Diketopiperazines are the smallest cyclic peptides known. 90% of Gram-negative bacteria produce diketopiperazines and they have also been isolated from Gram-positive bacteria, fungi and higher ...organisms. Biosynthesis of cyclodipeptides can be achieved by dedicated nonribosomal peptide synthetases or by a novel type of synthetases named cyclopeptide synthases. Since the first report in 1924 a large number of bioactive diketopiperazines was discovered spanning activities as antitumor, antiviral, antifungal, antibacterial, antiprion, antihyperglycemic or glycosidase inhibitor agents. As infections are of increasing concern for human health and resistances against existing antibiotics are growing this review focuses on the antimicrobial activities of diketopiperazines. The antibiotic bicyclomycin is a diketopiperazine and structure activity studies revealed the unique nature of this compound which was finally developed for clinical applications. The antimicrobial activities of a number of other diketopiperazines along with structure activity relationships are discussed. Here a special focus is on the activity-toxicity problem of many compounds setting tight limitations to their application as drugs. Not only these classical antimicrobial activities but also proposed action in modulating bacterial communication as a new target to control biofilms will be evaluated. Pathogens organized in biofilms are difficult to eradicate because of the increase of their tolerance for antibiotics for several orders. Diketopiperazines were reported to modulate LuxR-mediated quorum-sensing systems of bacteria, and they are considered to influence cell-cell signaling offering alternative ways of biofilm control by interfering with microbial communication. Concluding the review we will finally discuss the potential of diketopiperazines in the clinic to erase biofilm infections.
Recently, the ANITA collaboration reported on two upward-going extensive air shower events consistent with a primary particle that emerges from the surface of the Antarctic ice sheet. These events ...may be of ν τ origin, in which the neutrino interacts within the Earth to produce a τ lepton that emerges from the Earth, decays in the atmosphere, and initiates an extensive air shower. In this paper we estimate an upper bound on the ANITA acceptance to a diffuse ν τ flux detected via τ -lepton-induced air showers within the bounds of standard model uncertainties. By comparing this estimate with the acceptance of Pierre Auger Observatory and IceCube and assuming standard model interactions, we conclude that a ν τ origin of these events would imply a neutrino flux at least two orders of magnitude above current bounds.
The first flight of the Antarctic Impulsive Transient Antenna (ANITA) experiment recorded 16 radio signals that were emitted by cosmic-ray induced air showers. The dominant contribution to the ...radiation comes from the deflection of positrons and electrons in the geomagnetic field, which is beamed in the direction of motion of the air shower. For 14 of these events, this radiation is reflected from the ice and subsequently detected by the ANITA experiment at a flight altitude of ∼36 km. In this paper, we estimate the energy of the 14 individual events and find that the mean energy of the cosmic-ray sample is 2.9 × 1018 eV, which is significantly lower than the previous estimate. By simulating the ANITA flight, we calculate its exposure for ultra-high energy cosmic rays. We estimate for the first time the cosmic-ray flux derived only from radio observations and find agreement with measurements performed at other observatories. In addition, we find that the ANITA data set is consistent with Monte Carlo simulations for the total number of observed events and with the properties of those events.
The continuing circulation of African swine fever (ASF) in Russia and in the Trans-Caucasian countries has led to increased efforts in characterizing the epidemiology of ASF. For a better insight in ...epidemiology, quantitative data on virus excretion is required. Until now, excretion data has mainly focused on the initial stages of the disease. In our study we have studied ASF virus (ASFV) excretion dynamics in persistently infected animals. For this purpose, virus excretion through different routes was quantified over 70days after infection. Three virus isolates of moderate virulence were used: the Brazil’78, the Malta’78 (a low and a high inoculation dose) and the Netherlands’86 isolate. For each isolate or dose, 10 animals were used. All (Brazil’78 group), or three animals per group were inoculated and the other animals served as contact animals. It was shown that dose (Malta’78 low or high) or infection route (inoculated or naturally infected) did not influence the ASFV excretion (p>0.05). Nasal, ocular and vaginal excretions showed the lowest ASFV titres. Virus was consistently present in the oropharyngeal swabs, showing two peaks, for up to 70days. Virus was occasionally present in the faeces, occasionally with very high titres. Viral DNA persisted in blood for up to 70days. The results presented in this study show that a high proportion of persistently infected animals shed virus into the environment for at least 70days, representing a possible risk for transmission and that should be considered in future epidemiological analysis of ASF.
We report on a terrestrial gamma ray flash (TGF) that occurred on 15 August 2014 coincident with an altitude‐triggered lightning at the International Center for Lightning Research and Testing (ICLRT) ...in North Central Florida. The TGF was observed by a ground‐level network of gamma ray, close electric field, distant magnetic field, Lightning Mapping Array (LMA), optical, and radar measurements. Simultaneous gamma ray and LMA data indicate that the upward positive leader of the triggered lightning flash induced relativistic runaway electron avalanches when the leader tip was at about 3.5 km altitude, resulting in the observed TGF. Channel luminosity and electric field data show that there was an initial continuous current (ICC) pulse in the lightning channel to ground during the time of the TGF. Modeling of the observed ICC pulse electric fields measured at close range (100–200 m) indicates that the ICC pulse current had both a slow and fast component (full widths at half maximum of 235 μs and 59 μs) and that the fast component was more or less coincident with the TGF, suggesting a physical association between the relativistic runaway electron avalanches and the ICC pulse observed at ground. Our ICC pulse model reproduces moderately well the measured close electric fields at the ICLRT as well as three independent magnetic field measurements made about 250 km away. Radar and LMA data suggest that there was negative charge near the region in which the TGF was initiated.
Key Points
Best documented TGF observed at ground
Second TGF induced by triggered lightning
An ICC pulse occurred simultaneously (within 20 μs) of the TGF
The main objective of this study was to evaluate the relationship between circulating anti-Müllerian hormone (AMH) and superovulatory response of dairy cows. Holstein cows (n=72) were milked twice ...daily and housed and fed individually in tiestalls. All animals were synchronized and flushed at 70±3 d in milk (DIM), near peak production (39.6kg/d). Blood samples for AMH analysis were collected at 3 different stages of a synchronized estrous cycle at a random stage (40±3 DIM), proestrus (50±3 DIM), and diestrus (57±3 DIM). Body weights were measured weekly from calving until embryo collection. Statistical analyses were performed with Proc CORR and Proc GLIMMIX of SAS (SAS Institute Inc., Cary, NC). The 3 AMH samples from individual cows were correlated and not influenced by day of cycle. Surprisingly, AMH tended to be negatively correlated with body weight loss from calving to embryo collection (r=−0.22). More importantly, average AMH was highly associated (r=0.65) with superovulation response (number of corpora lutea on the day of the flush, CLN), total structures collected (r=0.48), and total transferable embryos (r=0.37), but not percentage of fertilized embryos (r=−0.20) or degenerate embryos (r=0.02). When cows were classified into quartiles (Q) of circulating AMH (Q1=0.01 to 82.6pg/mL; Q2=91.1 to 132.5pg/mL; Q3=135.3 to 183.8pg/mL; Q4=184.4 to 374.3pg/mL), we observed a >2-fold difference between first and fourth AMH quartiles in superovulation response (CLN: Q1=12.0±1.5; Q2=14.7±2.0; Q3=17.2±1.2; Q4=25.6±1.5) and embryo production. In conclusion, circulating AMH concentration was strongly associated with superovulation response, and evaluation of AMH could be used to identify cows with greater responses to superstimulation and thus improve efficiency of superovulation programs in dairy cows.
In this work, we study in detail the sensitivity of the Antarctic Impulsive Transient Antenna (ANITA) to possible ντ point source fluxes detected via τ-lepton-induced air showers. This investigation ...is framed around the observation of four upward-going extensive air shower events very close to the horizon seen in ANITA-IV. We find that these four upgoing events are not observationally inconsistent with τ-induced EASs from Earth-skimming ντ both in their spectral properties as well as in their observed locations on the sky. These four events as well as the overall diffuse and point source exposure to Earth-skimming ντ are also compared against published ultrahigh-energy neutrino limits from the Pierre Auger Observatory. While none of these four events occurred at sky locations simultaneously visible by Auger, the implied fluence necessary for ANITA to observe these events is in strong tension with limits set by Auger across a wide range of energies and is additionally in tension with ANITA’s Askaryan in-ice neutrino channel above 1019 eV. We conclude by discussing some of the technical challenges with simulating and analyzing these near horizon events and the potential for future observatories to observe similar events.
This study aimed to develop and validate an index of surgical difficulty for the removal of impacted lower third molars. The study was performed in two steps. The first was a cross-sectional analysis ...of clinical, demographic, and radiographic variables collected from patients undergoing the removal of an impacted lower third molar between 2008 and 2012. The second step was a prospective cohort study involving the same surgical procedures to validate the index; this was performed between 2013 and 2016. Univariate regression analysis was applied, followed by multiple linear regression analysis. A total of 753 surgical procedures were analyzed in the first stage, which led to the identification of the most important variables and their levels of significance. The index was then applied to 280 surgical procedures. The preoperative difficulty was in concordance with the index results in all cases. Among cases with a low level of difficulty, 93.1% had been indexed as low difficulty; likewise, among cases with a high level of difficulty, there was 87.9% concordance with the index. With the use of reference statistics in the development and quality assurance processes, this validated index has proven to be a reliable and easily applicable instrument, with high sensitivity, specificity, and accuracy.
Development of cavity ring-down spectroscopy (CRDS) has enabled real-time monitoring of carbon stable isotope ratios of carbon dioxide and methane in air. Here we demonstrate that CRDS can be adapted ...to assess aquatic carbon cycling processes from microbial to ecosystem scales. We first measured in situ isotopologue concentrations of dissolved CO2 (12CO2 and 13CO2) and CH4 (12CH4 and 13CH4) with CRDS via a closed loop gas equilibration device during a survey along an estuary and during a 40 h time series in a mangrove creek (ecosystem scale). A similar system was also connected to an in situ benthic chamber in a seagrass bed (community scale). Finally, a pulse-chase isotope enrichment experiment was conducted by measuring real-time release of 13CO2 after addition of 13C enriched phytoplankton to exposed intertidal sediments (microbial scale). Miller-Tans plots revealed complex transformation pathways and distinct isotopic source values of CO2 and CH4. Calculations of δ13C-DIC based on CRDS measured δ13C-CO2 and published fractionation factors were in excellent agreement with measured δ13C-DIC using isotope ratio mass spectroscopy (IRMS). The portable CRDS instrumentation used here can obtain real-time, high precision, continuous greenhouse gas data in lakes, rivers, estuaries and marine waters with less effort than conventional laboratory-based techniques.
Discrepancies in oxygen saturation measured by pulse oximetry (Spo2), when compared with arterial oxygen saturation (Sao2) measured by arterial blood gas (ABG), may differentially affect patients ...according to race and ethnicity. However, the association of these disparities with health outcomes is unknown.
To examine racial and ethnic discrepancies between Sao2 and Spo2 measures and their associations with clinical outcomes.
This multicenter, retrospective, cross-sectional study included 3 publicly available electronic health record (EHR) databases (ie, the Electronic Intensive Care Unit-Clinical Research Database and Medical Information Mart for Intensive Care III and IV) as well as Emory Healthcare (2014-2021) and Grady Memorial (2014-2020) databases, spanning 215 hospitals and 382 ICUs. From 141 600 hospital encounters with recorded ABG measurements, 87 971 participants with first ABG measurements and an Spo2 of at least 88% within 5 minutes before the ABG test were included.
Patients with hidden hypoxemia (ie, Spo2 ≥88% but Sao2 <88%).
Outcomes, stratified by race and ethnicity, were Sao2 for each Spo2, hidden hypoxemia prevalence, initial demographic characteristics (age, sex), clinical outcomes (in-hospital mortality, length of stay), organ dysfunction by scores (Sequential Organ Failure Assessment SOFA), and laboratory values (lactate and creatinine levels) before and 24 hours after the ABG measurement.
The first Spo2-Sao2 pairs from 87 971 patient encounters (27 713 42.9% women; mean SE age, 62.2 17.0 years; 1919 2.3% Asian patients; 26 032 29.6% Black patients; 2397 2.7% Hispanic patients, and 57 632 65.5% White patients) were analyzed, with 4859 (5.5%) having hidden hypoxemia. Hidden hypoxemia was observed in all subgroups with varying incidence (Black: 1785 6.8%; Hispanic: 160 6.0%; Asian: 92 4.8%; White: 2822 4.9%) and was associated with greater organ dysfunction 24 hours after the ABG measurement, as evidenced by higher mean (SE) SOFA scores (7.2 0.1 vs 6.29 0.02) and higher in-hospital mortality (eg, among Black patients: 369 21.1% vs 3557 15.0%; P < .001). Furthermore, patients with hidden hypoxemia had higher mean (SE) lactate levels before (3.15 0.09 mg/dL vs 2.66 0.02 mg/dL) and 24 hours after (2.83 0.14 mg/dL vs 2.27 0.02 mg/dL) the ABG test, with less lactate clearance (-0.54 0.12 mg/dL vs -0.79 0.03 mg/dL).
In this study, there was greater variability in oxygen saturation levels for a given Spo2 level in patients who self-identified as Black, followed by Hispanic, Asian, and White. Patients with and without hidden hypoxemia were demographically and clinically similar at baseline ABG measurement by SOFA scores, but those with hidden hypoxemia subsequently experienced higher organ dysfunction scores and higher in-hospital mortality.
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