Skeletal muscle wasting is a devastating consequence of cancer that contributes to increased complications and poor survival, but is not well understood at the molecular level. Herein, we investigated the role of Myocilin (Myoc), a skeletal muscle hypertrophy-promoting protein that we showed is downregulated in multiple mouse models of cancer cachexia. Loss of Myoc alone was sufficient to induce phenotypes identified in mouse models of cancer cachexia, including muscle fiber atrophy, sarcolemmal fragility, and impaired muscle regeneration. By 18 months of age, mice deficient in Myoc showed significant skeletal muscle remodeling, characterized by increased fat and collagen deposition compared with wild-type mice, thus also supporting Myoc as a regulator of muscle quality. In cancer cachexia models, maintaining skeletal muscle expression of Myoc significantly attenuated muscle loss, while mice lacking Myoc showed enhanced muscle wasting. Furthermore, we identified the myocyte enhancer factor 2 C (MEF2C) transcription factor as a key upstream activator of Myoc whose gain of function significantly deterred cancer-induced muscle wasting and dysfunction in a preclinical model of pancreatic ductal adenocarcinoma (PDAC). Finally, compared with noncancer control patients, MYOC was significantly reduced in skeletal muscle of patients with PDAC defined as cachectic and correlated with MEF2c. These data therefore identify disruptions in MEF2c-dependent transcription of Myoc as a novel mechanism of cancer-associated muscle wasting that is similarly disrupted in muscle of patients with cachectic cancer.Significance:This work identifies a novel transcriptional mechanism that mediates skeletal muscle wasting in murine models of cancer cachexia that is disrupted in skeletal muscle of patients with cancer exhibiting cachexia.

BACKGROUND AND PURPOSE:

Endovascular embolization only has been advocated for treatment of brain arteriovenous malformations in recent trials. Our aim was to evaluate the results of embolization only in a cohort of patients who were enrolled in the A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) study at 39 clinical sites in 9 countries.

MATERIALS AND METHODS:

We analyzed the rates and severity of stroke and death in patients who underwent embolization only. Events were identified through in-person neurologic follow-up visits performed at 6-month intervals during the first 2 years and annually, with telephone contact every 6 months thereafter. All event-related data were reviewed by independent adjudicators.

RESULTS:

Among 30 patients who had embolization planned, 26 underwent embolization only. A total of 13 stroke events were reported in the follow-up period among 26 subjects (ischemic, hemorrhagic, or both in 4, 7, and 2 subjects, respectively). The adverse event occurred after the first embolization in 11 of 13 patients. One patient had a major motor deficit, and 2 patients developed major visual field deficits. One event was fatal. The modified Rankin Scale score was 0–2 at last follow-up in 11 of the 12 stroke survivors. Estimated stroke-free survival was 46% at 12 months.

CONCLUSIONS:

Although the rates of stroke and/or death were high in patients treated with embolization only in ARUBA, the rates of favorable outcomes following stroke were high during follow-up.

BACKGROUND AND PURPOSE:

Embolization is widely performed to treat brain arteriovenous malformations, but little has been reported on factors contributing to complications. We retrospectively reviewed a nationwide surveillance to identify risk factors contributing to complications and short-term clinical outcomes in the endovascular treatment of brain arteriovenous malformations.

MATERIALS AND METHODS:

Data for endovascular treatment of brain arteriovenous malformations were extracted from the Japanese nationwide surveillance. Patient characteristics, brain arteriovenous malformation features, procedures, angiographic results, complications, and clinical outcomes at 30 days postprocedure were analyzed.

RESULTS:

A total of 1042 endovascular procedures (788 patients; mean, 1.43 ± 0.85 procedures per patient) performed in 111 institutions from 2010 to 2014 were reviewed. Liquid materials were used in 976 procedures (93.7%): to perform presurgical embolization in 638 procedures (61.2%), preradiosurgical embolization in 160 (15.4%), and as sole endovascular treatment in 231 (22.2%). Complete or near-complete obliteration of brain arteriovenous malformations was obtained in 386 procedures (37.0%). Procedure-related complications occurred in 136 procedures (13.1%), including hemorrhagic complications in 59 (5.7%) and ischemic complications in 57 (5.5%). Univariate analysis identified deep venous drainage, associated aneurysms, infratentorial location, and preradiosurgical embolization as statistically significant risk factors for complications. Multivariate analysis showed that embolization of brain arteriovenous malformations in the infratentorial location was significantly associated with complications. Patients with complications due to endovascular procedures had worse clinical outcomes 30 days after the procedures than those without complications.

CONCLUSIONS:

Complications arising after endovascular treatment of brain arteriovenous malformations are not negligible even though they may play a role in adjunctive therapy, especially in the management of infratentorial brain arteriovenous malformations.

SUMMARY:

Use of mechanical thrombectomy for stroke has increased since the publication of trials describing outcome improvement when used in the anterior circulation. These results, however, cannot be directly translated to the posterior circulation. While a high NIHSS score has demonstrated an association with poor outcomes in posterior stroke, the NIHSS is weighted toward hemispheric disease, and complex scores potentially delay definitive imaging diagnosis. We performed a retrospective analysis to ascertain whether any rapidly obtainable demographic or clinical and imaging data have a correlation with patient outcome postthrombectomy. Seventy-three cases were audited between September 2010 and October 2017. Presenting with a Glasgow Coma Scale score of >13 meant that the odds of reaching the primary end point of functional independence (defined as a 90-day modified Rankin Scale score of 0–2) were 5.70 times greater; similarly, presenting with a posterior circulation ASPECTS of >9 resulted in the odds of reaching the primary end point being 4.03 times greater. Older age correlated to a lower odds of independence (0.97, p = .04).

SUMMARY:

The remarkable temperature sensitivity of the brain is widely recognized and has been studied for its role in the potentiation of ischemic and other neurologic injuries. Pyrexia frequently complicates large-vessel acute ischemic stroke and develops commonly in critically ill neurologic patients; the profound sensitivity of the brain even to minor intraischemic temperature changes, together with the discovery of brain-to-systemic as well as intracerebral temperature gradients, has thus compelled the exploration of cerebral thermoregulation and uncovered its immutable dependence on cerebral blood flow. A lack of pragmatic and noninvasive tools for spatially and temporally resolved brain thermometry has historically restricted empiric study of cerebral temperature homeostasis; however, MR thermometry (MRT) leveraging temperature-sensitive nuclear magnetic resonance phenomena is well-suited to bridging this long-standing gap. This review aims to introduce the reader to the following: 1) fundamental aspects of cerebral thermoregulation, 2) the physical basis of noninvasive MRT, and 3) the physiologic interdependence of cerebral temperature, perfusion, metabolism, and viability.

Phoenix Legend Ha Long Bay Hotel and Residences được thiết kế là khu phức hợp hiện đại gồm căn hộ nghỉ dưỡng, khu biệt thự cao cấp, khách sạn tiêu chuẩn quốc tế 5 sao.

Cập nhật mới nhất nhà Lavender City Thạnh Phú, Vĩnh Cửu, Đồng Nai, hỗ trợ vay ngân hàng từ 800 - 1 tỷ. Lãi suất ưu đãi 0,9%/tháng. * E4 - 17 72m2 4*18m (trệt lửng) hướng Bắc: 1,25 tỷ. * B5 - 15 75m2 5*15m (trệt lửng) Tây Nam; 1,35 tỷ. * B5 - 21 75m2 5*15m (1 lầu 1 trệt) Tây Nam: ...

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Azumi Serviced Offices is a company specializing in leasing model of a virtual office and serviced offices.Address: No. 04 Pham Ngu Lao, Trang Tien Ward, Hoan Kiem District, HanoiComing to Azumi Serviced Offices, customers will be inspired by professional working space.The soluti...

Nguyen Tran Nam, former Deputy Minister of Construction, also President of the Vietnam Real Estate Association (VNREA) says in comparison to buying, renting a home is a better solution for young Vietnamese.

To ensure that you can afford for your living expenditures, you should not spend more than 30-40% of income on housing.

Along with the recovery of market, property investment also rebounds with new trends. Here are three new trends of property investment that become more and more popular in 2015.

Khu đô thị Việt Đức Legend City được đầu tư bởi Công ty Ống thép Việt Đức với quy mô 620.798m2, toạ lạc tại nút giao thông trục chính giữa KĐT Mê Linh với QL 2A thuộc địa phận xã Đạo Đức, huyện Bình Xuyên, tỉnh Vĩnh Phúc.

Season 5 of Respawn Entertainment’s hero-based battle royale kicks off next week and it looks like they’re doing more than just blowing up the map. This new Apex Legends trailer shows off what appears to be a horde mode PvE quest initiated by the newest Legend of the bunch: Loba. It looks like you’ll be […]

Crawling on his belly through a sewer pipe beneath the streets of Warsaw, Poland, with a battle raging overhead, 16-year-old Lucjan Krause could scarcely have imagined he would survive the fighting, let alone go on to build a globally admired atomic physics program at the University of Windsor. Now 92 and still in full command […]

Honeywell, the same company that might make your humidifier or home security system, is unveiling a powerful quantum computer that will be available to the public

Always forgetting birthdays? Terrible at staying in touch? New tech promises to turn you into the best buddy ever. We put it to the test

Get an all day breakfast on a pizza before you go on your killing spree. Only psychopaths will order this, is what I'm saying.

With the acquisition of a start-up specialising in encrypted messaging and cloud services, Zoom will finally be able to make good on its claims of offering end-to-end encryption.

SpaceX is partnering with a US start-up called Axiom Space to launch three space tourists on a 10-day trip to the International Space Station

Your weekly selection of awesome robot videos

In response to the ongoing COVID-19 pandemic.

An overlooked member of The Eddy band steps into the spotlight for a bittersweet—mostly bitter—story about his troubled past and uncertain future.

This is a terrifying elevator cam gif from Korea of an elevator that begins ascending before a man enters, tripping him and almost creating a classic horror movie death scene in real life. Thankfully he was able to escape. And this is exactly why I don't take elevators -- or escalators. "So you're a stair guy?" Please *jiggling belly* jetpack or grappling gun only. Thanks to PK, who agrees they always say use the stairs in case of emergency, and what's 2020 if not a nonstop emergency? Besides, how do you social distance in an elevator? I mean if somebody farts everyone smells it.

Failed to get friends list and several more Pokemon GO friends list errors are once again impacting players on iOS and Android.

Manny gives fashion advice. Chris learns that he doesn’t know how to Kindle. And Anna Marie orders avatar tuna. Is it a slow news week?

While Chris is tempted by another physical collector’s edition, Kelley drowns in chili dogs. Alice survives Mars and seems to enjoy FFXV to boot. Josh,...

This week, Alex and Anna Marie can talk about their embargoed games, Peter finishes a game, and Chris worries about his cats. Kelley’s question of the week leads us down rabbit holes we probably shouldn’t have explored, but we’re doing it live and that’s how we roll.

From tiny sunglasses to leather coats, the film’s costume designer Kym Barrett writes about why the film’s look feels so relevant in our uncertain world

• Read more from the spring/summer 2020 edition of The Fashion, our biannual style supplement

I never thought The Matrix would have the impact it has had on fashion. But from long leather coats to so-called “Matrix-style” sunglasses, the costumes I designed in the 90s continue to have influence to this day.

Part of the reason they are still in the ether is because they were so iconic. The silhouettes, for instance, had to be instantly recognisable so that viewers could tell who each character was, even in the dark. All of the costumes are fairly immune to period, which is what makes them relatable, even now.

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Zayn Malik and Virgil Abloh are among male celebrities decking out their ears, necks and wrists

There was a time when wearing a boyband-style dogtag was seen as the peak of male adornment, but now men are increasingly embracing jewellery, stacking rings and bracelets and adorning ears with multiple gems.

This week, the former One Direction singer Zayn Malik was announced as the face of the unisex jewellery label Martyre. Virgil Abloh, a weather vane for fashion’s direction of travel, this week launched more office supplies-inspired jewellery – paperclip bracelets, earrings and necklaces decorated with colourful diamonds – and was pictured wearing one of the collection’s bejewelled necklaces.

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People who attended religious services at least once a week were significantly less likely to die from 'deaths of despair,' including deaths related to suicide, drug overdose, and alcohol poisoning, according to new research.

The I, Daniel Blake star on her parents’ generosity, working in a call centre and her love of ice-cream

Born in London, Squires, 32, studied at Rose Bruford College in London. She starred in the Ken Loach film, I, Daniel Blake in 2016, earning a Bafta nomination and winning most promising newcomer at the British Independent Film awards. Her West End debut in Cat On A Hot Tin Roof followed in 2017. Her television work includes The Miniaturist and Collateral; in the autumn she will play the lead in the Channel 4 drama, Adult Material.

What is your greatest fear?
Snakes.

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Alan Yang’s film about the lack of understanding between generations strikes a chord, and is so relevant as coronavirus racism spreads

• Read all the Lockdown watch films here
• The best arts and entertainment during self-isolation

Inflamed by President Trump’s casual phrase “Chinese virus”, anti-Asian sentiment is erupting all over the world. As a British-Vietnamese person who has been spat on because of the colour of her skin, the film Tigertail is a glimmer of hope – a way of showing the truth, and connecting Asian communities at a time when panic and misinformation serve to break us apart. Alan Yang’s multi-generational love story Tigertail weaves in Yang’s cultural self-discovery and features memories of Taiwan, as experienced by the protagonist Pin-Jui. Weighted against the present tide of anti-Asian bigotry, this tender story about honesty and lost love is more relevant than ever.

“American culture has been negligent in portraying Asian-American people as fully realised human beings,” Yang told the Deadline podcast. Yang, who worked on Parks and Recreation before co-creating Master of None, recalled the trepidation he felt in the early days of his career, in a cultural landscape where east Asians were rarely represented, or stereotyped as hardworking automatons. Yang said he had felt restricted to using only white characters in his early pilots, fearing that all-Asian or Asian-American scripts would never be accepted. But this was before the film successes of Crazy Rich Asians, The Farewell and Parasite brought real Asian faces to mainstream culture.

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Kirk Douglas, Hollywood legend and star of Spartacus, has died aged 103. Douglas was nominated for three Oscars and his extensive filmography includes Paths of Glory, 20,000 Leagues Under the Sea and Lust for Life. The Hollywood legend's death was announced by his son, fellow actor Michael Douglas

• Kirk Douglas, Hollywood legend and star of Spartacus, dies aged 103

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An affectionate and absorbing documentary from film-maker Rachel Mason about her devout parents, who ran a famous adult bookstore in early-80s LA

Here is a documentary with an absorbing and unexpectedly complicated story to tell, whose paradoxes and sadnesses are not entirely resolved by the end. Artist and film-maker Rachel Mason has created an affectionate portrait of her elderly parents, Karen and Barry, who in many ways are like one of the (fictional) old couples in When Harry Met Sally.

Karen is a former journalist, devoutly Jewish, and Barry is a former special visual effects engineer who worked on Stanley Kubrick’s 2001 and invented a modification for kidney dialysis machines. But they found themselves in a tough financial spot in the early 1980s and took over Circus of Books, a gay porn bookstore in Los Angeles that also sold movies called things like Confessions of a Two Dick Slut and Don’t Drop the Soap, and was one of Larry Flynt’s first distribution points. Under their shrewd management, the store boomed, opened another branch and became a well-known meeting place for LGBT people, while all the time, the Masons were a conventional family who kept their three children well away from the business. Karen movingly – and honestly – recounts how upset she was to discover that one of her sons was gay: the business and family life were that separate.

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Screenshots showing repugnant and insulting remarks — some misogynistic, some racist, others hinting at drug use and sexual conquests — from a private group chat between several hockey players, including ...

The fallout came swiftly Thursday after vulgar and insulting messages traded on a private Instagram chat surfaced on social media a day earlier. The University of Manitoba Bisons released Jeremey Leipsic ...

"I just couldn't be more proud of you and the prospect of your presidency," Newsom told Biden Friday during a campaign event.

The singer who played a key role in early rock music's popularity died Saturday at 87 years old.

Nintendo is selling a lot of Switches. The convertible console has been a lifesaver for people sheltering in place around the world. COVID-19-induced travel restrictions and the long-awaited arrival of Animal Crossing: New Horizons have proven to be a perfect storm for the three-year-old platform. New numbers out from NPD this morning shed some light […]

Nintendo today confirmed earlier reports of account breaches dating back over the past few weeks. The gaming giant issued an update (via Nintendo Japan) noting that around 160,000 Nintendo Accounts were impacted, which found multiple being used to purchase digital items without the owner’s consent. Along with the purchasing powers, the offending parties may have […]

A couple of weeks ago, we noted some new NPD numbers pointing to a very good March for the Switch. Nintendo’s financials this week bear out the predicted surge in popularity for the three-year-old console. The company has sold 21 million Switch units in the past year, handily beating a 19.5 million forecast; 6.2 million […]

Following a healthy diet or exercising could impact how your brain ages, but the effects on cognitive skills later in life depend on specific gene variants that not everyone has

There are three main strategies for leaving coronavirus lockdown, but each risks a dangerous second wave and further lockdowns if things don't go as planned

An end to lockdown is many weeks away for some nations, but decisions on how to do it need to be made now so we can make preparations and communicate it clearly