Title: OxyContin Maker Purdue Offering Up to $12 Billion to Settle Opioid Claims
Category: Health News
Created: 8/27/2019 12:00:00 AM
Last Editorial Review: 8/28/2019 12:00:00 AM

Title: AHA News: Preeclampsia May Double a Woman's Chances for Later Heart Failure
Category: Health News
Created: 8/24/2020 12:00:00 AM
Last Editorial Review: 8/25/2020 12:00:00 AM

Title: Parents, Look Out for Mental Health Issues as College Kids Return to Class
Category: Health News
Created: 8/24/2021 12:00:00 AM
Last Editorial Review: 8/24/2021 12:00:00 AM

Title: As Classes Resume, Some Health Tips From the CDC
Category: Health News
Created: 8/27/2021 12:00:00 AM
Last Editorial Review: 8/27/2021 12:00:00 AM

The transcription factor (TF) cone-rod homeobox (CRX) is essential for the differentiation and maintenance of photoreceptor cell identity. Several human CRX variants cause degenerative retinopathies, but most are variants of uncertain significance. We performed a deep mutational scan (DMS) of nearly all possible single amino acid substitutions in CRX using a cell-based transcriptional reporter assay, curating a high-confidence list of nearly 2000 variants with altered transcriptional activity. In the structured homeodomain, activity scores closely aligned to a predicted structure and demonstrated position-specific constraints on amino acid substitution. In contrast, the intrinsically disordered transcriptional effector domain displayed a qualitatively different pattern of substitution effects, following compositional constraints without specific residue position requirements in the peptide chain. These compositional constraints were consistent with the acidic exposure model of transcriptional activation. We evaluated the performance of the DMS assay as a clinical variant classification tool using gold-standard classified human variants from ClinVar, identifying pathogenic variants with high specificity and moderate sensitivity. That this performance could be achieved using a synthetic reporter assay in a foreign cell type, even for a highly cell type-specific TF like CRX, suggests that this approach shows promise for DMS of other TFs that function in cell types that are not easily accessible. Together, the results of the CRX DMS identify molecular features of the CRX effector domain and demonstrate utility for integration into the clinical variant classification pipeline.

The class F of G protein-coupled receptors (GPCRs) consists of 10 Frizzleds (FZD_1–10) and Smoothened (SMO). FZDs bind and are activated by secreted lipoglycoproteins of the Wingless/Int-1 (WNT) family, and SMO is indirectly activated by the Hedgehog (Hh) family of morphogens acting on the transmembrane protein Patched. The advance of our understanding of FZDs and SMO as dynamic transmembrane receptors and molecular machines, which emerged during the past 14 years since the first-class F GPCR IUPHAR nomenclature report, justifies an update. This article focuses on the advances in molecular pharmacology and structural biology providing new mechanistic insight into ligand recognition, receptor activation mechanisms, signal initiation, and signal specification. Furthermore, class F GPCRs continue to develop as drug targets, and novel technologies and tools such as genetically encoded biosensors and CRISP/Cas9 edited cell systems have contributed to refined functional analysis of these receptors. Also, advances in crystal structure analysis and cryogenic electron microscopy contribute to the rapid development of our knowledge about structure-function relationships, providing a great starting point for drug development. Despite the progress, questions and challenges remain to fully understand the complexity of the WNT/FZD and Hh/SMO signaling systems.

Here, we highlight the case of a 31-yr-old man who had clinical features of primary hypertrophic osteoarthropathy (PHOAR) and harbored a homozygous variant (c.38C > A, p.Ala13Glu) in the HPGD gene, as indicated by whole-exome sequencing (WES). This variant has been previously classified by our laboratory as a variant of uncertain significance (VUS). However, another patient with the same phenotype and the same homozygous variant in HPGD was subsequently reported. In reassessing the variant, the absence of this variant in the gnomAD population database, supporting computational predictions, observation in homozygosity in two probands, and specificity of the phenotype for HPGD, all provide sufficient evidence to reclassify the HPGD c.38C > A, p.Ala13Glu variant as likely pathogenic.

The deadline to claim part of the $15 million Cash App settlement is November 18. Here's what to know.

The leak caught national intelligence officials by surprise and led to an embarrassing Air Force Inspector General investigation.

"I look forward to any contest, where of course it will be for branch members to select those they wish to represent them in Holyrood in the 2026 Scottish Parliament elections.”

Up to 650 houses could be built on land at the golf club

I would never have predicted there'd be an isometric tactics game based on run-and-gun series Metal Slug, yet here Metal Slug Tactics is, and I am here for it. We've been following its development for a while but it's out now on Steam, and seemingly as strong as its demo suggested.

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Sega are delisting several bundles of 'classic' games from digital stores, along with "select individual" games. On Steam specifically, this adds up to over 60 games in total, including several actual classics including the original Streets Of Rage trilogy, Crazy Taxi, and Jet Set Radio.

The games will be removed on December 6th but will remain playable to those who already own them.

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The developers of hero shooter Overwatch 2 must have dropped a box full of old photographs while clearing the attic, spilling old snapshots of Route 66 onto the floor and getting snared in a nostalgic daze. The game is launching a "Classic" mode today that will let you play the first-person payload pusher as it (mostly) was back in 2016 when the first Overwatch launched. That means 6v6 fights, the original abilities of its heroes, and no limits to stop the entire team picking the same character.

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My strongest and most enduring memory of Grand Theft Auto will always be creasing into complete hysterics watching my mate pile into a crumpled police officer with a wooden baseball bat in GTA 3 after school one time. Young’uns these days just don’t appreciate how revolutionary it was to be able to hit a cop with a thing after he’d already fallen over. Suffice it to say I’ve got good memories of the open world series’ nascent forays into 3D, though never enough to tempt me into revisiting them, especially given the poor reception to Grand Theft Auto: The Trilogy - The Definitive Edition. I can sympathise. I’m annoyed just having to type a semicolon and a dash in the same game name.

If you’re in a similarly non-fussed position (I will never not be annoyed that ‘nonplussed’ doesn’t mean what it sounds like it should mean) I can’t imagine a lighting update that’s been available on the mobile versions for a while is enough to tempt you back. But what is a reporter's job if not pathetically treading water between chunklets of Grand Theft Auto news, upon the publishing of which Graham presses the button to release the nutritious pellets on which we all wholly subsist? I hope he doesn’t read that last sentence. I don’t get my pellet if the syntax becomes too convoluted. Moving swiftly on.

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WASHINGTON — For U.S. presidents, meeting the families of military personnel killed in war is about as wrenching as the presidency gets. President Donald Trump’s suggestion Monday that his predecessors fell short in that duty brought a visceral reaction from those who witnessed those grieving encounters.

“He’s a deranged animal,” Alyssa Mastromonaco, a former deputy chief of staff to President Barack Obama, tweeted about Trump. With an expletive, she called Trump’s statement in the Rose Garden a lie.

Trump said in a news conference he had written letters to the families of four soldiers killed in an Oct. 4 ambush in Niger and planned to call them, crediting himself with taking extra steps in honoring the dead properly. “Most of them didn’t make calls,” he said of his predecessors. He said it’s possible that Obama “did sometimes” but “other presidents did not call.”

The record is plain that presidents reached out to families of the dead and to the wounded, often with their presence as well as by letter and phone. The path to Walter Reed and other military hospitals, as well as to the Dover, Delaware, Air Force Base where the remains of fallen soldiers are often brought, is a familiar one to Obama, George W. Bush and others.

Bush, even at the height of two wars, “wrote all the families of the fallen,” said Freddy Ford, spokesman for the ex-president. Ford said Bush also called or met “hundreds, if not thousands” of family members of the war dead.

READ MORE: What Trump said about his drug czar pick, health care fixes

Obama’s official photographer, Pete Souza, tweeted that he photographed Obama “meeting with hundreds of wounded soldiers, and family members of those killed in action.” Others recalled his frequent visits with Gold Star families, and travels to Walter Reed, Dover and other venues with families of the dead and with the wounded.

Retired Gen. Martin E. Dempsey, the former chairman of the Joint Chiefs of Staff, confirmed these contacts, tweeting: “POTUS 43 & 44 and first ladies cared deeply, worked tirelessly for the serving, the fallen, and their families. Not politics. Sacred Trust.”

Trump addressed the matter when asked why he had not spoken about the four soldiers killed in Niger. They died when militants thought to be affiliated with the Islamic State group ambushed them while they were patrolling in unarmored trucks with Nigerien troops.

“I actually wrote letters individually to the soldiers we’re talking about, and they’re going to be going out either today or tomorrow,” he said, meaning he wrote to the families of the fallen soldiers. He did not explain why letters had not been sent yet, more than a week after the attack.

“If you look at President Obama and other presidents, most of them didn’t make calls,” Trump said.

Pressed on that statement later, he said of Obama: “I was told that he didn’t often, and a lot of presidents don’t. They write letters.” He went on: “President Obama, I think, probably did sometimes, and maybe sometimes he didn’t. I don’t know. That’s what I was told. … Some presidents didn’t do anything.”

Press Secretary Sarah Huckabee Sanders said later that Trump “wasn’t criticizing predecessors, but stating a fact.” She argued that presidents didn’t always call families of those killed in battle: “Sometimes they call, sometimes they send a letter, other times they have the opportunity to meet family members in person.”

She said anyone claiming a former president had called every family was “mistaken.”

Bush’s commitment to writing to all military families of the dead and to reaching out by phone or meeting with many others came despite the enormity of the task. In the Iraq war alone, U.S. combat deaths were highest during his presidency, exceeding 800 each year from 2004 through 2007. The number fell to 313 in Bush’s last year in office as the insurgency faded. Bush once said he felt the appropriate way to show his respect was to meet family members in private.

READ MORE: What the Bannon vs. McConnell fight means for Trump and the GOP

Obama declared an end to combat operations in Iraq in August 2010 and the last U.S. troops were withdrawn in December 2011. As Obama wound down that war, he sent tens of thousands more troops into Afghanistan in 2009 and 2010, and the death count mounted. From a total of 155 Americans killed in Afghanistan in 2008, which was Bush’s last full year in office, the number jumped to 311 in 2009 and peaked the next year at 498. In all, more than 1,700 died in Afghanistan on Obama’s watch.

Among other rituals honoring military families, the Obamas had a “Gold Star” Christmas tree in the White House decorated with hundreds of photos and notes from people who had lost loved ones in war. Gold Star families visited during the holidays, bringing ornaments.

Trump visited Dover early in his presidency, going in February with his daughter Ivanka for the return of the remains of a U.S. Navy SEAL killed during a raid in Yemen, William “Ryan” Owens.

Trump’s relations with Gold Star families have not always been smooth, dating from his belittlement of the parents of slain U.S. soldier Humayun Khan, who was Muslim. Trump was angered when the soldier’s father, Khizr Khan, was given a platform to criticize him at the Democratic National Convention.

Owens’ grieving father said he didn’t want to talk with Trump at Dover. But the sailor’s widow, Carryn, attended Trump’s address to Congress and wept as he thanked her.

___

Associated Press writers Robert Burns and Jesse J. Holland contributed to this report.

The post Trump’s claim about predecessors, fallen troops disputed appeared first on PBS NewsHour.

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JUDY WOODRUFF: Now: new questions surrounding the deaths of four Green Berets in the Western African nation of Niger and the role of the president as consoler in chief.

John Yang has the story.

JOHN YANG: Sending young Americans into harm’s way can be the most serious decision a president makes. Consoling the families of the fallen has become the latest controversy to engulf President Trump.

To bolster his claim that he does more than his predecessors, Mr. Trump today invoked the dead son of his chief of staff, retired Marine general John Kelly.

PRESIDENT DONALD TRUMP: To the best of my knowledge, I think I have called every family of somebody that’s died. Now, as far as other representatives, I don’t know. I mean, you could ask General Kelly, did he get a call from Obama?

JOHN YANG: Kelly’s 29-year-old son, Robert, a Marine lieutenant, was killed in 2010 when he stepped on a land mine in Afghanistan, an episode Kelly rarely talks about publicly. Kelly and his wife did attend a 2011 Memorial Day breakfast President Obama hosted for Gold Star families.

President Trump ignited the furor when he was asked about his public silence on four Green Berets killed two weeks ago in Niger.

PRESIDENT DONALD TRUMP: If you look at President Obama and other presidents, most of them didn’t make calls. A lot of them didn’t make calls. I like to call when it’s appropriate, when I think I’m able to do it.

JOHN YANG: Reporters pressed him to back up the claim.

PRESIDENT DONALD TRUMP: I don’t know. That’s what I was told. All I can do — all I can do is ask my generals.

JOHN YANG: The response from former Obama officials was swift and forceful.

Former Attorney General Eric Holder tweeted this photo and insisted: “Stop the damn lying. I went to Dover Air Force base with 44 and saw him comfort families,” a reference to one of Mr. Obama’s late-night trips to pay his respects to troops killed in Afghanistan.

Mr. Obama and President George W. Bush often visited wounded warriors at Walter Reed and Bethesda hospitals, a practice Mr. Trump has continued. In February, the president and his daughter Ivanka went to Dover for the return of the remains of a Navy SEAL killed in Yemen, the first casualty of his administration.

So far this year, the Pentagon says 16 Americans have been killed in action. Another 17 sailors died in accidents. In the first year of the Obama presidency, 344 were killed in action.

During last year’s campaign, Mr. Trump publicly feuded with the Khans, the parents of a Muslim American soldier killed in Iraq, after they criticized him at the Democratic Convention.

Today, the Khans said: “President Trump’s selfish and divisive actions have undermined the dignity of the high office of the presidency.”

The current controversy comes as questions are being raised about how and why the four soldiers died in Niger.

Senator Jack Reed is the top Democrat on the Armed Services Committee.

SEN. JACK REED, D-R.I.: I think the administration has to be much more clear about our role in Niger and our role in other areas in Africa and other parts of the globe.

JOHN YANG: The Pentagon is investigating the deaths. Reportedly among the questions, did commanders adequately assess the risk, and was there ready access to medical support?

Today, President Trump called the families of the four dead Green Berets.

For the PBS NewsHour, I’m John Yang.

The post Trump ignites furor with claim past presidents didn’t console military families by phone appeared first on PBS NewsHour.

A DWP employee who has been working in the welfare system for 42 years has shared some key advice for new claims for the likes of PIP and Attendance Allowance

The energy bill support has been described as a "crucial lifeline" for certain individuals who are often "overlooked".

A new supercapacitor design that uses only water, clay and graphene could source material on Mars and be more sustainable and accessible than traditional batteries

From Goats to airplanes, Xbox Game Pass has another bumper month in store for subscribers. Here's everything you need to know about what is heading to PC and console this November 2024

Death Stranding, originally launched in 2019, has finally come to Xbox consoles five years after its initial debut as a Director's Cut version from Hideo Kojima.

Overwatch 2 is bringing 6v6 gameplay back from Overwatch 1 - and fans are overjoyed. Here's all we know so far, including when you can finally play the Classic mode

As artificial intelligence becomes more common in university classrooms, some professors are weighing the benefits — and downsides — of students using it for research projects.

However, the comparative Win 11 AMD tests were on an unpatched (L3 cache, CPPC2) PC.

Senator-elect Jim Justice's office has clarified reports that his famous pooch Babydog was banned from the Senate floor, saying Justice never intended to bring the dog onto the floor.

Both hit weeks after OpenAI released a ChatGPT app.

The parents of the 23-year-old Black man, who died last year, sued police and medical officials.

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Critics worry Anthropic is endangering its "ethical" AI stance due to defense associations.

The new Louisiana requirement that the Ten Commandments be displayed in every public classroom by Jan. 1 was temporarily blocked Tuesday. The judge said the law is "unconstitutional on its face."

Caitlin Clark took more than her fair share of verbal abuse during the WNBA season. Now, even though the season has long since passed, she's still taking abuse.

The post Knicks Legend Throws Shade at Caitlin Clark During Live Broadcast appeared first on Breitbart.

The Federal Emergency Management Agency supervisor fired for telling workers to avoid homes with Trump signs or flags said in an interview Tuesday that "senior leadership" at FEMA was well-aware of this guidance and it was not an isolated incident.

The post Ex-FEMA Worker Claims Leadership Knew Workers Were Avoiding Homes with Trump Signs appeared first on Breitbart.

Election deniers have spent the past four years focused on false claims that 2020 was rigged. This year, it raised similar alarms about fraud — only for those claims to evaporate as returns came in.

All the kit balancing, squad leading, and lore you could want, if you want it.

Nobody loses games they already bought, but the clock is ticking.

Pat McLaughlin is stepping down as Hockey Canada's chief operating officer and executive vice-president of strategy, the governing body announced Monday.

Canadian soccer great Christine Sinclair played her final pro game on Sunday when her Portland Thorns were eliminated from the NWSL playoffs by Gotham FC.

Shea Weber is member of the Hockey Hall of Fame. The former defenceman headlined the 2024 class inducted Monday, joining Pavel Datsyuk, Jeremy Roenick, Natalie Darwitz and Krissy Wendell in the player category. David Poile and Colin Campbell entered as builders.

For a lot of folks who have been following Capcom’s fighting games over the years, the Marvel vs Capcom Fighting …

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Every county in Georgia has certified its general election results. There had been concerns about election certification, but with Donald Trump's victory, those worries have largely gone away.

Though many amature divers claim to have found the famous shipwreck, it's likely still below Lake Michigan's waves.

‘They acted like Republicans for the last four months,’ Stewart lamented in a scathing monologue

Actor recalled angry phone call with Murphy in which she claims he ‘ripped’ into her

I’m a Celebrity... Get Me Out of Here!’s 2024 campmates were finally confirmed on Monday, 11 November.

The former striker will depart the programme at the end of the 2024/25 season