To stabilise the Central African Republic (CAR), the transitional government and its international partners need to prioritise, alongside security, action to fight corruption and trafficking of natural resources, as well as revive the economy.

The U.S. Education Department says the states need more evidence to use the popular admissions test to measure high school achievement.

Malaria parasites invade and replicate within red blood cells (RBCs), extensively modifying their structure and gaining access to the extracellular environment by placing the plasmodial surface anion channel (PSAC) into the RBC membrane. Expression of members of the cytoadherence linked antigen gene 3 (clag3) family is required for PSAC activity, a process that is regulated epigenetically. PSAC is a well-established route of uptake for large, hydrophilic antimalarial compounds and parasites can acquire resistance by silencing clag3 gene expression, thereby reducing drug uptake. We found that exposure to sub-IC50 concentrations of the histone methyltransferase inhibitor chaetocin caused substantial changes in both clag3 gene expression and RBC permeability, reversing acquired resistance to the antimalarial compound blasticidin S that is transported through PSAC. Chaetocin treatment also altered progression of parasites through their replicative cycle, presumably by changing their ability to modify chromatin appropriately to enable DNA replication. These results indicate that targeting histone modifiers could represent a novel tool for reversing epigenetically acquired drug resistance in P. falciparum.

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.

Since 2012, single low dose of primaquine (SLDPQ, 0.25mg/kg) has been recommended with artemisinin-based combination therapies, as first-line treatment of acute uncomplicated Plasmodium falciparum malaria, to interrupt its transmission, especially in low transmission settings of multidrug, including artemisinin, resistance. Policy makers in Cambodia have been reluctant to implement this recommendation due to primaquine safety concerns and lack of data on its efficacy.

In this randomized controlled trial, 109 Cambodians with acute uncomplicated P. falciparum malaria received dihydroartemisinin-piperaquine (DP) alone or combined with SLDPQ on the first treatment day. Transmission-blocking efficacy of SLDPQ was evaluated on Days 0, 1, 2, 3, 7, 14, 21, 28 and recrudescence by reverse transcriptase polymerase chain reaction (RT-PCR) (gametocyte prevalence) and membrane-feeding assays with Anopheles minimus mosquitoes (gametocyte infectivity). Without the influence of recrudescent infections, DP+SLDPQ reduced gametocyte carriage 3 fold compared to DP. Of 48 patients tested on Day 0, only three patients were infectious to mosquitoes (~6%). Post-treatment, three patients were infectious: on D14 (3.5%, 1/29), and on the first and seventh day of recrudescence (8.3%, 1/12 for each); this overall low infectivity precluded our ability to assess its transmission blocking efficacy.

Our study confirms effective gametocyte clearance of SLDPQ when combined with DP in multidrug resistant P. falciparum and the negative impact of recrudescent infections due to poor DP efficacy. Artesunate-mefloquine (ASMQ) has replaced DP and ASMQ-SLDPQ has been deployed to treat all P. falciparum symptomatic patients to further support the elimination of multidrug resistant P. falciparum in Cambodia.

Multidrug resistant strains belonging to the Enterobacter cloacae complex (ECC) group, and especially those belonging to clusters C-III, C-IV and C-VIII, have increasingly emerged as a leading cause of healthcare-associated infections, with colistin used as one of the last line of treatment. However, colistin-resistant ECC strains have emerged. The aim of this study was to prove that MgrB, the negative regulator of PhoP/PhoQ two-component regulatory system, is involved in colistin resistance in ECC of cluster C-VIII, formerly referred to as Enterobacter hormaechei subsp. steigerwaltii. An in vitro mutant (Eh22-Mut) was selected from a clinical isolate of Eh22. The sequencing analysis of its mgrB gene showed the presence of one nucleotide deletion leading to the formation of a truncated protein of six instead of 47 amino acids. Wild-type mgrB gene from Eh22, as well as that of a clinical strain of Klebsiella pneumoniae used as controls, were cloned and the corresponding recombinant plasmids were used for complementation assays. Results showed a fully restored susceptibility to colistin, and confirmed for the first time that mgrB gene expression plays a key role in acquired resistance to colistin in ECC strains.

Ceftazidime–avibactam and cefiderocol are two of the latest generation β-lactam agents that possess expanded activity against highly drug-resistant bacteria, including carbapenem-resistant Enterobacterales. Here we show that structural changes in AmpC β-lactamases can confer reduced susceptibility to both agents. A multidrug-resistant Enterobacter cloacae clinical strain (Ent385) was found to be resistant to ceftazidime–avibactam and cefiderocol without prior exposure to either agent. The AmpC β-lactamase of Ent385 (AmpC^Ent385) contained an alanine–proline deletion at positions 294–295 (A294_P295del) in the R2 loop. AmpC^Ent385 conferred reduced susceptibility to ceftazidime–avibactam and cefiderocol when cloned into Escherichia coli TOP10. Purified AmpC^Ent385 showed increased hydrolysis of ceftazidime and cefiderocol compared with AmpC^Ent385Rev, in which the deletion was reverted. Comparisons of crystal structures of AmpC^Ent385 and AmpC^P99, the canonical AmpC of E. cloacae, revealed that the two-residue deletion in AmpC^Ent385 induced drastic structural changes of the H-9 and H-10 helices and the R2 loop, which accounted for the increased hydrolysis of ceftazidime and cefiderocol. The potential for a single mutation in ampC to confer reduced susceptibility to both ceftazidime–avibactam and cefiderocol requires close monitoring.

Importance Ceftazidime–avibactam and cefiderocol are newly approved β-lactam agents that possess broad spectrum activity against multidrug-resistant (MDR) Gram-negative bacteria. We show here that a two amino-acid deletion in the chromosomal AmpC β-lactamase, identified in a clinical strain of Enterobacter cloacae, confers reduced susceptibility to both agents. By crystallographic studies of free and drug-bound forms of enzyme, we demonstrate that this deletion in AmpC induces slanting of the H-9 helix that is directly connected with the R2 loop, and disappearance of the H-10 helix, is directly responsible for increased hydrolysis of ceftazidime and cefiderocol. These findings provide novel insights into how MDR Gram-negative bacteria may evolve their β-lactamases to survive selective pressure from these newly developed β-lactam agents.

Meropenem/vaborbactam resistance in Klebsiella pneumoniae is associated with loss of function mutations in the OmpK35 and OmpK36 porins. Here we identify two previously unknown loss of function mutations that confer cefuroxime resistance in K. pneumoniae. The proteins lost were NlpD and KvrA; the latter is a transcriptional repressor controlling capsule production. We demonstrate that KvrA loss reduces OmpK35 and OmpK36 porin production, which confers reduced susceptibility to meropenem/vaborbactam in a KPC-3 producing K. pneumoniae isolate.

Objectives: Empiric antibiotic prescribing can be supported by guidelines and/or local antibiograms, but these have limitations. We sought to use data from a comprehensive electronic health record to use statistical learning to develop predictive models for individual antibiotics that incorporate patient-, and hospital-specific factors. This paper reports on the development and validation of these models on a large retrospective cohort.

Methods: This is a retrospective cohort study including hospitalized patients with positive urine cultures in the first 48 hours of hospitalization at a 1500 bed, tertiary care hospital over a 4.5 year period. All first urine cultures with susceptibilities were included. Statistical learning techniques, including penalized logistic regression, were used to create predictive models for cefazolin, ceftriaxone, ciprofloxacin, cefepime, and piperacillin-tazobactam. These were validated on a held-out cohort.

Results: The final dataset used for analysis included 6,366 patients. Final model covariates included demographics, comorbidity score, recent antibiotic use, recent antimicrobial resistance, and antibiotic allergies. Models had acceptable to good discrimination in the training dataset and acceptable performance in the validation dataset, with a point estimate for area under the receiver operating characteristic curve (AUC) that ranged from 0.65 for ceftriaxone to 0.69 for cefazolin. All models had excellent calibration.

Conclusion: In this study we used electronic health record data to create predictive models to estimate antibiotic susceptibilities for UTIs in hospitalized patients. Our models had acceptable performance in a held-out validation cohort.

As resistance to artemisinins (current frontline drugs in malaria treatment) emerges in south East Asia, there is an urgent need to identify the genetic determinants and understand the molecular mechanisms underpinning such resistance. Such insights could lead to prospective interventions to contain resistance and prevent the eventual spread to other malaria endemic regions. Artemisinin reduced susceptibility in South East Asia (SEA) has been primarily linked to mutations in P. falciparum Kelch-13, which is currently widely recognised as a molecular marker of artemisinin resistance. However, 2 mutations in a ubiquitin hydrolase, UBP-1, have been previously associated with artemisinin reduced susceptibility in a rodent model of malaria and some cases of UBP-1 mutation variants associating with artemisinin treatment failure have been reported in Africa and SEA. In this study, we have employed CRISPR-Cas9 genome editing and pre-emptive drug pressures to test these artemisinin susceptibility associated mutations in UBP-1 in P. berghei sensitive lines in vivo. Using these approaches, we have shown that the V2721F UBP-1 mutation results in reduced artemisinin susceptibility, while the V2752F mutation results in resistance to chloroquine and moderately impacts tolerance to artemisinins. Genetic reversal of the V2752F mutation restored chloroquine sensitivity in these mutant lines while simultaneous introduction of both mutations could not be achieved and appears to be lethal. Interestingly, these mutations carry a detrimental growth defect, which would possibly explain their lack of expansion in natural infection settings. Our work has provided independent experimental evidence on the role of UBP-1 in modulating parasite responses to artemisinin and chloroquine under in vivo conditions.

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

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 AND OBJECTIVES:

Children born very preterm (VPT) are at high risk of cognitive impairment that impacts their educational and social opportunities. This study examined the predictive accuracy of assessments at 2, 4, 6, and 9 years in identifying preterm children with cognitive impairment by 12 years.

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

Are you unhappy with your credit provider? Have you been given more debt than you can afford to pay back? Help is at hand, and it’s just an SMS away.

Credit card fraud increased to 19.47% as at the end of March 2019, compared to 12.2% reported at the beginning of January 2019.

With credit card fraud rising at an alarming rate in the first quarter of the year, the Ombudsman for Banking Services has provided 10 tips to avoid becoming a victim of scammers.

The coronavirus closures are shaping a disruptive end to a tumultuous academic career for the Class of 2020.

RANGERS vice-chairman John Bennett last night dismissed a claim that Ibrox chairman Douglas Park had threatened SPFL chief executive Neil Doncaster as “unfounded”.

T. Michael O'Shea
Jul 1, 1999; 104:15-21
ARTICLES

David Gozal
Sep 1, 1998; 102:616-620
ARTICLES

Maureen Hack
Aug 1, 2005; 116:333-341
ARTICLES

Andrew T. Shennan
Oct 1, 1988; 82:527-532
ARTICLES

Vinod K. Bhutani
Jan 1, 1999; 103:6-14
ARTICLES

The IMpact-RSV Study Group
Sep 1, 1998; 102:531-537
ARTICLES

Like other Americans, liberal and conservative teachers perceive news sources' credibility differently. How does that affect their teaching of media literacy?

UEFA's 'Women's football across the national associations 2017' report shows how the female game has evolved over the past five years, and offers a snapshot of the sport in each of UEFA's 55 member associations.

The new foldable phone from Pablo Escobar's brother is a Samsung Galaxy Fold with no changes to the software, according to a YouTuber and a journalist who obtained the products amid consumer worries the business is a scam.

Each spring, the Athletics department at Penn State Behrend honors the college’s best student-athletes for their performances on and off the field. This year, because of the transition to the remote-learning environment, the awards were announced on video by Senior Director of Athletics Brian Streeter.

The experiences that Chris Eggerman, a 2017 graduate, had while at Penn State gave him a glimpse of the challenges and rewards he would enjoy in a career, and, paired with his education in the College of Information Sciences and Technology, equipped him with the skills he uses in his current profession as a security adviser at Liberty Mutual.

The Laurel Highlands boys basketball team will be honored at the USCAA Men’s Division II Basketball National Championship Game on Wednesday, March 11, at Penn State Fayette, The Eberly Campus.

The Unremembered Places

Payback

A multi-disciplinary collaborative relationship, developed between Penn State EMS Energy Institute researchers and a Pittsburgh-based start-up company, may hold the answer to reducing global greenhouse gas (GHG) emissions while also paving the way to disrupt the chemical and material industries.

Cecelia Minnick, who will graduate this Saturday with a 3.98 GPA in accounting and minors in information systems management and legal environment of business, has been selected as Smeal’s spring 2020 accounting student marshal.

Debra Roach, director of workforce development and continuing education at Penn State Beaver, has been honored with the 2020 Shirley Hendrick Award, presented by the Penn State Commission for Adult Learners for service to adult learners.

While Acer's Predator CG437K aims for the stars with its impressive feature set, this gaming monitor's achievements aren't as lofty as its goals. Some gamers may be willing to sacrifice picture quality for its size, but others should save their money and look at alternatives.

Source: www.npr.org - Thursday, May 07, 2020
The version published in China Daily omitted a reference to the illness originating in China and spreading to the rest of the world. The piece was published in full on the authors' websites. (Image credit: Jason Lee/Reuters)

Accreditation process starts on 1 June 2013

2019 is nearly over, so let's look ahead to what awaits the video game industry in the first year of the new decade. Informed opinions and hot takes abound.

The pandemic has disrupted internships and student teaching in Pennsylvania’s teacher education programs. Teacher educators in K-4 Professional Development School partnership between Penn State and the State College Area School District have taken an inquiry stance to empower interns to navigate learning to teach during these times.

An education professor at Penn State is investigating how educators can adopt mindfulness practices to keep stress and anxiety at bay.

Too many districts that use a lot of credit recovery to enable students to finish high school don't have sufficient policy safeguards to ensure that those catch-up courses are high quality, according to a new report.

CNA Staff, May 2, 2020 / 04:30 pm (CNA).- A man claiming to have killed the murdered Nigerian seminarian Michael Nnadi has given an interview in which he says he executed the aspiring priest because he would not stop announcing the Christian faith in captivity.

Mustapha Mohammed, who is currently in jail, gave a telephone interview to the Nigerian newspaper Daily Sun on Friday. He took responsibility for the murder, according to the Daily Sun, because Nnadi, 18 years old, “continued preaching the gospel of Jesus Christ” to his captors.

According to the newspaper, Mustapha praised Nnadi’s “outstanding bravery,” and that the seminarian “told him to his face to change his evil ways or perish.”

Nnadi was kidnapped by gunmen from Good Shepherd Seminary in Kaduna on January 8, along with three other students. The seminary, home to some 270 seminarians, is located just off the Abuja-Kaduna-Zaria Express Way. According to AFP, the area is “notorious for criminal gangs kidnapping travelers for ransom.”

Mustapha, 26, identified himself as the leader of a 45-member gang that preyed along the highway. He gave the interview from a jail in Abuja, Nigeria, where he is in police custody.

On the evening of the abduction, gunmen, disguised in military camouflage, broke through the fence surrounding the seminarians' living quarters and opened fire. They stole laptops and phones before kidnapping the four young men.

Ten days after the abduction, one of the four seminarians was found on the side of a road, alive but seriously injured. On Jan. 31, an official at Good Shepherd Seminary announced that another two seminarians had been released, but that Nnadi remained missing and was presumed still in captivity.

On Feb. 1, Bishop Matthew Hassan Kukah of the Diocese of Sokoto, Nigeria, announced that Nnadi had been killed.

“With a very heavy heart, I wish to inform you that our dear son, Michael was murdered by the bandits on a date we cannot confirm,” the bishop said, confirming that the rector of the seminary had identified Nnadi’s body.

The newspaper reported that from “the first day Nnadi was kidnapped alongside three of his other colleagues, he did not allow [Mustapha] to have peace,” because he insisted on announcing the gospel to him.

According to the newspaper, Mustapha “did not like the confidence displayed by the young man and decided to send him to an early grave.”

According to the Daily Sun, Mustapha targeted the seminary knowing it was a center for training priests, and that a gang member who lived nearby had helped conduct surveillance ahead of the attack. Mohammed believed that it would be a profitable target for theft and ransom.

Mohammed also said that the gang used Nnadi’s mobile telephone to issue their ransom demands, asking for more than $250,000, later reduced to $25,000, to secure the release of the three surviving students, Pius Kanwai, 19; Peter Umenukor, 23; and Stephen Amos, 23.

Nnadi’s murder is one of an series of attacks and killings on Christians in the country in recent months.

Archbishop Ignatius Kaigama of Abuja called on Nigerian President Muhammadu Buhari to address the violence and kidnappings in a homily March 1 at a Mass with the Catholic Bishops’ Conference of Nigeria.

“We need to have access to our leaders; president, vice president. We need to work together to eradicate poverty, killings, bad governance and all sorts of challenges facing us as a nation,” Kaigama said.

In an Ash Wednesday letter to Nigerian Catholics, Archbishop Augustine Obiora Akubeze of Benin City called for Catholics to wear black in solidarity with victims and pray, in response to “repeated” executions of Christians by Boko Haram and “incessant” kidnappings “linked to the same groups.”

Other Christian villages have been attacked, farms set ablaze, vehicles carrying Christians attacked, men and women have been killed and kidnapped, and women have been taken as sex slaves and tortured—a “pattern,” he said, of targeting Christians.

On Feb. 27, U.S Ambassador at Large for Religious Freedom Sam Brownback told CNA that the situation in Nigeria was deteriorating.

“There's a lot of people getting killed in Nigeria, and we're afraid it is going to spread a great deal in that region,” he told CNA. “It is one that's really popped up on my radar screens -- in the last couple of years, but particularly this past year.”

“I think we’ve got to prod the [Nigerian President Muhammadu] Buhari government more. They can do more,” he said. “They’re not bringing these people to justice that are killing religious adherents. They don’t seem to have the sense of urgency to act.”

It no longer looks like a syringe, so parents can stop being suspicious their kid is doing drugs.

Rural schools struggle with high and lows more commonly associated with urban schools, including high rates of poverty, low literacy rates, and low college attendance rates, a new report finds.

To view more press releases, please visit http://ir.wintrust.com/news.aspx?iid=1024452.