In response to growing demand from trainees, many pediatric residency programs offer global health (GH) experiences for their residents. There is diversity in what is offered at programs across the country.

This is the most comprehensive assessment of US pediatric residency training opportunities in GH. These opportunities are prevalent and increasingly formalized as tracks. However there remain gaps in universal pretravel preparation and coordination across GH partnerships nationally. (Read the full article)

Preschool language delay predicts poorer academic performance, employment opportunities, and social relationships. Language for Learning, a systematic, population-based intervention for 4-year-olds with low language, is feasible, acceptable and has short-term benefits, but long-term benefits are unknown.

Population ascertainment at age 4 followed by a yearlong, one-on-one home program benefited phonological skills (an important literacy determinant) at age 6, but not the primary language outcomes. To be cost-effective, future follow-up would need to demonstrate lasting academic benefits. (Read the full article)

Although nonphysician reentry transitions have been characterized in the literature, little is known about the reentry of residents after either short-term (1-month elective) or long-term (12-month training) global health experiences abroad.

Reverse culture shock may be a useful conceptual framework for understanding the range of emotions felt by pediatric residents when they reenter residency after global health experiences, particularly if these experiences were long term. (Read the full article)

Endotracheal intubation is a mandatory skill for neonatal trainees. It is a difficult skill to acquire, and success rates of junior doctors are low and falling.

Videolaryngoscopy allows the supervisor to share the intubator’s view of the airway and provide more informed guidance. Teaching intubation using a videolaryngoscope with the screen visible to the instructor results in significantly higher success rates for inexperienced doctors. (Read the full article)

Source: www.mirror.co.uk - Saturday, May 09, 2020
At least the garish crystal cheetah clutches aren't as saucy as the hamper sent to Kim Kardashian from cheeky Khloé as the family shower each other with odd gifts

The National Math and Science Initiative's new tool aims to help the field look for patterns in STEM data, so educators and policy folks can fill in holes.

Minister of Finance Tito Mboweni has announced a number of "exceptional tax measures as part of the fiscal package outlined by President Cyril Ramaphosa to fight the coronavirus pandemic.

Boston Public Schools is turning innovative ideas into action through a new professional development network.

The planning team of the district's Innovation Incubator applied the same hacking mindset taught in the professional-development program to improve the program itself.

Valve's tweet describes the upcoming title Half-Life: Alyx as the company's 'flagship VR game.' So you'll probably need a virtual headset to play it. The company will reveal more details on Thursday.

Target is offering a buy two, get one free deal on hundreds of Star Wars items, including toys, clothing, bedding, and more.

The new Arcade1Up NBA Jam cabinet is the first to feature Wi-Fi internet connectivity, enabling multiplayer with other cabinet owners.

Barcelona made the UEFA Women's Champions League final and could reach the men's decider too, setting up an unprecedented feat.

Lyon will play their eighth final in a decade while Barcelona are there for the first time when they meet in Budapest on Saturday.

Equipping teachers to help transgender students feel safe and included requires special training, advocates say.

A new brief from the Brookings Institution poses the question: Is overrepresentation of women in the teaching force negatively affecting boys' achievement?

Advocates for increased federal funding for special education cheered Thursday when the issue was raised on the Democratic presidential debate stage in Los Angeles.

The growing popularity of voice-activated technologies is forcing educators to think about the role such tools play in preparing students for the jobs of the future.

Amid coronavirus-related school closures, advocates worry Education Secretary Betsy DeVos may waive requirements of special education law if Congress signs off. Schools say it's difficult to meet some requirements during the pandemic.

Source: www.thestar.com - Saturday, May 09, 2020
Canada approved a verbal demarche to two senior WHO executives that urged them to allow Taiwan to be admitted as an observer to an upcoming meeting because its input would be “meaningful and important.”

A drill focused on improving movement, teamwork and making the most of scoring chances.

A guide to the fundamentals of heading featuring Sweden women's international Kosovare Asllani.

England U21 coach Stuart Pearce discusses a position he used to master.

FC Barcelona's talisman tells us about his appetite for goals.

Former Tottenham Hotspur FC manager David Pleat analyses FC Barcelona's winning formation from 2009.

A panel of experts—including a national teacher's union president and an official from the Department of Education—discussed how to make teaching a more attractive profession.

Teachers are the experts of the classroom, so they should be empowered to lead professional development, educators said at a forum that included the two national teachers' union presidents.

Some educators and advocates fear the rule will dissuade immigrants from seeking certain government benefits, and that further burdens will fall on schools.

The heads of Deutsche Bank and Siemens, two of Germany’s biggest companies, are among a dwindling number of high-profile delegates still scheduled to attend an investment conference in Saudi Arabia following the disappearance of dissident journalist Jamal Khashoggi.

The founder and chief of his eponymous investment bank traveled to Riyadh to extol the virtues of friendship. He stood out as many of the titans of U.S. finance sat out the kingdom’s signature investment summit amid international outrage over the killing of government critic Jamal Khashoggi.

For a moment, Wall Street seemed to be inching away from Saudi Arabia. Now, it’s already inching back.

Banks can be as powerful and valued as the big technology firms. Yes, those trillion-dollar titans.

The furore surrounding the arrival of over 200 Cuban medical doctors in South Africa to fight the coronavirus has highlighted a failure on the part of the SA government to explain the nature and drivers of our country’s relationship with Cuba, says Mills Soko.

Our economy is in deep trouble, from whichever perspective you look at it. The economic battering taken by economically strong countries is frightening, leaving us in South Africa to fear the worst.

L’indifférence internationale est un facteur aggravant pour les conflits dans les petits pays. Cependant, en ce qui concerne la République centrafricaine (RCA), le contexte est paradoxalement différent.

Depuis jeudi et l’attaque de Bangui par les groupes anti-balaka qui viennent de province et sont composés de villageois et d’anciens militaires constitués en milices d’autodéfense, un calme précaire est revenu dans la capitale centrafricaine grâce au déploiement des militaires français.

Alors qu’une tentative de coup d’Etat contre Pierre Nkurunziza, émanant de l’ex-chef d’état-major, Godefroid Niyombaré, est en cours au Burundi, Thierry Vircoulon chercheur à l'International Crisis Group, explique qui est le général putschiste et analyse, plus généralement, l'appareil sécuritaire du Burundi.

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.

Objectives. The aim of this study was to assess the safety of early oral switch (EOS) prior to 14 days for low-risk Staphylococcus aureus bacteremia (LR-SAB), which is the primary treatment strategy employed at our institution. Usually recommended therapy is 14 days of intravenous (IV) antibiotics.

Methods. All patients with SAB at our hospital were identified between 1 January 2014 and 31 December 2018. Those meeting low-risk criteria (healthcare-associated, no evidence of deep infection or demonstrated involvement of prosthetic material, and no further positive blood cultures after 72-hours) were included in the study. The primary outcome was occurrence of a SAB-related complication within 90 days.

Results. There were 469 SAB episodes during the study period, 100 (21%) of whom met inclusion criteria. EOS was performed in 84 patients. In this group, line infection was the source in 79%, methicillin-susceptible S. aureus caused 95% of SABs and 74% of patients received IV flucloxacillin. The median duration of IV and oral antibiotics in the EOS group was 5 (IQR 4-6) and 10 days (IQR 9-14), respectively. Seventy-one percent of patients received flucloxacillin as their EOS agent. Overall, 86% of oral step-down therapy was with beta-lactams. One patient (1%) undergoing EOS had SAB relapse within 90 days. No deaths attributable to SAB occurred within 90 days.

Conclusions. In this low MRSA prevalence LR-SAB cohort, EOS was associated with a low incidence of SAB-related complications. This was achieved with oral beta-lactam therapy in most patients. Larger prospective studies are needed to confirm these findings.

Carbapenems are currently the preferred agents for the treatment of serious Acinetobacter infections. However, whether cefepime/cefpirome can be used to treat Acinetobacter bloodstream infection (BSI) if it is active against the causative pathogens is not clear. This study aimed to compare the efficacy of cefepime/cefpirome and carbapenem monotherapy in patients with Acinetobacter BSI. The population included 360 patients with monomicrobial Acinetobacter BSI receiving appropriate antimicrobial therapy admitted to four medical centres in Taiwan in 2012–2017. The predictors of 30-day mortality were determined by Cox regression analysis. The overall 30-day mortality rate in the appropriate antibiotic treatment group was 25.0% (90/360 patients), respectively. The crude 30-day mortality rates for cefepime/cefpirome and carbapenem therapy were 11.5% (7/61 patients) and 26.3% (21/80 patients), respectively. The patients receiving cefepime/cefpirome/carbapenem therapy were infected by Acinetobacter nosocomialis (51.8%), A. baumannii (18.4%) and A. pittii (12.1%). After adjusting for age, Sequential Organ Failure Assessment (SOFA) score, invasive procedures, and underlying diseases, cefepime/cefpirome therapy was not independently associated with a higher or lower 30-day mortality compared to the carbapenem therapy. SOFA score (hazard ratio [HR], 1.324; 95% confidence interval [CI], 1.137–1.543; P < 0.001) and neutropenia (HR, 7.060; 95% CI, 1.607–31.019; P = 0.010) were independent risk factors for 30-day mortality of patients receiving cefepime/cefpirome or carbapenem monotherapy. The incidence density of 30-day mortality for cefepime/cefpirome versus carbapenem therapy was 0.40% versus 1.04%. The therapeutic response of cefepime/cefpirome therapy was comparable to that of carbapenems among patients with Acinetobacter BSI receiving appropriate antimicrobial therapy.

Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo β-lactamase (MBL) families. The recent introduction of SBL carbapenemase-inhibitors has provided alternative therapeutic options. Unfortunately, there are no approved inhibitors of MBL-mediated carbapenem-resistance and treatment options for infections caused by MBL-producing Gram-negatives are limited. Here, we present ZN148, a zinc-chelating MBL-inhibitor capable of restoring the bactericidal effect of meropenem and in vitro clinical susceptibility to carbapenems in >98% of a large international collection of MBL-producing clinical Enterobacterales strains (n=234). Moreover, ZN148 was able to potentiate the effect of meropenem against NDM-1-producing Klebsiella pneumoniae in a murine neutropenic peritonitis model. ZN148 showed no inhibition of the human zinc-containing enzyme glyoxylase II at 500 μM and no acute toxicity was observed in an in vivo mouse model with cumulative dosages up to 128 mg/kg. Biochemical analysis showed a time-dependent inhibition of MBLs by ZN148 and removal of zinc ions from the active site. Addition of exogenous zinc after ZN148 exposure only restored MBL activity by ~30%, suggesting an irreversible mechanism of inhibition. Mass-spectrometry and molecular modelling indicated potential oxidation of the active site Cys221 residue. Overall, these results demonstrate the therapeutic potential of a ZN148-carbapenem combination against MBL-producing Gram-negative pathogens and that ZN148 is a highly promising MBL inhibitor, capable of operating in a functional space not presently filled by any clinically approved compound.

Ceftobiprole medocaril is an advanced-generation cephalosporin prodrug that has qualified infectious disease product status granted by the US-FDA and is currently being evaluated in phase 3 clinical trials in patients with acute bacterial skin and skin structure infections (ABSSSIs) and in patients with Staphylococcus aureus bacteremia. In this study, the activity of ceftobiprole and comparators was evaluated against more than 7,300 clinical isolates collected in the United States from 2016 through 2018 from patients with skin and skin structure infections. The major species/pathogen groups were S. aureus (53%), Enterobacterales (23%), Pseudomonas aeruginosa (7%), β-hemolytic streptococci (6%), Enterococcus spp. (4%), and coagulase-negative staphylococci (2%). Ceftobiprole was highly active against S. aureus (MIC_50/90, 0.5/1 mg/L; 99.7% susceptible by EUCAST criteria; 42% methicillin-resistant S. aureus [lsqb]MRSA[rsqb]). Ceftobiprole also exhibited potent activity against other Gram-positive cocci. The overall susceptibility of Enterobacterales to ceftobiprole was 84.8% (>99.0% susceptible for isolate subsets that exhibited a non-extended-spectrum β-lactamase [lsqb]ESBL[rsqb]-phenotype). A total of 74.4% of P. aeruginosa, 100% of β-hemolytic streptococci and coagulase-negative staphylococci, and 99.6% of Enterococcus faecalis isolates were inhibited by ceftobiprole at ≤4 mg/L. As expected, ceftobiprole was largely inactive against Enterobacterales that contained ESBL genes and Enterococcus faecium. Overall, ceftobiprole was highly active against most clinical isolates from the major Gram-positive and Gram-negative skin and skin structure pathogen groups collected at U.S. medical centers participating in the SENTRY Antimicrobial Surveillance Program during 2016–2018. The broad-spectrum activity of ceftobiprole, including potent activity against MRSA, supports its further evaluation for the potential ABSSSI indication.

Bacteria of the genus Campylobacter are major foodborne pathogens which have become increasingly resistant to clinically important antimicrobial agents (1)....

The Cpx stress response is widespread among Enterobacteriaceae. We have previously reported a mutation in cpxA in a multidrug resistant strain of Klebsiella aerogenes isolated from a patient treated with imipenem. This mutation yields to a single amino acid substitution (Y144N) located in the periplasmic sensor domain of CpxA. In this work, we sought to characterize this mutation in Escherichia coli by using genetic and biochemical approaches. Here, we show that cpxA^Y144N is an activated allele that confers resistance to β-lactams and aminoglycosides in a CpxR-dependent manner, by regulating the expression of the OmpF porin and the AcrD efflux pump, respectively. We also demonstrate the intimate interconnection between Cpx system and peptidoglycan integrity on the expression of an exogenous AmpC β-lactamase by using imipenem as a cell wall active antibiotic or inactivation of penicillin-binding proteins. Moreover, our data indicate that the Y144N substitution abrogates the interaction between CpxA and CpxP and increase phosphotransfer activity on CpxR. Because the addition of a strong AmpC inducer such as imipenem is known to causes abnormal accumulation of muropeptides (disaccharide-pentapeptide, N-acetylglucosamyl-1,6-anhydro-N-acetylmuramyl-l-alanyl-d-glutamy-meso-diaminopimelic-acid-d-alanyl-d-alanine) in the periplasmic space, we propose these molecules activate the Cpx system by displacing CpxP from the sensor domain of CpxA. Altogether, these data could explain why large perturbations to peptidoglycan caused by imipenem lead to mutational activation of the Cpx system and bacterial adaptation through multidrug resistance. These results also validate the Cpx system, in particular the interaction between CpxA and CpxP, as a promising therapeutic target.

QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor that demonstrates inhibition of key serine and metallo beta-lactamases at a nano molar range in biochemical assays with purified enzymes. The broad-spectrum inhibitory activity of QPX7728 observed in biochemical experiments translates into enhancement of the potency of many beta-lactams against strains of target pathogens producing beta-lactamases. The impact of bacterial efflux and permeability on inhibitory potency were determined using isogenic panels of KPC-3 producing isogenic strains of K. pneumoniae and P. aeruginosa and OXA-23-producing strains of A. baumannii with various combinations of efflux and porin mutations. QPX7728 was minimally affected by multi-drug resistance efflux pumps in either Enterobacteriaceae, or in non-fermenters such as P. aeruginosa or A. baumannii. In P. aeruginosa, the potency of QPX7728 was further enhanced when the outer membrane is permeabilized. The potency of QPX7728 in P. aeruginosa is not affected by inactivation of the carbapenem porin OprD. While changes in OmpK36 (but not OmpK35) reduced the potency of QPX7728 (8-16-fold), QPX7728 (4 μg/ml) nevertheless completely reversed KPC-mediated meropenem resistance in strains with porin mutations, consistent with a lesser effect of these mutations on the potency of QPX7728 compared to other agents. The ultra-broad-spectrum beta-lactamase inhibition profile combined with enhancement of the activity of multiple beta-lactam antibiotics with varying sensitivity to the intrinsic resistance mechanisms of efflux and permeability indicate QPX7728 is a useful inhibitor for use with multiple beta-lactam antibiotics.