Increase in complicated upper respiratory tract infection in children during the 2022/2023 winter season-a post coronavirus disease 2019 effect?

BACKGROUND: Upper respiratory tract infections usually peak during winter months. OBJECTIVE: The purpose of this study was to evaluate whether imaging of complicated upper airway infection in children increased during the winter season of 2022/2023. MATERIALS AND METHODS: In a retrospective study setting, pediatric magnetic resonance imaging (MRI) and computed tomography (CT) scans for evaluation of upper respiratory tract infection performed between October 2022 and April 2023 were analyzed regarding presence of the following complications: mastoiditis, abscess, phlegmon, meningitis, reactive vasculitis, and sinus vein thrombosis. Pathogen detection, surgery, and infection parameters were obtained. Data were compared with MRI and CT scans performed in the same months of the preceding five years, distinguishing between pandemic and pre-pandemic years. RESULTS: During the 2022/2023 winter season, the number of MRI and CT scans in children with upper airway infections, the complication rate, the rate of detected streptococcal infections, and the rate of surgery increased significantly compared to expectations based on the five prior winter seasons (all P<0.05). During the first complete pandemic winter season in Europe (2020/2021), the number of MRI and CT scans in children with upper airway infection, the complication rate, and the rates of streptococcal detection and surgery decreased significantly compared to expectations based on the pre-pandemic, the second pandemic, and the post-pandemic winter seasons (all P<0.05). CONCLUSION: After a decline during the first pandemic winter season, there was a marked rebound in complicated upper airway infection in children, with a significant increase in cases during the 2022/2023 winter season compared to the pre-pandemic and pandemic years.

Nucleosome Remodeling at the Yeast PHO8 and PHO84 Promoters without the Putatively Essential SWI/SNF Remodeler.

Chromatin remodeling by ATP-dependent remodeling enzymes is crucial for all genomic processes, like transcription or replication. Eukaryotes harbor many remodeler types, and it is unclear why a given chromatin transition requires more or less stringently one or several remodelers. As a classical example, removal of budding yeast PHO8 and PHO84 promoter nucleosomes upon physiological gene induction by phosphate starvation essentially requires the SWI/SNF remodeling complex. This dependency on SWI/SNF may indicate specificity in remodeler recruitment, in recognition of nucleosomes as remodeling substrate or in remodeling outcome. By in vivo chromatin analyses of wild type and mutant yeast under various PHO regulon induction conditions, we found that overexpression of the remodeler-recruiting transactivator Pho4 allowed removal of PHO8 promoter nucleosomes without SWI/SNF. For PHO84 promoter nucleosome removal in the absence of SWI/SNF, an intranucleosomal Pho4 site, which likely altered the remodeling outcome via factor binding competition, was required in addition to such overexpression. Therefore, an essential remodeler requirement under physiological conditions need not reflect substrate specificity, but may reflect specific recruitment and/or remodeling outcomes.

Absolute nucleosome occupancy map for the Saccharomyces cerevisiae genome.

Mapping of nucleosomes, the basic DNA packaging unit in eukaryotes, is fundamental for understanding genome regulation because nucleosomes modulate DNA access by their positioning along the genome. A cell-population nucleosome map requires two observables: nucleosome positions along the DNA ("Where?") and nucleosome occupancies across the population ("In how many cells?"). All available genome-wide nucleosome mapping techniques are yield methods because they score either nucleosomal (e.g., MNase-seq, chemical cleavage-seq) or nonnucleosomal (e.g., ATAC-seq) DNA but lose track of the total DNA population for each genomic region. Therefore, they only provide nucleosome positions and maybe compare relative occupancies between positions, but cannot measure absolute nucleosome occupancy, which is the fraction of all DNA molecules occupied at a given position and time by a nucleosome. Here, we established two orthogonal and thereby cross-validating approaches to measure absolute nucleosome occupancy across the Saccharomyces cerevisiae genome via restriction enzymes and DNA methyltransferases. The resulting high-resolution (9-bp) map shows uniform absolute occupancies. Most nucleosome positions are occupied in most cells: 97% of all nucleosomes called by chemical cleavage-seq have a mean absolute occupancy of 90 ± 6% (±SD). Depending on nucleosome position calling procedures, there are 57,000 to 60,000 nucleosomes per yeast cell. The few low absolute occupancy nucleosomes do not correlate with highly transcribed gene bodies, but correlate with increased presence of the nucleosome-evicting chromatin structure remodeling (RSC) complex, and are enriched upstream of highly transcribed or regulated genes. Our work provides a quantitative method and reference frame in absolute terms for future chromatin studies.

Not all that looks fractured is broken-multipartite humeral epicondyles in children.

OBJECTIVE: Multipartite epicondyles may mimic fractures in the setting of pediatric elbow trauma. This study examines the prevalence of multipartite epicondyles during skeletal development and their association with pediatric elbow fractures. MATERIALS AND METHODS: In this retrospective analysis, 4282 elbow radiographs of 1265 elbows of 1210 patients aged 0-17 years were reviewed. The radiographs were analyzed by two radiologists in consensus reading, and the number of visible portions of the medial and lateral epicondyles was noted. For elbows in which epicondylar ossification was not yet visible, the epicondyles were already fused with the humerus or could not be sufficiently evaluated due to projection issues or because osteosynthesis material was excluded. In total, 187 elbows were included for the lateral and 715 for the medial epicondyle analyses. RESULTS: No multipartite medial epicondyles were found in patients without history of elbow fracture, whereas 9% of these patients had multipartite lateral epicondyles (p < 0.01). Current or previous elbow fractures increased the prevalence of multipartite epicondyles, with significant lateral predominance (medial epicondyle + 9% vs. lateral + 24%, p < 0.0001). Including all patients regardless of a history of elbow fracture, multipartite medial epicondyles were observed in 3% and multipartite lateral epicondyles in 18% (p < 0.0001). There was no gender difference in the prevalence of multipartition of either epicondyle, regardless of a trauma history. CONCLUSION: Multipartite medial epicondyles occur in patients with current or previous elbow fractures only, whereas multipartite lateral epicondyles may be constitutional. Elbow fractures increase the prevalence of multipartite epicondyles on both sides, with significant lateral predominance. KEY POINTS: • Multipartite medial epicondyles should be considered of traumatic origin. • Multipartite lateral epicondyles may be constitutional. • Elbow fractures increase the prevalence of multipartite epicondyles on both sides with lateral predominance.

Decreasing Clostridium difficile infections by an antimicrobial stewardship program that reduces moxifloxacin use.

Clostridium difficile infections (CDI) in hospitalized patients are known to be closely related to antibiotic exposure. Although several substances can cause CDI, the risk differs between individual agents. In Vienna and other eastern parts of Austria, CDI ribotype 027 is currently highly prevalent. This ribotype has the characteristic of intrinsic moxifloxacin resistance. Therefore, we hypothesized that moxifloxacin restriction can decrease the number of CDI cases in hospitalized patients. Our antibiotic stewardship (ABS) group applied an information campaign on CDI and formal restriction of moxifloxacin in Wilhelminenspital (Vienna, Austria), a 1,000- bed tertiary care hospital. The preintervention period (period 1) was January through May 2013, and the intervention period (period 2) was June through December 2013. We recorded the defined daily doses (DDD) of moxifloxacin and the number of CDI patients/month. Moxifloxacin use was reduced from a mean (±standard error of the mean [SEM]) of 1,038±109 DDD per month (period 1) to 42±10 DDD per month (period 2) (P=0.0045). Total antibiotic use was not affected. The mean (±SEM) numbers of CDI cases in period 1 were 59±3 per month and in period 2 were 32±3 per month (46% reduction; P=0.0044). Reducing moxifloxacin use in combination with providing structured information on CDI was associated with an immediate decrease in CDI rates in this large community teaching hospital.

ORE-Seq: Genome-Wide Absolute Occupancy Measurement by Restriction Enzyme Accessibilities.

Digestion with restriction enzymes is a classical approach for probing DNA accessibility in chromatin. It allows to monitor both the cut and the uncut fraction and thereby the determination of accessibility or occupancy (= 1 - accessibility) in absolute terms as the percentage of cut or uncut molecules, respectively, out of all molecules. The protocol presented here takes this classical approach to the genome-wide level. After exhaustive restriction enzyme digestion of chromatin, DNA is purified, sheared, and converted into libraries for high-throughput sequencing. Bioinformatic analysis counts uncut DNA fragments as well as DNA ends generated by restriction enzyme digest and derives thereof the fraction of accessible DNA. This straightforward principle is technically challenged as preparation and sequencing of the libraries leads to biased scoring of DNA fragments. Our protocol includes two orthogonal approaches to correct for this bias, the "corrected cut-uncut" and the "cut-all cut" method, so that accurate measurements of absolute accessibility or occupancy at restriction sites throughout a genome are possible. The protocol is presented for the example of S. cerevisiae chromatin but may be adapted for any other species.

Diffusion-weighted Breast MRI at 3 Tesla: Improved Lesion Visibility and Image Quality with a Combination of Water-excitation and Spectral Fat Saturation.

RATIONALE AND OBJECTIVES: In breast MRI with diffusion-weighted imaging (DWI), fat suppression is essential for eliminating the dominant lipid signal. This investigation evaluates a combined water-excitation-spectral-fatsat method (WEXfs) versus standard spectral attenuated inversion recovery (SPAIR) in high-resolution 3-Tesla breast MRI. MATERIALS AND METHODS: Multiparametric breast MRI with 2 echo-planar DWI sequences was performed in 83 patients (50.1 ± 12.6 years) employing either WEXfs or SPAIR for fat signal suppression. Three radiologists assessed overall DWI quality and delineability of 88 focal lesions (28 malignant, 60 benign) on images with b values of 800 and 1600 s/mm2, as well as apparent diffusion coefficient (ADC) maps. For each fat suppression method and b value, the longest lesion diameter was determined in addition to measuring the signal intensity in DWI and ADC value in standardized regions of interest. RESULTS: Regardless of b values, image quality (all p < 0.001) and lesion delineability (all p ≤ 0.003) with WEXfs-DWI were deemed superior compared to SPAIR-DWI in benign and malignant lesions. Irrespective of lesion characterization, WEXfs-DWI provided superior signal-to-noise, contrast-to-noise and signal-intensity ratios with 1600 s/mm2 (all p ≤ 0.05). The lesion size difference between contrast-enhanced T1 subtraction images and DWI was smaller for WEXfs compared to SPAIR fat suppression (all p ≤ 0.007). The mean ADC value in malignant lesions was lower for WEXfs-DWI (p < 0.001), while no significant ADC difference was ascertained between both techniques in benign lesions (p = 0.947). CONCLUSION: WEXfs-DWI provides better subjective and objective image quality than standard SPAIR-DWI, resulting in a more accurate estimation of benign and malignant lesion size.

Dual-Energy CT Angiography in Peripheral Arterial Occlusive Disease: Diagnostic Accuracy of Different Image Reconstruction Approaches.

OBJECTIVES: To evaluate the diagnostic accuracy of five DE-CTA image reconstruction approaches for detection of lower extremity arterial stenosis using digital subtraction angiography as reference standard. METHODS: One hundred and eleven patients (63 males; mean age, 75.0 ± 9.7 years) who underwent clinically indicated lower extremity DE-CTA were included in this IRB-approved, HIPAA-compliant retrospective study. Routine multiplanar reconstructions (MPR), curved MPR (cMPR), DE-bone-and-calcified-plaque-subtraction (DE-CS), maximum-intensity projections (MIP), and DE-CS MPR were visually assessed for stenoses > 50%. Automatic objective stenosis grading was implemented on cMPRs. The effect of vessel calcification and luminal contrast on diagnostic performance was evaluated. RESULTS: Sensitivity for stenosis detection was high (96.4%-98.6%) with no significant differences among reconstruction approaches. Specificity (74.9%-92.2%) and accuracy (86.9%-94.5%) varied significantly. Pronounced vessel wall calcification and inferior intraluminal contrast attenuation had no significant effect on sensitivity (calcification: p = 0.167 for MPR; 0.567 DE-CS MPR; 0.057 DE-CS MIP; 0.272 cMPR; 0.185 automatic grading; contrast attenuation: p = 1.000 for all reconstructions), but lead to reduced specificity in visual assessment (calcification: p = 0.002 for MPR; <0.001 DE-CS MPR, DE-CS MIP, and cMPR; contrast attenuation: p = 0.844 for MPR; 0.001 DE-CS MPR and DE-CS MIP; 0.420 cMPR). Routine MPR showed highest overall diagnostic performance. CONCLUSION: Regardless of image reconstruction approach, vessel calcification and intraluminal contrast attenuation, lower extremity DE-CTA possesses high sensitivity for detection of significant stenoses. Specificity and accuracy vary between reconstruction approaches, indicating the need for additional verification of potential stenotic lesions by use of MPR to reduce the number of unnecessary invasive DSAs due to false-positive CTA findings.

Effective dynamics of nucleosome configurations at the yeast PHO5 promoter.

Chromatin dynamics are mediated by remodeling enzymes and play crucial roles in gene regulation, as established in a paradigmatic model, the Saccharomyces cerevisiae PHO5 promoter. However, effective nucleosome dynamics, that is, trajectories of promoter nucleosome configurations, remain elusive. Here, we infer such dynamics from the integration of published single-molecule data capturing multi-nucleosome configurations for repressed to fully active PHO5 promoter states with other existing histone turnover and new chromatin accessibility data. We devised and systematically investigated a new class of 'regulated on-off-slide' models simulating global and local nucleosome (dis)assembly and sliding. Only seven of 68,145 models agreed well with all data. All seven models involve sliding and the known central role of the N-2 nucleosome, but regulate promoter state transitions by modulating just one assembly rather than disassembly process. This is consistent with but challenges common interpretations of previous observations at the PHO5 promoter and suggests chromatin opening by binding competition.

Ruler elements in chromatin remodelers set nucleosome array spacing and phasing.

Arrays of regularly spaced nucleosomes dominate chromatin and are often phased by alignment to reference sites like active promoters. How the distances between nucleosomes (spacing), and between phasing sites and nucleosomes are determined remains unclear, and specifically, how ATP-dependent chromatin remodelers impact these features. Here, we used genome-wide reconstitution to probe how Saccharomyces cerevisiae ATP-dependent remodelers generate phased arrays of regularly spaced nucleosomes. We find that remodelers bear a functional element named the 'ruler' that determines spacing and phasing in a remodeler-specific way. We use structure-based mutagenesis to identify and tune the ruler element residing in the Nhp10 and Arp8 modules of the INO80 remodeler complex. Generally, we propose that a remodeler ruler regulates nucleosome sliding direction bias in response to (epi)genetic information. This finally conceptualizes how remodeler-mediated nucleosome dynamics determine stable steady-state nucleosome positioning relative to other nucleosomes, DNA bound factors, DNA ends and DNA sequence elements.

Sex- and age-specific reference curves for serum markers of bone turnover in healthy children from 2 months to 18 years.

INTRODUCTION: This study aimed to establish sex- and age-specific reference curves enabling the calculation of z-scores and to examine correlations between bone markers and anthropometric data. METHODS: Morning blood samples were obtained from 572 healthy children and adolescents (300 boys) aged 2 months to 18 yr. Height, weight, and pubertal stage were recorded. Serum osteocalcin (OC), bone-specific alkaline phosphatase (BALP), type-1 collagen degradation markers [carboxyterminal telopeptide region of type I collagen (ICTP), carboxyterminal telopeptide alpha1 chain of type I collagen (CTX)], and tartrate-resistant acid phosphatase (TRAP5b) were measured. Cross-sectional centile charts were created for the 3rd, 50th, and 97th centiles. RESULTS: Apart from TRAP5b, all bone markers were nonnormally distributed, requiring logarithmic (BALP, OC, ICTP) or square root (CTX) transformation. Back-transformed centile curves for age and sex are presented for practical use. All bone markers varied with age and pubertal stage (P < 0.001). Significant correlations were found between sd score (SDS) for bone formation markers BALP and OC (r = 0.13; P = 0.004), SDS for collagen degradation markers ICTP and CTX (r = 0.14; P = 0.002), and SDS for the phosphatases (r = 0.34, P < 0.001). Height and weight SDS correlated weakly with some bone marker SDS, particularly with lnBALP SDS (r = 0.20 and 0.24, respectively; both P < 0.001). CONCLUSION: This study provides reference curves for OC, BALP, CTX, ICTP, and TRAP5b in healthy children. Taller and heavier individuals for age had greater bone marker concentrations, likely reflecting greater growth velocity. SDS for markers of bone formation, collagen degradation, and phosphatases were each independently correlated, suggesting they derive from the same biological processes. The possibility of calculating SDS will facilitate monitoring of antiresorptive therapy or disease progression in children with metabolic bone disease.

Reaching for better image quality and lower radiation dose in head and neck CT: advanced modeled and sinogram-affirmed iterative reconstruction in combination with tube voltage adaptation.

OBJECTIVES: The aim of this study was to evaluate image quality and radiation dose in low-dose head and neck CT comparing two different commercially available iterative reconstruction algorithms: sinogram-affirmed iterative reconstruction (SAFIRE) and advanced modeled iterative reconstruction (ADMIRE) with fixed and automated tube voltage adaptation (TVA). METHODS: CT examinations of 103 patients were analysed. 58 patients were examined on a single-source CT at fixed tube voltage of 120 kV and reconstructed with filtered back projection (FBP) and SAFIRE (Strength Level 3). 45 patients were examined in a single-source mode on a dual-source CT with automated TVA and reconstructed with FBP and ADMIRE (Strength Levels 2 and 3). Image noise was calculated in seven anatomical volumes of interest. Subjective evaluation of the CT images was performed using a four-grade scale. RESULTS: Mean CT numbers of FBP and the corresponding iterative reconstruction did not differ significantly (p = 0.74-0.99). Image noise was lower with both iterative reconstruction techniques than with FBP (SAFIRE 3: -22.3%; ADMIRE 2: -14.9%; ADMIRE 3: -24.2%; all p < 0.05); hence, the signal-to-noise ratio and the contrast-to-noise values were higher. Subjective image quality revealed a more favourable result for the iterative reconstruction. ADMIRE 3 in combination with automated TVA showed 14.4% (p < 0.05) less image noise with a 7.5% lower radiation dose than SAFIRE 3 with fixed tube voltage. CONCLUSIONS: Higher image quality at lower radiation dose can be achieved using ADMIRE in combination with automated TVA.

Low temperature growth of cobalt on Cr2O3(0 0 0 1).

The thickness and temperature dependence of in situ grown cobalt thin films on Cr2O3(0 0 0 1) single crystalline substrate has been studied by low energy electron microscopy (LEEM). The LEEM images indicate that growth of thin Co films (⩽5 monolayers) on chromia at 100 K tends to be continuous and flat with suppressed island growth compared to films grown on chromia at room temperature and above (to ~440 K). Low energy electron diffraction indicates that disorder builds and crystallinity of the cobalt thin film decreases with increased film thickness. Compared with cobalt thin films on Al2O3(0 0 0 1) single crystalline substrate, cobalt thin films on Cr2O3(0 0 0 1) show larger magnetic contrast in magnetic force microscopy indicating enhancement of perpendicular anisotropy induced by Cr2O3.

Role of plerixafor in autologous stem cell mobilization with vinorelbine chemotherapy and granulocyte-colony stimulating factor in patients with myeloma: a phase II study (PAV-trial).

Current practice in Switzerland for the mobilization of autologous stem cells in patients with myeloma is combining vinorelbine chemotherapy and granulocyte-colony stimulating factor (G-CSF) cytokine stimulation. We prospectively investigated adding intravenous plerixafor to the vinorelbine/G-CSF combination (VGP), and compared it with vinorelbine/plerixafor (VP) and G-CSF/plerixafor (GP) combinations. In a final cohort (VP-late), plerixafor was given on the first day of CD34 + cells increasing to > 15,000/mL peripheral blood. Four consecutive cohorts of 10 patients with myeloma were studied. We observed that intravenously administered plerixafor can be safely combined with vinorelbine/G-CSF. VGP was superior in mobilizing peripheral stem and progenitor cells compared to the three double combinations (VP, GP and VP-late), and GP mobilized better than VP. Our data indicate that the triple combination of VGP is an efficient strategy to collect autologous CD34 + cells, with G-CSF contributing predominantly in this concept. Plerixafor can be safely added to G-CSF and/or vinorelbine chemotherapy.

Modeling hepatic osteodystrophy in Abcb4 deficient mice.

Hepatic osteodystrophy (HOD) denotes the alterations in bone morphology and metabolism frequently observed in patients with chronic liver diseases, in particular in case of cholestatic conditions. The molecular mechanisms underlying HOD are only partially understood. In the present study, we characterized the bone phenotypes of the ATP-binding cassette transporter B4 knockout mouse (Abcb4(-/-)), a well-established mouse model of chronic cholestatic liver disease, with the aim of identifying and characterizing a mouse model for HOD. Furthermore, we investigated the influence of vitamin D on bone quality in this model. The bone morphology analyses revealed reduced bone mineral contents as well as changes in trabecular bone architecture and decreased cortical bone densities in Abcb4(-/-) mice with severe liver fibrosis. We observed dysregulation of genes involved in bone remodeling (osteoprotegerin, osteocalcin, osteopontin) and vitamin D metabolism (7-dehydrocholesterol reductase, Gc-globulin, Cyp2r1, Cyp27a1) as well as alterations in calcium and vitamin D homeostasis. In addition, serum RANKL and TGF-ß levels were increased in Abcb4(-/-) mice. Vitamin D dietary intervention did not restore the bone phenotypes of Abcb4(-/-) animals. We conclude that the Abcb4(-/-) mouse provides an experimental framework and a preclinical model to gain further insights into the molecular pathobiology of HOD and to study the systemic effects of therapeutic interventions.

Frequency and pattern of medical emergency team activation among medical cardiology patient care units.

Medical emergency teams are developing across the United States. The organization and implementation for a rapid response team to failing medical-surgical patients has been shown to reduce in-house cardiac arrest rates. Further investigation into the frequency and pattern for rapid response team calls has been shown to have a diurnal pattern and clustered around times associated with routine care activities. The medical emergency calls in the descriptive analysis reveal that calls to the medical cardiology units constitute--% of the total calls. The calls are found to be called with--frequency during the hours of 7 AM and 7 PM. The frequency of calls is shown to be clustered around the times of. The small descriptive analysis here suggests that further investigation in the patterns and monitoring of patient for early recognition to call for help is still needed.

Redundancy of chromatin remodeling pathways for the induction of the yeast PHO5 promoter in vivo.

Induction of the yeast PHO5 and PHO8 genes leads to a prominent chromatin transition at their promoter regions as a prerequisite for transcription activation. Although induction of PHO8 is strictly dependent on Snf2 and Gcn5, there is no chromatin remodeler identified so far that would be essential for the opening of PHO5 promoter chromatin. Nonetheless, the nonessential but significant involvement of cofactors can be identified if the chromatin opening kinetics are delayed in the respective mutants. Using this approach, we have tested individually all 15 viable Snf2 type ATPase deletion mutants for their effect on PHO5 promoter induction and opening. Only the absence of Snf2 and Ino80 showed a strong delay in chromatin remodeling kinetics. The snf2 ino80 double mutation had a synthetic kinetic effect but eventually still allowed strong PHO5 induction. The same was true for the snf2 gcn5 and ino80 gcn5 double mutants. This strongly suggests a complex network of redundant and mutually independent parallel pathways that lead to the remodeling of the PHO5 promoter. Further, chromatin remodeling kinetics at a transcriptionally inactive TATA box-mutated PHO5 promoter were affected neither under wild type conditions nor in the absence of Snf2 or Gcn5. This demonstrates the complete independence of promoter chromatin opening from downstream PHO5 transcription processes. Finally, the histone variant Htz1 has no prominent role for the kinetics of PHO5 promoter chromatin remodeling.

Failure to rescue: a literature review.

Rapid response teams have been advocated as an intervention to reduce failure to rescue events. Such teams can improve nurse autonomy and control to rescue patients deteriorating in a medical surgical setting. The purpose of this review is to enhance nurse executives' understanding of failure to rescue as a nurse sensitive outcome, tested interventions, and implications for future research. The emergence of failure to rescue as an outcome measure will be initially discussed. Research regarding the relationship between failure to rescue and registered nurse staffing as well as research examining the potential to reduce failure-to-rescue events will be explored.