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.

Dihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 patients, mostly children enrolled in a multicentre trial from 10 sites in Africa. A linear relationship described the QTc-prolonging effect of piperaquine, estimating a 5.90ms mean QTc-prolongation per 100ng/mL increase in piperaquine concentration. The effect of piperaquine on absolute QTc-interval estimated a mean maximum QTc-interval of 456ms (EC₅₀=209ng/mL). Simulations from the pharmacokinetic-pharmacodynamic models predicted 1.98-2.46% risk of having QTc-prolongation > 60ms in all treatment settings. Although piperaquine administration resulted in QTc-prolongation, no cardiovascular adverse events were found in these patients. Thus, the use of dihydroartemisinin-piperaquine should not be limited by this concern.

Background

Optimal concentrations of unbound antimicrobials are essential for maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare effects of different albumin states on total and unbound concentrations of ertapenem and ceftriaxone using an ovine model.

Methods

Design

Prospective, three phase intervention observational study.

Subjects

Healthy Merino sheep.

Interventions

Eight sheep were subject to three experimental phases; normoalbuminemia, hypoalbuminemia using plasmapheresis and albumin replacement using a 25% albumin solution. In each phase, ceftriaxone 40 mg/kg and ertapenem 15 mg/kg were given intravenously. Blood samples were collected at pre-defined intervals and analyzed using an ultra-high-performance liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters such as area under the curve (AUC_0-24), plasma clearance (CL) and apparent volume of distribution in the terminal phase (V_d) were estimated and compared between the phases.

Results

The protein and albumin concentrations were significantly different between phases. Hypoalbuminemia resulted in a significantly lower AUC_0-24 and higher CL of total and unbound concentrations of ceftriaxone compared to the other phases. Whereas albumin replacement led to higher AUC_0-24 and lower CL compared to other phases for both drugs. The V_d for total drug concentrations for both drugs were significantly lower with albumin replacement.

Conclusions

For highly protein-bound drugs such as ceftriaxone and ertapenem, both hypoalbuminemia and albumin replacement may affect unbound drug exposure.

The surge in stocks was on the back of positive news from trials being conducted on a potential treatment for the coronavirus. With most economies looking to partially reopen their economies, this brought a jump across most asset classes including commodities.

BACKGROUND:

The ability of the decades-old Boston and Philadelphia criteria to accurately identify infants at low risk for serious bacterial infections has not been recently reevaluated.

BACKGROUND:

Approximately 25% of children with concussion have persistent postconcussive symptoms (PPCS) with resultant significant impacts on quality of life. Melatonin has significant neuroprotective properties, and promising preclinical data suggest its potential to improve outcomes after traumatic brain injury. We hypothesized that treatment with melatonin would result in a greater decrease in PPCS symptoms when compared with a placebo.

Penn State Health Milton S. Hershey Medical Center has begun enrolling participants in an international clinical trial evaluating an investigational antiviral drug, remdesivir, for treatment of coronavirus disease 2019 (COVID-19).

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Shoo K. Lee
Nov 1, 2000; 106:1070-1079
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T. Michael O'Shea
Jul 1, 1999; 104:15-21
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Paul L. Aronson
Oct 1, 2014; 134:667-677
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Robert Guthrie
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G. C. Liggins
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The STOP-ROP Multicenter Study Group
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Julie A. Jaskiewicz
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Sony's Xperia 5 smartphone features flagship-level hardware and build quality, but falls short on a number of other key factors.

We're living through a moment that will be written about in history books. Personal journals, blogs and oral histories could help shape the narrative, according to historians at Penn State Behrend.

Tom Nigl, doctoral candidate in materials science and engineering (MatSE), was awarded the Intercollege Graduate Student Outreach Achievement Award from the Graduate School for outreach efforts that promote science within society.

Bernadette Lear, Penn State University Libraries behavioral sciences and education librarian and coordinator of library instruction at the Penn State Harrisburg Library, has been elected vice chair/chair elect of the Library History Round Table, a membership group of the American Library Association.

Bria Nickerson turned her love of true crime television into a passion for criminal justice. During her time at Penn State Schuylkill, this administration of justice major has distinguished herself in the classroom and as a campus leader, earning her this year's Student Life Chancellor's Award for Student Leadership for contributions to the improvement and advancement of campus life.

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Rebecca Mattson, head of faculty and research services for the H. Laddie Montague Jr. Law Library, Penn State University Libraries, and professor of legal research at Penn State Law at University Park, has been elected vice chair/chair elect of the Research Instruction and Patron Services Special Interest Section of the American Association of Law Libraries.

Crisis Group mourns the passing today of Sandy Berger, a tremendous friend and colleague who worked tirelessly to promote greater peace and security in a troubled world. He died of cancer at the age of 70.

Source: www.youtube.com - Friday, May 08, 2020

As scheduled, trial operations began at the Airport Berlin Brandenburg, BER, on 30 April with around 280 employees.

Washington D.C., Mar 22, 2020 / 04:00 am (CNA).- The Syrian civil war has led to one of the largest refugee crises of modern times, and presented unique problems for Syria’s ancient Christian communities. Marginalized for centuries, persecuted by ISIS, afraid to attract any attention from the West, Syrian Christians remain, by most accounts, the war’s most invisible victims.

Seta Kale, a Syrian with a Syriac and Armenian descent, was born and raised in Qamishli and fled to Sweden at the age of 16. Today, as a 23-year-old, she’s studying business and economics at Jönköping International Business School, while working part-time as a cashier at a supermarket called Coop, and as a saleswoman at Rituals Cosmetics. Kale likes to sing to cope with her stress, and she likes to read poetry.

In partnership with the Philos Project, CNA sat down with Seta Kale:

When and how did you flee to Sweden?

I moved to Sweden seven years ago in December 2012, a couple of days before Christmas. We flew from Syria to Armenia, and from there we came to Sweden as tourists. We are some of the lucky ones as there were not many who could flee safely. But it was not as easy as it sounds. My family and I had to split up and travel on different dates in order to avoid the suspicion that we were refugees. We had no idea how we were going to be treated upon our arrival in Sweden, and therefore did not want to take any risks by travelling together.

We have seven people in our family. My mom, two of my brothers and I went first. After six months my older sister and third brother came, and a year later my dad arrived. My dad had to take the most difficult route, one that was filled with risks. He couldn’t get a tourist visa, so he had to travel between countries (Turkey, Italy, Greece and France) to be able to come to Sweden. At one point, he had to cross the sea in a small boat together with 30 other people and walk through a forest for several days. Some days he was unreachable, and I’ve never felt that kind of fear ever before. It was a kind that I will never forget.

When did you start feeling the war?

As I mentioned before, I lived in Qamishli. It is a city in northeast Syria, and it was one of the cities that was least affected by war in the beginning unlike, for example, Aleppo and Raqqa. There still were bombs and shootings. The violence started when our bread factory was bombed. It then escalated to hospitals, schools and many public places. Everything became more expensive and there was no access to electricity and clean water 24/7. People were afraid to go to work and children were afraid to go to school. Qamishli felt like a haunted city.

It was when my school was bombed only minutes after my sister and I had left that my dad decided that we had to flee Syria. I will never forget the memory of that day. The ground was shaking under our feet as my mom and aunt ran towards us. After that, people became desperate to flee the war. Houses and apartments were quickly emptied. The feelings and stories that Syria has carried together with her people since 2011 is indescribable.

Tell me about your hometown in Syria.

In Qamishli, Syriacs, Armenians, Assyrians, Arabs, Kurds, Christians, Muslims all lived together. There were as many churches as there were mosques. People worked alongside one another. They were humble, loving, loyal and respectful towards each other. We felt secure because we knew that if we ever were in danger, the whole city would come and help. Religion and ethnicity did not matter to us, and this was the case in the whole country, not only in my hometown. We never thought “he’s Muslim” or “she’s Christian.”

The social life never stopped in Qamishli. There were things to do 24/7 with friends and family. Christians and Muslims celebrated Christmas, Eid al-fitr, Easter and Eid al-adha together.

When I came to Sweden, everyone thought I lived in a tent in the desert. But the more they got to know me, they were surprised by my knowledge and all the languages I could speak. Unfortunately, people tend to believe things about Syria that are not true. We had access to development, education, jobs and more. People say that nothing is perfect, but Syria was perfect in my eyes. We were very rich, but not in a materialistic way. We were rich in culture, religion, knowledge, history, tradition, peoples and so much more. Everything had a reason and I am the way I am today mostly because of what and who Syria is.

What are your best and worst memories from Qamishli?

Wow, I don’t know where to begin. I have so many good memories imprinted in my heart. I cannot choose one because there are so many; from silly things in school with friends, to mini trips with the family throughout Syria, to celebrations of Christmas and Easter.

The worst memory I have was a time when I was on my way from Qamishli to Aleppo while we were fleeing the war. It was a 9-hour drive by bus. Before, it used to be a beautiful ride with beautiful buildings, houses, people and restaurants on the road. But that day I saw a completely different scene. It was filled with sorrow, and the beautiful buildings were reduced to stones on the ground. There were no houses, no restaurants and no people. During the trip to Aleppo the bus had to stop more than five times at checkpoints. Some checkpoints belonged to the Syrian military and some were controlled by ISIS. Once, my sister and I had to hide under the seats so the ISIS soldiers wouldn’t take us. Another horrible memory is simply when I realized that this is it, I will never go back to my country. I cried the entire flight.

Have you lost any friends or family members during the war?

I was one of the lucky ones who didn’t lose any friends or family members. But in Qamishli, everyone knows everyone, and we heard a lot of incredibly sad stories about people who disappeared during bombings and shootings. I had family members and friends, both boys and girls, who were drafted to the military. It was during the worst time in the war and the military needed as many people as possible. When these people would return, they were very different. What they witnessed during their time in the military changed them. In that way, I’ve lost loved ones.

If you could go back, would you stay in Sweden or move back to Syria?

I would definitely go back. Besides the fact that I miss it, I want to help rebuild what the war has destroyed. I want to see my country back on its feet and stronger than ever. I want to start a family there and I want my children to grow up in the country that I grew up in.

If you could send a message to Christians in the West, what would you want them to know about Syria?

I want people not to only think of war when they hear “Syria,” because it’s so much more. I want them to know that the Syrian people are struggling and fighting for the country to remain. But most of all, I want them to continue to pray every day for the people there and know that any contribution is an enormous help for the Syrians.

 

 

Washington D.C., Apr 30, 2020 / 06:00 am (CNA).- The Syrian civil war has led to one of the largest refugee crises of modern times, and presented unique problems for Syria’s ancient Christian communities. Marginalized for centuries, persecuted by ISIS, afraid to attract any attention from the West, Syrian Christians remain, by most accounts, the war’s most invisible victims.

In partnership with the Philos Project, CNA sat down with Mary Sayegh, a Syrian who lives now in the United States:

Tell me a bit about yourself.

My name is Mary Sayegh. I am 22 years old and live in the United States. I was born and raised in my beloved hometown of Aleppo, Syria. I moved to New Jersey about six years ago, running away from war to build a better future for myself. It was hard to leave my parents, family and friends behind and start all over. To be honest, it wasn’t easy to fit in a new country, even though I’m an extrovert. In America, I had to try and rebuild my social life in a strange land. As for Syria, I was involved in the scouts in church, Sunday school, computer program classes, art, and basketball.

When I came here, I started high school as a junior. I was held back for a year because I had to do ESL and take two courses in US history. During that time, I started planning for college and eventually got accepted to Montclair State University as a biology major and a public health minor. During my studies I also worked several part-time jobs in retail, as an executive office assistant and a front desk receptionist for a doctor. I tried to find balance by going to the gym, hanging out with friends and volunteering at the hospital.

When and how did you flee to the US?

Before my dad was married, he lived in the US, and therefore had American citizenship. Naturally, he passed it on to the rest of the family when he got married and settled in Aleppo again. The American citizenship made it possible for me to have a safe flight to the US when I left Aleppo. I flew from Lebanon to Spain to spend 6 weeks with my uncle and his family. Then my aunt (from New Jersey) came and took me to the States because I was too afraid to fly alone. On September 27, 2014 I landed in America. My mom and brother came three months later, and I didn’t see my dad until a couple of years later. 

When did you start recognizing that there was a war going on in Syria?

I have lost track of the years. I have no idea what happened when. In general, everything started changing when they hit my hometown and we became more in danger. We couldn’t stay out late anymore or go to certain areas. It got to the point where I would walk in the streets and couldn’t find a familiar face. I didn’t recognize anyone on the streets mainly because many Christians in my neighborhood had fled Aleppo. Bombs, shootings and noises became a daily experience for us. On the contrary, it felt weird when nothing was happening.

Tell me about Aleppo.

Aleppo was one of the most beautiful cities. It is famous for its architecture, the churches, mosques, schools, tombs and baths. As an important center for culture and as one of the oldest continuously inhabited cities in the world, Aleppo was loved by all Syrians.

The Citadel of Aleppo was one of the things that made the city special. The Citadel is considered to be one of the oldest and largest ones in the world. It is the best place to watch the sunset and learn about our ancestors’ history. During the siege, the Citadel of Aleppo was partly destroyed, unlike its surrounding buildings that were left in ruins. Today, the area is filled with locals and even tourists that enjoy nice meals in the newly built restaurants around it.

Did you ever feel like you were less valued because you were a Christian in Aleppo/Syria?

I never felt that way. Maybe back in the day. But in my days, we never felt a difference. We felt we were all equal and we treated each other as human beings, brothers and sisters, regardless of our religious differences.

What are your best and worst memories from Syria?

My best memories were every second I spent in Syria growing up until I moved to the States. I would say my worst memory was having to attend friends’ funerals at a time when I thought I would be attending their graduations and weddings.

Tell me about Aleppo when it was under siege.

I consider myself one of the lucky ones. There were obviously people who lived under better conditions during this horrible time because they were rich, and my dad owned his own business, so we were considered upper middle class. However, days passed when we would not have water or electricity. Still, we were fortunate to at least have had a roof over our heads. Close to my home, al-Assad School opened up for the people whose homes had been destroyed in the clashes. So, one really gets a perspective.

A lot of young girls and boys helped their parents to buy or bring gallons of water or fuel to their homes. I would help my dad fill up huge bottles with water so we would always have some when needed. We also filled up our bathtub as soon as water was available. We had three buckets: one for clean water, one with the soap for when we would wash our hands, and one for when we rinse our hands. The latter one was later reused as water to flush in the toilet.

We never really knew which groups were fighting, or where, unless we saw it on the news. We just heard the bombs and the shootings. There would also be snipers on buildings that would shoot as soon as someone would pass by. Once, a sniper shot at our car, but it wasn’t critical, so we just continued driving.

I was also lucky because I didn’t lose any loved ones in the war. I had a fellow peer in the church scouts who was killed by a bomb. That was really emotional because it was the first time my scout played at a funeral and not a wedding of a person belonging to the scouts. Another scout lost his mother.

If there were to be peace in Syria tomorrow would you move back?

As much as it hurts me to say this, I wouldn’t go back. I will go to visit but not live there anymore. It’s just impossible for our young generation to go and build everything all over. And to be honest, what’s left for us to even go back to? Even if I want to what would I do with my degree?

 

 

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.”

The lawsuit, filed in 2014, alleges that the state was severely underfunding schools, forcing school districts to lean heavily on property taxes, which especially disadvantages students in property-poor areas.

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The Delaware Tourism Office (Visit Delaware) has received for the first time a coveted Adrian Award, the largest and most prestigious global travel marketing honor. The award, often described as the Oscar of the travel world, comes to Delaware for the most recent edition of the Official State Travel Guide, which was released in May. […]

  When/Where: Saturday, May 26th @ 10:30am – Parade Field Grounds of the Delaware Veterans Memorial Cemetery, 2465 Chesapeake City Road, Bear, DE  19701. When/Where: Wednesday, May 30th @ 10:am – War Memorial Plaza, 163 Cherry Lane, New Castle, DE  19720. The Delaware Commission of Veterans Affairs will like to invite you to their annual […]

Event provides visitors with an opportunity to experience seafaring lives of adventure, romance, excitement and hardships, and to honor mariners who made the ultimate sacrifice.

The Goldberg Variations: 32 Miniatures Based on Bach’s Keyboard Masterpiece, an exhibition of mixed media works by Gregg Silvis, will be on view in the Mezzanine Gallery from November 1-27, 2019.

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The Bisi Bele Bath is one dish that deserves this spotlight. 'Bele' refers to lentil and this flavourful dish combines rice, lentils and a medley of fragrant spices that is usually drenched in ghee.

Sonam, who is currently in Delhi with her husband and in-laws, has been posting pictures of the arrangements of the intimate celebration at the Ahuja household.

President Donald Trump evoked the coronavirus crisis ahead of a wreath-laying ceremony Friday at the World War II memorial in Washington to mark the 75th anniversary of the Allied victory in Europe.

Governor Markell has ordered the American and Delaware flags at state buildings and facilities be flown at half-staff on Peace Officers Memorial Day, Thursday, May 15.

In recognition of National Fallen Firefighters Memorial Weekend, Governor Markell has ordered the American and Delaware flags at state buildings and facilities to be lowered to half-staff.