If you believe you don't have anything to offer
When I was diagnosed with Cushing’s disease
like I was on an island surrounded by raging waves I couldn’t possibly swim through
I built a community of understanding people
as well as by meeting up with local Cushing’s disease friends
I assumed that no one other than people with Cushing’s disease could understand what I was going through
when I shared social media posts about my insomnia
People reached out to me for advice regarding their own insomnia and told me what had worked for them
It changed my entire outlook when I realized there was a larger community to unlock
Because of that, I’ve expanded my community into other illnesses, partly because of my work here at Bionews
One thing I’ve noticed is that my “island” was a figment of my imagination
we’re a web of people who’ve all had similar experiences
Since there are often overlapping symptoms with various conditions
it’s good to have discussions about how they affect us day to day
which isn’t very common in the Cushing’s community
But my expanded community taught me to put ice on my neck
But it’s not just symptoms that connect us. We all know what MRIs, CT scans, and ultrasounds are. We overlap on mobility aids, pain relief, and even reactions from family and friends
I’m in the process of getting a new mobility aid thanks to one of my new chronically ill friends
I still think that our various chronic illness communities are still too disconnected
and we’d be stronger and have more support if we joined together
If you’re having doubts about joining the conversation
or different enough to put yourself out there and become part of this larger community
by building a community for Cushing’s disease
I highlight the stories of people with other illnesses and disabilities and share connections with people who feel lonely
when someone with disabilities needs crowdfunding
I’ve been able to crowdfund clothing and blanket donations, help people get diagnosed and connect with doctors
Those of us with chronic illnesses and disabilities are both a community and a culture
There’s so much beauty to be found in widespread understanding and acceptance
I commit to expanding our community and connecting with others who share similar experiences
You can also follow my journey on TikTok and YouTube
Note: Cushing’s Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment
This content is not intended to be a substitute for professional medical advice
Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition
Never disregard professional medical advice or delay in seeking it because of something you have read on this website
The opinions expressed in this column are not those of Cushing’s Disease News or its parent company
and are intended to spark discussion about issues pertaining to Cushing’s
This site is strictly a news and information website about the disease
the editor’s role is usurped by a rogue reporter who declares breaking news nonstop
flooding the newsroom with bulletins and sending everyone into overdrive
The newsroom—your body—responds with metabolic fluctuations
Cushing’s Disease can cause lasting deterioration of the body: osteoporosis
It’s a common disease and easier to detect in canines
University of Georgia researchers are leveraging canine treatments to find new solutions to battle the condition in humans
This collaboration between veterinary medicine and human health is just one example of how UGA uses a Precision One Health approach to find and tailor new medical treatments for people and animals
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"A life well lived is a precious gift of hope
and grace from someone who has made our world a brighter
Kathleen Ruth Cushing passed away last week at the age of 93 after a long and courageous battle with illness
and always more concerned with giving than receiving
Kathleen lived a life defined not by wealth or status but by faith
Born in 1931 in a small copper-mining town near Antofagasta
Kathleen was raised amid sweeping landscapes and the traditions of the "gauchos" she so fondly remembered
But her early years were also marked by loss and upheaval
and World War II forced the family's return to the United States under the cover of blackout-aboard a ship navigating dangerous waters patrolled by German submarines
Kathleen began working as a housekeeper at age 12 to help support her mother and brothers
she carried with her a lifelong commitment to frugality
"You have to understand," she would often say
"there are people who have nothing." She graduated from Jefferson Township High School in Upland
Jack Walz--a handsome athlete who won her heart (and shared his sandwich at lunch)
seeking a drier climate to ease Kathleen's health issues
Kathleen earned her nursing credentials and began a lifetime of service-working in clinics and hospitals
she and Jack moved the family from a downtrodden trailer park and expanded a modest concrete house on Market Street into a home large enough for their growing family and her beloved mother
"Grammy," who lived with them until her passing
The family did most of the work sometimes at night under flood lamps
Kathleen picked up extra shifts and private nursing jobs to send her children to St
Kathleen reinvented her life once again--opening a teen hangout called "The Place" in Silver City
It was there she met the great love of her life
a big-hearted tradesman with an infectious laugh
they moved to Houston during Kathleen's cancer treatment
they bought an ice cream shop in Cedar Crest and turned it into Burger Boy-a quirky
beloved institution that served up not just some of New Mexico's best green chile cheeseburgers
Kathleen and Bill poured themselves into the business-cooking
and never turning away anyone who couldn't pay
The restaurant's walls told the story: governors
and neighbors of all kinds proudly displayed in snapshots alongside a mural of "Green Chile Bill." Their partnership was a love story in every sense-one built on mutual respect
Kathleen kept his spirit alive through Burger Boy and her service to the East Mountain community
who left a successful nursing career to care for her mother and run the restaurant
Kathleen made sure Burger Boy remained a warm and welcoming place for everyone
Their efforts were recognized by KOB-TV's Pay It Forward
they stepped up to feed firefighters and neighbors alike
Kathleen and Barbara sold the Burger Boy to grandsons
Eric and Ryne Walz-fulfilling Kathleen's wish to keep the restaurant in the family
always worried people might think she was slacking off
Kathleen loved nothing more than sitting on her porch in Cedar Crest
chatting away as birds flitted to the feeder and the fountain gurgled in the background
"I have been blessed." And so were all who knew her
Kathleen is survived by four of her five children:
a trial attorney and author also of Albuquerque who has argued more than 50 cases in the 10th Circuit Court of Appeals
a certified legal nurse consultant who cared for Kathleen through her final years
MBA and former insurance and financial planning professional
She was preceded in death by her beloved daughter
a decorated nurse and heart transplant specialist
Kathleen spoke of her often and tenderly as "my Martha."
and 4 great-great-grandchildren: • Russell Walz (Tulsa
NM) • Christopher Johnstad (Albuquerque
• Brandon Walz and Jordan Walz (Albuquerque
Kathleen's deep Catholic faith brought her strength in times of hardship
She found great comfort in Father John Carney's friendship and spiritual guidance
She was cherished by local sheriff's deputies
self-taught pianist who played entirely by ear
Her favorite songs-Back Home Again in Indiana
and You'll Never Walk Alone-will echo in the memories of those who loved her
followed by a liturgical service at 9:30 a.m.
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New York City FC announced today that the Club has parted company with Head Coach Nick Cushing.
Cushing’s departure comes after guiding the team to a sixth-place finish and an Audi 2024 MLS Cup Playoffs Eastern Conference Semifinals appearance this season.
“Whilst we are incredibly appreciative for all he has done for the Club, at this current time, we believe it’s best to move the team in a new direction as we plan for the 2025 season and beyond. We would like to sincerely thank Nick for his contributions and wish him and his family all the very best in their future endeavors.”
Following Cushing’s departure from New York City FC, the Club will begin their search for a new Head Coach ahead of the start of the 2025 MLS season.
Cushing was appointed as the Club’s Interim Head Coach in June 2022. In that role, he managed the ‘Boys in Blue’ to a third-place finish in the Eastern Conference and made a run to the Eastern Conference Finals of the Audi 2022 MLS Cup Playoffs.
Cushing has been an important part of City Football Group for almost two decades, initially joining the organization in 2006. He progressed through the ranks as a coach in the Manchester City Academy before being appointed as the manager of Manchester City Women’s Team in 2013. Cushing quickly became one of the most decorated coaches in the women’s game, leading the team to an impressive six trophies.
“Nick has created many wonderful memories for the Club, and our players and staff have benefited immensely from his guidance and experience. His passion for the game is infectious, and we have nothing but immense gratitude for Nick and the success he brought to the Club,” said New York City FC CEO Brad Sims.
“I would like to take this opportunity to thank our fans for their unrivaled support throughout the year. We set ourselves the highest possible standards and targets each season, and we are already fully focused on preparations for the 2025 season.”
Fourth-placed City needed to beat rivals Manchester United at Old Trafford to keep alive their hopes of European football next season, but drew 2-2 after leading 2-0 in the first half
Cushing, who managed City from 2013-2020, took over on an interim basis until the end of the season following Gareth Taylor's sacking in March and was tasked with steering the club to a top-three finish in the Women's Super League
it was about winning trophies and qualifying and we haven't been able to be able to deliver that," he said
"We have been a team that has delivered trophies consistently over a seven-year period when I've been involved
This team should always be delivering trophies and competing in the Champions League
"The league position is far below what I expect
Victory over third-placed United would have taken City to within one point of them in the table and set up an exciting finish to the race for European football on the final day of the season
City host already-relegated Crystal Palace on 10 May
Last year City pushed Chelsea all the way in an enthralling title race - coming second only on goal difference - but will end this season with no silverware and no European football
They also went out of the FA Cup at the semi-final stage to United
while Chelsea dumped them out of the Champions League quarter-finals and beat them in the League Cup final
Their campaign has been blighted by injuries
forward Vivianne Miedema and top goalscorer Khadija Shaw all enduring long stints on the sidelines
"We're trying to build a puzzle here with a piece missing," added Cushing
"We are forever trying to complete it
but it has been tough with all the players injured."
who has often played out of position this season because of the injury issues
"Sometimes when there's obstacles we need to get together and not give up
We will be better and we will be a winning team I'm sure."
Man Utd comeback against Man City seals Europe spot
What's gone wrong for Man City in trophyless season
What are Man Utd's next steps after sealing European spot
Dwelling outside of the Champions League places is unfamiliar territory for Cushing
who led City to their first and only WSL title in 2016 along with four other major trophies
"It's painful," he admitted
this falls below the standards we set at the start of the season and what we expect
but it's football and it's been a challenging moment."
Whether the 40-year-old will remain at City beyond the end of this season remains to be seen, but the club have said they would be open to it
The former New York City FC boss was brought back to Manchester to try to instil some stability and there were positive signs
but ultimately he did not have enough time to turn things around
"I will be involved in the review process because this team is engrained in me
Unless told they don't want me involved
I will be involved," added Cushing when asked about his City future
"This team will be forever engrained in me
It is a team I have followed throughout my time in America
"There has been no conversations from myself either
We have been concentrating on the challenges we have had and we have had many things to focus on."
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A new exhibit at Texas A&M University reveals the full range of Gorey’s creative legacy — marking the 100th anniversary of his birth
Rare works from Edward Gorey’s personal collection are featured in “Ubiquitous Edward Gorey,” a retrospective on view at Texas A&M’s Cushing Memorial Library through September
The Edward Gorey of “Mystery!” or “Dracula” or even the “Gashlycrumb Tinies” may be familiar
artist and designer Edward Gorey (1925-2000) created work that has permeated both our commercial and cultural worlds
“Ubiquitous Edward Gorey,” opens April 10 at Texas A&M University’s Cushing Memorial Library & Archives and runs through Sept
The exhibition features more than 600 items including books from Cushing’s extensive Gorey holdings and biographic materials
personal items and examples of Gorey’s creative output from the Miller Family Edward Gorey Collection
On view will be largely unknown drawings and paintings from Gorey’s youth
first editions of his early primary books and other rare materials.
“The exhibition honors the centenary of Gorey’s birth and also provides a biographical context to explore his wide range of work,” said Beth Kilmarx
assistant university librarian for special collections and co-curator of the exhibit.
While his best-known creations include the illustrations for the animated introduction to PBS’ long-running “Mystery!” series and designs for the 1977 Broadway revival of “Dracula,” those are just two achievements
Gorey authored and illustrated more than 100 of his own books and fully illustrated
chose typography and designed hundreds of books by authors including T.S
who wrote “The House with a Clock in its Walls.”
But all these are still just a part of the enigmatic artist’s vast creative pursuits
Gorey designed costumes and sets for the ballet and the opera; illustrated magazine stories and articles; and created advertising artwork throughout his long career
Gorey appreciated the company of friends and family,” according to collector and co-curator Patrice Miller
fun-loving person who left behind a vast trove of work to study and enjoy.”
Texas A&M affords a unique opportunity: to view the broadest range of Gorey’s work ever shown in one location
outside of the Edward Gorey House Museum.
“Ubiquitous Edward Gorey” has been made possible through the cooperation of the Edward Gorey Charitable Trust.
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Cushing returns to women's soccer and to the exact job he held before becoming Ronny Deila's NYCFC assistant in 2020
at least if you're former New York City FC Head Coach Nick Cushing
Cushing is returning to women's soccer and returning to the job he held before he became Ronny Deila's NYCFC assistant coach in 2020
Manchester City Women's Football Club today announced they'd fired Gareth Taylor
the longtime manager of the Women's Super League team
who will serve as interim manager through the end of the 2024-2025 season
It's an interesting comeback for Cushing, as he was relieved of his duties as NYCFC Head Coach on November 26
three days after his team's season ended at the hands of the rival Red Bulls in the MLS Eastern Conference Semifinals
Cushing ended his two-and-change seasons as Head Coach of New York City with a mixed record of 37 W-31 D-39 L in all competitions
In the time since his firing, he's been busy on media duty. He appeared on talkSPORT in his native England
forced to sit through a red-faced rant from Simon Jordan about MLS and its place in the sporting and world soccer pecking order
Cushing also gave an exclusive interview to The Daily Mail in which he said of his NYCFC firing
"I was a little bit disappointed that it was now after this season – just purely based on what we achieved this year – but it probably is a good time and the right time for me to take on a new challenge
move forward and test myself at the highest level."
The first post-NYCFC test for Cushing will be something of a make-up exam
or maybe just a second test on the same material that he mastered once but hasn't looked at in five years
That's how long it's been since Cushing last coached the Manchester City Women
as Gareth Taylor held the role since May 2020 when he replaced a bound-for-MLS Cushing
Cushing had a strong first spell with the City women
leading the team for the first six incredibly successful seasons of its existence
Cushing won trophies aplenty with the Man City women
which included capturing both the WSL title and the FA WSL Manager of the Year award in 2016
The Man City website did a nice feature on Cushing's first tenure with the women's team right before he came to New York City
which is worth checking out for a reminder of just how successful he was during his first stint in charge
and Arsenal eventually settled on Renée Slegers as their manager
it's a return to the warm embrace of City Football Group
an organization he's worked with since he started coaching in the Manchester City youth academy in 2007
His return is happening because the success the women's squad enjoyed under Cushing has not lasted under Gareth Taylor
The City Women currently sit in Fourth Place in the WSL with six league games left to play this season
outside the places required to qualify for the UEFA Women's Champions League
In the statement announcing Taylor's firing
the objective for Cushing was laid out clearly by Charlotte O’Neill
"We believe that a change of management will breathe fresh life into our bid to ensure qualification for the 2025/26 UEFA Women’s Champions League."
Cushing is tasked with guiding Man City up the table but he's also got big cup matches to handle
with the Man City Women will be in a cup final
taking charge just in time for Manchester City to face Chelsea FC in the Women's League Cup Final this weekend
What better way to kick off The Second Cushing Era than by lifting a trophy
He did it during his last time serving as an interim coach
helping his NYCFC team win the 2022 Campeones Cup – so now he'll look to duplicate his interim success while returning to where his head coaching journey started in earnest in 2014
(Update 3/11/25: According to a Manchester Evening News report
Cushing "has no interest in taking the job full time past the summer as he looks for a permanent job in the men's game.")
The loaned-out New York City FC midfielder needed surgery to correct "a complex right ankle injury involving a fractured fibula and torn medial collateral ligament."
The coach who won MLS Cup 2021 with New York City FC and then left midseason in 2022 has made the move back to MLS and the Eastern Conference
The longtime New York City FC defender publicly clashed with Luc Holtz
head coach of the Luxembourg national team
and appears to be done receiving international call-ups
The former Golden Boot winner with New York City FC will be with the Argentina national team for two FIFA World Cup qualifiers in September
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The stalemate was almost broken by 14-year-old McKenna Whitham of Gotham FC
but the game finished scoreless as Chicago Stars FC go home with a point
Following the departure of Gareth Taylor earlier this week
Nick Cushing has stepped into the dugout as Manchester City Women’s interim manager for the remainder of the season
With just days to prepare, the Englishman’s first game in charge will be the League Cup final against Chelsea on Saturday — the first of four consecutive games against the reigning Women’s Super League champions over 12 days
The 40-year-old will be at the helm for several season-defining matches: City are also into the FA Cup semi-finals and the last eight of the Women’s Champions League
facing Chelsea over two legs in the latter
Cushing left his role as head coach at MLS club New York City in November
where the best of his three seasons was a third-place finish in the Eastern Conference in 2022
He returns to NYCFC’s sister club Manchester City
where he cut his teeth first as an academy coach and then as manager of the women’s team from 2012 to 2020
“Coaching is about people and developing people
It’s about supporting and challenging people,” Cushing says
It’s a little more complex coming in mid-season
I took the interim head coach role (midway through that 2022 season
stepping up from an assistant position) and we got to a final
I’m confident in my ability as a coach and when I look around the dressing room
He enjoyed plenty of success in that first stint with City’s women
guiding them to their only Women’s Super League (WSL) title to date
But what should the fans expect from Cushing now
and can he successfully steer the team to glory in the three cup competitions they are still in contention for this season
Taylor’s exit was described as a “shock” by City defender Alex Greenwood
though he seems to have paid the price for an inconsistent season
City are fourth in the WSL table, one point off third-placed Arsenal, who currently occupy its final Champions League qualification spot
but have played a game more than the north Londoners
Leaders Chelsea are 12 points ahead of City
who they beat to the title last season only on goal difference
with the latter’s 2024-25 campaign having been marred by injuries to key players — winger Lauren Hemp
summer signing Vivianne Miedema and defender Greenwood
Recurring individual and team errors have also been an issue
signed a new three-year contract extension last March despite a relatively modest trophy haul
with the FA Cup in 2020 and the League Cup in 2022 his only major silverware during a four-and-a-half-year tenure
Twice City finished second in the league under him but he was unable to emulate predecessor Cushing by winning the title
Cushing’s history and emotional attachment to the club played a significant factor in his decision to rejoin them after almost five years with New York City
but his long-term ambition remains to test himself at the highest levels of men’s football
“One piece of advice I give coaches all the time is you never know what’s around the corner,” Cushing says
reflecting on how each of his coaching stops have changed his view of what’s possible
Cushing’s original spell as manager of City Women was the team’s most successful in recent seasons
his faith in young players and for forging a strong
While his first two seasons were a slow burn — City finished fifth and second in an eight-team WSL — victory in the 2014 League Cup final against Arsenal was a sign of what was to come
City claimed a domestic double with the WSL and League Cup
the title arriving via an unbeaten campaign in which they conceded four goals in total
City added the FA Cup with a victory against Birmingham City
and then won that competition again in 2018-19
Cushing’s City twice reached the Champions League semi-finals
losing to eight-time winners Lyon on both occasions by aggregate scores of 3-2 and 1-0
the performances were significant given the French team’s European pedigree
“It’s a good challenge because we’re playing against the best in the league
playing in an amazing stadium with an opportunity to win,” Cushing said of the meeting with Chelsea at men’s Championship side Derby County’s 33,000-capacity Pride Park
“I’ve always said in my career that this cup – which was my first trophy in 2014 – since then
To have the opportunity to win another one for this group and organisation is enough motivation.”
The obvious hope at City is that Cushing will be able to build a rapport with the players and oversee more trophy success in the latter stages of this season
the WSL landscape has changed significantly in the five years his first spell in charge ended
not least with five-time champions Chelsea’s hegemony of the league
because I have a real emotional attachment to Manchester City women,” Cushing said
my daughter was born on the day of the League Cup final in 2016
We were in this stadium here (that final was played at City’s academy stadium) and went to extra time
and she was literally born five minutes after I got to the hospital after we lifted the trophy
I don’t overlook things and overcomplicate things
We’ve got to embrace that we’re a good team
We’ve got to understand that although change sometimes brings instability
confusion and a little bit of apprehension
we’ve got to fall back on the fact that we are in all four competitions
that we are in a Champions League quarter-final
we are in a League Cup final and an FA Cup semi-final
The desire and the hunger to get into the Champions League next year has to be the driving factor.”
Another factor is Cushing’s goal of returning to men’s football following this interim period back in the women’s game
The sentiment has not gone down well with some sections of the fanbase
who viewed his original decision to leave the top job at City Women midway through their 2019-20 season to become an assistant in MLS as uninspiring
Turning what could be viewed as a managerial disruption into a catalyst for the remainder of a season will be put to the test in Derby tomorrow
and I think you have to deal with the people that you have in front of you
and you have to make sure that you support and challenge and improve whoever you have in front of you.”
Having risen through the City Football Group (CFG) ranks, Cushing prefers his sides to have high levels of possession, which he considers valuable in both attack and defence. However, speaking to The Coaches’ Voice in October
Cushing emphasised his preference for his teams to “press high and counter-press aggressively”
he orchestrated a possession-based scheme while looking to generate direct attacks and force high turnovers
New York allowed the fifth-shortest average possession time to its opponents (22.8 seconds) in the 29-team MLS
only four teams saw a lower rate of their total possessions end in a shot than their 35 per cent rate
suggesting there were chances left to be made and a lot of touches without productive intentionality
New York were among the league’s lowest in set-piece goals per 100 attempts and set-piece goal share last season and also performed around the league average in terms of dropping points from winning positions
while lingering just below average in points regained from losing ones
He often cites his time with Manchester City as being essential to guiding his ideology
It feels as though he’s finally doing the work to differentiate himself as a manager rather than a coaching cog in the CFG machine
he was keen to play something that was more efficient than City men’s first-team manager Pep Guardiola’s ideology
with a more direct approach (with the ball and without) than New York FC had played in previous seasons
Cushing left that first stint with City for New York
taking the assistant-manager role before becoming interim boss in June 2022 following Ronnie Deila’s move to Belgian club Standard Liege
After leading New York to the final four of the 2022 MLS title play-offs
he was named permanent coach in the November
following a sixth-place finish in the 15-team Eastern Conference last season and a last-eight exit from the play-offs
Cushing predominantly lined his team up in a 4-2-3-1
with his wingers playing more narrowly in the channels while his full-backs provided width closer to the touchlines
his team were a chance-creation juggernaut
racking up 2.7 xG in his last win as New York manager
a 3-1 upset of FC Cincinnati during those play-offs
His team’s best looks often involved a well-positioned centre-forward finishing off team sequences
or his full-backs crossing towards the edge of the box with a late runner ready to reward that service with a well-taken attempt on goal
(Top photo: Andrew Katsampes/ISI Photos/Getty Images)
The duo missed the first leg of the quarterfinal, which City won 2-0, as well as the league clash against Chelsea on Sunday after picking up muscular injuries in the Subway Cup final
Obviously you can see after the game on Sunday
But the medical team and the performance team are doing an incredible job working through the team," Cushing told a news conference on Wednesday
"So the likes of Aoba and Bunny [Shaw] won't make the game
but it wasn't ideal to take off some key players
But we've worked really hard this week to make sure that the squad will be competitive for the game."
City have contended well in their absence in this run of four games in 12 days against Chelsea. They condemned the west London side to their first loss in all competitions this season in the first leg of their Champions League quarterfinal, and were an injury-time Erin Cuthbert winner away from taking points off them in the league
In Sunday's clash, Yui Hasegawa and captain Laia Aleixandri went off late with injuries
They both returned to training on Wednesday but Cushing didn't confirm if Hasegawa
who had to leave the Etihad Stadium on crutches
will be back for the quarterfinal second leg
Cushing believes his side's confidence in themselves remains unaffacted
"And it's not been ideal over the last two weeks to lose Bunny Shaw and Aoba Fujino and it wasn't ideal on Sunday
I thought we had an incredible threat in the game and I know we will tomorrow night
I believe we can score in the game and that gives us an incredible chance of progressing
So although we know that we're going to play a really
I believe we've got a really special group here that actually believes and just wants to go play an attacking team."
The loss in the first leg was Sonia Bompastor's first taste of defeat since taking over at Chelsea at the start of the season
But she believes her side have the quality to overturn the 2-0 deficit at Stamford Bridge
but we are ready to embrace the challenge," she told a news conference on Wednesday
"I think this is what this squad and this club is about
We have never been in that situation in this season before
but we are ready and I just want my players at the end of the game to not have any regrets and this is what we want to go for."
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Cushing expects positive reaction to a season of near misses | OneFootballManchester City F.C
Nick Cushing admits City have fallen short of our usual standards across 2024/25 but is confident there will be a response to that disappointment
The Blues were held to a 2-2 draw against Manchester United at Old Trafford
meaning we’re forced to settle for a fourth-placed WSL finish in 2024/25
City had raced into a two-goal lead thanks to strikes from Laia Aleixandri and Rebecca Knaak
but the hosts responded to get the point they needed to secure the third and final Champions League spot
It was a bitter pill to swallow for Cushing and his team
who’d also been edged out in the FA Cup semi-finals by United and lost to Chelsea in the League Cup final earlier this season
But our Interim Head Coach insists those margins are incredibly tight
and that the Blues aren’t far away from competing for top honours again in the near future
WATCH: We’ll keep giving everything for the fans, says Aleixandri
we can do it tactically or with quality but also mentality and character
“We’ve not been able to deliver that over the last six to eight games
but the reality is the margin is really small
“I was disappointed we fell the wrong side of the result in League Cup final
I was disappointed we lost the Etihad game against Chelsea
“I could sit here and say we’re not good enough or it’s this or that
“You have to react to these moments and build a belief that no matter how the season looks
The boss also confirmed that Leila Ouahabi’s injury which forced her off inside ten minutes of the contest was an ankle issue
Ouahabi was involved in a heavy collision with United’s Celine Bizet early on at Old Trafford and
Cushing admitted he’d have to wait for a more detailed assessment from the Club’s medical team before understanding the extent of the injury
She couldn't carry on and will be with the medical team,” he added
The game was very much the story of our season
then ten players is the rollercoaster we’ve had
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Jason was employed as a supervisor with NOVO Health Services in Ravenna
and more recently was employed with Cleveland Steel Corporation
was very outgoing and was always trying to make people laugh
Louis Cardinals and will be deeply missed by all who knew and loved him
He was preceded in death by his grandfather Roland Meiller
He leaves his mother Lee Ann Cushing; fiancée Crystal Caskey; sons
Benny and Ethan Levandowski; brother Marty (Tina) Reynolds; sister Chrissy Lang; grandmother Barbara Meiller and many nieces and nephews
Jason will be cremated and a Celebration of Life will be held on Sunday
memorial donations may be made to the Autism Society of Greater Akron
Services in the care of Bissler and Sons Funeral Home and Crematory
Metrics details
Cushing’s syndrome is caused by an elevation of endogenous or pharmacologically administered glucocorticoids
encoded by the gene diazepam binding inhibitor
Dbi) stimulates food intake and lipo-anabolic reactions
Here we found that plasma ACBP/DBI concentrations were elevated in patients and mice with Cushing’s syndrome
We used several methods for ACBP/DBI inhibition in mice
(2) injection of a neutralizing monoclonal antibody
(3) body-wide or hepatocyte-specific knockout of the Dbi gene
(4) mutation of the ACBP/DBI receptor Gabrg2 and (5) injections of triiodothyronine or (6) the thyroid hormone receptor-β agonist resmetirom to block Dbi transcription
These six approaches abolished manifestations of Cushing’s syndrome such as increased food intake
it appears that ACBP/DBI constitutes an actionable target that is causally involved in the development of Cushing’s syndrome
Intrigued by the possibility that ACBP/DBI is (one of) the phylogenetically most ancient peptide hormone(s)29
we became interested in its (patho)physiological roles
we used an in vitro screen to identify other neuroendocrine factors that regulate ACBP/DBI
We found that glucocorticoid receptor activation stimulates the release of ACBP/DBI from cultured cells and increases plasma ACBP/DBI concentrations in mice
thyroid hormone transcriptionally downregulates ACBP/DBI
In a mouse model of iatrogenic Cushing’s syndrome
antibody-mediated neutralization of ACBP/DBI or transcriptional downregulation of ACBI/DBI by thyroid hormone all prevent the metabolic consequences of chronic glucocorticoid administration
Our observations suggest that important facets of Cushing’s syndrome are mediated by a surge in extracellular ACBP/DBI
H4 cells expressing GFP–LC3 were treated with agonists and antagonists of neurotransmitter and hormone receptors (5 µM)
Scaled ACBP fluorescence intensity and viability are depicted (a) together with representative images (b)
Torin-1 (0.3 µM) and DMSO (control) were used as controls
The plots show ACBP fluorescence (c) and GFP–LC3 puncta (d) (16 h; 0.01
HCS and T3 in dialysed foetal bovine serum (AU
and ACBP mRNA levels were measured by qRT–PCR (RU
Female C57BL/6J (8-week-old) mice (n = 5 per group) were treated with HCS (10
Plasma ACBP was measured by ELISA (g) and hepatic Acbp mRNA was assessed by qRT–PCR (h)
LC3 conversion and p62 degradation were measured in liver tissue (representative blots in (i and quantifications of the ratios of the indicated proteins in j–l) (n = 3 per group))
Mice were fasted or received HCS (100 mg kg−1; i.p.) for 24 h combined with SAFit2 (40 mg kg−1; i.p.) or vehicle
and plasma ACBP was measured by ELISA (n = 15
PBMCs were treated with HCS (0.5 μM) for 16–18 h
Plasma ACBP levels were measured in dermatology patients receiving (n = 53) or not (n = 39) glucocorticoid treatment (o)
The Wilcoxon test was used and P values were calculated according to a multivariate model including age and BMI
Plasma ACBP was measured in ACTH-dependent patients with Cushing’s syndrome with hypercortisolaemia (n = 11) or in remission (n = 13); an unpaired t-test was used for analysis
Plasma ACBP was plotted against BMI in the hypercortisolaemia group (n = 11) (r) and against daily HCS dose (in the case of corticotroph deficiency) in the remission group (n = 10) (s)
One-way ANOVA with Dunnet correction (c–h and j–m)
unpaired t-test (two tailed) (q and n) and Pearson correlation (r and s) were used for statistical analysis (P values are indicated)
Source data
our data indicate that corticosteroids reduce the cellular content of ACBP/DBI through its autophagy-associated release into the extracellular space
while T3 downregulates ACBP/DBI expression at the mRNA level
The experimental schedule of CORT administration in auto-immunized C57BL/6J female mice against ACBP/DBI
Female C57BL/6J mice were treated with KLH–ACBP for autoimmunization or KLH alone
both administered intraperitoneally for 4 weeks (n = 10 mice per group)
mice received CORT (100 μg ml−1) or vehicle control (control) in drinking water orally (p.o.) for an additional 5 weeks (n = 10 mice per group)
Plasma levels of ACBP were measured by ELISA
Hepatic ACBP and NR3C1 were analysed by immunoblot
Representative blots (c) and quantifications of the indicated protein ratios (d and e) are shown (n = 3 per group)
The average food intake (n = 4 cages per group) (f) and body weight (n = 10 mice per group) (g) was monitored in the indicated groups
The P value represents the comparison of areas under the curve
Representative frontal and longitudinal photographs of one mouse of each group are shown (h)
and facial angles were measured (i) at the end of week 5 (n = 3 mice per group)
The lines indicate the measurement of the facial angle in mice
The heatmap shows the standardized deviations (z scores) of tissue weights relative to body weight and the quantification of various biochemical parameters across the treatment groups (n = 10 per group)
Statistical comparisons were performed by pairwise (two-tailed) Wilcoxon test with false discovery rate correction for multiple comparisons (P values are indicated)
GTT (n = 10 mice per group) (k) and ITT (n = 10 mice per group) (m) were monitored in the indicated groups
The P value represents the comparison of areas under the curve (GTT (l) and ITT (n))
The curves in f and g were longitudinally analysed with type II ANOVA and pairwise comparisons
l and n were analysed using one-way ANOVA with Tukey correction
Source data
autoantibodies neutralizing ACBP/DBI blunt major phenotypic and metabolic manifestations of Cushing’s syndrome including an increase in appetite
Source data
Source data
it appears that genetic inhibition of the ACBP/DBI system can prevent weight gain and other metabolic manifestations of Cushing’s syndrome induced by CORT
strongly suggesting that the results obtained with autoantibodies are due to on-target effects
Source data
Metabolic parameters in mice subjected to vehicle
CORT or a combination of CORT and ACBP/DBI mAb (αACBP
sum of the ambulatory and fine movements (XT + YT yielding counts (Ctns)
and speed (h) were measured in metabolic cages
Daily CORT exposure was adjusted to 500 µg
The data are presented as standard box plots (the centre line represents the median
box limits represent upper and lower quartiles
and whiskers represent minimum and maximum values) of metabolic parameters (n = 2
Metabolic parameters are means evaluated over each 12 h period (night or day) and further averaged over every night and day period for each animal and for each week
cumulative values over 12 h periods are used instead of means
The P values were calculated by Fisher’s meta-analysis method
Source data
Source data
This finding suggests that ACBP/DBI neutralization is reducing appetite only when ACBP/DBI is elevated in the circulation
a mAb neutralizing ACBP/DBI phenocopies the effects of autoantibody-mediated or genetic inhibition of ACBP/DBI
thus preventing the metabolic manifestations of Cushing’s syndrome
Source data
T3 as well as the selective THR-β agonist RES decreased Acbp/Dbi expression and reversed metabolic signs of Cushing’s syndrome
mice treated with glucocorticoids showed an increase in circulating ACBP/DBI protein levels
and patients under corticotherapy or with endogenous Cushing’s syndrome also exhibited elevated ACBP/DBI levels
T3 reduced ACBP/DBI mRNA without autophagy and without increasing extracellular ACBP/DBI in cell cultures or in the plasma of mice
T3 administration could block the corticotherapy-induced surge in ACBP/DBI plasma concentrations
are completely different nosological entities
these findings suggest that ACBP is necessary but not sufficient for the induction of Cushing’s syndrome
it is not clear whether the anti-Cushing’s effects of T3 and RES are entirely due to ACBP/DBI downregulation or whether they involve additional effects mediated by THR-β
in a heterogeneous population of individuals with overweight or obesity
elevated plasma ACBP/DBI concentrations might constitute a biomarker that predicts sensitivity to ACBP/DBI inhibition
this conjecture requires further scrutiny in suitable pre-clinical models and future clinical trials
pair-feeding experiments in which caloric intake (and
body weight) are kept constant indicate that glucocorticoids can induce signs of metabolic syndrome (such as dyslipidaemia and insulin resistance) in the absence of weight gain and that ACBP/DBI neutralization reverses such effects independently from its effects on food intake
ACBP/DBI might have been placed under the control of these hormones during (pre-)vertebrate evolution
While glucocorticoids increase circulating ACBP/DBI levels
inhibition of ACBP/DBI does not affect the level of circulating endogenous glucocorticoids in unstressed mice
indicating a clearly hierarchical relationship without feedback loops
Future work must understand through which (direct or indirect) mechanisms ACBP/DBI controls other neuroendocrine factors
including those involved in metabolic regulation (such as insulin and leptin)
and when this control has been established during vertebrate evolution
it appears that a glucocorticoid-induced increase in extracellular (plasma) ACBP/DBI levels is mechanistically involved in the phenotypic manifestation of several signs of Cushing’s syndrome including increased appetite
These results obtained in a murine model of Cushing’s syndrome require future clinical validation
All animal experimentation procedures applied to institutional rules and guidelines and were approved by the Gustave Roussy ethics committee (project numbers 2023_011_40501
ATCC) or stably expressing GFP–LC3 were cultured in Dulbecco’s modified Eagle medium (cat
supplemented with 10% (v/v) foetal bovine serum (cat
100 U ml−1 penicillin and 100 μg ml−1 streptomycin (cat
Thermo Fisher Scientific) at 37 °C in a humidified atmosphere with 5% CO2
Human hepatocellular carcinoma HepG2 cells wild type (cat
ATCC) or stably expressing GFP–LC3 were cultured in Eagle’s Minimum Essential Medium (cat
patients with ACTH-dependent Cushing’s syndrome (21 with ACTH-dependent pituitary Cushing’s syndrome
and 3 with ectopic ACTH secretion due to a bronchial carcinoid) (median age 56.5 years
range 22–73 years) were prospectively recruited from 2014 to 2017 at Marseille University Hospital
The ‘active’ group consisted of 11 newly diagnosed patients
The ‘remission’ group consisted of 13 patients in remission for at least 2 years
and CORT concentration was adjusted to maintain an average daily CORT exposure of approximately 500 μg per mouse
The control group received 0.66% vehicle in drinking water
C57BL/6 Gabrg2tm1Wul/J Gabra flox mice came from the Jackson Laboratory
All mice used for experimentation were female
C57BL/6J Acbpfl/fl with loxP sites flanking Acbp exon 2 was generated by Ozgene
at a dosage of 75 mg kg−1 body weight per mouse per day for five consecutive days
Tamoxifen was diluted in 90% corn oil and 10% EtOH (v/v) at a concentration of 20 mg ml−1 and was agitated overnight at 37 °C
mice underwent a washout period of at least 1 week before the commencement of treatments
This knockout strategy was applied in combination with the expression of either a ubiquitous or hepatocyte-specific CRE recombinase (genotypes: UBC-cre-ERT2 or TTR-creTam
mice were kept for at least a week before starting the treatment
For the neutralization of DBI by anti-ACBP mAb
experiments were conducted with 8-week-old female C57BL/6J mice
Passive immunization was performed by semiweekly i.p
injections of 5 mg kg−1 body weight anti-ACBP mAb (clone 7G4a
MedChemExpress) was prepared in 10% dimethyl sulfoxide (DMSO)
Merck) was 3.3 μg ml−1and was adjusted to maintain an average daily exposure of approximately 10 μg per mouse
Lundbeck) was administered at a concentration of 0.15 mg ml−1 (diluted in water)
body weight and food intake were measured semiweekly
Experiments were conducted with 8-week-old female C57BL/6J mice
Merck) was diluted in 10% DMSO and 90% corn oil (v/v) and administered i.p
Merck) was diluted in drinking water containing 1% carboxymethyl cellulose (cat
Merck) (v/v) and administered by oral gavage (120 mg kg−1 body weight)
Mifepristone was administered from day 7 to day 14
HY102080 MedChemExpress) was solubilized in vehicle (4% EtOH
and 5% PEG400 (v/v) in 0.9% saline (Veh-1))
to a final EtOH concentration of 0.66% (Veh-2)
Fasting was performed by removing food for 24 h
and CORT (500 µg per mouse) was given by oral gavage
Daily CORT exposure was adjusted to approximately 500 µg per mouse
C57BL/6J female mice were housed under standard conditions with a 12 h light–dark cycle and ad libitum access to water
Mice were randomly assigned to four treatment groups: vehicle
anti-ACBP/DBI antibody and CORT plus anti-ACBP/DBI antibody
baseline body weights and food consumption were measured over a 3-day period to establish average intake
The vehicle-treated group served as the control for food intake
The average daily food intake of the vehicle-treated group was calculated and used to determine the amount of food provided to the other groups
anti-ACBP/DBI antibody and CORT plus anti-ACBP/DBI antibody groups were given the same amount of food consumed by the control group on the previous day
Food intake and body weights were recorded daily to ensure precise matching of food quantities across groups
Adjustments in food allocation were made on the basis of the control groups’ consumption
Indirect calorimetry was conducted using automated metabolic cages (Labmaster
in which mice were individually housed for consecutive 7-day periods over 4 weeks
and mice were provided unrestricted access to food and water
Food and water consumption was continuously monitored
Measurements included oxygen (O2) consumption
the respiratory exchange rate (RER = VCO2/VO2) and heat production
including ambulatory and fine movements as well as speed
was tracked using an infrared light beam-based system
O2 and CO2 volumes were assessed at the inlet ports of each cage and periodically calibrated against a reference empty cage
All measurements were conducted at 4-min intervals throughout the experiment
ensuring continuous recording during both light and dark phases
mice were placed in a vertical glass cylinder filled with water and behaviour was observed for 5 min
Distinct phases of active swimming and immobility were documented
The time spent immobile during the test was considered an indicator of behavioural despair
less time spent immobile suggested potential antidepressant effects
Mice were anaesthetized and placed on a scaled matrix with a protractor
Bird’s-eye-view images were taken and then analysed to measure the angle between the edges of the two cheeks considering the tip of the nose as the vertex
cells were washed twice with with PBS and collected in radioimmunoprecipitation assay buffer (cat
subjected to ultrasonication for three pulses of 10 s on ice and then centrifuged for 10 min at 13,000g
Analogously 30 μg liver tissues and 60 μg adipose tissue were collected in Precellys lysing kits (cat
Bertin Technologies) with radioimmunoprecipitation assay buffer and protease/phosphatase inhibitors (cat
followed by two cycles of homogenization for 20 s at 5,500 rpm using a Precellys homogenizer (Bertin Technologies)
samples were centrifuged at 13,000g for 30 min and supernatants were collected
The Bio-Rad BCA assay (DC Protein Assay Kit II
Bio-Rad) was used for protein concentration assessment
Thermo Fisher Scientific) were added before denaturation (100 °C for 15 min)
After SDS–PAGE and electrotransfer to polyvinylidene fluoride membranes
unspecific binding sites were blocked for 1–2 h with 5% BSA at RT
followed by overnight incubation at 4 °C with primary anti-human ACBP/DBI antibody (1:500; cat
anti-mouse ACBP/DBI antibody (1:1,000; cat
anti-glucocorticoid receptor (D6H2L) XP antibody (1:1,000; cat
Cell Signaling Technology) or horseradish peroxidase (HRP)-coupled anti-β-actin antibody (1:2,000; cat
Membranes were washed and processed by incubation with HRP-coupled secondary antibody (1:2,000; cat
Imaging and quantification were conducted by using an ImageQuant LAS4000 and ImageJ software
Cells were treated and culture supernatants were collected
centrifuged at 500g for 5 min and stored at −80 °C until analysis
mouse plasma was collected with lithium heparin separator (cat
and ACBP/DBI levels were measured by ELISA
MyBioSource) and murine anti-ACBP/DBI capture antibodies (cat
Abcam) diluted 1 µg ml−1 in PBS were used for coating high-binding 96-well plates (Corning) with 100 μl per well overnight at 4 °C
plates were washed twice with washing solution (0.05% Tween 20 (v/v) in PBS)
and unspecific binding was blocked with 100 μl sterile blocking buffer (1% BSA and 0.05% Tween 20 (v/v) in PBS) for 2 h at RT
100 μl per well of either sample or standard (human serum at 1:50–1:75
murine plasma at 1:20 and cell culture supernatant at 1:4 dilution
with the flexibility to adjust as dictated by experimental requirements) was incubated for 2 h at RT and subsequently rinsed 3× with washing buffer
Then 100 μl per well human anti-ACBP/DBI (LS-C299614
Lifespan Biosciences) and murine anti-ACBP/DBI detection antibodies (cat
MyBioSource) diluted 1 µg ml−1 in PBS were added for 1 h at RT followed by 3× rinsing with washing buffer
plates were incubated 30 min at RT with 100 μl of HRP-coupled avidin diluted in PBS (1/5,000 for human and 1/1,000 for murine samples)
Subsequently plates were rinsed 4× with washing buffer
100 μl of 1-Step Ultra TMB-ELISA substrate solution (cat
Thermo Fisher Scientific) was added and incubated 10–30 min at RT in the dark
50 μl of stop solution (2 N H2SO4) was added and absorbance was measured at 450 nm using a FLUOstar OPTIMA microplate reader
Small interfering RNAs (siRNAs) were purchased from Horizon Discovery (ON-TARGETplus
GE Healthcare Dharmacon) and used following the manufacturer’s protocol and employing the following siRNA oligos:
ELISA kits were used for detecting biochemical indices
Plasma CORT samples were collected during the first hour of light at 8:00
and the collection process was performed under general anaesthesia using isoflurane inhalation
All procedures strictly followed the manufacturer’s protocol
plasma was collected in an EDTA anti-coagulant collecting tube with additional dipeptidyl peptidase IV inhibitor
aprotinin and serine protease inhibitor (Merck)
then centrifuged for 10 min at 1,000g within 30 min of collection
Mouse hormones were detected by using the mouse metabolic hormone magnetic bead panel (cat
Merck) by Luminex following the manufacturer’s protocol
Mice were trained for tail pinch adaptation 1 week in advance
Animals were fasted for 6 h to perform a GTT
Blood for glycaemia measurement was collected from tail vein incisions 0
90 and 120 min after the injection of d-glucose (2 g kg−1 body weight
animals were fasted 2–4 h before injection of insulin (NovoRapid
and glucose was measured using a precision glucometer (Accu-Chek Performa)
and hypoglycaemic shock was avoided by administration of 20% glucose solution
The HOMA-IR is calculated using the following formula: fasting plasma glucose (measured after 16 h of fasting
in millimolar) multiplied by fasting plasma insulin (measured after 16 h of fasting
Fresh tissue was collected and fixed in 4% paraformaldehyde (or 10% formalin) for a maximum of 24 h at RT
then processed by serial paraffin embedment
Ten-micrometre-thick slices were obtained with a microtome
Standard haematoxylin–eosin staining was performed
and slides were scanned by a semi-automatic slide scanner (Nanozoomer 2.0 HT
Hamamatsu) equipped with 20× and 40× objectives
The images were analysed and quantified using Fiji software
About 25–30 mg of tissue was collected in lysis buffer (Buffer RLT Plus)
The tissue was homogenized in two cycles using a Precellys homogenizer (Bertin Technologies) for 20 s at 5,500 rpm
The lysate was centrifuged and subjected to further purification procedures as described by the manufacturer
About 1 μg total RNA was reversed transcribed using the Maxima First Strand cDNA Synthesis Kit (cat
Quantitative real-time PCR (qRT–PCR) was conducted by using PowerUp SYBR Green Master Mix (cat
Thermo Fisher Scientific) with a StepOnePlus Real-Time PCR System (Applied Biosystems
The 2−ΔΔCT method was used for the analysis of real-time PCR data with the following primers (Eurofins Scientific):
ACBP/DBI forward primer: CAGAGGAGGTTAGGCACCTTA;
ACBP/DBI reverse primer: TATGTCGCCCACAGTTGCTTG;
GAPDH forward primer: TGTGGGCATCAATGGATTTGG;
GAPDH reverse primer: ACACCATGTATTCCGGGTCAAT;
Acbp/Dbi forward primer: GCTTTCGGCATCCGTATCAC;
Acbp/Dbi reverse primer: ACATCGCCCACAGTAGCTTG;
Gapdh forward primer: CGACTTCAACAGCAACTCCCACTCTTCC;
Gapdh reverse primer: TGGGTGGTCCAGGGTTTCTTACTCCTT
The gene background was defined using all sequenced genes
Data analysis and visualization were performed using AreaQCorrLog2Cen in R (version 4.2.1)
All other statistical analyses were performed using GraphPad Prism 9 or R software
Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article
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Qiu, S. & Zeng, B. Advances in understanding the acyl-CoA-binding protein in plants, mammals, yeast, and filamentous fungi. J. Fungi https://doi.org/10.3390/jof6010034 (2020)
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acyl-CoA binding protein and GABAA receptor
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Acyl-CoA-binding protein (ACBP): a phylogenetically conserved appetite stimulator
Acyl-CoA binding protein for the experimental treatment of anorexia
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Metabolic and psychiatric effects of acyl coenzyme A binding protein (ACBP)/diazepam binding inhibitor (DBI)
Effects of acyl-coenzyme A binding protein (ACBP)/diazepam-binding inhibitor (DBI) on body mass index
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Genome-wide screen in Saccharomyces cerevisiae identifies vacuolar protein sorting
and tRNA methylation genes involved in life span regulation
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Acyl coenzyme A binding protein (ACBP): an aging- and disease-relevant ‘autophagy checkpoint’
Evolution of vertebrate hormones and their receptors: insights from non-osteichthyan genomes
Quantification of intracellular ACBP/DBI levels
Stress-primed secretory autophagy promotes extracellular BDNF maturation by enhancing MMP9 secretion
Immunization of mice with the self-peptide ACBP coupled to keyhole limpet hemocyanin
Chronic hypercortisolism causes more persistent visceral adiposity than HFD-induced obesity
The central effects of thyroid hormones on appetite
Agonist ligands selective for the thyroid receptor beta1
controlled trial of resmetirom in NASH with liver fibrosis
Distinct diagnostic and prognostic values of gamma-aminobutyric acid type A receptor family genes in patients with colon adenocarcinoma
Glucocorticoid-induced apoptosis in the thymus
An updated view of hypothalamic-vascular-pituitary unit function and plasticity
Dexamethasone-induced autophagy mediates muscle atrophy through mitochondrial clearance
CB1 receptor mediates the effects of glucocorticoids on AMPK activity in the hypothalamus
Anorexia nervosa and adrenal hormones: a systematic review and meta-analysis
Effects of the glucocorticoid antagonist RU 486 on pituitary-adrenal function in patients with anorexia nervosa and healthy volunteers: enhancement of plasma ACTH and cortisol secretion in underweight patients
Endocrinologic and psychological effects of short-term dexamethasone in anorexia nervosa
Neuroendocrinology of protochordates: insights from Ciona genomics
Mechanisms for the evolution of a derived function in the ancestral glucocorticoid receptor
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clusterProfiler 4.0: a universal enrichment tool for interpreting omics data
The intracellular metabolome of starving cells
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we appreciate the technical support from H
Xia from the National Key Laboratory of Immunity and Inflammation
Chinese Academy of Medical Sciences and Peking Union Medical College
the Imaging and Cytometry platform of the Gustave Roussy Institute and G
Zadigue from the CEF platform of the Centre de Recherche des Cordeliers for technical support
Boedec from platform of Biochemistry and Biophysics of the Institut de Psychiatrie et Neurosciences de Paris
Parts of the figures have been created with licensed version of BioRender.com
receives funding by Association pour la recherche sur le cancer (ARC) and Institut National du Cancer (INCa)
is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; AMMICa US23/CNRS UMS3655; ARC; Cancéropôle Ile-de-France; Fondation pour la Recherche Médicale (FRM); a donation by Elior; Equipex Onco-Pheno-Screen (ANR 21-ESRE-0028); European Joint Programme on Rare Diseases (EJPRD); European Research Council Advanced Investigator Award (ERC-2021-ADG
European Union Horizon 2020 Projects Oncobiome
101016923); Fondation Carrefour; INCa; Institut Universitaire de France; LabEx Immuno-Oncology (ANR-18-IDEX-0001); a Cancer Research ASPIRE Award from the Mark Foundation; the RHU Immunolife; Seerave Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and SIRIC Cancer Research and Personalized Medicine (CARPEM)
were supported by the China Scholarship Council (CSC
is supported by Science and Technology Innovation 2030 Major Project (STI2030-Major Projects 2022ZD0205700)
Natural Science Foundation of China (NSFC; grant no
CAMS Innovation Fund for Medical Sciences (CIFMS; 2021-I2M-1-074
National special support plan for high-level talents
Suzhou Municipal Key Laboratory (SZS2023005) and the NCTIB Fund for R&D Platform for Cell and Gene Therapy
is supported by grants from the National Key R&D Program of China (2019YFE0113300)
These authors contributed equally: Hui Pan
Equipe labellisée par la Ligue contre le cancer
National Key Laboratory of Immunity and Inflammation
Platform for Neurobehavioral and Metabolism
Department of Respiratory and Critical Care Medicine
Huazhong University of Science and Technology
West China Hospital/West China School of Medicine
Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs
Institute of Dermatology and Hospital for Skin Diseases
performed most of the in vitro and in vivo experiments together with A.-L.T.
performed ELISAs to measure human or mouse ACBP/DBI
performed cellular and histological image analyses
performed the swim test and metabolic cage monitoring
performed MS metabolomics analysis and constructed heat maps
performed bioinformatics gene expression analyses and constructed heat maps
collected serum samples from patients under or without corticotherapy and performed ACBP/DBI ELISA assays
provided samples from patients with Cushing’s syndrome
supervised the study and wrote the paper with input from all other authors
is a scientific co-founder of Samsara Therapeutics
has been holding research contracts with Daiichi Sankyo
is on the Board of Directors of the Bristol Myers Squibb Foundation France
Samsara Therapeutics and Therafast Bio; is in the scientific advisory boards of Hevolution
Longevity Vision Funds and Rejuveron Life Sciences; and is the inventor of patents covering therapeutic targeting of ageing
‘Methods for weight reduction’ (US11905330B1)
was an employee of Sanofi and now consults for Boehringer-Ingelheim
was on the on the Board of Directors of Transgene
is a co-founder of everImmune and holds patents covering the treatment of cancer and the therapeutic manipulation of the microbiota
The funders had no role in the design of the study
in the writing of the manuscript or in the decision to publish the results
The other authors declare no competing interests
Nature Metabolism thanks Ashley Barry Grossman and the other
reviewer(s) for their contribution to the peer review of this work
Editor recognition statement: Revati Dewal
in collaboration with the Nature Metabolism team
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations
(a-c) H4 cells were treated with dexamethasone (DEX)
or corticosterone (CORT) (1 μM) for 6 h with/without bafilomycin A1 (BafA1
Representative immunoblots of LC3 conversion are shown in (a) and quantifications in (b) (n=3/group)
(c) Cells were transfected with siRNA targeting ATG5 and ATG7 or control siRNA (siCtrl) and then treated as indicated (n=3/group; RU
(d-g) Cells were transfected with siRNA targeting NR3C1 or siCtrl
(d) Representative immunoblots show NR3C1 and ACBP levels in NR3C1 knockdowns with/without DEX (1 μM
(e-f) Scatter plot shows the ratio of NR3C1/β-actin (e) and ACBP/β-actin (f) with the indicated treatments
(g) ACBP release from cells with the indicated treatments is shown in (d) (RU; n=3; One-way ANOVA; P-values are indicated)
(h) Scheme shows the schedule of hydrocortisone (HCS
i.p.) administration to female C57BL/6J mice (n=5/group)
(i) Percentage of mouse thymus relative to body weight following HCS treatment at the specified doses (n=5/group)
k) Representative immunoblot (j) showing ACBP levels in WAT treated with HCS at different dose (n=5/group)
Scatter plot (k) shows the ratio of ACBP/β-actin (k)
(l) Scheme shows the schedule of hydrocortisone (HCS
i.p.) administration to female C57BL/6J mice for the indicated duration
(m) Percentage of mouse thymus relative to body weight following HCS treatment at various time points (n=5/time point)
(n) Plasma ACBP level under HCS treatments at various time points (n=5/time point)
(o) Representative immunoblots show hepatic ACBP upon treatment with HCS at various time points (n=5/group)
Scatter plots show the ratio of ACBP/β-actin (p)
(h) Scheme shows the schedule of mifepristone (Mif
i.g.) administration and fasting in female C57BL/6J mice for 24 h
r) Scheme of the experiment (q) and plasma ACBP levels (r) upon Mif treatment and fasting for 24 h
One-way ANOVA with Dunnett correction was used for statistical analysis (i,k,m,n,p,r)
Data in b,c,e,f,g were analyzed using two-way ANOVA with Tukey correction
Source data
(a-d) Cells were treated with siRNA targeting the thyroid hormone receptor (THR) α and β genes or control siRNA (siCtrl) and then cultured in the presence of triiodothyronine (T3)
Then cells were subjected to the quantification of the mRNA coding for THRα
(e) Scheme of T3 administration to female C57BL/6 mice for 16 h
(f) Plasma ACBP was assessed by ELISA after T3 treatment at different doses (n=6/group)
(h) Representative immunoblot of ACBP after T3 treatment (n=3/group)
(i) Scatter plot showing the ACBP/β-actin ratio
One-way ANOVA with Tukey correction was used for statistical analysis (P-values are indicated)
Source data
(a) Representative hematoxylin and eosin stains of liver
and interscapular brown adipose tissue (iBAT) of female C57BL/6J mice treated with corticosterone (CORT; 100 μg/mL or vehicle control (Ctrl) in drinking water
p.o.) for 5 weeks together with KLH-ACBP for autoimmunization or KLH alone both administered i.p
iBAT and hepatocytes was assessed in the indicated groups (n=4-5 mice tissue sections/condition)
Source data
and interscapular brown adipose tissue (iBAT) of female C57BL/6J mice treated with corticosterone (CORT) (100 μg/mL
p.o.) with or without αACBP (5 mg/kg body weight
Source data
Female C57BL/6J mice were treated with corticosterone (CORT) (100 μg/mL
Abundance of plasma hormones was assessed by Luminex multiplex assay (n=10,10,9,10/group)
The heatmap displays z-scores of the indicated metabolic hormones in the indicated treatment groups
Statistical comparisons were performed by pairwise (two tailed) Wilcoxon test with FDR correction for multiple comparisons
Source data
(a) At the end of the corticosterone (CORT) and anti-ACBP/DBI (αACBP) mAb experiment
liver tissue was collected for RNAseq analysis (n=5/group)
Genes with a differential expression P-value ≤ 0.05 (Wald test) and abs (fold change) ≥ 2 were selected in (a)
(b) Volcano plot of differential genes between isotype + CORT and isotype + Ctrl groups
(c) Volcano plot of differential genes between αACBP + CORT and isotype + CORT groups
(d,e) Venn diagrams illustrate overlaps of the transcriptomic CORT effects on isotype and αACBP mAb neutralization
(f) GO enrichment analysis of the genes obtained from the overlap in (d) (58 genes)
(g) GO enrichment analysis of the genes obtained from the overlap in (e) (442 genes)
Data were analyzed using R software with the DESeq2 package
Source data
Source data
(a) Male C57BL/6J mice were treated with CORT (100 μg/mL) in drinking water (p.o.) for 5 weeks (n=10/group)
(b) Plasma ACBP was quantified by ELISA (n=10/group)
(c) Average food intake (n=3 cages/group) and (d) body weight (n=10 mice/group) were monitored
(e) The heatmap shows the standardized deviations (z-scores) of tissue weights relative to body weight and the quantification of various biochemical parameters across the treatment groups (n=10 mice/group)
(f-i) Glucose tolerance tests (GTT) (n=10 mice/group) (f) and insulin tolerance tests (ITT) (n=10 mice/group) (h) were performed in the indicated groups
P-value refer to the comparison of areas under the curve (g,i)
Statistical comparisons were performed by pairwise Wilcoxon tests with FDR correction for multiple comparison in the heatmaps
All curves were longitudinally analyzed with type II ANOVA and pairwise comparisons (c,d)
One-way ANOVA with Tukey correction was used for statistical analysis (P-values are indicated) (d,g,i)
Source data
(a) Scheme showing the experimental schedule of triiodothyronine (T3; i.p.) administration to female C57BL/6J mice treated with corticosterone (CORT) for 5 weeks
Liver (b) and WAT (c) Acbp mRNA levels (n=6/group; RU
(d) Representative immunoblot shows ACBP level treated with different doses of T3 (n=3/group)
Scatter plots show the ratio of ACBP/β-actin in liver (e) and in WAT (f)
(g) Plasma ACBP were assessed by ELISA (n=10/group)
(h) Average food intake (n=3 cages/group) and (i) body weight (n=10 mice/group) were monitored
(j) The heatmap shows the standardized deviations (z-scores) of tissue weights relative to body weight and the quantification of various biochemical parameters (n=10 mice/group)
Statistical comparisons were performed by pairwise Wilcoxon tests with FDR correction for multiple comparison in the heatmaps (P-values are indicated)
All curves were longitudinally analyzed with type II ANOVA and pairwise comparisons (h,i)
One-way ANOVA with Tukey correction was used for statistical analysis (P-values are indicated) (b,c,e-g)
Source data
1–15 and Source data of immunoblots included in supplementary figures
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The US Food and Drug Administration (FDA) has approved a new indication for osilodrostat (Isturisa
Recordati) as second-line treatment of endogenous hypercortisolemia in adults with Cushing syndrome
Endogenous Cushing syndrome is a condition of excess cortisol that can result in complications such as weight gain
Osilodrostat, an oral cortisol synthesis inhibitor, was previously approved for treating adults with Cushing disease
a subtype of Cushing syndrome in which the hypercortisolemia is due to pituitary overstimulation
Both indications are for people who can’t undergo surgery or who have had surgery that wasn’t curative
The new indication was supported by an “extensive clinical development program” involving more than 350 adults with Cushing syndrome
The most common side effects of osilodrostat are adrenal insufficiency
and swelling of the legs and ankles or other signs of edema
Its efficacy and safety in children isn’t known
Tucker is a freelance journalist based in the Washington DC area
She is a regular contributor to Medscape Medical News
with other work appearing in the Washington Post
She is on X @MiriamETucker and BlueSky @miriametucker.bsky.social
Send comments and news tips to news@medscape.net
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Manchester City boss Nick Cushing has said he expects Vivianne Miedema to miss the rest of the season through injury
Miedema went off with a hamstring issue in Netherlands' Nations League clash against Austria earlier this week
Dutch national coach Andreas Jonker said he was "extremely disappointed" about her injury setback and did not foresee a speedy return to action
Cushing shared Jonker's pessimism about Miedema's injury
"We've lost Viv and that's something the medical team are ongoing with
She's positive but it's not looking good in the sense of being able to imminently impact any of our games," he told a news conference on Friday
"It's hugely disappointing for Viv because of the role she's played on the pitch and for me personally because she's been so pivotal in the results I've got with this team
"She's played a huge role in dragging this team up and she's done the same today in the meeting room and on the training pitch
Vivianne Miedema picked up a hamstring injury while on international duty. Getty"She's positive and concentrating on rehab now
and we'll give her all the support she needs to be back out there as quick as possible."
The forward, who joined City in the summer on a free transfer, has already missed three months of the season after undergoing another operation on her knee in October last year
Miedema's latest setback comes just as she has started to hit her stride at City -- she won the club's player of the month award in March for her six goal involvements, including a brace against Chelsea in the first leg of the Champions League quarterfinal
She also got on the scoresheet for her country in the ill-fated game against Austria
and now faces a race to get fit in time for the Women's Euros this summer
Information from ESPN Netherlands contributed to this report
New York City FC have parted ways with head coach Nick Cushing
initially as interim head coach before getting the permanent role in November 2022
He posted a 40W-40L-27D record across all competitions
Cushing guided NYCFC to the Audi MLS Cup Playoffs in two of three seasons, including a 2022 Eastern Conference Final run. This year, NYCFC finished sixth in the Eastern Conference (50 points) before losing in the Eastern Conference Semifinals, 2-0, to rivals New York Red Bulls on Saturday night
"Whilst we are incredibly appreciative for all [Cushing] has done for the club
we believe it’s best to move the team in a new direction as we plan for the 2025 season and beyond," said sporting director David Lee
"We would like to sincerely thank Nick for his contributions and wish him and his family all the very best in their future endeavors."
Cushing has been part of City Football Group for almost two decades
He progressed from the Manchester City Academy to leading the Manchester City women’s team in 2013
The England native then joined NYCFC in 2020, first as an assistant under former manager Ronny Deila. Cushing was part of NYCFC's MLS Cup 2021-winning staff, and led the Cityzens to the 2022 Campeones Cup title
"Nick has created many wonderful memories for the club
and our players and staff have benefited immensely from his guidance and experience
and we have nothing but immense gratitude for Nick and the success he brought to the club," said CEO Brad Sims
“I would like to take this opportunity to thank our fans for their unrivaled support throughout the year
We set ourselves the highest possible standards and targets each season
and we are already fully focused on preparations for the 2025 season."
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who served as a priest for nearly seven decades
Patrick Parish and attended the parochial school
He then completed his seminary training at St
Kearney at Rochester’s Sacred Heart Cathedral
His first assignment was at Holy Cross Parish in Charlotte
where he served as assistant pastor from 1956-62
Father Cushing left the parish and became chaplain at St
an all-girls school operated by the Sisters of St
He served at the Rochester school until 1979
This assignment was significant to Father Cushing for several reasons
Not only did the assignment mark Father Cushing’s first — and only — pastorate
but the priest was just the second pastor in the Irondequoit parish’s history
Cecilia Parish had been founded in 1949 by Father Bernard Newcomb
Patrick Parish in Corning when Father Cushing was a child
“I think (Father Cushing) was inspired by Father Newcomb
and he stayed there until he retired,” Father Leone said
The parishioners of St. Cecilia and later St. Kateri were quite fond of Father Cushing, according to Father Leone, who served at St. Cecilia from 2008-11.
“They really loved him. He was so dedicated to them. He was there for them, said Mass faithfully, administered the sacraments,” Father Leone said. “He was a very dedicated priest. He was a good man.”
While the bulk of Father Cushing’s priesthood was devoted to his three assignments at Holy Cross, St. Agnes High School and St. Cecilia, he also served for a time as chaplain at the Monroe County Jail and as assistant director of the Diocese of Rochester’s Family Life Bureau, which coordinated marriage-preparation courses and other diocesan functions.
In his free time, Father Cushing loved photography, working with audio-visual equipment and watching the New York Yankees, Father Leone said.
Father Cushing was predeceased by his parents, Thurza and Walter; and his sister, Sharon Scott. He is survived by his nephews, David (Lois) Scott, Ronald (Sue) Scott and Timothy (Jill) Scott; nieces, Bonnie (Larry) Folden, Sheryl (Harold) Luckner, Kathleen Ross (John) and Kimberly (Matthew) Eiffert; and caregiver and family friend, Doug Crooker.
Visitation for Father Cushing will take place March 14, 2025, at 10 a.m. at St. Cecilia Church, 2732 Culver Road in Irondequoit. Immediately after the visitation, Father Cushing’s funeral liturgy will begin at 11 a.m.
Choose from news (Monday), leisure (Thursday) or worship (Saturday) — or get all three!
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by such means as framing or other digital copying and/or distribution methods
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playThiago Martins' header doubles NYCFC's lead (0:35)Thiago Martins is at the right place at the right time to head NYCFC into a two-goal lead over FC Cincinnati
New York City FC head coach Nick Cushing confirmed he will remain with the club in 2025, dispelling rumors linking him to the managerial role at the Arsenal women's team
Though Cushing quickly emerged as a potential candidate to take over Arsenal following the departure of former manager Jonas Eidevall in October, the MLS coach insists there has been no contact from the English club
once last week if there's been contact and then about the story still living," he told ESPN
but from within myself and within here [at the organization]
"I just confirmed I will be here next year
Cushing first joined City Football Group in 2006, boasting a junior role at Manchester City Women before earning the managerial position in 2013
He led the team to lift the 2014 FA Women's League Cup and 2016 Women's Super League title during his seven-year spell
Cushing moved away from Manchester City Women to become the assistant coach to Ronny Deila at New York City FC
aiding the team during the 2021 MLS Cup-winning season prior to replacing Deila as interim manager in 2022 and permanent coach in 2023
Nick Cushing confirmed he will extend his contract with New York City FC. Tom Horak-USA TODAY SportsDespite the speculation
his focus remains on leading NYCFC to the MLS Cup once again
"Hopefully we can take this team far this year
Ultimately the reality is my focus now is on playoffs and my team beyond the playoffs
My focus is how do we get this team from seven to four
where I believe we are going to get from three to one," he said
"Developing the style and the identity that we've got now because it's the way I see the game
I want to go on attack teams and be on the front foot
Developing that has been probably my favorite part of the training programme and the team now."
New York City FC concluded the 2024 MLS campaign in sixth place on the Eastern Conference table with 50 points, and now heads into the third match of the Round 1 best-of-three series against FC Cincinnati
forcing Cushing to earn a victory during Saturday's game at TQL Stadium in order to advance to the Conference semifinals
Nick Cushing confirmed his players and staff are excited to return to action at home this weekend
New York City FC hosts FC Cincinnati on Saturday at Citi Field for Game 2 of the Round One Best-of-3 Series
City must secure a win to extend their postseason run
Cushing shared that his players are excited to be back home and eager to deliver a victory for the Club's supporters
“We love playing at home in front of our people,” he explained
“I said post-game - irrelevant of what happened in Cincinnati - we're now playing in front of our people
and that is where we play our best football
They have a huge desire to win this football game and to make sure that we win the game with our people
I can always go back to the Miami game [this season]
“It was actually interesting because the Miami game at Yankee Stadium was an amazing game in front of our fans
but the last playoff game I did at Citi Field was also against Miami
“That was an incredible atmosphere and a good performance from the team
We know that if we play well and we start well we get our people behind us
“We aim to make sure that we deliver for our fans
so that together we can create an incredible atmosphere
City have been busy on the training field this week as they seek to secure a victory against Pat Noonan’s side
Head Coach Cushing and his players have closely analyzed Monday's game
Cushing emphasized the importance of character as they head into Saturday's match
“This week has been all about showing our character,” Cushing said
the character that we have shown on multiple occasions this year in big football games
“Now we have to deliver it from the first whistle in front of our people at Citi field
it's about the crowd and the energy and our fans
“They feed off the energy that we give them and the character that we show as a team
I've been really clear with the team this week that it is a must from the first whistle.”
You can purchase tickets to Saturday's game by clicking here.
Erin Cuthbert scored a stoppage-time winner for the visitors at the Etihad Stadium after Aggie Beever-Jones' strike cancelled out Kerolin's opener
City could have been 2-0 up in the first half had referee Kirsty Dowle played the advantage after Kerolin was fouled on the edge of the area
Dowle's decision to prematurely blow her whistle for a free-kick meant Park's effort on the follow-up did not count
opening the door for Chelsea to mount their comeback
"The officials admit they got it wrong and should have played on," Cushing said after the match
"The frustrating thing is after the [Laura] Coombs foul earlier on
because we were so dangerous on the counter attack when the whistle was blown on Coombs I asked her to play advantage
Chelsea boss Sonia Bompastor sympathised with Cushing's frustrations but praised her side for their tenacity in the second half
even when the ball was not going into the goal so I think she made the right decision and it's difficult after when you see the result," she said
"If I was the City manager I would probably be in the same place
I don't think it changed our belief going into the second half
Internet trolls partly aided doctors in diagnosing Amy Schumer with Cushing syndrome
but patients can go years without a diagnosis
Schumer opened up about her February 2024 diagnosis on the “Call Her Daddy” podcast Wednesday
crediting online criticism about her swollen face – a telltale sign of the hormonal disorder
Cushing syndrome is an uncommon condition when the body has too much cortisol
medical director of the pituitary center at the Cleveland Clinic
known as the "stress hormone," influences how the body handles stress and plays a vital in keeping the body healthy
keeps our energy steady throughout the day and dips in the evening so that we can sleep," she said
Cushing syndrome can be difficult to diagnose because providers don’t immediately think of the condition when a patient comes into the office reporting fatigue and weight gain
It's also often confused with polycystic ovary syndrome
Medical mystery solved: Why do some people develop Huntington's earlier than others?
it can take years to figure out what's going on," she said
"The average diagnostic delay in Cushing's syndrome is approximately two to three years."
are also at increased risk of developing Cushing syndrome
Schumer said her diagnosis was the result of steroid injections from her breast reduction and Cesarean section after her first child
affecting up to 70 out of a million people each year
About 70% of people with Cushing syndrome are women or people assigned female at birth, according to the Cleveland Clinic
People between 25 and 50 are most likely to be affected by the condition
round face; easy bruising and poor wound healing; high blood pressure; excessive hair growth in the face
breast or thighs; purple stretch marks over the abdomen; a fat pad between shoulders; general weakness or tiredness; blurry vision and dizziness; weakened muscles; thinner arms and legs; and libido changes
the Cleveland Clinic said high cortisol levels could lead to other health problems such as infections
To determine if a patient has Cushing syndrome
doctors conduct tests to find out if the body is making too much cortisol
They can also check for another hormone called ACTH
which is made by the pituitary gland when the body is stressed
Most cases are caused by either a medication or tumor
If a patient is taking medication that could lead to Cushing syndrome
the doctor will lower the dosage or prescribe a non-glucocorticoid medication
which can reduce inflammation without steroids
the doctor will order scans to see if there might be a tumor causing Cushing syndrome
Tumors in the adrenal gland account for up to 20% of Cushing syndrome cases
Adrianna Rodriguez can be reached at adrodriguez@usatoday.com
Nick Cushing has left New York City FC. Andrew Katsampes/ISI Photos/Getty ImagesNew York City FC have dismissed head coach Nick Cushing
The decision comes after NYCFC finished sixth in the MLS Eastern Conference this season and were knocked out in the MLS Cup Playoffs Eastern Conference semifinals
"Whilst we are incredibly appreciative for all he has done for the club
we believe it's best to move the team in a new direction as we plan for the 2025 season and beyond," sporting director David Lee said
Cushing was an assistant at the club before taking over as interim head coach in June 2022
he led NYCFC to the Eastern Conference finals of the Audi 2022 MLS Cup Playoffs
and we have nothing but immense gratitude for Nick and the success he brought to the club," CEO Brad Sims said
The club said they are now looking for a replacements ahead of the 2025 season
Nick Cushing is keen for his side to maintain the momentum generated from their unbeaten run as they prepare for Decision Day
New York City FC will travel to Canada on Decision Day to take on CF Montréal
The Boys in Blue are already guaranteed a place in the playoffs
but they can still secure home advantage with the right results on Saturday
City are currently on a three-game unbeaten run
and while speaking with the media on Thursday Cushing emphasized the need for his team to maintain their momentum heading to postseason
“The preparation is fairly similar in the sense of the intensity that we've trained at,” he said
“The buy-in and the focus of the team is very similar to last year
The difference is we're fighting for a totally different opportunity
and that was the aim and the goal at the start of the year
to be in a position to finish in the top four
We've got a really good feeling among the group
and that has to continue going into the postseason
fourth place is our target and our eyes are on that.”
We don't achieve anything in the sense of finishing in fourth place if we don't win the game
We've reviewed the Nashville game and there was some really good bits and some bits that we know we have to improve on
“The game isn't finished until that referee blows the whistle so we will believe we can get something from the game in every moment of the game.”
Reflecting on the challenge Montréal will represent on Saturday
Cushing praised his opposite number Laurent Courtois
“I think the first challenge will be that they have to get a result to get in [to the playoffs],” Cushing said
They're at home in front of a sellout crowd
It’s a great opportunity for them to improve on last season
which is the mindset that we've been in all year
They can have long periods of possession with the ball and create chances
“They have a number nine in Joseph Martinez
We know that this game is going to be difficult
We're going to have to be incredibly focused throughout the game
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Lee served in the United States Army during the Korean Conflict
He was a member of Marshfield Assembly of God
He loved spending time with his grandchildren and great-grandchildren
He is preceded in death by his parents; his wife
Randy and Michele Cushing of Marshfield; fourteen grandchildren
Interment will follow in Marshfield Cemetery
Memorial contributions may be made to the family and may be left in the care of Fraker Funeral Home
website by Online Masterminds
NYCFC have fired head coach Nick Cushing
Cushing took over on an interim basis in July 2022 for former head coach Ronny Deila and was brought on board permanently at the end of that season
having led the club to the Eastern Conference finals
Cushing compiled a 40-27-40 record in all competitions across his time in New York
NYCFC were eliminated from the MLS Cup playoffs last week after a disappointing 2-0 home loss to crosstown rivals New York Red Bulls
“We would like to thank Nick for his incredible dedication to the club and this city,” sporting director David Lee said in the club’s statement
playing an important role in delivering the Club’s first MLS Cup as an assistant coach and then leading the team as interim head coach to a Campeones Cup victory in 2022.”
Lee added: “Whilst we are incredibly appreciative for all he has done for the club
we believe it’s best to move the team in a new direction as we plan for the 2025 season and beyond.”
— New York City FC (@newyorkcityfc) November 26, 2024
Before working in MLS
Cushing was manager of Manchester City’s women’s team from 2013 to 2020
The 40-year-old has been considered a potential candidate for the head coaching vacancy at Arsenal’s women’s side following the departure of their previous head coach
Cushing himself rebuffed reports of Arsenal’s interest some three weeks ago during a news conference
“The whole story is news to me,” Cushing told the assembled media
“There has been no contact from anybody outside this organisation with myself
New York City FC's new stadium to be called Etihad Park
(Andrew Katsampes / ISI Photos / Getty Images)
Nick Cushing has encouraged his players to play their football and dig deep as they pursue victory in Cincinnati this week
New York City FC travels to TQL Stadium this Saturday to face FC Cincinnati in the decisive third game of a best-of-three series
A win would secure City a spot in the next round of the Audi MLS Playoffs and set up a showdown with the Red Bulls
Cushing discussed how his side can harness the momentum generated from their 3-1 victory last time out
“It’s about trying to show our players how much our fans enjoy seeing that type of performance from our players,” he said
but the guts and the fight and the desire to ensure that we are the team that goes through the next game right
“The performance at Citi Field had everything
Not only did we play well and create chances
as was the desire to make sure that we didn't give the second goal away.”
“We've got to make sure that we play the football that our fans deserve and that we know we can play
We’ve just got to make sure that we go prepared and we deliver everything that we've got.”
and Santiago Rodríguez secured City a 3-1 win in their last meeting on Saturday
The win set up a decisive third game in Cincinnati
with Cushing expressing confidence that his players are prepared for the challenge awaiting them in Ohio
“This is going to be a tough game,” Cushing said
“With regards to it [the game] swinging both ways
I think that's natural in playoff football
“You’ve got to be prepared to absorb the pressure and you’ve got to make sure that you capitalize on the moments that you get
“I was pleased that in the game at Citi Field
we were putting the pressure in the second half
that we have to go through to look at how we minimize the amount of pressure that we absorb and how we control Cincinnati in the moments where they become strong
This will be the sixth matchup between New York and Cincinnati in 2024
the teams faced each other in both the Leagues Cup and the MLS Regular Season
Cushing acknowledged the sense of familiarity that exists between the two teams
while discussing his focus on crafting a strategy to help his side deal with the pressure they expect to experience on Saturday
It's unique for us in the sense of the three-game series
but it is actually going to be the sixth time that we've played this team
because we played them in Leagues Cup and twice in the regular season
“You become really familiar with each other
There are going to be elements of all the games that we've played present in this upcoming game
“You have to be prepared to compete in the game
This is more like the playoff football I’ve known since 2020
“You win and you go through you lose and you're out
There are some considerations that I'm making in the sense of changes
If you go back to the first league game there
thought we competed really well in a different way
“We’re trying to work through some small stuff now to make sure we have a strategy during the difficult moments
and you’ve got to be ready to go and compete.”
Zurich North America appointed Tobias “Toby” Cushing to the newly created role of deputy chief underwriting officer
Cushing previously served as casualty technical director
Cushing is responsible for supporting Zurich North America’s underwriters across all lines of business
who is based out of Zurich’s New York City Offices
joined Zurich as head of construction Casualty in 2022
he has held several underwriting leadership roles of increasing responsibility
Cushing held a variety of roles at The Hartford
including serving as head of construction for middle and large commercial
Earlier in his career Cushing practiced law as an insurance coverage litigator and advisor for complex insurance transactions
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American Parkinson Disease AssociationP.O. Box 61420, Staten Island NY 10306Tel: 1-800-223-2732Email: apda@apdaparkinson.orgWeb: https://www.apdaparkinson.org
Amy Schumer is opening up further about how internet commenters led her to a revealing medical diagnosis
The comedian, during an appearance on the "Call Her Daddy" podcast Wednesday
said she originally ignored criticism about her swollen face until doctors jumped in the chat
According to Mayo Clinic, Cushing syndrome "happens when the body has too much of the hormone cortisol for a long time." The syndrome can cause "moon face," or a puffy appearance
Schumer said her diagnosis was the result of steroid injections from her breast reduction and Cesarean section after her first child
Schumer has opened up a number of times about her health conditions
including her happenstance Cushing syndrome diagnosis
What is cortisol face? TikTok keeps talking about moon face, hormones.
Last year, the comedian spoke candidly to journalist Jessica Yellin about her health journey in the News Not Noise column on Substack
"I was also in MRI machines four hours at a time
having my veins shut down from the amount of blood drawn and thinking I may not be around to see my son grow up
So finding out I have the kind of Cushing that will just work itself out and I'm healthy was the greatest news imaginable," Schumer said in the interview with Yellen
Schumer said she felt "reborn" while sharing the news amid the criticism she received
The "Trainwreck" star had previously called out the critics
"Thank you so much for everyone's input about my face
I've enjoyed feedback and deliberation about my appearance as all women do for almost 20 years
And you're right it is puffier than normal right now," Schumer said in February
The actress added that "there are some medical and hormonal things going on in my world right now but I’m okay." She has also previously opened up about having endometriosis
a condition in which tissue that resembles cells found in the lining of a uterus grows outside of the organ
There are many signs and symptoms of Cushing syndrome
Cortisol is a hormone that helps the body respond to stress and is important for other body functions such as controlling blood pressure and blood sugar
helping the body use food for energy and helping the heart and blood vessels work correctly
visited A&M's sci-fi and fantasy collection
featuring the repository of the author who imagined her
Texas A&M Class of 1998 teaching his wife
actress Lena Headey how to Gig ’em at Cushing Library on Nov
Texas A&M University, the Texas A&M Foundation, and the College of Performance, Visualization and Fine Arts welcomed former student
to College Station this past weekend for a multi-site visit around campus
We chatted with Menchaca earlier this year and he told us about his marriage to Headey, who played the infamous Queen Cersei Lannister on the hit HBO series “Game of Thrones.”
He also mentioned they were up for a campus visit
and a stop at the world-renowned Cushing Memorial Library & Archives seemed fitting for the queen
Cushing houses the personal collection of author George R.R
who wrote the book series “A Song of Ice and Fire” upon which the “Game of Thrones” series
as well as HBO’s current series “House of the Dragon,” are based
Tolkien’s 1937 classic “The Hobbit,” illustrated by Tolkien himself
For those unfamiliar with “Game of Thrones,” Headey’s character is a series legend, as it was her who sat on the most coveted throne for much of the series. Spoiler alert: Cersei Lannister indisputably loses “the game” in the end. Headey herself, though, won the hearts of fans worldwide with her portrayal of the complex character
30; Headey and Menchaca were joined by family members
Menchaca studied English at Texas A&M and has gone on to dozens of series and film roles
including the role of Russ Langmore in the hit Netflix show “Ozark.”
curator of the sci-fi and fantasy collection
pulling pieces from the Martin collection and a few other rare finds
who has extraordinary knowledge and a healthy sense of humor
was sure to gather Lannister swords for the start of our tour
“We’re in House Lannister today,” he told us quite seriously
Next, we traveled to the historic Kelsey Reading Room; its ceiling was originally hand-painted by Aggie architecture students in the early 1930s
Brett told the stories behind some of the items from the Martin collection
including original manuscripts and artwork that feature the author’s handwritten notes
we asked the couple how they were enjoying their stay in Aggieland
and Headey said she’d taken in her first Yell Practice the evening prior
Menchaca said he was “a little anxious” bringing his British family members to Kyle Field
the largest stadium in the Southeastern Conference and one of the largest in the U.S.
What has he brought me to?’ It was really very exciting
it was a bit like going to King’s Landing.”
The endowment is the first of its kind at Cushing and supports a range of sci-fi and fantasy initiatives
If you would like to support the collection, visit the Texas A&M Foundation website
The couple also attended a lunch hosted by College of Performance, Visualization and Fine Arts Dean Tim McLaughlin, during which Menchaca met with Rayna Middleton Dexter, interim program director for the new theatre degree
College officials say they hope to bring him back in the spring to meet with students
To support programs in the College of Performance, Visualization and Fine Arts, visit pvfa.tamu.edu/about/giving
Spring graduations will be celebrated May 8-10 across nine ceremonies at Reed Arena
The annual awards recognize individual staff members
teams and student employees for their contributions to the university community
The Friars honor their beloved dachshunds and support Texas A&M’s veterinary hospital through a heartfelt gift that reflects their love for animals and the Aggie Spirit
Manchester City women’s interim head coach Nick Cushing says he is not thinking about his long-term future beyond the end of the season but “you never know what is around the corner”
On Monday, Cushing was named as the women’s team’s new interim boss for the rest of the 2024-2025 season following the dismissal of Gareth Taylor five days before the Subway Cup final
The move marks his return to the women’s side five years after he left for New York City FC
“It is definitely until the end of the season,” Cushing said on his interim position
“It would be crazy to look any further than the end of the season based on the games we’ve got coming up
One thing I’ve been really clear on since I came out of New York is that my development in this organisation (City Football Group) has been the one thing that has continued to give me the hunger and desire to keep improving football players
“I went from (City) boys’ academy to the women’s team
from the women’s team to New York as the assistant coach and then as head coach
Those conversations for me are about continuing my experiences
To have new experiences as coaches is something that will continue to develop here.”
Cushing spent seven years as Manchester City head coach, before joining Major League Soccer (MLS) side NYCFC initially as assistant to Ronny Deila, before stepping into the head coach role in 2022. He was sacked in November 2024
The 40-year-old did not state that he would definitely return to the men’s game following his interim spell at City
I was working (with) under 12 and under 13 (teams) as an assistant coach
and I never thought I would coach in the women’s game,” he said
“Then when I was winning trophies in the women’s game
I didn’t even know any teams in MLS and I landed in MLS
So one piece of advice I give coaches all the time is you never know what’s around the corner
City face Chelsea on Saturday in the Subway Cup final in what is their first of four consecutive games across three different competitions against the reigning Women’s Super League (WSL) champions
(Andrew Katsampes/ISI Photos/Getty Images)
Charlotte Harpur is a football writer covering Manchester United and women's football for The Athletic UK. Follow Charlotte on Twitter @charlotteharpur
in a recent episode of the 'Call Her Daddy' podcast
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The "Kinda Pregnant" star said doctors began commenting on her swollen appearance
which led her to seek a diagnosis for her swollen face
Todd Owyoung/NBC/Getty; Karwai Tang/Getty
Amy Schumer shared a selfie that she labeled "no filter" and "no filler" on Instagram Jan
three days after giving insight into her Cushing syndrome diagnosis
Amy Schumer is feeling pretty
The Kinda Pregnant star shared a candid photo of herself that she labeled "no filter, no filler," days after revealing that comments about her appearance online last year led to her Cushing's syndrome diagnosis
Amy reposted the selfie onto her grid, writing
"What can I say It was a good night."
The 43-year-old's post came three days after explaining that comments on social media about her "puffier" face weren't all ill-intentioned
and the internet really came for me after doing a bunch of press
relax,'" she told host Alex Cooper on the Jan
"But then doctors were chiming in in the comments."
Amy went on to explain that she noticed medical professionals expressing genuine concern
your face looks so crazy and we think something's up.'"
The Trainwreck actress—who shares son Gene
with husband Chris Fischer—recalled how these doctors she had never met were accurate in their hypotheses about her health
I'm getting trolled by doctors?" Amy said
'We think you have something called Cushing and it's like
When the comedian learned that Cushing syndrome can be caused from high-dose steroid injections—which she had been getting to treat scars from a breast reduction and her C-section—she realized they were onto something
Their suspicions were confirmed when Amy was diagnosed with Cushing last February
right before she started filming Kinda Pregnant in March
"Right before we started rolling was when I learned I had this condition," she explained
"and that I had something called moon face."
While she was initially scared she had the version of Cushing where "you could die," which led her to be "really down" on herself during that time
she ultimately learned that she had a type that she could overcome
Those sentiments echoed what she said when she initially shared the news of her diagnosis with the public a year ago
"Finding out I have the kind of Cushing that will just work itself out and I'm healthy," Amy said at the time
"was the greatest news imaginable."
2025—The National Ski Areas Association (NSAA) has named two longtime ski industry leaders as the recipients of two of its most prestigious awards
Chris Cushing and Chip PerfectResort planner Chris Cushing is the 2025 NSAA Industry Impact Award honoree
and Perfect North Slopes (Ind.) owner Chip Perfect is the recipient of the 2025 NSAA Lifetime Achievement Award
working on a total of more than 200 ski area projects on five continents
He’s been involved in such major resort revitalizations and expansions as Deer Valley
Cushing comes from a strong background of resort planning
in the 1960s and is widely considered an originator of modern mountain planning
“For those of us who have been in the business this long
“NSAA has been a big part of my life,” he continued
“To be honored with this award from the people with whom I’ve shared my career
it’s the ultimate confirmation that whatever we all did
Read Cushing’s full bio on NSAA’s website
Perfect grew up on his family’s farm in southern Indiana
A college student approached the family about turning a portion of the property into a ski area
and Perfect North Slopes became a reality in 1980 with two handle tows
Perfect has grown the ski area into one of the most successful operations in the Midwest
The ski area was an early adopter of high-capacity snowmaking
allowing Perfect North to capitalize on short windows of opportunity to make a lot of snow
Perfect also pioneered innovative ticketing and lesson options for guests to get the most bang for their buck
joining the NSAA board of directors in 2004
becoming part of the NSAA executive committee in 2007
and being elected as the first board chair from the Midwest in 2012
Perfect was honored by the Midwest Ski Areas Association in 2018 with the Jim VanderKelen Lifetime Achievement Award
He now owns and operates three ski areas—Perfect North Slopes
In addition to these ventures and being an Indiana State Senator from 2014-2023
Perfect is involved in a variety of other businesses
Read Perfect’s full bio on NSAA’s website
Cushing and Perfect will be formally honored at the 2025 NSAA National Convention
Ski Area Management - SAM | P.O. Box 644 Woodbury, CT 06798 | Tel. (203) 263-0888 | Fax (203) 266-0452 | Email news@saminfo.com
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Metrics details
Research siloes slow the translation of scientific discovery to patient care and limit progress in improving treatments for Cushing disease to incremental advances
Facilitating collaborative efforts that study the complexity of pituitary neuroendocrine tumours would advance the development of targeted treatments for patients who experience a low quality of life for years owing to this rare and understudied disease
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Research reported in this publication was supported by the National Institute of Diabetes and Digestive And Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) under award number RC2DK140838
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health
Department of Interdisciplinary Biomedical Sciences
The author declares no competing interests
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DOI: https://doi.org/10.1038/s41574-024-01080-x
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Amy Schumer has shared how she was diagnosed with Cushing syndrome after people pointed out to her a noticeable change in her appearance
Amy Schumer is looking back at how her followers helped her reach a medical diagnosis
Nearly one year after sharing her diagnosis of Cushing's syndrome
a disorder that occurs when your body makes too much of the hormone cortisol
the comedian detailed how comments about her "puffier" face—especially from doctors—led to finally getting to the bottom of what was going on with her body
It was that concern that led to her seeing the comments through a different lens
I'm getting trolled by doctors?" she noted
Flash forward to last February when the I Feel Pretty actress confirmed that she had been diagnosed with Cushing syndrome caused from high-dose steroid injections
"I was like, wait, I have been getting steroid injections for my scars," the Trainwreck actress said on Call Her Daddy. "I had a breast reduction, you know, C-section
with husband Chris Fischer—confirmed she received her diagnosis not long before she started filming her upcoming Netflix comedy movie
Schumer said she initially feared the worst
"There are two kinds of Cushing and [with] one of them
So I was feeling really down on myself before I started filming this movie."
If you’re concerned you have a “cortisol face” or “moon face,” it’s best to talk with your doctor
Most people who are concerned about this do not have Cushing syndrome
but it’s possible you have a different underlying condition
Oregon Health & Science University. Cushing Disease/Cushing Syndrome
National Institute of Diabetes and Digestive and Kidney Diseases. Cushing’s syndrome
National Library of Medicine: MedlinePlus. Cushing disease
Johns Hopkins Diabetes Guide. Cushing syndrome