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Health
'A cure of HIV is possible': UNMC, Temple researchers eliminate virus in humanized mice

For the first time since the 1980s AIDS epidemic began, researchers say they’ve taken an important step toward a possible cure for HIV, thanks to technologies developed in labs at the University of Nebraska Medical Center and Temple University.

People living with HIV currently have to take drugs every day for the rest of their lives to keep the virus at bay.

But the virus continues to hide out in some tissues, its DNA tucked into that of its host, ready to flare again if the drugs are stopped.

Now researchers at UNMC and Temple University say they have eliminated HIV for the first time from the genomes of a small number of humanized mice using a combination of two different therapies.

“This is proof of concept that a cure of HIV is possible,” said Dr. Howard Gendelman, chairman of UNMC’s pharmacology and experimental neuroscience department and a senior investigator on the study.

The researchers first used a slow-release, long-lasting formulation of HIV drugs developed at UNMC to suppress the virus in infected mice and then followed with a gene-editing therapy that Temple scientists in Philadelphia created to cut the virus’ DNA from their genomes.

Of the mice that received the treatment, about a third showed no signs of HIV infection for up to five weeks after treatment, according to a report published Tuesday in the journal Nature Communications. The research is receiving international attention.

Both scientists acknowledged that plenty of work lies ahead, starting with more studies in animals. But they said combining the two therapies provides a “clear path to move ahead” in further trials in animals and possibly clinical trials in humans.

“What we’ve done is we’ve showed that HIV can be cured,” Gendelman said.

Kamel Khalili, chairman of the neuroscience department at Temple’s Lewis Katz School of Medicine in Philadelphia, said the fact that no technology since the AIDS epidemic began has been able to eliminate HIV has created the impression that the disease is incurable.

“This is the first time we’ve shown together the disease can be eliminated if we use a combination therapy,” said Khalili, the study’s other senior investigator.

Dr. Robert Gallo, who co-discovered HIV as the cause of AIDS in 1984, offered congratulations.

“In my view, this is the most interesting and important therapy-related research advance I have seen in many, many years,” Gallo said in a statement. He is the co-founder and director of the Institute of Human Virology at the University of Maryland School of Medicine.

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Zandrea Ambrose, an HIV researcher with the University of Pittsburgh Medical Center, called the study promising but said she’s not sure the researchers yet have demonstrated with 100% certainty that they’ve eliminated the virus.

The study followed the mice for a relatively short time. In several human cases in which the virus was believed to have been eliminated, including a Mississippi baby given HIV drugs from an early age, it eventually came back.

Many groups are working toward a cure, said Ambrose, who was not involved in the study. “This is probably one of the most promising studies that have come out, but there’s some work that still needs to be done,” she said.

Given the effectiveness of the HIV drug therapies now available, she added, “We’d want to make sure the system is as safe as possible before we deliver it to humans.”

Gendelman noted that the researchers conducted exhaustive testing in their search for remaining virus. “There was no trace of the virus there,” he said.

According to estimates by the United Nations, more than 36.7 million people worldwide are infected with the virus, about 1.2 million of them in the United States. Some 5,000 people are newly infected every day around the world.

Gendelman and fellow UNMC researchers previously have worked to modify HIV drugs to create the long-acting, slow-release forms. They’ve demonstrated in previous research that their system extends the life of the drugs and helps them reach cells and tissues where the virus hides. The strategy was co-developed by Benson Edagwa, an assistant professor of pharmacology at UNMC.

But Gendelman said that method alone couldn’t eliminate HIV. The Temple group, meantime, had found a way to cut out the virus’ DNA using a modified version of the CRISPR-Cas9 gene editing system. (Think of CRISPR-Cas9 as molecular scissors.) But it wasn’t very effective with a lot of virus present.

Combining the two allowed the researchers to suppress viral activity, which allowed the Temple team’s system to be more effective.

The combination was effective in about one-third of mice treated. Khalili called that a good first step. By comparison, the researchers could readily detect HIV in mice that had received either therapy separately.

“That shows the system works,” he said. “Now you have to optimize the situation to bring it up to 100% of animals. We’re working on it.”

And the CRISPR system stayed on target. Concerns previously have arisen that CRISPR could make cuts in the wrong places.

Gendelman said the researchers went as far as to analyze the genetic sequences of the human cells in the mice and found no harmful effects.

Potential therapies that work in mice often don’t make the jump to humans. Gendelman said that using mice with humanized immune systems partially closed that gap. The humanized mice were developed at UNMC.

The researchers already are proceeding with next steps. The UNMC team has begun moving ahead with research in primates. The Temple team plans to begin testing for toxicity in a small number of humans, using conventional HIV drugs, in 2020.

Meantime, UNMC’s tech transfer office, UNeMed, is working to commercialize the long-lasting drugs, said Michael Dixon, its president and CEO.

The benefits of the drugs, known by the acronym LASER ART, are significant on their own, he said. Gendelman’s previous research suggests that they can be taken less often than the current daily routines.

Dixon cautioned that bringing a drug to market is not a fast process. It took five to 10 years to commercialize current HIV drugs, which essentially have changed the virus from a death sentence to a chronic illness.

Both Gendelman and Khalili hailed the collaborative nature of the project — the report lists more than 30 authors. Prasanta Dash, an instructor in UNMC’s pharmacology and experimental neuroscience department, was the paper’s lead author.

Khalili said he doesn’t believe the work would have been possible in a single laboratory because of the expertise required at each.

Said Gendelman: “It’s the first time anyone has eliminated HIV from an animal with the prospect of moving to humans.”

17 rare and unusual health stories out of Omaha

Courts
Aubrey Trail and Bailey Boswell had spoken of a desire to torture and kill someone, 3 women testify

WILBER, Neb. — Three young women — all of whom said they were lured into group sex and other activities orchestrated by Aubrey Trail and Bailey Boswell — testified Tuesday that the pair spoke more than once about a desire to torture and kill someone.

The talk, they said, came both before and after the Nov. 16, 2017, disappearance of Sydney Loofe, the Lincoln store clerk Trail and Boswell are accused of killing and dismembering.

One woman testified that the pair put off a “weird vibe” that made her suspect something “bad” had happened when she was picked up by Trail and Boswell in Omaha on Nov. 17.

The three women all said they met Boswell on the online dating app Tinder — as did Loofe, 24 — and were later introduced to her “sugar daddy,” Trail, who promised to help them financially.

All three testified that they were threatened by Trail and Boswell if they didn’t obey the pair’s rules and follow their wishes. Their fear continued even after the pair were apprehended in Branson, Missouri, two weeks after Loofe is believed to have been killed.

“It crossed my mind multiple times,” said one of the women, “if I said the wrong thing (to police) that my life and my family’s lives were still threatened.”

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The women — whose names were ordered not to be published by the trial judge on Tuesday — were key witnesses to bolster the prosecution’s argument that Trail and Boswell had conspired for months to lure a young woman via social media for the purpose of homicide.

Trail and Boswell are both charged with first-degree murder and face the possibility of the death penalty if convicted. Trail’s attorney, and Trail himself, have maintained that Loofe died accidentally, by choking, during a sexual fantasy involving Trail and two unidentified women that went too far.

Trail’s murder trial is scheduled to continue into next week, after a four-day break starting on the Fourth of July. Boswell’s trial is scheduled for October.

Tuesday’s testimony revealed bizarre and scary allegations from several weeks just prior to Loofe’s disappearance and a few from just afterward.

That’s the time period in which the three women said they lived and traveled, mostly at separate times, with the two murder suspects.

Among the details in Tuesday’s testimony:

  • That Trail and Boswell wanted one of the women to select someone to kill and torture so they could videotape the act and sell it.

“They said they would make $1 million to do it, then split it and go separate ways,” the woman said.

  • That Boswell wanted one of the women to torture and kill someone to prove her loyalty to Boswell in their dominant/submissive sexual relationship. The woman said the order was later dropped after she proved her worth.
  • That each of the women, who mostly met up with the pair individually, was paid between $150 and $200 a week as an “allowance.” But, they said, the payments came with a set of rules, including calling Trail “daddy” and Boswell “mommy,” participating in group sex sessions and accepting punishment, including whippings.
  • That Trail insisted that he had supernatural powers, including the ability to fly and to put Boswell in a trance — powers that elicited skepticism from most of the women.
  • That one of the women had a fantasy of being a cat, complete with a leash and collar. But she said she was humiliated when she was ordered to eat cat food out of a bowl.
  • That Boswell enjoyed pain during sex and wanted one of the young women to talk about acts of torture while engaging in sex with her. Boswell, the woman testified, also talked of dismembering a body and breaking someone’s fingers as a form of torture.
  • That Trail had what he called a “kill bag” that contained a hammer, pliers and a sauna suit.

Such a plastic suit was found with Loofe’s body parts.

  • That one of the women, after learning that Loofe was missing, suggested that someone kidnap Trail’s daughter to force him to exchange her for Loofe.

Tuesday also included a rare order from a judge to not publish the names of the three women who testified Monday afternoon and Tuesday in open court.

Before the trial began, Saline County District Judge Vicky Johnson had ordered that photographs and video not be broadcast of the three women when they testified, to protect their privacy.

In that May 22 order, the judge also added: “This does not restrict the media from otherwise reporting on their testimony.”

On Tuesday, however, the judge clarified her order and ordered reporters to not publish the women’s names, which had been revealed in open court during testimony this week and last week.

One of Trail’s court-appointed attorneys, Ben Murray of Hebron, used his cross-examination to question the women about their fantasies — and whether those fantasies included an interest in torture and murder. He also asked them whether they had participated in the killing of Loofe, as well as the dismemberment and disposal of her body, which law enforcement said occurred on Nov. 16, 2017 — the day after Loofe met Boswell for a Tinder date.

“Isn’t it possible you helped dispose of the body?” Murray asked one of the women, the one with the cat fantasy. “How did the (cat) leash get out (where the body parts were found)?”

“I don’t know,” responded the woman.

But under additional questioning by Sandra Allen, one of the prosecutors from the Nebraska Attorney General’s Office, the woman — by now dabbing tears with a tissue — said that on Nov. 16 she was in Omaha playing with her younger brother and visiting a doctor to obtain an inhaler for asthma.

Another of the women, under questioning by Murray, acknowledged that she asked Trail to choke her during sex with Boswell, and that Trail was reluctant to do so, saying he could hurt someone.

The last woman to testify acknowledged that she was interested in torture and serial killers, but said that it was an academic interest about Renaissance-era practices, and not a sexual interest.

Trail did not attend the court proceedings again on Tuesday. He has been absent since June 24, when he slashed his neck in court in an apparent suicide attempt.

Tuesday’s testimony by the three woman also included new allegations about the path taken by Trail and Boswell after the slaying.

They first went to Omaha, where they picked up one of the women, and then checked into the Ameristar Casino in Council Bluffs. They stayed until Nov. 19, leaving Trail’s car at a Walmart and leaving in the woman’s vehicle for a supposed “cocaine run” to Grand Island that was supposed to make them $25,000.

The woman said the cocaine run, in which the drug was supposed to be dropped from a plane, “absolutely made zero sense,” but she went along, in part to be obedient.

After spending three days in Grand Island without getting the drugs, the woman said, Trail and Boswell began talking of traveling to Kearney, where they could find a victim to torture and kill “who would not be missed.” Trail, she said, wanted to watch the two women commit the slaying.

The woman said they drove to Kearney and checked into a hotel but quickly left after she saw a message on her cellphone from the Lincoln Police Department.

“I freaked out,” the woman said, adding that Trail and Boswell got “very serious” and explained that they were being blamed for the disappearance of a young woman Boswell had dated.

“For the first time, I was super scared,” said the woman, who was then driven back to the Omaha area and dropped off.

Notable crime news of 2019

Articles
No citizenship question, so questionnaire goes to print

2020 CENSUS

WASHINGTON — The Trump administration has decided to give up its fight to add a question about citizenship to next year's census.

The U.S. Census Bureau on Tuesday started printing the questionnaire without the controversial query.

President Donald Trump had said after the U.S. Supreme Court decision last week to halt the addition of the question that he would ask his attorneys about possibly delaying next spring's census.

But Justice Department spokeswoman Kelly Laco confirmed Tuesday there would be "no citizenship question on 2020 Census."

Some states' officials as well as neutral experts said the question would result in an undercount of immigrants, which could cost some states billions in federal funds and shift congressional districts from states with large numbers of immigrants to those with fewer.

The Supreme Court last week blocked the administration's effort to add the question on citizenship to the census, saying Commerce Secretary Wilbur Ross, whose agency oversees the Census Bureau, provided a contrived answer for why he wanted to make the move.

But the 5-4 ruling by Chief Justice John Roberts gave the administration a chance to start over and try to come up with a new rationale for adding the question to the once-a-decade head count of the U.S. population.

As recently as Monday, Trump had said the census should include a question about citizenship. "I think it's very important to find out if somebody is a citizen as opposed to an illegal," he said at the White House.

Many conservative legal scholars and advocates who believed the justices went too far in their decision had urged the administration to move aggressively to revive the citizenship question.

Democrats had argued that adding a question on citizenship would have been a partisan ploy to reduce minority participation in the census. The top House and Senate Democrats hailed Tuesday's news.

Opponents of the question said it would discourage participation by immigrants and residents who are in the country illegally, potentially providing inaccurate figures for a count that determines the distribution of some $675 billion in federal money and how many congressional districts each state gets.

"Everyone in America counts in the census, and today's decision means we all will," said Dale Ho, who argued the Supreme Court case as director of the American Civil Liberties Union's Voting Rights Project.

Because the census by law must keep responses anonymous, putting a citizenship question on the survey would not actually let officials know who is a legal resident and who isn't. But it could have had a major impact on the distribution of billions of dollars in federal funds and the balance of political power in the country, hurting states, including California, that have large numbers of residents who are immigrants.

Ross said that while he respected the Supreme Court's decision, he strongly disagreed with it. "The Census Bureau has started the process of printing the decennial questionnaires without the question," Ross said Tuesday.

The administration faced time pressure to make a decision because of a deadline for starting to print millions of census forms. Most people are expected to fill out the census forms online, however. Responses also can be given by phone.

This report includes material from the Associated Press.


Military
75 years later, Nebraska Guard hits French beaches to commemorate its bloodiest battle

Inch by bloody inch, the Nebraskans from the 134th Infantry Regiment fought through the open fields and dense hedgerows of Normandy.

They staked their claim and made their names on Hill 122, just outside the French village of St. Lô. The fierce battle, under intense fire from German artillery, made July 15, 1944, the bloodiest day the Nebraska National Guard has ever known, and probably ever will.

The Nebraska regiment fought its way through the rest of the Normandy campaign, the infamous Battle of the Bulge, and on through Victory in Europe Day the following spring. But that first day of combat, just 23 miles from Omaha Beach, was the one that stuck with every veteran who survived it.

“St. Lô was always their reference point for all their loss and pain,” said Jerry Meyer, the Nebraska National Guard’s historian. “Nothing else was as bad as St. Lô.”

The Guard is taking time to commemorate the 75th anniversary of the battle of St. Lô this month, both here and in France.

This week, Meyer is putting the finishing touches on a long-awaited permanent exhibit at the Nebraska National Guard Museum in Seward called “Cornrow to Hedgerow,” dramatizing the St. Lô fight.

NEBRASKA NATIONAL GUARD MUSEUM 

The new 4-D exhibit at the Nebraska National Guard Museum, “Cornrow to Hedgerow,” is based on a Keith Rocco painting called “From Cronrow to Hedgerow — The 134th Infantry at St. Lo, Normandy, France, on July 15, 1944.”

The walk-through diorama simulates the sights and sounds of the battle and is modeled on a painting by Keith Rocco of the same name. The museum spent two years raising $232,000 to build the display. It will be unveiled publicly for the first time Thursday, during Seward’s huge annual Fourth of July celebration.

“It’s our cornerstone exhibit,” Meyer said. “Seventy-five years later, we can really honor the 52 Nebraskans who were killed in that battle.”

The exhibit has been assembled by Omahan Doug Hartman, of Hartman Historical Services. The former Nebraska National Guard officer has done extensive research and writing on the St. Lô battle.

The 134th Infantry Regiment was part of the 35th Infantry Division, which had been federalized in December 1940 and filled out with draftees from around the country. After the Pearl Harbor attack, the division was assigned to Southern California for defense of the southwestern United States. The landing at Omaha Beach a month after D-Day — which was June 6, 1944 — represented the unit’s first combat action.

The planners of D-Day had expected the units landing at Omaha Beach to push forward and take St. Lô by the evening of the first day.

That forecast proved to be wildly optimistic. The troops struggled to establish a beachhead. Once they did, German reinforcements moved to surround the Normandy beaches and pen in the Allied invaders.

Instead of one day, it took more than a month to reach the outskirts of St. Lô. The 134th Regiment was sent as a relief unit to take over for units that had been battling constantly since the beginning of the invasion.

Meyer is escorting a group of about 45 civilians — including Guard veterans, descendants of men who served in the 134th, Gold Star family members and history buffs — on a 10-day tour that will start on Omaha and Utah Beaches and follow the route of the 134th through Normandy, St. Lô, Nancy and the Ardennes forest, where the regiment fought the Battle of the Bulge.

They’ll wind up in Rheinberg, Germany, where the Nebraskans crossed the Rhine River near the end of the war.

The group will take part in multiple ceremonies of commemoration along the way. They will visit U.S. military cemeteries at Normandy, Lorraine and Luxembourg.

“At each one, we’ll lay a wreath,” Meyer said. “There will be lots of keys to cities, proclamations.”

Maj. Gen. Daryl Bohac, the state’s adjutant general, is leading another group — as many as 40 Nebraska National Guard soldiers — on visits to Normandy and St. Lô for 75th anniversary ceremonies. Their tour is being framed as a “staff ride,” an Army term for an educational tour of important military sites.

NEBRASKA NATIONAL GUARD MUSEUM 

Nebraska National Guardsmen from the 134th Infantry Regiment enter St. Lô, France, in July 1944. Nebraska soldiers fought a brutal battle up a hill and eventually into St. Lô — nearly 800 of the regiment’s 3,000 men were either killed or wounded during the 48 hours before the Nebraskans entered the French village. The regiment’s commander, the World-Herald reporter stationed with the regiment during World War II and a Nebraska historian have long argued that the 134th Infantry Regiment has never received the credit it deserved for liberating St. Lô.

The military and civilian group will see Hill 122, so named because it stood 122 meters (400 feet) high. The Germans commanded the heights and opened fire on U.S. forces trying to take the town, which was at a strategic crossroads.

The Nebraska regiment fought fiercely to seize the hill. Nearly 800 of the 3,000 soldiers from the 134th who fought there were killed or wounded.

The regiment used more ammunition in one day than any two divisions had used in any previous day, reported Omaha World-Herald war correspondent Lawrence Youngman, who accompanied the 134th during the Normandy campaign. The unit’s rallying cry was, and still is, “All Hell Can’t Stop Us.”

The Army, though, shifted credit for the capture of St. Lô to another unit. The 134th, under the command of Col. Butler Miltonberger, of North Platte, was ordered to pull back from the ruined town while members of the 29th Infantry Division, made up mostly of soldiers from Virginia and Maryland, marched into the city July 18. The 29th had landed more than a month earlier, on D-Day.

One of Youngman’s 1944 dispatches was headlined “134th Enters City First; Others Get Credit.”

Miltonberger, who went on to head the Nebraska National Guard after the war, seethed over the slight. Many of his soldiers did, too. He wrote letters to newspapers and magazines trying to correct the record, until his death in 1977.

The opening of a St. Lô museum in the 1990s that honored both groups of soldiers eased the burn a little. So did the dedication of the monument at St. Lô 10 years ago in honor of Lt. Col. Alfred Thomsen of Omaha, commander of the regiment’s 3rd Battalion, who died of wounds suffered in combat two weeks after the St. Lô battle.

“We have always kind of felt overlooked,” James Huston, an officer with the 134th during the war and a close friend of Thomsen’s, told The World-Herald in 2009. “We’re overlooked no more.”

Huston died in 2017, at age 98. He was one of the unit’s last survivors. Meyer said he doesn’t believe any are still living now.

Honoring our heroes: A gallery of Nebraska veterans