Linezolid has strong antimicrobial activity against the multidrug-resistant (MDR) strains of Mycobacterium tuberculosis. Little is known about the distribution of linezolid in tuberculosis (TB) lesions in patients with MDR-TB. The aim of this study is to evaluate the distribution of linezolid in TB lesions in patients with spinal MDR-TB. Nine patients with spinal MDR-TB were enrolled prospectively from August 2019 to February 2020. The patients received a linezolid-containing anti-TB treatment regimen and needed surgery for the removal of TB lesions. During the operation, nine blood samples, eight diseased bone tissue samples, seven pus samples and four granulation tissue samples were collected simultaneously and 2 h after the oral administration of 600 mg of linezolid. Linezolid concentrations in plasma, diseased bone tissue, pus, and granulation tissue samples were subjected to high-performance liquid chromatography–tandem mass spectrometry. At sample collection, the mean concentrations of linezolid in plasma, diseased bone tissue, pus, and granulation tissue samples of the nine patients were 11.14 ± 5.82, 5.94 ± 4.27, 11.09 ± 4.58, 14.08 ± 10.61 mg/L, respectively. The mean ratios of linezolid concentration in diseased bone/plasma, pus/plasma, and granulation/plasma were 53.84%, 91.69%, and 103.57%, respectively. The mean ratios of linezolid concentration in pus/plasma and granulation/plasma were higher than those in diseased bone/plasma, and the difference was statistically significant (t =-2.810, p = 0.015; t =-4.901, p = 0.001). In conclusion, linezolid had different concentration distributions in different types of TB infected tissues in patients with spinal MDR-TB.

Treatment of exacerbations of chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) is highly challenging due to hypermutability, biofilm formation and an increased risk of resistance emergence. We evaluated the impact of ciprofloxacin and meropenem as monotherapy and in combination in the dynamic in vitro CDC biofilm reactor (CBR). Two hypermutable P. aeruginosa strains, PAOmutS (MIC_{ciprofloxacin} 0.25 mg/L, MIC_meropenem 2 mg/L) and CW44 (MIC_{ciprofloxacin} 0.5 mg/L, MIC_meropenem 4 mg/L), were investigated for 120h. Concentration-time profiles achievable in epithelial lining fluid (ELF) following FDA-approved doses were simulated in the CBR. Treatments were ciprofloxacin 0.4g every 8h as 1h-infusions (80% ELF penetration), meropenem 6 g/day as continuous infusion (CI; 30% and 60% ELF penetration) and their combinations. Counts of total and less-susceptible planktonic and biofilm bacteria and MICs were determined. Antibiotic concentrations were quantified by UHPLC-PDA. For both strains, all monotherapies failed with substantial regrowth and resistance of planktonic (≥8log₁₀ CFU/mL) and biofilm (>8log₁₀ CFU/cm²) bacteria at 120h (MIC_{ciprofloxacin} up to 8 mg/L, MIC_meropenem up to 64 mg/L). Both combination treatments demonstrated synergistic bacterial killing of planktonic and biofilm bacteria of both strains from ~48h onwards and suppressed regrowth to ≤4log₁₀ CFU/mL and ≤6log₁₀ CFU/cm² at 120h. Overall, both combination treatments suppressed amplification of resistance of planktonic bacteria for both strains, and biofilm bacteria for CW44. The combination with meropenem at 60% ELF penetration also suppressed amplification of resistance of biofilm bacteria for PAOmutS. Thus, combination treatment demonstrated synergistic bacterial killing and resistance suppression against difficult-to-treat hypermutable P. aeruginosa strains.

We thank Kim and colleagues for their interest in our study....

Drug repositioning is the only feasible option to address the COVID-19 global challenge immediately. We screened a panel of 48 FDA-approved drugs against SARS-CoV-2 which were pre-selected by an assay of SARS-CoV and identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low micromolar IC50s and in particular, two FDA-approved drugs - niclosamide and ciclesonide – were notable in some respects.

Peroxidases are a group of heterogeneous family of enzyme that plays diverse biological functions. Ascorbate peroxidase is a redox enzyme that is reduced by trypanothione, which plays a central role in the redox defence system of Leishmania. In view of developing new and novel therapeutics, we have performed in silico studies in order to search for ligand library and identification of new drug candidates and its physiological role against promastigotes and intracellular amastigotes of Leishmania donovani. Our results demonstrated that the selected inhibitor ZINC96021026 has significant anti-leishmanial effect and effectively killed both free and intracellular forms of the parasite. ZINC96021026 was found to be identical to ML-240, a selective inhibitor of Valosin-containing protein (VCP) or p97, a member of AAA-ATPase protein family which was derived from the scaffold of DBeQ, targeting the D2-ATPase domain of the enzyme. ZINC96021026 (ML-240) thus have broad range of cellular functions, thought to be derived from its ability to unfold proteins or disassemble protein complexes besides inhibiting the ascorbate peroxidase activity. ML-240 may inhibits the parasite's ascorbate peroxidase leading to extensive apoptosis and inducing generation of reactive oxygen species. Taken together, our results demonstrated that ML-240 could be an attractive therapeutic option for treatment against leishmaniasis.

The off-label use of third generation cephalosporin (3GC) during in ovo vaccination or vaccination of newly hatched chicks, was a common practice worldwide. CMY-2-producing Escherichia coli have been disseminated among broiler production. The objectives of this study were to determine the epidemiological linkage of bla_CMY-2-positive plasmids among broilers both within and outside Japan because grandparent stock and parent stock were imported in Japan. We examined the whole genome sequences of 132 3GC-resistant E. coli isolates collected from healthy broilers during 2002-2014. The predominant 3GC-resistance gene was bla_CMY-2, which was detected in the plasmids of 87 (65.9%) isolates. The main plasmid replicon types were IncI1-I (n=21; 24.1%), IncI (n=12; 13.8%), IncB/O/K/Z (n=28; 32.2%), and IncC (n=22; 25.3%). Those plasmids were subjected to gene clustering and network analyses and plasmid multi-locus sequence typing (pMLST). The chromosomal DNA of isolates was subjected to MLST and single nucleotide variant (SNV)-based phylogenetic analysis.

MLST and SNV-based phylogenetic analysis revealed high diversity of E. coli isolates. ST429 harboring bla_CMY-2-positive IncB/O/K/Z was closely related to isolates from broiler in Germany harboring bla_CMY-2-positive IncB/O/K/Z. pST55-IncI and pST12-IncI1-I and pST3-IncC were prevalent in western Japan. pST12-IncI1-I and pST3-IncC were closely related to those detected in E. coli isolates from chicken in American continent, whereas 26 IncB/O/K/Z were related to those in Europe. These data will be useful to reveal the whole picture of transmission of CMY-2-producing bacteria in and out of Japan.

Google's Takeout service was designed to let people download their data, but accidentally sent videos from Google Photos accounts to strangers.

In number 10 in our countdown, I tried to offer a few thoughts to funders as they embraced new agendas and looked to avoid repeating yesterday's missteps.

BACKGROUND:

Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly with a mortality of ~27%. The Congenital Diaphragmatic Hernia Study Group (CDHSG) developed a simple postnatal clinical prediction rule to predict mortality in newborns with CDH. Our aim for this study is to externally validate the CDHSG rule in the European population and to improve its prediction of mortality by adding prenatal variables.

BACKGROUND:

Elevated non–high-density lipoprotein cholesterol (HDL-C) levels are used to identify children at increased cardiovascular risk, but the use of non–HDL-C in childhood to predict atherosclerosis is unclear. We examined whether the National Heart, Lung, and Blood Institute classification of youth non–HDL-C status predicts high common carotid artery intima-media thickness in adulthood.

OBJECTIVES:

Infantile hemangiomas (IHs) are common; some cases require timely referral and treatment to prevent complications. We developed and validated a reliable instrument for timely and adequate referral of patients with IH to experts by nonexpert primary physicians.

Who takes the penalties? Who can't you afford to ignore? And who are the bargain signings that could make all the difference?

A first-leg comeback has put Manchester City in the driving seat as Real Madrid travel to north-west England facing a 2-1 deficit.

Key differentials were once again to the fore in the round of 16 first legs, although Serge Gnabry took the headlines again.

Doron's experience on Logos Hope shows him God's faithfulness and uncovers leadership abilities he is using today in a new role.

Two of Penn State’s most generous supporters and prominent alumni leaders have made a new commitment to support students impacted by the COVID-19 crisis. Helen S. Hintz, 1960, and Edward “Ed” R. Hintz, 1959, have directed $100,000 to the Student Care and Advocacy Emergency Fund.

Rachel Hooker, who will graduate May 9 with a 3.99 GPA in supply chain and information systems, has been selected as the Smeal College of Business’ spring 2020 supply chain and information systems student marshal.

In an effort to help mitigate the disruptive effects of the deadly COVID-19 virus, an interdisciplinary team of Penn State researchers are developing a novel methodology to analyze its spread and the impacts on policy to create better-prepared and more-resilient health care systems.

Penn State Health has appointed Don McKenna as president of Penn State Health Hampden Medical Center.

Penn State University Libraries has developed a curated guide to COVID-19 related resources for researchers, including ongoing research at Penn State.

With speed and ingenuity, more than 100 researchers across Penn State are shifting their research programs to address the COVID-19 crisis, thanks to funding from a seed grant initiative led by the Huck Institutes of the Life Sciences. In total, the initiative awarded $2.25 million to 47 teams of researchers from three campuses, 10 colleges and more than 25 departments.

Penn State Health has enrolled its first COVID-19 patient into an experimental treatment program called convalescent plasma therapy.

To assess public perceptions about COVID-19 and identify populations whose behaviors put them at risk of infection, researchers at Penn State have released an online survey for the general public.

MASC has successfully designed and delivered critical equipment and supplies needed to protect health care workers and patients during the COVID-19 pandemic.

Two alumni and one community partner contribute clinical medicine and research experience during the pandemic

Using their unique skills and experiences, three LaunchBox grant recipients are providing a variety of COVID-19 relief efforts.

Russell B. Toomey
Oct 1, 2018; 142:e20174218-e20174218
ARTICLES

Kristina R. Olson
Mar 1, 2016; 137:e20153223-e20153223
ARTICLES

Ana L. Creo
Dec 1, 2017; 140:e20171486-e20171486
STATE-OF-THE-ART REVIEW ARTICLES

Marco Denina
Apr 21, 2020; 0:peds.2020-1157v1-e20201157
Research Brief

Andrea T. Cruz
Apr 8, 2020; 0:peds.2020-0834v2-e20200834
COMMENTARY

Yuanyuan Dong
Apr 8, 2020; 0:peds.2020-0702v2-e20200702
ARTICLES

Africa can be a challenging place to do business and property investment is not exempt from some, often unique, challenges, says a Nedbank expert.

As shootings break out at high school athletic events, districts must grapple with major questions about their role in keeping venues safe.

Ebonie Slade, a senior majoring in biobehavioral health at Penn State Greater Allegheny, is the recipient of the 2020 Jackson Lethbridge Tolerance Award.

Seven of the 12 places at UEFA Futsal EURO 2018 in Slovenia will be decided when the main round is played between Saturday and Tuesday, with Spain beginning their title defence.

The laws of futsal are similar to those of football but with some important differences: let us talk you through the rolling substitutions, accumulated fouls, double penalties and four-second count.

Doron's experience on Logos Hope shows him God's faithfulness and uncovers leadership abilities he is using today in a new role.

Happy Valley LaunchBox powered by PNC Bank is accepting applications through May 15 for its Idea TestLab that will now be hosted virtually in June. Open to the community, the four-week Idea TestLab program is designed to help teams evaluate the viability of their business ideas by coaching them through a proven method of customer discovery and problem analysis.

As the COVID-19 pandemic continues to spread across the nation, nurses worldwide are coming to the frontlines of health care to help patients every day. Penn State student nurses, Megan Lucas and Lorrie Youngs, are among the ones helping those in need and their experiences have reinforced their passions about becoming a nurse in the first place.

After a successful pilot, a professional development program is looking to expand its lesson-study approach to rural teachers.

The UEFA Futsal Cup elite round runs from Wednesday to Sunday, with holders Inter FS and former champions Kairat Almaty and Barcelona among those chasing four available finals spots.

"It's like a cinderblock," one seven-year-old said of Apple's original MP3 player.

If you love Metal Gear Solid, have some money to burn, and live in Japan, Sony has something special for you.

A new high-res audio player looks like a wooden flask and has a tie-up with Tidal.

Lenovo's IdeaCentre 510A is an unassuming budget desktop in every sense. It'll perform basic tasks without hurting your wallet, but some alternatives do it better at this price point.

While we wait for Apple Arcade to launch for iOS devices, Google is preparing its own app/game subscription service for Android called Play Pass.

Android may be leaving dessert names behind with Android 10, but its OS market share is still a buffet of Pie, Oreos, Nougat, Marshmallows, Lollipops, and even a couple of KitKats.