United States President Donald Trump told CBS’s 60 Minutes that he would added pressure on Saudi Arabia, vowing "severe punishment" should the kingdom’s leaders be linked to the disappearance of Washington Post columnist Jamal Khashoggi.

An op-ed in Saudi-owned Al Arabiya news has warned of repercussions should the US impose sanctions on Saudi Arabia over the disappearance of journalist Jamal Khashoggi.

Political power is a slippery thing. Even in an absolute monarchy, it can get away from you with one wrong move.

There’s always been massive inequality in South Africa, but those who have the money and power still aren’t getting it, says Carmen Williams.

Los conflictos en los países pequeños suelen agravarse debido a la indiferencia internacional. Sin embargo, en el caso de la República Centroafricana (RCA), el problema es ligeramente distinto. Hay una importante presencia internacional en este Estado, pero los actores principales han decidido mantenerse al margen y esperar en vez de intervenir activamente en la crisis.

Sensible, inclusive regulation of pastoralism that has mitigated tension in parts of the Sahel should be extended to the Democratic Republic of Congo (DRC) and the Central African Republic (CAR), where conflicts have worsened with the southward expansion of pastoralism.

​Religious intolerance is a growing but seriously underestimated risk in Cameroon, both between and inside the major faiths. To halt the spread of violent extremism in the country, Cameroon needs to bring all sects into a new social compact and within the bounds of a charter for religious tolerance.

L’image de havre de paix dans une région en proie aux conflits dont bénéficiait le Cameroun a volé en éclats depuis l’irruption de Boko Haram en 2013 au nord du pays. Ce mouvement, devenu l’Etat islamique en Afrique de l’Ouest en mars 2015, revendique son affiliation à Daech. Néanmoins, l’apparition brutale et sanglante de ce djihadisme africain est moins liée à l’essor de Daech en Irak et en Syrie qu’aux bouleversements du paysage religieux de l’Afrique en général et du Cameroun en particulier.

Federal law requires states to report student test scores in achievement levels, but leaders in the Golden State want to take a different approach.

Objectives: Carbapenemase-producing Enterobacterales and specifically KPC-producing Klebsiella pneumoniae (KPC-Kp) are rapidly spreading worldwide. The prognosis of ventilator-associated pneumonia (VAP) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) is not well known. Our study tries to assess whether ventilator-associated pneumonia caused by a KPC-Kp strain is associated with higher all-cause mortality than if caused by carbapenem-susceptible isolates.

Study design and methods: This is a retrospective cohort study of patients with VAP due to K. pneumoniae from a 35-bed polyvalent Intensive Care Unit in a university hospital (> 40,000 annual admissions) between January 2012 and December 2016. Adjusted multivariate analysis was used to study the association of KPC-Kp with 30-day all-cause mortality (Cox regression).

Results. We analyze 69 cases of K. pneumoniae VAP of which 39 were produced by a KPC-Kp strain with high-level resistance to meropenem (MIC > 16 mg/mL). All-cause mortality at 30 days was 41% in the KPC-Kp group (16/39) and 33.3% in the carbapenem-susceptible cases (10/30). KPC-Kp etiology was not associated with higher mortality when controlled for confounders (adjusted hazard ratio [lsqb]HR[rsqb] 1.25; 95% CI: 0.46–3.41). Adequate targeted therapy (HR 0.03; 95% CI: <0.01–0.23) was associated with all-cause mortality.

Conclussion. Assuming the limitations due to the available sample size, the prognosis of VAP caused by KPC-Kp is similar to VAPs caused by carbapenem-susceptible K. pneumoniae when appropriate treatment is used.

Periodontitis as a biofilm-associated inflammatory disease is highly prevalent worldwide. It severely affects oral health and yet closely links to systemic diseases like diabetes and cardiovascular disease. Porphyromonas gingivalis as a ‘keystone' periodontopathogen drives the shift of microbe-host symbiosis to dysbiosis, and critically contributes to the pathogenesis of periodontitis. Persisters are a tiny subset of biofilm-associated microbes highly tolerant to lethal treatment of antimicrobials, and notably metronidazole-tolerant P. gingivalis persisters have recently been identified by our group. This study further explored the interactive profiles of metronidazole-treated P. gingivalis persisters (M-PgPs) with human gingival epithelial cells (HGECs). P. gingivalis cells (ATCC 33277) at stationary phase were treated with lethal dosage of metronidazole (100 μg/ml, 6 hours) for generating M-PgPs. The interaction of M-PgPs with HGECs was assessed by microscopy, flow cytometry, cytokine profiling and qPCR. We demonstrated that the overall morphology and ultra-cellular structure of M-PgPs remained unchanged. Importantly, M-PgPs maintained the capabilities to adhere to and invade into HGECs. Moreover, M-PgPs significantly suppressed pro-inflammatory cytokine expression in HGECs at a comparable level with the untreated P. gingivalis cells, through the thermo-sensitive components. The present study reveals that P. gingivalis persisters induced by lethal treatment of antibiotics could maintain their capabilities to adhere to and invade into human gingival epithelial cells, and perturb the innate host responses. Novel strategies and approaches need to be developed for tackling P. gingivalis and favourably modulating the dysregulated immuno-inflammatory responses for oral/periodontal health and general wellbeing.

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.

OptrA is an ATP-binding cassette (ABC)-F protein that confers resistance to oxazolidinones and phenicols, and can be either plasmid or chromosomally encoded. We isolated 13 Enterococcus faecalis strains possessing linezolid MIC ≥ 4 mg/L from nursery pigs in swine herds located across Brazil. Genome sequence comparison showed that these strains possess optrA in different genetic contexts occurring in 5 different E. faecalis sequence type backgrounds. The optrA gene invariably occurred in association with an araC regulator and a gene encoding a hypothetical protein. In some contexts, this genetic island was able to excise and form a covalently closed circle within the cell which appeared to occur in high abundance, and to be transmissible by co-resident plasmids.

Spectinomycin is a ribosome-binding antibiotic that blocks the translocation step of translation. A prevalent resistance mechanism is the modification of the drug by aminoglycoside nucleotidyl transferase (ANT) enzymes of the spectinomycin-specific ANT (9) family or by the dual-specificity ANT(3") (9) family that also acts on streptomycin. We previously reported the structural mechanism of streptomycin modification by the ANT(3") (9) AadA from Salmonella enterica. ANT (9) from Enterococcus faecalis adenylates the 9-hydroxyl of spectinomycin. We here present the first structures of spectinomycin bound to an ANT enzyme. Structures were solved for ANT (9) in apo form, in complex with ATP, spectinomycin and magnesium or in complex with only spectinomycin. ANT (9) shows similar overall structure as AadA with an N-terminal nucleotidyltransferase domain and a C-terminal α-helical domain. Spectinomycin binds close to the entrance of the interdomain cleft, while ATP is buried at the bottom. Upon drug binding, the C-terminal domain rotates by 14 degrees to close the cleft, allowing contacts of both domains with the drug. Comparison with AadA shows that spectinomycin specificity is explained by a straight α₅ helix and a shorter α_5-α₆ loop that would clash with the larger streptomycin substrate. In the active site, we observe two magnesium ions, one of them in a previously un-observed position that may activate the 9-hydroxyl for deprotonation by the catalytic base Glu-86. The observed binding mode for spectinomycin suggests that also spectinamides and aminomethyl spectinomycins, recent spectinomycin analogues with expansions in position 4 of the C ring, will be subjected to modification by ANT (9) and ANT(3") (9) enzymes.

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.

Cyclophilins play a key role in the lifecycle of coronaviruses. Alisporivir (Debio 025) is a non-immunosuppressive analogue of cyclosporin A with potent cyclophilin inhibition properties. Alisporivir reduced SARS-CoV-2 RNA production in a dose-dependent manner in VeroE6 cell line, with an EC₅₀ of 0.46±0.04 μM. Alisporivir inhibited a post-entry step of the SARS-CoV-2 lifecycle. These results justify that a proof-of-concept Phase 2 trial be rapidly conducted with alisporivir in patients with SARS-CoV-2 infection.

BACKGROUND:

For children who cannot be discharged from the emergency department, definitive care has become less frequent at most hospitals. It is uncertain whether this is true for common conditions that do not require specialty care. We sought to determine how the likelihood of definitive care has changed for 3 common pediatric conditions: asthma, croup, and gastroenteritis.

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.

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.

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.

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.

New research has found that inequality in SA has increased, with wealth becoming ever more concentrated among the rich.

The elite round line-up is set, with 26 teams earning spots alongside Germany and holders Spain in the 23 November draw.

The 2019/20 qualifying round draw has been made, setting the first steps on the road to Sweden.

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

Dedication to student print journalism paid off for several Penn State Greater Allegheny student reporters and designers.

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.

Italy, Azerbaijan, Ukraine, Portugal, Spain, Kazakhstan and Russia joined hosts Slovenia in the finals by winning their main round groups while the eight play-off contenders are confirmed.

The future of European futsal – male and female – was displayed over the last week in qualifying for the 2018 Youth Olympic games with Russia and Portugal coming out on top.

Education Week's top English-language learner stories on 2019 explored who's teaching the nation's English-learners and the struggles those educators encounter on the job, how the Trump administration's immigration policies affected students and their families and examined why more schools in the Un

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.

IT’S a bank holiday weekend and we are now several weeks into a gruelling lockdown.

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The 2018/19 UEFA European Under-19 Championship qualifying round draw has been made in Nyon, starting the road to the July 2019 finals in Armenia.

The 13 qualifying round groups are complete, with 26 teams through to join top seeds Portugal and Germany in the elite round.

See who is through after October's mini-tournaments; the remaining groups run from 13 to 19 November.

Rio de Janeiro, Brazil, Apr 20, 2020 / 09:25 am (CNA).- On Friday, Brazil’s Federal Supreme Court will hold a virtual hearing to consider whether to decriminalize abortion for pregnant women infected with the Zika virus.

The legal intervention, called “Direct Action on Unconstitutionality-ADI 5581,” was filed with Brazil’s highest court by the National Association of Public Defenders. Supreme Court Justice Cármen Lúcia Antunes Rocha will present the legal action to the court, whose 11 members will have until April 30 to vote on the issue.

Several pro-life organizations have come out strongly against efforts to expand abortion, which is illegal in Brazil but is considered a “non-punishable crime” in cases of rape, a proven risk to life of the mother and, as of 2012, babies diagnosed with anencephaly.

“It’s a usurpation of powers because the Supreme Court does not have competency to rule on this matter,” said jurist José Miranda de Siqueira, president of the National Association of Citizens for Life. “This is a crime against the Federal Constitution of Brazil which in Article V guarantees the inviolability of the right to life.”

“We’re working with the Union of Catholic Jurists of Rio de Janeiro and will soon issue a strong statement on the issue,” continued Miranda, who is also a bioethics professor and authored a book on euthanasia, “O Poder sobre a Vida” (The Power over Life), which specifically addresses ADI 5581.

“Life is a preeminent right in the legal world. I’m asking people to pray and publicize this serious situation which is going on,” the lawyer added.

In an open letter to all Brazilians, the National Network for the Defense of Life and Family argued that the court challenge is “part of a strategy to introduce abortion in case of disabilities in general, or even abortion on demand, with the weak justification that the pregnant woman would be in a state of distress.”

“Eugenic abortion carries an enormous burden of prejudice and discrimination towards people with disabilities, sending an unseemly message that it would be better if they did not exist,” the pro-life organization added.

The Zika virus garnered international attention in 2015 after areas of Brazil noted a spike in cases of the birth defect microcephaly – a condition marked by abnormally small heads, brains, and developmental delays – following a recent outbreak of the virus in areas of northeastern Brazil.

Research on the virus suggested a link between Zika virus infection during pregnancy and severe neurological birth defects, including microcephaly and incomplete brain development.

A CitizenGo petition addressed to the Supreme Court justices called for the case to be removed from the docket and for the lives of the unborn to be respected. The petition was launched April 16. Within 24 hours, it had garnered 35,000 signatures and as of April 20 has 85,000.