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BackgroundEarly detection of acute kidney injury (AKI) in severely burn-injured patients can help alter treatment to prevent progression to acute failure and reduce the need for renal replacement therapy. We hypothesized that whole blood neutrophil gelatinase-associated lipocalin (NGAL) will be increased in severely burn-injured patients who develop AKI during acute resuscitation.Materials and methodsWe performed a prospective observation study of adult burn patients with a 20% total body surface area (TBSA) burned or greater burn injury. Two-hour serial measurements of NGAL, serum creatinine (Cr), and hourly urine output (UO) were collected for 48 h after admission. Our primary goal was to correlate the risk of AKI in the first week after burn injury with serial NGAL levels in the first 48 h after admission. Our secondary goal was to determine if NGAL was an earlier independent predictor of AKI compared with Cr and UO.ResultsWe enrolled 30 adult (age ≥ 18 y) burn patients with the mean ± standard deviation age of 40.9 ± 15.4 and mean TBSA of 46.4 ± 22.4. Fourteen patients developed AKI within the first 7 d after burn injury. There were no differences in age, TBSA, fluid administration, mean arterial pressure, UO, and Cr between AKI and no-AKI patients. NGAL was significantly increased as early as 4 h after injury (182.67 ± 83.3 versus 107.37 ± 46.15) in the AKI group. Controlling for age, TBSA, and inhalation injury, NGAL was a predictor of AKI at 4 h after injury (odds ratio, 1.02) and remained predictive of AKI for the period of more than the first 24 h after admission. UO and Cr were not predictive of AKI in the first 24 h after admission.ConclusionsWhole blood NGAL is markedly increased in burn patients who develop AKI in the first week after injury. In addition, NGAL is an early independent predictor of AKI during acute resuscitation for severe burn injury. UO and Cr are not predictive of AKI during this time period.

Ever since the resolution revolution in 2013, cryo-electron microscopy (cryo-EM) has become a powerful methodology in structural biology that is especially suited to study the structure of large flexible molecular complexes. Since then, the need of setting up state-of-the-art cryo-EM facilities around the world has increased tremendously. Access to high-end cryo-EM instrumentation is however expensive and requires expertise. The establishment of large cryo-EM centers worldwide, many of which provide academic users free access for both data collection and user training, has been possible with the support of government agencies across the globe. In addition, many universities, and private institutions like the Van Andel Institute (VAI) have made significant investments to establish their own cryo-EM core facilities, ensuring on-site access to their researchers. This paper aims to serve as a blueprint for establishing a new mid-sized cryo-EM facility, as it provides key information based on our experience at VAI and discusses strategies used to optimize routine operation towards high performance and efficiency for single-particle cryo-EM. Information regarding initial planning, selection of equipment as well as the development of IT solutions that were required to improve data collection and analysis are included. In addition, we present an account of the most common issues affecting operation as well as the needs for maintenance over a 6-year period, which can help interested parties to estimate the long-term costs of running this type of facility. Lastly, a brief discussion on the pros and cons of establishing the facility is also included.

[This corrects the article DOI: 10.1371/journal.ppat.1011461.].

Aqueous sodium hypochlorite is cited widely as an effective oxidant in the transformation of secondary alcohols to ketones as well as for a range of other reactions. The kinetic studies, conducted in air of substituted 1-phenylethanols as well as benzyl alcohols have shown that such oxidations are facilitated by electron withdrawing substituents and point toward an ionic reaction mechanism.

In this study, we evaluated the impact of viral variant, in addition to other variables, on within-host viral burden, by analysing cycle threshold (Ct) values derived from nose and throat swabs, collected as part of the UK COVID-19 Infection Survey. Because viral burden distributions determined from community survey data can be biased due to the impact of variant epidemiology on the time-since-infection of samples, we developed a method to explicitly adjust observed Ct value distributions to account for the expected bias. By analysing the adjusted Ct values using partial least squares regression, we found that among unvaccinated individuals with no known prior exposure, viral burden was 44% lower among Alpha variant infections, compared to those with the predecessor strain, B.1.177. Vaccination reduced viral burden by 67%, and among vaccinated individuals, viral burden was 286% higher among Delta variant, compared to Alpha variant, infections. In addition, viral burden increased by 17% for every 10-year age increment of the infected individual. In summary, within-host viral burden increases with age, is reduced by vaccination, and is influenced by the interplay of vaccination status and viral variant.

The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden. Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia (VITT) are both associated with thrombosis and thrombocytopenia; however, the underlying mechanisms remain inadequately understood. Both infection and vaccination utilize the spike protein receptor-binding domain (RBD) of SARS-CoV-2. We found that intravenous injection of recombinant RBD caused significant platelet clearance in mice. Further investigation revealed the RBD could bind platelets, cause platelet activation, and potentiate platelet aggregation, which was exacerbated in the Delta and Kappa variants. The RBD–platelet interaction was partially dependent on the β3 integrin as binding was significantly reduced in β3−/− mice. Furthermore, RBD binding to human and mouse platelets was significantly reduced with related αIIbβ3 antagonists and mutation of the RGD (arginine-glycine-aspartate) integrin binding motif to RGE (arginine-glycine-glutamate). We developed anti-RBD polyclonal and several monoclonal antibodies (mAbs) and identified 4F2 and 4H12 for their potent dual inhibition of RBD-induced platelet activation, aggregation, and clearance in vivo, and SARS-CoV-2 infection and replication in Vero E6 cells. Our data show that the RBD can bind platelets partially though αIIbβ3 and induce platelet activation and clearance, which may contribute to thrombosis and thrombocytopenia observed in COVID-19 and VITT. Our newly developed mAbs 4F2 and 4H12 have potential not only for diagnosis of SARS-CoV-2 virus antigen but also importantly for therapy against COVID-19.

Globally the population of older adults is the fastest growing age group. Estimated glomerular filtration rate (eGFR) is an estimation of true kidney function with lower eGFR associated with higher mortality. However, few studies explore eGFR’s prognostic value in the nonagenarian. We investigated the association between eGFR on admission and mortality among the nonagenarians hospitalised with acute illness. A retrospective analysis of a prospective cohort study included patients aged ≥ 90 admitted into three acute medical assessment units or acute geriatric wards in England and Scotland between November 2008 and January 2009. Association between eGFR and all-cause mortality was evaluated using the Cox proportional hazard models controlling for potential confounders including frailty. 392 patients with mean (SD) 93.0 ± 2.6 years (68.45% women) were included. The median (IQR) eGFR was 26.61 (18.41–40.41) mL/min/1.732. 63 died in in hospital. Low eGFR was not associated with mortality (Hazard ratio (HR) 1.00 (95% CI 0.98–1.02) overall or in sub–group analysis by frailty (HR 0.96 (0.92–1.01)) or by eGFR of ≤30 (HR 1.01 (0.95–1.06). We found no evidence of prognostic value of eGFR in predicting in–hospital mortality in the acutely unwell hospitalised nonagenarians.

Traps baited with the sex pheromone blend of (Z7)- and (Z5)-tetradecenyl acetate captured significant numbers of male spotted cutworm moths, Xestia c-nigrum (L.) compared to unbaited traps. Nearly no males were captured in traps baited with (Z7)-tetradecenyl acetate, the major pheromone component. Antennae of spotted cutworm males responded to (Z7)-, (E7)-, (Z5)- and (E5)-tetradecenyl acetate in the laboratory; however there was no response by moths in the field to the E isomers when presented in traps as major and minor components respectively of a binary blend or to the (E7) isomer as a single component. These findings clarify the makeup of a sex attractant that can be used for monitoring X. c-nigrum on agricultural crops in Washington. However, multi-year season-long monitoring of spotted cutworm moths in Yakima Valley apple orchards revealed differential responses to pheromone and blacklight traps. A spring flight period showed a strong moth response to the pheromone compared to blacklight, while a later summer flight period showed a weak moth response to the pheromone relative to blacklight. At this time, we do not know which trap type might best indicate spotted cutworm abundance and risk to crops. [ABSTRACT FROM AUTHOR]

Bacterial growth in batch cultures occurs in four phases (lag, exponential/log, stationary and death phase) that differ distinctly in number of different bacteria, biochemistry and physiology. Knowledge regarding the growth phase and its kinetics is essential for bacterial research, especially in taxonomic identification and monitoring drug interactions. However, the conventional methods by which to assess microbial growth are based only on cell counting or optical density, without any insight into the biochemistry of cells or processes. Both Raman and Fourier transform infrared (FTIR) spectroscopy have shown potential to determine the chemical changes occurring between different bacterial growth phases. Here, we extend the application of spectroscopy and for the first time combine both Raman and FTIR microscopy in a multimodal approach to detect changes in the chemical compositions of bacteria within the same phase (intra-phase). We found a number of spectral markers associated with nucleic acids (IR: 964, 1082, 1215 cm−1; RS: 785, 1483 cm−1), carbohydrates (IR: 1035 cm−1; RS: 1047 cm−1) and proteins (1394 cm−1, amide II) reflecting not only inter-, but also intra-phase changes in bacterial chemistry. Principal component analysis performed simultaneously on FTIR and Raman spectra enabled a clear-cut, time-dependent discrimination between intra-lag phase bacteria probed every 30 min. This demonstrates the unique capability of multimodal vibrational spectroscopy to probe the chemistry of bacterial growth even at the intra-phase level, which is particularly important for the lag phase, where low bacterial numbers limit conventional analytical approaches.