Regular snoring is associated with uncontrolled hypertension - npj Digital Medicine

Rightwing Candidate Tried To Shame Pup-play Pride "perverts." It Didn't Work.

Porky Grinds put on his pup mask, mitts, jean shorts, and rubber dog tail and climbed into the back of a truck to ride in the July 21st Portland Pride Parade with Portland Pups and Handlers (PDX PAH), a group for human-pet play enthusiasts — people who play the role of a dog, a house pet, or their human owner. About 200 people marched with the group, including furries wearing their mascot costume heads, leather men, and "littles" (people who role-play as infants).

"I was barking and having a great time with all of the families and people out there," Grinds told LGBTQ Nation. "[The marchers and parade goers] were all just losing their minds to see themselves represented."

Later that evening, Brandon Farley—a self-described independent journalist and far-right Portland city council candidate with no prior government experience—posted a video on X of Grinds and his fellow marchers.

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Farley's video caption read, "Obese shirtless men wearing dog masks with dildos affixed to their a**es were prominently featured at the #Portland Gay Pride Parade." Two hours later, Farley posted an image from the PDX-PAH website showing the faces and names of the group's board members, which included Grinds.

"All these people are mentally ill," Farley wrote. "Being sexual around children is what's making them happy. I don't give a s**t about their fulfillment. These people are perverts who fetishize dogs, the worst animal on Earth."

Farley posted other videos from the parade on X, including one of an LGBTQ+-affirming church in the parade. He wrote, "Religious organizations in #Portland love to attach themselves to the Gay Pride movement, despite what it says in the Holy Bible about homosexuality being a sin."

Oregon's lesbian Gov. Tina Kotek (D) posted photos of the parade and wrote, "Portland Pride—you just get better and better each year."

Farley commented, "I don't care that you like to munch carpet. Just stop rubbing it in everyone's faces."

A friend told Grinds about Farley's posts. When Grinds watched the video, he noticed that Farley spent most of his time focused on him. He told LGBTQ Nation that he wasn't wearing a dildo and neither were any of the marchers in his group.

Quickly, the board members of PDX-PAH began discussing Farley's post in a group chat.

"[Our] people were like, 'Wow, really?'" Grinds said. "And then there was immediate concern that someone could be identified and have their personal life ruined. We messaged back and forth—both in the board chat and offline—trying to make sure that everybody was happy with where they were and with the amount of risk that they were in."

Most board members weren't too concerned because they had used their pseudonymous pup names or covered their faces in the images on the PDX-PAH website. Others worried that local Proud Boys or other anti-LGBTQ+ activists could hunt down and add their names to a target list.

"There was concern," Grinds says, "but it was more making sure that everybody was safe than it was like, you know, 'Everybody hit the ground.' You know, we're not running scared from this guy."

Pride parade haters are nothing new. For decades, they've protested events, holding picket signs about queers burning in hell. Social media and the rise of the far-right, however, have made "sneak videographers" like Farley more common. They troll the events, trying to capture images of adults acting in ways that could be interpreted as sexual around kids or saying controversial things. These have coincided with Republican claims that LGBTQ+ people and their allies are "groomers" looking to "sexualize" kids.

This rhetoric turns into real-world violence. This year, the State Department, the Department of Homeland Security (DHS), and the FBI all issued warnings about possible anti-LGBTQ+ violence during Pride events. A 2022 report found that anti-LGBTQ+ mobilization had more than quadrupled from 2020 to 2021 and worsened again in 2022. A separate 2023 report found thrice as many incidents of anti-LGBTQ+ extremism and hate as in the previous year. Nearly half were perpetrated by members of groups like the Proud Boys and Patriot Front.

Farley is cut from this same cloth. He has previously made posts on X against transgender people and drag performers. His stated goals as a city council candidate are to "Make Portland Great Again" and "combat far-left lunacy in gov."

He also ran for city council in 2022 but withdrew, citing mental health reasons.

Grinds and his fellow board members aren't discouraged by Farley's actions, and they see nothing wrong with their group. For one, their group only allows members above the age of 21. Second, the group and its gatherings aren't inherently sexual. Last, they see pup play, furrydom, and littles as innocent and imaginative forms of pretend that have been a part of countless cultures throughout history.

"Kids do this kind of thing every single day at every elementary school in the nation, right?" he told LGBTQ Nation. "They like to pretend. They like to engage. They like to get into a space where they're pretending to be part of a family, or a pet from a family, or younger than they actually are. Kids do this kind of thing, and also, like, be perfectly honest, adults do this kind of thing. Actors do this kind of thing, and it's public. Like the dog in the Peter Pan play has always been played by like an adult. "

"It's just one of those things that kids get intrinsically and when they turn into teenagers and become obsessed with, like, fitting in and not making themselves separate, being part of the group, that that's when they like lose that [impulse]. At least some of them do," he adds.

For Grinds, who is PDX-PAH's events coordinator, pup play has presented an opportunity for him and others to be more playful and publicly outgoing than they might otherwise be.

"It's so much about, like, love and interacting and connecting with people in a way that's maybe, I mean, it's definitely nonstandard. But like, we live in a world where guys can't get hugged, and nobody just praises you for no reason. But as soon as you're on all fours, you're a good boy no matter what you do. And it's special. It's amazing. It's a great way to connect with people. And it's the fastest growing kink for a reason, because people relate to it. They connect."

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New Insights And Potential Treatments For Pulmonary Hypertension

A new study from researchers with UCLA Health and collaborating organizations has found that asporin, a protein encoded by the ASPN gene, plays a protective role in pulmonary arterial hypertension (PAH).

Their findings, published on August 21 in the peer-reviewed journal Circulation, offer new insights into this incurable, often-fatal disease and suggest potential new ways to treat it.

"We were surprised to find that asporin, which previously had not been linked to PAH, gets upregulated to increased levels as a response to counteract this disease process," said Dr. Jason Hong, a pulmonary and critical care physician at UCLA Health and the study's corresponding author. "This novel finding opens up new avenues for understanding PAH pathobiology and developing potential therapies."

Pulmonary hypertension is a serious medical condition characterized by high blood pressure in the arteries that supply the lungs. It causes these arteries to narrow or become blocked, which, in turn, slows blood flow to the heart, requiring it to work harder to pump blood through the lungs. Eventually, the heart muscle becomes weak and begins to fail.

Need for New Therapies

According to recent estimates, PAH affects about 1% of the global population, but that number climbs to 10% in people who are 65 or older.

There's no cure for the disease, but medications and lifestyle changes can help slow progression, manage symptoms and prolong life.

The urgent need for new therapies, combined with the potential of multiomics -- an integrated approach to drive discovery across multiple levels of biology -- inspired Hong and research colleagues, including co-first author Lejla Medzikovic and senior author Mansoureh Eghbali to take a deep dive into the disease. Both work at UCLA's Eghbali Laboratory.

Methodology

For the study, the researchers applied novel computational methods, including transcriptomic profiling and deep phenotyping, to lung samples of 96 PAH patients and 52 control subjects without the condition from the largest multicenter PAH lung biobank available to-date. They integrated this data with clinical information, genome-wide association studies, graphic models of probabilities and multiomics analysis.

"Our detailed analysis found higher levels of asporin in the lungs and plasma of PAH patients, which were linked to less severe disease," Hong said.

Additionally, Medzikovic noted that their cell and living-organism experiments found that asporin inhibited pulmonary artery smooth muscle cell proliferation and a key signaling pathway that occurs with PAH.

"We also demonstrated that recombinant asporin treatment reduced PAH severity in preclinical models," said Medzikovic.

Next Steps

Hong and colleagues plan to further investigate the mechanisms by which asporin exerts its protective effects in PAH and explore potential therapeutic applications, focusing on how to translate their findings into clinical trials.

"Asporin represents a promising new target for therapeutic intervention in pulmonary arterial hypertension," he explained. "Enhancing asporin levels in PAH patients could potentially lead to improved clinical outcomes and reduced disease progression."

Authors: Jason Hong, MD, PhD,* Lejla Medzikovic, PhD*, Wasila Sun, BS‡, Brenda Wong, BA‡, Gregoire Ruffenach, PhD, Christopher J. Rhodes, PhD, Adam Brownstein, MD, Lloyd L. Liang, MS, Laila Aryan, PhD, Min Li, PhD, Arjun Vadgama, Zeyneb Kurt, PhD, Tae-Hwi Schwantes- An, PhD, Elizabeth A. Mickler, MS, Stefan Graf, PhD, Melanie Eyries, PhD, Katie A. Lutz, BS, Michael W. Pauciulo, MBA, Richard C. Trembath, MD, Frederic Perros, PhD, David Montani, MD, PhD, Nicholas W. Morrell, MD, Florent Soubrier, MD, PhD, Martin R. Wilkins, MD, William C. Nichols, PhD, Micheala A. Aldred, PhD, Ankit A. Desai, MD, David-Alexandre Tregouet, PhD, Soban Umar, MD, PhD, Rajan Saggar, MD, Richard Channick, MD, Rubin M. Tuder, MD, Mark W. Geraci, MD, Robert S. Stearman, PhD†, Xia Yang, PhD†, and senior author, Mansoureh Eghbali, PhD†. Legend: *Joint first authors; ‡ Joint second authors; †Joint last authors

Funding: This work was supported by American Heart Association grant 23POST1022457 (L.M.), American Thoracic Society Early Career Investigator Award in Pulmonary Vascular Disease (J.H.), and U.S. NIH grants K08HL169982 (J.H.), R01HL147586 (M.E.), R01HL162124 (M.E.), R01HL159865 (M.E.), R01HL147883 (X.Y.), R24HL105333 (W.N. And M.P.), R01HL160941 (W.N., A.D., and M.P.), British Heart Foundation Senior Basic Science Fellowship FS/SBSRF/21/31025 (C.R.), and funding for the PHBI is provided by NHLBI R24HL123767 and by the Cardiovascular Medical Research and Education Fund (MAA).

European Commission Approves Merck's Winrevair In Combo With Other PAH Therapies To Treat PAH In Adult Patients With Functional Class II-III

Merck, known as MSD outside of the United States and Canada, announced that the European Commission (EC) has approved Winrevair (sotatercept), in combination with other pulmonary arterial hypertension (PAH) therapies, for the treatment of PAH in adult patients with World Health Organization (WHO) Functional Class (FC) II to III, to improve exercise capacity.

Winrevair is the first and only activin signalling inhibitor therapy for PAH approved in all 27 member states of the EU, as well as Iceland, Liechtenstein and Norway. Winrevair works by improving the balance between pro- and anti-proliferative signalling to regulate vascular cell proliferation underlying PAH. The EC approval of Winrevair is based on safety and efficacy results from the phase 3 STELLAR trial.

"The European Commission's approval of Winrevair is an important step for patients," said Dr. Joerg Koglin, senior vice president and head of general medicine, global clinical development, Merck Research Laboratories. "Winrevair is the first therapy targeting the activin signalling pathway. We are proud to bring this innovative treatment to more patients and remain committed to further investigating the potential of Winrevair in areas where there are unmet needs in the management of PAH."

"Pulmonary arterial hypertension is a devastating disease for patients, who suffer from debilitating symptoms that can severely limit their daily activities," said Dr. Marc Humbert, Professor of Medicine and Director of the Pulmonary Hypertension Reference Center at Université Paris-Saclay. "New treatment opinions continue to be needed for patients. Based on the phase 3 STELLAR study, adding Winrevair to background PAH therapy improved exercise capacity, reduced the risk of death or clinical worsening events and improved functional class compared to background PAH therapy alone. These findings are significant and reinforce that Winrevair, in combination with other PAH therapies, should be considered as a new standard of care for the treatment of functional class II and III adult patients."

The EC approval is based on the phase 3 STELLAR trial, which compared Winrevair (n=163) to placebo (n=160), both in combination with background standard of care therapies in adult patients with PAH (WHO Group 1, FC II or III). The primary efficacy endpoint was change from baseline at Week 24 in six-minute walk distance. Treatment with Winrevair resulted in a statistically significant and clinically meaningful improvement in six-minute walk distance of 40.8 meters over placebo (95% CI: 27.5, 54.1; p<0.001). Winrevair also significantly improved multiple important secondary outcome measures, including reducing the risk of death or clinical worsening. In a post hoc analysis provided to EMA, time to death or clinical worsening was defined as the time from randomization to the first occurrence of deterioration of PAH, PAH-specific hospitalization, worsening-related listing for lung and/or heart transplant, need for atrial septostomy, or death from any cause. There was an 82% reduction in the risk of death or clinical worsening with Winrevair on top of background therapy versus background therapy alone (number of events: 7 vs 29, HR=0.182; 95% CI: 0.075, 0.441; p<0.001).

Winrevair is administered once every 3 weeks as a single injection under the skin and may be administered by patients or caregivers with guidance, training and follow-up from a healthcare provider. Healthcare providers and patients/caregivers should refer to the Instructions for Use for information on the proper preparation and administration of Winrevair.

This approval by the EC for Winrevair is valid in all 27 member states of the EU, as well as Iceland, Liechtenstein and Norway. Winrevair was previously granted Priority Medicines (PRIME) and orphan designation by the EMA for the treatment of PAH.

On March 26, 2024, the FDA approved Winrevair in the US for the treatment of adults with pulmonary arterial hypertension (PAH, WHO Group 1) to increase exercise capacity, improve WHO functional class (FC) and reduce the risk of clinical worsening events.

The STELLAR study (NCT04576988) was a global, double-blind, placebo-controlled, multicenter, parallel-group clinical trial in which 323 patients with PAH (WHO Group 1 FC II or III) were randomized 1:1 to Winrevair (target dose 0.7 mg/kg) (n=163) or placebo (n=160) plus stable background therapy administered subcutaneously once every 3 weeks.

The most common PAH etiologies were idiopathic PAH (59%), heritable PAH (18%), and PAH associated with connective tissue diseases (CTD) (15%). Most participants were receiving either three (61%) or two (35%) background drugs for PAH, and 40% were receiving prostacyclin infusions. The mean time from PAH diagnosis was 8.8 years. Patients had a WHO FC II (49%) or III (51%) at baseline.

Winrevair, the first activin signaling inhibitor therapy approved to treat PAH, improves the balance between pro-proliferative and anti-proliferative signalling to modulate vascular proliferation. In preclinical models, Winrevair induced cellular changes that were associated with thinner vessel walls, partial reversal of right ventricular remodelling, and improved hemodynamics.

WINREVAIR is the subject of a licensing agreement with Bristol Myers Squibb.

Pulmonary arterial hypertension (PAH) is a rare, progressive and life-threatening blood vessel disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation. Approximately 40,000 people in the US and 30,000 people in the EU are living with PAH. The disease progresses rapidly for many patients. PAH results in significant strain on the heart, leading to limited physical activity, heart failure and reduced life expectancy. The five-year mortality rate for patients with PAH is approximately 43%, based on data from the REVEAL registry (patients enrolled between March 2006 and December 2009).

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