Antibacterial Properties of Rose Bengal Conjugated to Hyaluronic Acid.

Dental diseases, including conditions affecting oral structures, have become more common due to unhealthy lifestyle choices. Traditional antibiotic treatments face challenges related to the development of antibiotic resistance in bacteria. Photodynamic antibacterial chemotherapy is emerging as a promising alternative using photosensitizers to generate reactive oxygen species upon exposure to light. This article examines the photosensitizer Rose Bengal (RB) immobilized in hyaluronic acid (HA) for prolonged antibacterial action. The RB-HA conjugate demonstrated a molar ratio of approximately three RB residues to each of the ten units of HA. RB-HA exhibited a high singlet oxygen quantum yield (ΔΦ = 0.90), suggesting its efficacy in photodynamic treatment. A photostability analysis revealed slower photobleaching of RB-HA, which is essential for prolonged application. Under visible light and ultrasonic treatment, RB-HA exhibited effective antibacterial activity against Gram-positive S. aureus and Gram-negative E. coli bacteria for at least 80 days. The gradual release of RB ensured sustained bactericidal concentration. The study establishes RB-HA as a promising candidate for antimicrobial photodynamic and sonodynamic therapy in dental and other medical fields, providing enhanced stability and prolonged antibacterial efficacy.

Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial (EASI-AS-ODT).

BACKGROUND: In the emergency department (ED), prompt administration of systemic corticosteroids for pediatric asthma exacerbations decreases hospital admission rates. However, there is sparse evidence for whether earlier administration of systemic corticosteroids by emergency medical services (EMS) clinicians, prior to ED arrival, further improves pediatric asthma outcomes. METHODS: Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial is a multicenter, observational, nonrandomized stepped-wedge design study with seven participating EMS agencies who adopted an oral systemic corticosteroid (OCS) into their protocols for pediatric asthma treatment. Using univariate analyses and multivariable mixed-effects models, we compared hospital admission rates for pediatric asthma patients ages 2-18 years before and after the introduction of a prehospital OCS and for those who did and did not receive a systemic corticosteroid from EMS. RESULTS: A total of 834 patients were included, 21% of whom received a systemic corticosteroid from EMS. EMS administration of systemic corticosteroids increased after the introduction of an OCS from 14.7% to 28.1% (p < 0.001). However, there was no significant difference between hospital admission rates and ED length of stay before and after the introduction of OCS or between patients who did and did not receive a systemic corticosteroid from EMS. Mixed-effects models revealed that age 14-18 years (coefficient -0.83, p = 0.002), EMS administration of magnesium (coefficient 1.22, p = 0.04), and initial EMS respiratory severity score (coefficient 0.40, p < 0.001) were significantly associated with hospital admission. CONCLUSIONS: In this multicenter study, the addition of an OCS into EMS agency protocols for pediatric asthma exacerbations significantly increased systemic corticosteroid administration but did not significantly decrease hospital admission rates. As overall EMS systemic corticosteroid administration rates were low, further work is required to understand optimal implementation of EMS protocol changes to better assess potential benefits to patients.

Evaluation of the implementation of evidence-based pediatric asthma exacerbation treatments in a regional consortium of emergency medical Services Agencies.

OBJECTIVE: Asthma exacerbations are a frequent reason for pediatric emergency medical services (EMS) encounters. The objective of this study was to examine the implementation of evidence-based treatments for pediatric asthma in a regional consortium of EMS agencies. METHODS: This retrospective study applied the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) implementation framework to data from an EMS agency consortium in the Cincinnati, Ohio region. The study analyzed one year before an oral systemic corticosteroid (OCS) option was added to the agencies' protocol, and five years after the protocol change. We constructed logistic regression models for the primary outcome of Reach, defined as the proportion of pediatric asthma patients who received a systemic corticosteroid. We modeled Maintenance (Reach measured monthly over time) using time series models. RESULTS: A total of 713 patients were included, 133 pre- and 580 post-protocol change. In terms of Reach, 3% (n = 4) of eligible patients received a systemic corticosteroid pre-OCS versus 20% (n = 116) post-OCS. Multivariable modeling of Reach revealed the study period, EMS transport time, months since implementation of OCS, and number of bronchodilators administered by EMS as significant covariates for the administration of a systemic corticosteroid. For Maintenance, it took approximately two years to reach maximal administration of systemic corticosteroids. CONCLUSIONS: Indicators of asthma severity and time since the protocol change were significantly associated with EMS administration of systemic corticosteroids to pediatric asthma patients. The two-year time for maximal Reach suggests further work is required to understand how to best implement evidence-based pediatric asthma treatments in EMS.

Examination of disparities in prehospital encounters for pediatric asthma exacerbations.

Introduction: There are disparities in multiple aspects of pediatric asthma care; however, prehospital care disparities are largely undescribed. This study's objective was to examine racial and geographic disparities in emergency medical services (EMS) medication administration to pediatric patients with asthma. Methods: This is a substudy of the Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial, which includes data from pediatric asthma patients ages 2-18 years. We examined rates of EMS administration of systemic corticosteroids and inhaled bronchodilators by patient race. We geocoded EMS scene addresses, characterized the locations' neighborhood-based conditions and resources relevant to children using the Child Opportunity Index (COI) 2.0, and analyzed associations between EMS scene address COI with medications administered by EMS. Results: A total of 765 patients had available racial data and 825 had scene addresses that were geocoded to a COI. EMS administered at least 1 bronchodilator to 84.7% (n = 492) of non-White patients and 83.2% of White patients (n = 153), P = 0.6. EMS administered a systemic corticosteroid to 19.4% (n = 113) of non-White patients and 20.1% (n = 37) of White patients, P = 0.8. There was a significant difference in bronchodilator administration between COI categories of low/very low versus moderate/high/very high (85.0%, n = 485 vs. 75.9%, n = 192, respectively, P = 0.003). Conclusions: There were no racial differences in EMS administration of medications to pediatric asthma patients. However, there were significantly higher rates of EMS bronchodilator administration for encounters in low/very low COIs. That latter finding may reflect inequities in asthma exacerbation severity for patients living in disadvantaged areas.

EMS Administration of Systemic Corticosteroids to Pediatric Asthma Patients: An Analysis by Severity and Transport Interval.

INTRODUCTION: Pediatric asthma exacerbations are a common cause of emergency medical services (EMS) encounters. Bronchodilators and systemic corticosteroids are mainstays of asthma exacerbation therapy, yet data on the efficacy of EMS administration of systemic corticosteroids are mixed. This study's objective was to assess the association between EMS administration of systemic corticosteroids to pediatric asthma patients on hospital admission rates based on asthma exacerbation severity and EMS transport intervals. METHODS: This is a sub-analysis of the Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial (EASI AS ODT). EASI AS ODT is a non-randomized, stepped wedge, observational study examining outcomes one year before and one year after seven EMS agencies incorporated an oral systemic corticosteroid option into their protocols for the treatment of pediatric asthma exacerbations. We included EMS encounters for patients ages 2-18 years confirmed by manual chart review to have asthma exacerbations. We compared hospital admission rates across asthma exacerbation severities and EMS transport intervals using univariate analyses. We geocoded patients and created maps to visualize the general trends of patient characteristics. RESULTS: A total of 841 pediatric asthma patients met inclusion criteria. While most patients were administered inhaled bronchodilators by EMS (82.3%), only 21% received systemic corticosteroids, and only 19% received both inhaled bronchodilators and systemic corticosteroids. Overall, there was no significant difference in hospitalization rates between patients who did and did not receive systemic corticosteroids from EMS (33% vs. 32%, p = 0.78). However, although not statistically significant, for patients who received systemic corticosteroids from EMS, there was an 11% decrease in hospitalizations for mild exacerbation patients and a 16% decrease in hospitalizations for patients with EMS transport intervals greater than 40 min. CONCLUSION: In this study, systemic corticosteroids were not associated with a decrease in hospitalizations of pediatric patients with asthma overall. However, while limited by small sample size and lack of statistical significance, our results suggest there may be a benefit in certain subgroups, particularly patients with mild exacerbations and those with transport intervals longer than 40 min. Given the heterogeneity of EMS agencies, EMS agencies should consider local operational and pediatric patient characteristics when developing standard operating protocols for pediatric asthma.

Synthesis and biological evaluation of theranostic Trastuzumab-SN38 conjugate for Near-IR fluorescence imaging and targeted therapy of HER2+ breast cancer.

Here, we report on the design, synthesis, and biological evaluation of a new theranostic antibody drug conjugate (ADC), Cy5-Ab-SS-SN38, that consists of the HER2-specific antibody trastuzumab (Ab) connected to the near infrared (NIR) pentamethine cyanine dye Cy5 and SN38, which is a bioactive metabolite of the anticancer drug irinotecan. SN38 is bound to an antibody through a glutathione-responsive self-immolative disulfide carbamate linker. For the first time, we explored this linker in ADC and found that it to reduce the drug release rate, which is important for safe drug delivery. The developed ADC exhibited specific accumulation and nanomolar anti-breast cancer activity on HER2-positive (HER2+) cell lines but no effect on HER2-. Animals treated with this ADC exhibited good tolerance. In vivo studies have shown that the ADC had good targeting ability for HER2+ tumors with much higher anticancer potency than trastuzumab itself or a mixture of trastuzumab with SN38. Side-by-side HER2+/HER2-xenograft at the 10 mg/kg dose exhibited specific accumulation and reduction of HER2+ tumor but not accumulation or growth inhibition of HER2-counterpart. The self-immolative disulfide linker implemented in this study was proven to be successful, broadening its utilization with other antibodies for targeted anticancer therapy in general. We believe that the theranostic ADCs comprising the glutathione-responsive self-immolative disulfide carbamate linker are applicable for the treatment and fluorescent monitoring of malignancies and anticancer drug delivery.

The Success of Resident-Associated Lumbar Punctures at a Large, Single-Center Children's Hospital.

OBJECTIVES: The frequency of lumbar punctures (LPs) has declined across US children's hospitals over the past decade, potentially decreasing procedural learning opportunities for pediatric resident trainees. Our study sought to determine whether the proportion of successful LPs performed by our pediatric residents has significantly changed over time. METHODS: This study is a single-center retrospective study to evaluate our pediatric resident LP success. We evaluated our primary outcome, proportion of overall LP success over time, using linear regression. We similarly used linear regression for proportion of successful resident-associated LPs over time. We calculated the median number of LPs of all pediatric residents during the study period. RESULTS: We analyzed 3143 LPs from April 2012 to December 2019. Both the overall number of LPs performed and the proportion of LPs that were successful have not significantly changed over an 8-year period ( P > 0.05, P > 0.05). Similarly, the number of our resident-associated LPs and the proportion of successful resident-associated LPs have not changed over the study period ( P > 0.05, P > 0.05). Our pediatric residents performed a median of 3 LPs (interquartile range: 2-4) in the pediatric emergency department (PED) over residency. CONCLUSIONS: Despite national trends showing decreased LP rates at pediatric hospitals, we demonstrated stable proportions of LPs and success by our pediatric residents. Pediatric residents perform a relatively low number of LPs in the PED setting alone. Future research is needed to demonstrate whether these overall low numbers in the PED translate to procedural competency after residency graduation.

Effect of Solubilizing Group on the Antibacterial Activity of Heptamethine Cyanine Photosensitizers.

Antibiotic resistance of pathogenic bacteria dictates the development of novel treatment modalities such as antimicrobial photodynamic therapy (APDT) utilizing organic dyes termed photosensitizers that exhibit a high cytotoxicity upon light irradiation. Most of the clinically approved photosensitizers are porphyrins that are poorly excitable in the therapeutic near-IR spectral range. In contrast, cyanine dyes function well in the near-IR region, but their phototoxicity, in general, is very low. The introduction of iodine atoms in the cyanine molecules was recently demonstrated to greatly increase their phototoxicity. Herein, we synthesized a series of the new iodinated heptamethine cyanine dyes (ICy7) containing various solubilizing moieties, i.e., negatively charged carboxylic (ICy7COOH) and sulfonic (ICy7SO3H) groups, positively charged triphenylphosphonium (ICy7PPh3), triethylammonium (ICy7NEt3) and amino (ICy7NH2) groups, and neutral amide (ICy7CONHPr) group. The effect of these substituents on the photodynamic eradication of Gram-positive (S. aureus) and Gram-negative (E. coli and P. aeruginosa) pathogens was studied. Cyanine dyes containing the amide and triphenylphosphonium groups were found to be the most efficient for eradication of the investigated bacteria. These dyes are effective at low concentrations of 0.05 µM (33 J/cm2) for S. aureus, 50 µM (200 J/cm2) for E. coli, and 5 µM (100 J/cm2) for P. aeruginosa and considered, therefore, promising photosensitizers for APDT applications. The innovation of the new photosensitizers consisted of a combination of the heavy-atom effect that increases singlet oxygen generation with the solubilizing group's effect improving cell uptake, and with effective near-IR excitation. Such a combination helped to noticeably increase the APDT efficacy and should pave the way for the development of more advanced photosensitizers for clinical use.

Prehospital Pediatric Asthma Care during COVID-19: Changes to EMS Treatment Protocols and Downstream Clinical Effects.

INTRODUCTION: During the COVID-19 pandemic, many emergency medical services (EMS) agencies modified treatment guidelines for clinical care and standard operating procedures. For the prehospital care of pediatric asthma exacerbations, modifications included changes to bronchodilator administration, systemic corticosteroid administration, and introduction of alternative medications. Since timely administration of bronchodilators and systemic corticosteroids has been shown to improve pediatric asthma clinical outcomes, we investigated the association of COVID-19 protocol modifications in the prehospital management of pediatric asthma on hospital admission rates and emergency department (ED) length-of-stay. METHODS: This is a multicenter, retrospective, observational cohort study comparing prehospital pediatric asthma patients treated by EMS clinicians from four EMS systems before and after implementation of COVID-19 interim EMS protocol modifications. We included children ages 2-18 years who were treated and transported by ground EMS for respiratory-related prehospital primary complaints, and who also had asthma-related ED discharge diagnoses. Patient data and outcomes were compared from 12 months prior to and 12 months after the implementation of interim COVID-19 prehospital protocol modifications using univariate and multivariable statistics. RESULTS: A total of 430 patients met inclusion criteria with a median age of 8 years. There was a slight male predominance (57.9%) and the majority of patients were African American (78.4%). There were twice as many patients treated prior to the COVID-19 protocol modifications (N = 287) compared to after (N = 143). There was a significant decrease in EMS bronchodilator administration from 76% to 59.4% of patients after COVID-19 protocol guidelines were implemented (p < 0.0001). Mixed effects models for hospital admission (to both pediatric inpatient units and pediatric intensive care units) as well as ED length-of-stay did not show any significant effect after the COVID-19 protocol change period (p = 0.18 and p = 0.55, respectively). CONCLUSIONS: Despite a decrease in prehospital bronchodilator administration after COVID-19 changes to prehospital pediatric asthma management protocols, hospital admission rates and ED length-of-stay did not significantly increase. However, this finding is tempered by the marked decrease in study patients treated after COVID-19 prehospital protocol modifications. Given the potential for future waves of COVID-19 variants, further studies with larger patient populations are warranted.

The metabolism of the synthetic cannabinoids ADB-BUTINACA and ADB-4en-PINACA and their detection in forensic toxicology casework and infused papers seized in prisons.

Early warning systems detect new psychoactive substances (NPS), while dedicated monitoring programs and routine drug and toxicology testing identify fluctuations in prevalence. We report the increasing prevalence of the synthetic cannabinoid receptor agonist (SCRA) ADB-BUTINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-butyl-1H-indazole-3-carbox-amide). ADB-BUTINACA was first detected in a seizure in Sweden in 2019, and we report its detection in 13 routine Swedish forensic toxicology cases soon after. In January 2021, ADB-BUTINACA was detected in SCRA-infused papers seized in Scottish prisons and has rapidly increased in prevalence, being detected in 60.4% of the SCRA-infused papers tested between January and July 2021. In this work, ADB-BUTINACA was incubated with human hepatocytes (HHeps), and 21 metabolites were identified in vitro, 14 being detected in authentic case samples. The parent drug and metabolites B9 (mono-hydroxylation on the n-butyl tail) and B16 (mono-hydroxylation on the indazole ring) are recommended biomarkers in blood, while metabolites B4 (dihydrodiol formation on the indazole core), B9, and B16 are suitable biomarkers in urine. ADB-4en-PINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-[pent-4-en-1-yl]-1H-indazole-3-carboxamide) was detected in Scottish prisons in December 2020, but, unlike ADB-BUTINACA, prevalence has remained low. ADB-4en-PINACA was incubated with HHeps, and 11 metabolites were identified. Metabolites E3 (dihydrodiol formed in the tail moiety) and E7 (hydroxylation on the linked/head group) are the most abundant metabolites in vitro and are suggested as urinary biomarkers. The in vitro potencies of ADB-BUTINACA (EC50 , 11.5 nM and ADB-4en-PINACA (EC50 , 11.6 nM) are similar to that of MDMB-4en-PINACA (EC50 , 4.3 nM). A third tert-leucinamide SCRA, ADB-HEXINACA was also detected in prison samples and warrants further investigation.

Phylogenetics of Bacillus anthracis isolates from Russia and bordering countries.

Anthrax is a concern for public health and veterinary medicine in Russia. The available phylogenetic data on isolates from Russia and neighboring CIS countries are clearly not enough to gain a better understanding of their position in the global phylogenetic population structure of this pathogen. In this study, we analyzed the genomes of 66 Bacillus anthracis strains, which were isolated between 1935 and 2019 from different sources in Russia, as well as in Ukraine, Azerbaijan, Georgia, Armenia and Moldova. Whole genome SNP analysis of genomes of 66 strains obtained in this study along with 222 B. anthracis genomes available in the GenBank database revealed 7242 SNPs used to construct a phylogenetic reconstruction with the method of Maximum Likelihood. Studied strains belong to 6 different genetic groups: A.Br.008(A.Br.008/009), A.Br.081(Ames), A.Br.014(A.Br.Aust94), A.Br.082(A.Br.001/002), A.Br.034(A.Br.005/006, Ancient A) and B.Br.002 (B.Br.001/002). Within the group A.Br.014(A.Br.Aust94) a subcluster A.Br.029 of strains isolated in Georgia, Armenia, Azerbaijan, Russia (Republic of Dagestan) and Turkey, named Caucasus-East Anatolia (CEA), was identified. In the subgroup A.Br.105(Tsiankovskii) the cluster A.Br.117 of strains from Russia, Ukraine and Slovakia are assigned, in the subgroup A.Br118 (STI) - cluster A.Br.123 with strains from Russia and Georgia and cluster A.Br.125 with strains from Republic of Dagestan. New subclusters B.Br.017("EUROPE") were identified in the B.Br.002(B.Br.001/002) cluster, represented by strains from the European part of Russia, as well as from South Korea and Finland. For 8 clusters and subclusters, the SNP markers were identified. The study confirmed a significant genetic diversity of the strains isolated in Russia and border countries and clarified their position in the phylogenetic structure of the global B. anthracis population. New genetic clusters A.Br.029 (CEA), A.Br.117, A.Br.123, A.Br.125, and B.Br.017 («EUROPE¼) were defined. 96 marker SNPs specific for these clusters were identified.

Spatial and Social Behavior of Single and Coupled Individuals of Both Sexes during COVID-19 Lockdown Regime in Russia.

Testing individual motivations for social activity in violation of the mandated lockdown regime is a challenging research topic for evolutionary psychology. To this purpose, we analyzed twenty popular weekly routes and the potential impact of sex and relationship status (single versus coupled) on the reported level of spatial-social activity during the quarantine in Russia between March and June 2020 (N = 492). Our study revealed a significant difference between men's and women's mobility: men, in general, tend to exhibit substantially higher spatial activity. The results have shown that individuals living on their own have more social interactions with friends and exhibit more profound spatial mobility via public transport. On the other hand, spatial activity of coupled individuals of both sexes were mostly devoted to solving a list of economic and matrimonial tasks. At the same time, men already cohabiting with a partner leave their homes for dating purposes more frequently than single men and women. We interpret these findings in the sense that both individual and sex-specific differences in observed sociality could be a result of a fine-tuned adaptive populational response to a contemporary virus threat, predominantly rooted in the evolution of behavioral strategies in the reproductive and economic spheres of each sex. Indeed, unlike women, coupled men have been preserving highly risky and intense social behavior during the COVID-19 pandemic.

Comparison of children receiving emergent sepsis care by mode of arrival.

OBJECTIVE: To determine if differences in patient characteristics, treatments, and outcomes exist between children with sepsis who arrive by emergency medical services (EMS) versus their own mode of transport (self-transport). METHODS: Retrospective cohort study of patients who presented to the Emergency Department (ED) of two large children's hospitals and treated for sepsis from November 2013 to June 2017. Presentation, ED treatment, and outcomes, primarily time to first bolus and first parental antibiotic, were compared between those transported via EMS versus patients who were self-transported. RESULTS: Of the 1813 children treated in the ED for sepsis, 1452 were self-transported and 361 were transported via EMS. The EMS group were more frequently male, of black race, and publicly insured than the self-transport group. The EMS group was more likely to have a critical triage category, receive initial care in the resuscitation suite (51.9 vs. 22%), have hypotension at ED presentation (14.4 vs. 5.4%), lactate >2.0 mmol/L (60.6 vs. 40.8%), vasoactive agents initiated in the ED (8.9 vs. 4.9%), and to be intubated in the ED (14.4 vs. 2.8%). The median time to first IV fluid bolus was faster in the EMS group (36 vs. 57 min). Using Cox LASSO to adjust for potential covariates, time to fluids remained faster for the EMS group (HR 1.26, 95% CI 1.12, 1.42). Time to antibiotics, ICU LOS, 3- or 30-day mortality rates did not differ, yet median hospital LOS was significantly longer in those transported by EMS versus self-transported (6.5 vs. 5.3 days). CONCLUSIONS: Children with sepsis transported by EMS are a sicker population of children than those self-transported on arrival and had longer hospital stays. EMS transport was associated with earlier in-hospital fluid resuscitation but no difference in time to first antibiotic. Improved prehospital recognition and care is needed to promote adherence to both prehospital and hospital-based sepsis resuscitation benchmarks.

Molecular genotyping of 15 B. anthracis strains isolated in Eastern Siberia and Far East.

Bacillus anthracis is a pathogenic bacterium, which causes anthrax disease. The ability of this bacterium to form spores, which can be preserved in soil for decades and cause outbreaks later on, makes this pathogen a serious problem for veterinary and health services of many countries. Siberia is one of the most anthrax-influenced regions of Russia. In this research we report on the results of genotyping based on whole genome SNP analysis of 15 strains, isolated on the territory of Eastern Siberia and the Far East in 1956-2018. In this research, we sequenced 15 genomes of B. anthracis strains isolated from infected humans and animals, and from soil samples from the territory of Eastern Siberia and the Far East in the period from 1956 to 2018. We used genomic sequences obtained in this study and 219 B. anthracis genomes available in the international GenBank database to perform a comparative analysis. As a result we detected 6400 chromosomal SNPs which allowed to differentiate the studied strains. We built phylogenetic reconstruction of the global B. anthracis population based on the detected SNPs using the Maximum Likelihood Method and described genetic diversity of the strains isolated on the territory of Eastern Siberia and the Far East. Strains, isolated on this territory from 1956 to 2018 belong to 5 different genetic groups: "Ames", "STI", "Tsiankovskii", "Siberia" and "Asia". The greatest diversity of the strains is registered for two regions of the southern part of Eastern Siberia - Tyva and Buryatia. This research expands current understanding of genetic diversity of B. anthracis strains circulating on the territory of Russia.

High-Flow Nasal Cannula in Bronchiolitis at a Pediatric Emergency Department: Trends and Outcomes.

OBJECTIVES: Use of high-flow nasal cannula (HFNC) for bronchiolitis has increased, but data describing the current use and impact of this therapy are limited. Our objective with this study was to describe the use of HFNC for bronchiolitis in a pediatric emergency department (ED) from 2013 to 2019 and to explore associations with clinical outcomes. METHODS: This was a retrospective cohort study of children aged 2 to 24 months with the diagnosis of bronchiolitis. The primary outcome was HFNC initiation in the ED. Secondary outcomes included admission rate, ICU (PICU) admission, transfer to PICU from floor, and endotracheal intubation. An adjusted interrupted times series analysis was performed to analyze changes in rates of primary and secondary outcomes over time. RESULTS: In total 11 149 children met inclusion criteria; 902 (8.1%) were initiated on HFNC. The rate of HFNC initiation increased from 1.3% in 2012-2013 to 17.0% in 2018-2019 (P trend ≤ .001). Less than 30% of children initiated on HFNC were hypoxic. There were no significant changes over time in rates of hospital admission, PICU admission, or PICU transfer, adjusting for clinical severity, seasonality, and provider variation. Intubation rate increased over the study period. CONCLUSIONS: We found a 13-fold increase in HFNC use over a 6-year period with no evidence of improvement in clinically meaningful outcomes. Clinical benefit should be clearly defined before further expansion of the use of HFNC for bronchiolitis in the ED.

Correlation of elastic and optoelectronic properties near structural phase transition in organic-inorganic lead iodide perovskite single crystals.

The experimental evidence of the influence of the structural phase transition on the elastic and optoelectronic properties of CH3NH3PbI3single crystals has been reported. A peak in the attenuation for longitudinal and shear ultrasonic waves and a step-like anomaly in their velocity have been found near the structural the orthorhombic-to-tetragonal phase transition (160 K). The narrow hysteresis observed in the temperature dependences of the elastic properties confirms that this is the first-order phase transition. A redshift of the absorption threshold (of about 110 meV) has been revealed both in the photocurrent (PC) and in the photoluminescence (PL) spectra with increasing temperature from 140 to 160 K. In the orthorhombic phase of CH3NH3PbI3single crystals, the fine exciton structure in the PC spectrum has been found with an exciton binding energy of 19-25 meV. The peculiarities of the PC and PL spectra near the phase transition temperature (160 K) have been observed within a wider temperature range in contrast to the elastic anomalies that can be explained by the complex structure of the near-surface region. It may be essential for the further development of optoelectronic devices based on hybrid halide perovskites.

Optimisation of pyruvate hyperpolarisation using SABRE by tuning the active magnetisation transfer catalyst.

Hyperpolarisation techniques such as signal amplification by reversible exchange (SABRE) can deliver NMR signals several orders of magnitude larger than those derived under Boltzmann conditions. SABRE is able to catalytically transfer latent magnetisation from para-hydrogen to a substrate in reversible exchange via temporary associations with an iridium complex. SABRE has recently been applied to the hyperpolarisation of pyruvate, a substrate often used in many in vivo MRI studies. In this work, we seek to optimise the pyruvate-13C2 signal gains delivered through SABRE by fine tuning the properties of the active polarisation transfer catalyst. We present a detailed study of the effects of varying the carbene and sulfoxide ligands on the formation and behaviour of the active [Ir(H)2(η2-pyruvate)(sulfoxide)(NHC)] catalyst to produce a rationale for achieving high pyruvate signal gains in a cheap and refreshable manner. This optimisation approach allows us to achieve signal enhancements of 2140 and 2125-fold for the 1-13C and 2-13C sites respectively of sodium pyruvate-1,2-[13C2].

Phylogenetic analysis of Bacillus anthracis strains from Western Siberia reveals a new genetic cluster in the global population of the species.

BACKGROUND: Anthrax is a zoonotic disease caused by the gram-positive bacterium Bacillus anthracis. The most anthrax-endemic regions of Russia are Siberia and North Caucasus. Previously, genotyping of Russian B.anthracis isolates was carried out using canSNP and MLVA data; these methods yield lower resolution results compared to whole genome SNP analysis (wgSNP). In this research, we have used wgSNP method for genotyping of 10 B.anthracis isolates, obtained during 1961-2016 in Russia on territory of Western Siberia. RESULTS: We have analyzed 185 B.anthracis genomes available in GenBank database and genomes of 10 isolates obtained in this study to determine the place of Russian isolates in the global phylogeny of B.anthracis. For the studied genomes we have detected 7203 SNPs, which were used for building a phylogenetic reconstruction with Maximum Likelihood Method. Results of the phylogenetic analysis indicate that Russian strains belong to three different genetic groups. Three strains belong to genetic group "Ames", two strains - to "STI" group. Five strains belong to the main genetic line B, and four of them form a subcluster, described for the first time, which we have named "Siberia". CONCLUSIONS: In this study, the data on genetic diversity of B.anthracis strains on the territory of Western Siberia is presented for the first time. As a result of complex phylogenetic analysis, the place of these isolates was determined in the global phylogenetic structure of the B.anthracis population. We describe a new cluster in the main genetic line B for the first time.

Electronic Health Record Classification of Tobacco Smoke Exposure and Cotinine Levels in Hospitalized Pediatric Patients.

OBJECTIVES: Documentation of children's tobacco smoke exposure (TSE) in the electronic health record (EHR) can have important implications for clinical care. However, it may not be accurate if it is not based on biochemical assessment, the most reliable method of verifying TSE. Our objectives were to compare the accuracy of EHR classification of TSE with cotinine verification and to explore parent and child variables associated with biochemically verified TSE. METHODS: Participants were 171 hospitalized pediatric patients (ages 0-17 years; mean age 5.1 [SD 3.7] years) who had EHR documentation of TSE and measured salivary cotinine. Children with cotinine levels >1 ng/mL were classified as having biochemical verification of TSE. Parents reported sociodemographic characteristics, and children's EHRs were abstracted for TSE status, past medical history, and diagnoses. We conducted χ2 tests to assess the agreement between EHR classification of TSE status and cotinine levels. Then, we assessed the relationship between sociodemographic and clinical variables and cotinine using crude and adjusted logistic regression models. RESULTS: Overall, 71% (121 of 171) of EHR classifications were correct on the basis of cotinine levels. Specificity analyses showed that 77% (53 of 69) were correctly identified as exposed to tobacco smoke. Sensitivity analyses showed that 67% (68 of 102) were correctly identified as unexposed. The negative predictive value was 0.61 (53 of 87); 39% (34 of 87) were misclassified as unexposed. The positive predictive value was 0.81 (68 of 84); 19% (16 of 84) were misclassified as exposed. CONCLUSIONS: Almost 40% of children were misclassified in the EHR as unexposed to tobacco smoke. Biochemical verification should be used as part of universal TSE screening during pediatric hospitalizations.