Necrotizing enterocolitis is associated with high mortality and morbidity in premature infants. Anaerobic antimicrobial therapy has been associated with increased risk of intestinal strictures in a small randomized trial. Optimal antimicrobial therapy for necrotizing enterocolitis is unknown.

Anaerobic antimicrobial therapy was associated with increased risk of stricture formation. Infants with surgical necrotizing enterocolitis treated with anaerobic antimicrobial therapy had lower mortality. For infants with medical necrotizing enterocolitis, there was no added benefit associated with anaerobic antimicrobial therapy. (Read the full article)

Suboptimal brain development and increased risk of cognitive deficits are well documented in very low birth weight children. Supplementation with docosahexaenoic acid and arachidonic acid has been associated with positive cognitive effects.

This follow-up study of a randomized controlled trial of supplementation with docosahexaenoic acid and arachidonic acid to very low birth weight infants is the first report on both cognition and brain macrostructure measured with MRI. No cognitive or neuroanatomical effects were detected at 8 years. (Read the full article)

A measure to renew the Elementary and Secondary Education Act faces steep political hurdles.

The Hasselblad X1D II 50C turns heads with its stunning industrial design and medium format image sensor, but is hampered by an underpowered battery and sluggish response.

David Figlio and Eduwonkette discuss if today's testing and accountability policies accurately depict student performance and the size of the achievement

Antimicrobial peptides and proteins play critical roles in the host defense against invading pathogens. We recently discovered that recombinantly expressed human and mouse serum amyloid A1 (rhSAA1 and rmSAA1) proteins have potent antifungal activities against the major human fungal pathogen Candida albicans. At high concentrations, rhSAA1 disrupts C. albicans membrane integrity and induces rapid fungal cell death. In the current study, we find that rhSAA1 promotes cell aggregation and targets the C. albicans cell wall adhesin Als3. Inactivation of ALS3 in C. albicans leads to a striking decrease in cell aggregation and cell death upon rhSAA1 treatment, suggesting that Als3 plays a critical role in SAA1 sensing. We further demonstrate that deletion of the transcriptional regulators controlling the expression of ALS3, such as AHR1, BCR1, and EFG1 in C. albicans results in similar effects to that of the als3/als3 mutant upon rhSAA1 treatment. Global gene expression profiling indicates that rhSAA1 has a discernible impact on the expression of cell wall- and metabolism-related genes, suggesting that rhSAA1 treatment could lead to a nutrient starvation effect on C. albicans cells.

Background. CLSI and EUCAST susceptibility breakpoints for voriconazole and C. albicans differ by one dilution (≤0.125 and ≤0.06 mg/l, respectively) whereas the epidemiological cutoff values (ECOFF/ECV) with both methodologies are the same (0.03 mg/L). We therefore determined the pharmacokinetic-pharmacodynamic (PK/PD) breakpoints of voriconazole against C. albicans for both methodologies with an in vitro PK/PD model, which was validated using existing animal PK/PD data.

Methods. Four clinical wild-type and non-wild-type C. albicans isolates (voriconazole MICs 0.008-0.125 mg/l) were tested in an in vitro PK/PD model. For validation purposes, mouse PK were simulated and in vitro PD were compared with in vivo outcome. Human PK were simulated and the exposure-effect relationship fAUC_0-24/MIC was described for EUCAST and CLSI24/48h methods. PK/PD breakpoints were determined using the fAUC_0-24/MIC associated with half-maximal activity (EI₅₀) and Monte Carlo simulation analysis.

Results. The in vitro 24h-PD EI₅₀ of voriconazole against C. albicans were 2.5-5 (1.5-17) fAUC/MIC. However, the 72h-PD were higher, 133 (51-347) fAUC/MIC for EUCAST and 94 (35-252) fAUC/MIC for CLSI. The mean (95% confidence interval) probability of target attainment (PTA) was 100(95-100)%, 97(72-100)%, 83(35-99)%, and 49(8-91)% and 100(97-100)%, 99(85-100)%, 91(52-100)% and 68(17-96)% for EUCAST and CLSI MICs 0.03, 0.06, 0.125, and 0.25 mg/L, respectively. Significantly, >95% PTAs were found for EUCAST/CLSI MICs ≤0.03 mg/ll. For MICs 0.06-0.125 mg/l trough levels 1-4 mg/ll would be required.

Conclusion. A PK/PD breakpoint of C. albicans voriconazole at the ECOFF/ECV of 0.03 mg/L was determined for both EUCAST/CLSI methods, indicating the need for breakpoint harmonization for the reference methodologies.

Background

Optimal concentrations of unbound antimicrobials are essential for maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare effects of different albumin states on total and unbound concentrations of ertapenem and ceftriaxone using an ovine model.

Methods

Design

Prospective, three phase intervention observational study.

Subjects

Healthy Merino sheep.

Interventions

Eight sheep were subject to three experimental phases; normoalbuminemia, hypoalbuminemia using plasmapheresis and albumin replacement using a 25% albumin solution. In each phase, ceftriaxone 40 mg/kg and ertapenem 15 mg/kg were given intravenously. Blood samples were collected at pre-defined intervals and analyzed using an ultra-high-performance liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters such as area under the curve (AUC_0-24), plasma clearance (CL) and apparent volume of distribution in the terminal phase (V_d) were estimated and compared between the phases.

Results

The protein and albumin concentrations were significantly different between phases. Hypoalbuminemia resulted in a significantly lower AUC_0-24 and higher CL of total and unbound concentrations of ceftriaxone compared to the other phases. Whereas albumin replacement led to higher AUC_0-24 and lower CL compared to other phases for both drugs. The V_d for total drug concentrations for both drugs were significantly lower with albumin replacement.

Conclusions

For highly protein-bound drugs such as ceftriaxone and ertapenem, both hypoalbuminemia and albumin replacement may affect unbound drug exposure.

BACKGROUND AND OBJECTIVES:

The albuterol dropper bottle used to prepare solutions for continuous nebulization contains the preservative benzalkonium chloride (BAC). BAC, by itself, has been shown to cause bronchospasm. We hypothesized that BAC would decrease the therapeutic efficacy of albuterol in patients with acute asthma exacerbations.

Saskia perseveres through language learning and connects with a young Albanian girl who becomes a follower of Jesus.

Beth E. Michalec, lecturer of corporate communication at Penn State Lehigh Valley, earned a doctorate in rhetoric from Duquesne University. Michalec was selected as a Fulbright specialist in June 2019 by the U.S. Department of State.

Although complications caused by the coronavirus pandemic have temporarily halted the Fulbright Specialist Program, Nichola D. Gutgold looks forward to officially joining the Roster after the U.S. Department of State determines that projects can resume.

Saskia perseveres through language learning and connects with a young Albanian girl who becomes a follower of Jesus.

Anna Squicciarini, associate professor of information sciences and technology, has received a Fulbright Cyber Security Award to conduct research in London in summer 2021.

Saskia perseveres through language learning and connects with a young Albanian girl who becomes a follower of Jesus.

Saskia perseveres through language learning and connects with a young Albanian girl who becomes a follower of Jesus.

What gets tested gets taught, so performance assessments that measure the competencies that matter can lead to instruction that yields those competencies, argues Ben Kornell of Envision Learning Partners.

The Center on Education Policy has two new reports pinpointing trouble spots in implementation of waiver plans under the No Child Left Behind Act.

A look back at prior attempts to renew the federal law makes one thing clear: We're drifting further and further away from the idea of a strong federal role in K-12 accountability.

The U.S. Department of Education continues to quietly approve and negotiate over states' teacher-evaluation systems as part of its No Child Left Behind Act waiver process.

House leaders may hold off on a final vote on a Republican-backed bill to rewrite the No Child Left Behind law, amid pushback from powerful GOP lobbying groups

Saskia perseveres through language learning and connects with a young Albanian girl who becomes a follower of Jesus.

Saskia perseveres through language learning and connects with a young Albanian girl who becomes a follower of Jesus.

WILMINGTON (January 28, 2019) – Delaware State Housing Authority (DSHA) and Federal Home Loan Bank of Pittsburgh (FHLBank Pittsburgh) announced today $1.2 million in Home4Good funding awarded to programs across the state working to reduce homelessness. DSHA provided $500,000 toward the effort, and FHLBank Pittsburgh provided $700,000. The funding will be used to address four key […]

DOVER – Delaware State Housing Authority (DSHA) and Federal Home Loan Bank of Pittsburgh (FHLBank Pittsburgh) announced today $1.2 million in Home4Good funding awarded to programs across the state working to reduce homelessness. DSHA provided $500,000 toward the effort, and FHLBank Pittsburgh provided $700,000. The funding will be used to address four key areas: homelessness […]

One of the easiest ways to dive into smart home technology is with smart light bulbs. Here's what you need to know to get started, along with reviews of the top Bluetooth and Wi-Fi LEDs we've tested.

Defender Sergio Ramos reckons Bilbao will be party central at UEFA EURO 2020.

SYNOPSIS:This article aims at answering the most pressing doubts that applicants usually have prior to an interview for an internship. The article highlights certain important questions that the applicants should always be prepared for and further el

 Review of Securities Lending and Borrowing (SLB) Framework

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