If we continue to focus on student growth and improvement as learners, keep track of that progress, and watch its impact on standard test results, will we be able to know if what we are doing is helping students develop as learners and thinkers.

Lipid II is an essential precursor of the bacterial cell wall biosynthesis and thereby an important target for various antibiotics. Several lanthionine-containing peptide antibiotics target lipid II with lanthionine-stabilized lipid II-binding motifs. Here, we used the biosynthesis system of the lantibiotic nisin to synthesize a two lipid II binding motifs-containing lantibiotic, termed TL19, which contains the N-terminal lipid II binding motif of nisin and the distinct C-terminal lipid II binding motif of one peptide of the two-component haloduracin (i.e. HalA1). Further characterization demonstrated that (i) TL19 exerts 64-fold stronger antimicrobial activity against E. faecium than nisin (1-22), which has only one lipid II binding site, and (ii) both the N- and C-terminal domains are essential for the potent antimicrobial activity of TL19, as evidenced by mutagenesis of each single and double domains. These results show the feasibility of a new approach to synthesize potent lantibiotics with two different lipid II binding motifs to treat specific antibiotic-resistant pathogens.

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.

Tedizolid has demonstrated its efficacy and safety in clinical trials, however, data concerning its tolerability in long-term treatments is scarce. The aim of the study was to assess the indications and to describe the long-term safety profile of tedizolid.

A multicentric, retrospective study of patients who received tedizolid for more than 6-days was conducted. Adverse events (AEs) were identified from patients' medical records and laboratory data. The World Health Organization causality categories were used to discern AEs probably associated with tedizolid.

Eighty-one patients, treated with tedizolid 200mg once-daily for a median (IQR) duration of 28 (14-59) days, were included, 36 (44.4%) had previously received linezolid. Most common reasons for selecting tedizolid were to avoid linezolid potential toxicities or interactions (53.1%) or due to previous linezolid-related toxicities (27.2%). Most common indications were off-label, including prosthetic joint infections, osteomyelitis and respiratory infections (77.8%). Overall, 9/81 patients (11.1%) experienced a probably associated AE. Two patients (2.5%) developed gastrointestinal disorders, 1 (1.2%) anemia and 6 thrombocytopenia (7.4%) after a median (IQR) duration of treatment of 26.5 (17-58.5) days. Four (5%) patients discontinued tedizolid due to AEs. Among 23 patients with chronic renal failure (CRF) the rate of mielotoxicity was 17.4% and only 8.7% had to stop tedizolid and 20 out of 22 with previous linezolid-associated toxicity had no AE.

Long-term tedizolid treatments had good tolerance with rates of gastrointestinal AE and hematological toxicity lower than those reported with linezolid, particularly in patients with CRF and in those with a previous history of linezolid-associated toxicity.

Introduction: This study was performed to evaluate the impacts of vanA-positivity of Enterococcus faecium (EFM) exhibiting diverse susceptibility phenotypes to glycopeptides on clinical outcomes in patients with a bloodstream infection (BSI) through a prospective, multicenter, observational study.

Methods: A total of 509 patients with an EFM BSI from eight sentinel hospitals in South Korea during a two-year period were enrolled in this study. Risk factors of the hosts and causative EFM isolates were assessed to determine associations with the 30-day mortality of EFM BSI patients via multivariable logistic regression analyses.

Results: The vanA gene was detected in 35.2% (179/509) of EFM isolates; 131 EFM isolates exhibited typical VanA phenotypes (group vanA-VanA), while the remaining 48 EFM isolates exhibited atypical phenotypes (group vanA-Atypical), including VanD (n = 43) and vancomycin-variable phenotypes (n = 5). A multivariable logistic regression indicated that vanA-positivity of causative pathogens was independently associated with the increased 30-day mortality rate in the patients with an EFM BSI; however, there was no significant difference in the survival rates between the patients of the vanA-VanA and vanA-Atypical groups (log-rank test, P = 0.904).

Conclusions: A high 30-day mortality rate was observed in patients with vanA-positive EFM BSIs, and vanA-positivity of causative EFM was an independent risk factor for early mortality irrespective of the susceptibility phenotypes to glycopeptides; thus, intensified antimicrobial stewardship is needed to improve clinical outcome of patients with vanA-positive EFM BSI.

Manogepix (APX001A) is the active moiety of the novel drug candidate fosmanogepix (APX001). We previously reported the broad-spectrum activity of manogepix but also observed a correlation between increased manogepix and fluconazole MICs. Here we extended this study and included isolates with acquired fluconazole resistance.

Isolates (n=835) were identified using CHROMagar, MALDI-TOF and, when needed, ITS-sequencing. EUCAST E.Def 7.3.1 susceptibility testing included manogepix, amphotericin B, anidulafungin, micafungin, fluconazole and voriconazole. Manogepix wildtype-upper-limit (WT-UL) values were established following EUCAST-principles for ECOFF setting allowing wildtype/non-wildtype classification. Drug-specific MIC correlations were investigated using Pearson's correlation.

Manogepix modal MICs were low (range 0.004-0.06 mg/L against 16/20 included species). Exceptions were C. krusei and C. inconspicua, and to a lesser extent C. kefyr and Pichia kluyveri. The activity was independent of Fks echinocandin hot-spot alterations (n=17). Adopting the WT-UL established for C. albicans, C. dubliniensis, C. glabrata, C. parapsilosis and C. tropicalis, 14/724 (1.9%) isolates were non-wildtype for manogepix. Twelve of these (85.7%) were also non-wildtype for fluconazole. A statistically significant correlation was observed between manogepix and fluconazole MICs for C. albicans, C. dubliniensis, C. glabrata, C. parapsilosis and C. tropicalis (Pearson r=0.401-0.575), but not between manogepix and micafungin or amphotericin B MICs for any species except C. tropicalis (r=0.519 for manogepix versus micafungin).

Broad-spectrum activity was confirmed for manogepix against contemporary yeast. However, a 1-4 two-fold-dilution increase in manogepix MICs is observed in a subset of isolates with acquired fluconazole resistance. Further studies on the potential underlying mechanism and implication for optimal dosing are warranted.

Oil was headed for the longest run of daily gains in more than nine months on signs the worst of the supply glut may be over as production cuts start to take effect.

BACKGROUND AND OBJECTIVES:

Runaway youth and homeless youth are at risk for adverse mental health outcomes. These 2 populations are frequently pooled together in both research and interventions yet may have unique health needs. We sought to assess differences in mental health outcomes among these populations.

UEFA.com studies the statistics to find out which players are predicted for big Matchday 7 totals.

As the knockout stage kicks off this week, The Scout has put together a squad drawing on players from nine teams.

UEFA.com delves into the numbers and finds clean sheets were at a premium in the first legs.

Led by Serge Gnabry's first-leg double, Bayern München have one foot in the quarter-finals as Chelsea come to Germany.

The start of the knockout rounds provided a reminder there is still plenty of value to be found at the defensive end of the field.

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

Erling Braut Haaland and Robert Lewandowski continued to hit the net, although injury means the latter is likely to miss the second leg.

Prospective transfer students can explore the Lehigh Valley Campus virtually during the Transfer Thursday events

Timing, preparation and control are essential to getting paid fairly. This infographic by Adzuna is guide on how you can navigate your way to a salary increase.

Automated EFT payments enabled by technology from fintech company Ozow may be a secure alternative method to transact than card payments.

The Fitbit Inspire HR, which earned an excellent rating in PCMag's review and our Editors' Choice award, is already a good deal at $99.95, but you can grab one right now for just $69.95.

A winner of the European Women's Under-17 Championship with Poland in 2013, Ewa Pajor urges the players taking part in this year's final tournament in Bulgaria to seize the moment.

Interest in Section 12J has grown each year, with the current financial year being no different, says Jonty Sacks, a partner at Jaltech.

Many investors do not fully understand the tax incentive and structure of a Section 12J venture capital investment, according to a managing director involved in this sector.

By the end of February, most taxpayers are looking for every opportunity to reduce their tax liabilities.

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

An unusual program in Cincinnati provides academic coaches to help high school players meet eligibility requirements to stay in the game.

The Czech Republic meet Serbia, France play Croatia, Romania take on Georgia and Hungary are up against Poland in September's UEFA Futsal EURO 2018 play-offs.

Serbia and Hungary secured narrow wins in the first legs of their play-offs while debut-chasing France and Georgia both found themselves pegged back. The second legs are on 26 September.

France beat Croatia to earn a final tournament debut, as they joined Serbia, Romania and Poland in qualifying for UEFA Futsal EURO 2018 via the play-offs.

Ricardinho has been named the first-ever official UEFA Futsal EURO Player of the Tournament after captaining Portugal to the title and finishing seven-goal top scorer.

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.

Google Translate is not the only app that can help you converse with someone speaking a different language. Here's how to translate real-time conversations with the Google Assistant.

"It's the same as an iPod except it sounds like God," Young said here at CES.

Yes, there are still portable music players in 2019, and we don't just mean the iPod touch. The question is whether you need one, and if so, which is the best MP3 player to buy?

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.

Don't take your safety for granted. These apps, services, and gadgets will help you communicate your location to trusted contacts and get help should trouble arise.

Free apps are cool, but a few bucks can get you so much more. If you are looking to buy in the Google Play store, here are the best paid Android apps to put on your phone.

The start of November has brought a ton of great deals, with some matching last year's Black Friday prices. The 512GB Samsung EVO Select microSDXC card is only $78.

At Amazon right now, you can save up to 47 percent on a Samsung Q60 series QLED 4K Ultra HD smart TV with HDR support and Alexa and Google Assistant compatibility.

In our review, we called this TV 'among the brightest we've tested.' It comes in five different sizes, all of which are currently between 18 and 39 percent off at Amazon.

Don't watch the Super Bowl on your old, grainy TV. Head over to the PCMag Shop to score a big discount on the 65-Inch LG OLED B9 Series 4K smart OLED TV.

Research firm IHS Markit expects the display panel factories in Wuhan, China, to struggle to resume full production when the Chinese New Year holiday ends on Feb. 2. As a result, supplies for panels for TVs and PCs are expected to be tight in the ensuing months.

The Government Accountability Office finds that parents often have a hard time initiating complaints about special education services, but that these barriers don't affect all parents in the same way.

The need for materials, training, guidance from district administrators, and access to staff with expertise in serving students with disabilities is especially acute in schools that serve primarily black and Latino students, a new survey finds.

Check out these quick tips to boost your wireless signal from your router, extend and optimize your Wi-Fi coverage, and speed up your surfing.

The popular Netgear Nighthawk R6700 wireless router is just $68 right now. Plus, you can save on a 32-inch Dell monitor and Apple AirPods with the wireless charging case.

Can you survive the holidays without Wi-Fi? No you cannot. Here's how to prepare your network for guests and safely share your password with them.

I was just sitting down to write this week's column when the Red Arrows flew right over my head.

When Celtic arrived home after their defeat by Feyenoord on May 6, 1970, everyone at Parkhead was understandably deflated, while the fans were in mourning for the lost chance of glory.

Perhaps there were some who had hoped for a dossier of lurid juiciness.

People travelling to the UK will be quarantined for two weeks upon arrival as part of measures to prevent a second peak of the coronavirus pandemic.