB) to identify <it>Borrelia </it>spp. in ticks collected from sheep and cattle in 7 Provinces covering the main extensive livestock regions in China.</p> <p>Results</p> <p>Four species-specific RLB oligonucleotide probes were deduced from the spacer region between the 5S-23S rRNA gene, along with an oligonucleotide probe which was common to all. The species specific probes were shown to discriminate between four genomic groups of <it>B. burgdorferi </it>sensu lato i.e. <it>B. burgdorferi </it>sensu stricto, <it>B. garinii, B. afzelii</it>, and <it>B. valaisiana</it>, and to bind only to their respective target sequences, with no cross reaction to non target DNA. Furthermore, the RLB could detect between 0.1 pg and 1 pg of <it>Borrelia </it>DNA.</p> <p>A total of 723 tick samples (<it>Haemaphysalis, Boophilus, Rhipicephalus </it>and <it>Dermacentor</it>) from sheep and cattle were examined with RLB, and a subset of 667 corresponding samples were examined with PCR as a comparison. The overall infection rate detected with RLB was higher than that of the PCR test.</p> <p>The infection rate of <it>B. burgdoreri </it>sensu stricto was 40% in south areas; while the <it>B. garinii infection rate </it>was 40% in north areas. The highest detection rates of <it>B. afzelii </it>and <it>B. valaisiana </it>were 28% and 22%, respectively. Mixed infections were also found in 7% of the ticks analyzed, mainly in the North. The proportion of <it>B. garinii </it>genotype in ticks was overall highest at 34% in the whole investigation area.</p> <p>Conclusion</p> <p>In this study, the RLB assay was used to detect <it>B. burgdorferi </it>sensu lato in ticks collected from sheep and cattle in China. The results showed that <it>B. burdorferi senso stricto </it>and <it>B. afzelii </it>were mainly distributed in the South; while <it>B. garinii </it>and <it>B. valaisiana </it>were dominant in the North. <it>Borrelia </it>spirochaetes were detected in <it>Rhipicephalus </it>spp for the first time. It is suggested that the <it>Rhipicephalus </it>spps might play a role in transmitting <it>Borrelia </it>spirochaetes.</p

Vagus nerve stimulation for refractory posttraumatic epilepsy: Efficacy and predictors of seizure outcome

BackgroundTraumatic brain injury (TBI) has been recognized as an important and common cause of epilepsy since antiquity. Posttraumatic epilepsy (PTE) is usually associated with drug resistance and poor surgical outcomes, thereby increasing the burden of the illness on patients and their families. Vagus nerve stimulation (VNS) is an adjunctive treatment for medically refractory epilepsy. This study aimed to determine the efficacy of VNS for refractory PTE and to initially evaluate the potential predictors of efficacy.MethodsWe retrospectively collected the outcomes of VNS with at least a 1-year follow-up in all patients with refractory PTE. Subgroups were classified as responders and non-responders according to the efficacy of VNS (≥50% or &lt;50% reduction in seizure frequency). Preoperative data were analyzed to screen for potential predictors of VNS efficacy.ResultsIn total, forty-five patients with refractory PTE who underwent VNS therapy were enrolled. Responders were found in 64.4% of patients, and 15.6% of patients achieved seizure freedom at the last follow-up. In addition, the responder rate increased over time, with 37.8, 44.4, 60, and 67.6% at the 3-, 6-, 12-, and 24-month follow-ups, respectively. After multivariate analysis, generalized interictal epileptic discharges (IEDs) were found to be a negative predictor (OR: 4.861, 95% CI: 1.145–20.632) of VNS efficacy.ConclusionThe results indicated that VNS therapy was effective in refractory PTE patients and was well tolerated over a 1-year follow-up period. Patients with focal or multifocal IEDs were recognized to have better efficacy after VNS therapy

Vagus nerve stimulation for pharmacoresistant epilepsy secondary to encephalomalacia: A single-center retrospective study

ObjectiveVagus nerve stimulation (VNS) is an adjunctive treatment for pharmacoresistant epilepsy. Encephalomalacia is one of the most common MRI findings in the preoperative evaluation of patients with pharmacoresistant epilepsy. This is the first study that aimed to determine the effectiveness of VNS for pharmacoresistant epilepsy secondary to encephalomalacia and evaluate the potential predictors of VNS effectiveness.MethodsWe retrospectively analyzed the seizure outcomes of VNS with at least 1 year of follow-up in all patients with pharmacoresistant epilepsy secondary to encephalomalacia. Based on the effectiveness of VNS (≥50% or &lt;50% reduction in seizure frequency), patients were divided into two subgroups: responders and non-responders. Preoperative data were analyzed to screen for potential predictors of VNS effectiveness.ResultsA total of 93 patients with epilepsy secondary to encephalomalacia who underwent VNS therapy were recruited. Responders were found in 64.5% of patients, and 16.1% of patients achieved seizure freedom at the last follow-up. In addition, the responder rate increased over time, with 36.6, 50.5, 64.5, and 65.4% at the 3-, 6-, 12-, and 24-month follow-ups, respectively. After multivariate analysis, seizure onset in adults (&gt;18 years old) (OR: 0.236, 95%CI: 0.059–0.949) was found to be a positive predictor, and the bilateral interictal epileptic discharges (IEDs) (OR: 3.397, 95%CI: 1.148–10.054) and the bilateral encephalomalacia on MRI (OR: 3.193, 95%CI: 1.217–8.381) were found to be negative predictors of VNS effectiveness.ConclusionThe results demonstrated the effectiveness and safety of VNS therapy in patients with pharmacoresistant epilepsy secondary to encephalomalacia. Patients with seizure onset in adults (&gt;18 years old), unilateral IEDs, or unilateral encephalomalacia on MRI were found to have better seizure outcomes after VNS therapy

Wars2 is a determinant of angiogenesis.

Coronary flow (CF) measured ex vivo is largely determined by capillary density that reflects angiogenic vessel formation in the heart in vivo. Here we exploit this relationship and show that CF in the rat is influenced by a locus on rat chromosome 2 that is also associated with cardiac capillary density. Mitochondrial tryptophanyl-tRNA synthetase (Wars2), encoding an L53F protein variant within the ATP-binding motif, is prioritized as the candidate at the locus by integrating genomic data sets. WARS2(L53F) has low enzyme activity and inhibition of WARS2 in endothelial cells reduces angiogenesis. In the zebrafish, inhibition of wars2 results in trunk vessel deficiencies, disordered endocardial-myocardial contact and impaired heart function. Inhibition of Wars2 in the rat causes cardiac angiogenesis defects and diminished cardiac capillary density. Our data demonstrate a pro-angiogenic function for Wars2 both within and outside the heart that may have translational relevance given the association of WARS2 with common human diseases

Neutrino Physics with JUNO

The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purposeunderground liquid scintillator detector, was proposed with the determinationof the neutrino mass hierarchy as a primary physics goal. It is also capable ofobserving neutrinos from terrestrial and extra-terrestrial sources, includingsupernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos,atmospheric neutrinos, solar neutrinos, as well as exotic searches such asnucleon decays, dark matter, sterile neutrinos, etc. We present the physicsmotivations and the anticipated performance of the JUNO detector for variousproposed measurements. By detecting reactor antineutrinos from two power plantsat 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4sigma significance with six years of running. The measurement of antineutrinospectrum will also lead to the precise determination of three out of the sixoscillation parameters to an accuracy of better than 1\%. Neutrino burst from atypical core-collapse supernova at 10 kpc would lead to ~5000inverse-beta-decay events and ~2000 all-flavor neutrino-proton elasticscattering events in JUNO. Detection of DSNB would provide valuable informationon the cosmic star-formation rate and the average core-collapsed neutrinoenergy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400events per year, significantly improving the statistics of existing geoneutrinosamples. The JUNO detector is sensitive to several exotic searches, e.g. protondecay via the $p\to K^++\bar\nu$ decay channel. The JUNO detector will providea unique facility to address many outstanding crucial questions in particle andastrophysics. It holds the great potential for further advancing our quest tounderstanding the fundamental properties of neutrinos, one of the buildingblocks of our Universe

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

In silico repurposed drugs against monkeypox virus

Monkeypox is an emerging epidemic of concern. The disease is caused by the monkeypox virus and an increasing global incidence with a 2022 outbreak that has spread to Europe amid the COVID-19 pandemic. The new outbreak is associated with novel, previously undiscovered mutations and variants. Currently, the US Food and Drug Administration (FDA) approved poxvirus treatment involves the use of tecovirimat. However, there is otherwise limited pharmacopoeia and research interest in monkeypox. In this study, virtual screening and molecular dynamics were employed to explore the potential repurposing of multiple drugs previously approved by the FDA or other jurisdictions for other applications. Several drugs are predicted to tightly bind to viral proteins, which are crucial in viral replication, including molecules which show high potential for binding the monkeypox D13L capsid protein, whose inhibition has previously been demonstrated to suppress viral replication.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Skin Research Institute of Singapore (SRIS)Published versionThis work is supported by the Singapore Ministry of Education (MOE) Tier 1 grant RG27/21 and Tier 2 grant MOE-T2EP30120-0007. Thomas Larry Dawson and Hilbert Lam Yuen In weresupported by funding from the Agency for Science, Technology and Research (A*STAR) and A*STARBMRC EDB IAF-PP grants (H17/01/a0/004, Skin Research Institute of Singapore, and H18/01a0/016,Asian Skin Microbiome Program)