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No In Vivo Evidence for Estrogen Receptor Density Changes in Human Neuroendocrine Aging or Their Relationship to Cognition and Menopausal Symptoms




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The 75-Year Anniversary of the Department of Physiology and Pharmacology at Karolinska Institutet--Examples of Recent Accomplishments and Future Perspectives [75th Anniversary Celebration Collection Special Section-Perspective]

Karolinska Institutet is a medical university encompassing 21 departments distributed across three departmental or campus groups. Pharmacological research has a long and successful tradition at the institute with a multitude of seminal findings in the areas of neuronal control of vasodilatation, cardiovascular pharmacology, neuropsychopharmacology, receptor pharmacology, and pharmacogenomics that resulted in, among many other recognitions, two Nobel prizes in Physiology and Medicine, one in 1970 to Ulf von Euler for his discovery of the processes involved in storage, release, and inactivation of neurotransmitters and the other in 1982 to Sune Bergström and Bengt Samuelsson for their work on prostaglandins and the discovery of leukotrienes. Pharmacology at Karolinska Institutet has over the last decade been ranked globally among the top 10 according to the QS World University Ranking. With the Department of Physiology and Pharmacology now celebrating its 75-year anniversary, we wanted to take this as an opportunity to showcase recent research achievements and how they paved the way for current activities at the department. We emphasize examples from preclinical and clinical research where the dpartment's integrative environment and robust infrastructure have successfully facilitated the translation of findings into clinical applications and patient benefits. The close collaboration between preclinical scientists and clinical researchers across various disciplines, along with a strong network of partnerships within the department and beyond, positions us to continue leading world-class pharmacological research at the Department of Physiology and Pharmacology for decades to come.

Significance Statement

Pharmacological research at Karolinska Institutet has a long and successful history. Given the 75-year anniversary of the Department of Physiology and Pharmacology, this perspective provides an overview of recent departmental achievements and future trajectories. For these developments, interdisciplinary and intersectoral collaborations and a clear focus on result translation are key elements to continue its legacy of world-leading pharmacological research.




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Enzyme Replacement Therapy for CLN2 Disease: MRI Volumetry Shows Significantly Slower Volume Loss Compared with a Natural History Cohort [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Neuronal ceroid lipofuscinoses are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for neuronal ceroid lipofuscinosis type 2 (CLN2), a subtype of neuronal ceroid lipofuscinoses. The aim of this study was to quantify brain volume loss in CLN2 disease in patients on ERT in comparison with a natural history cohort using MRI.

MATERIALS AND METHODS:

Nineteen (14 female, 5 male) patients with CLN2 disease at 1 UK center were studied using serial 3D T1-weighted MRI (follow-up time, 1–9 years). Brain segmentation was performed using FreeSurfer. Volume measurements for supratentorial gray and white matter, deep gray matter (basal ganglia/thalami), the lateral ventricles, and cerebellar gray and white matter were recorded. The volume change with time was analyzed using a linear mixed-effects model excluding scans before treatment onset. Comparison was made with a published natural history cohort of 12 patients (8 female, 4 male), which was re-analyzed using the same method.

RESULTS:

Brain volume loss of all segmented brain regions was much slower in treated patients compared with the natural history cohort. For example, supratentorial gray matter volume in treated patients decreased by a mean of 3% (SD, 0.74%) (P < .001) annually compared with an annual volume loss of a mean of 16.8% (SD, 1.5%) (P < .001) in the natural history cohort.

CONCLUSIONS:

Our treatment cohort showed a significantly slower rate of brain parenchymal volume loss compared with a natural history cohort in several anatomic regions. Our results complement prior clinical data that found a positive response to ERT. We demonstrate that automated MRI volumetry is a sensitive tool to monitor treatment response in children with CLN2 disease.




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General practice should tackle healthcare inequalities but not health inequalities




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'The Fellowship is breaking, it has already begun&#x2019;




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Can&#x2019;t prescribe, can&#x2019;t dispense: the challenge of medicine shortages




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Impact of Health Equity Fellowships [Family Medicine Updates]




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Guidance and Resources for Family Medicine Scholarship [Family Medicine Updates]




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Improving Access to Disability Assessment for US Citizenship Applicants in Primary Care: An Embedded Neuropsychological Assessment Innovation [Innovations in Primary Care]




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Using the Electronic Health Record to Facilitate Patient-Physician Relationship While Establishing Care [Innovations in Primary Care]




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Face-to-Face Relationships Still Matter in a Digital Age: A Call for a 5th C in the Core Tenets of Primary Care [Reflections]

We primary care clinicians, scholars, and leaders ascribe value to Barbara Starfield’s core tenets of primary care—the 4 Cs: first contact, comprehensiveness, coordination, and continuity. In today’s era of rapid technological advancements and dwindling resources, what are the implications for face-to-face interactions of patient-clinician relationships? We propose adding a 5th C: "Contiguity." Contiguity—or physical proximity and presence—is a key dimension that not only enables the necessary technical aspects of a physical exam but also authenticates the most human aspects of a relationship and occurs specifically when we are physically vulnerable and responsible for the other before us. This, in turn, may best enable us to bridge difference and nurture trust with our patients. We measure what we value and, thus, naming Contiguity as a core tenet assures that we will not lose sight of this keystone in a patient’s relationship with their personal physician.




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[Developmental Biology] Glial Cell Development and Function in the Zebrafish Central Nervous System

Over the past decades the zebrafish has emerged as an excellent model organism with which to study the biology of all glial cell types in nervous system development, plasticity, and regeneration. In this review, which builds on the earlier work by Lyons and Talbot in 2015, we will summarize how the relative ease to manipulate the zebrafish genome and its suitability for intravital imaging have helped understand principles of glial cell biology with a focus on oligodendrocytes, microglia, and astrocytes. We will highlight recent findings on the diverse properties and functions of these glial cell types in the central nervous system and discuss open questions and future directions of the field.




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Integration of lung function data: turning snapshots into stories

Missing or inaccessible lung function measurements, gathered over time, have the potential to stagnate or impair clinical care decisions being made. This jeopardises patient safety and often contributes to excessive resource utilisation. Data integration is fundamental to clinical decision-making and entails amalgamating lung function data from multiple sources in a user-friendly format. Despite this, current systems for recording lung function data are suboptimal, with copious gaps in the clinical picture arising from missing or inaccessible lung function measurements. This article discusses the importance of data integration for lung function, with a call to action for key stakeholders involved in the performance, management and interpretation of such tests.




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You Have Less Than a Week to File a Claim for Cash App’s $2,500 Payouts



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



  • Privacy and Security

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What We Do in the Shadows Champions Found Families, No Matter How Dysfunctional



Season six's latest episode introduced Laszlo's father—and chaos inevitably followed.




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Secret Level‘s Creator Hopes Concord Episode Showcases Its Lost Potential



Tim Miller hopes Amazon's anthology series will help viewers appreciate the "blood, sweat, and tears" Firewalk Studios put into the scrapped game.




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Hundreds dead after massive truck bomb strikes Mogadishu

Civilians evacuate from the scene of an explosion in KM4 street in the Hodan district of Mogadishu, Somalia October 14, 2017. Photo By Feisal Omar/Reuters

At least 231 people were killed and hundreds more wounded after a massive truck bomb on Saturday struck Somalia’s capital city of Mogadishu.

The Somali government has blamed the al-Qaida-linked militant group al-Shabab for the attack, and called it the deadliest ever to hit the nation.

The blast took place outside the Safari Hotel, where rescue workers dug through the rubble of collapsed buildings overnight in search of survivors. Witnesses described a devastating scene with large-scale carnage, as doctors worked feverishly to attend to the dead and injured, many badly burned.

“The hospital is overwhelmed by both dead and wounded,” Dr. Mohamed Yusuf, the director of Medina hospital located near the blast, told the Associated Press. “We also received people whose limbs were cut away by the bomb. This is really horrendous, unlike any other time in the past.”

Photos and videos of the bombing, which took place on a busy street near a section of the city housing foreign embassies, showed collapsed walls, twisted metal, and sporadic fires spewing smoke. The Qatari government said its embassy was “severely damaged” in the strike.

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Family members searched through the wreckage and waited at local hospitals with the hopes of finding relatives who survived the bombing.

Somali President Mohamed Abdullahi Mohamed announced three days of mourning. The attacks received international condemnation, including from the United States.

The post Hundreds dead after massive truck bomb strikes Mogadishu appeared first on PBS NewsHour.




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Iraqi, Kurdish forces in standoff, weeks after Kurdish vote for independence

Watch Video | Listen to the Audio

HARI SREENIVASAN: The desire of the Kurds along Iraq’s northern border to govern themselves is receiving more resistance from Iraq’s central government. Iraqi army forces are demanding Kurdish troops withdraw from oil fields and military bases around Kirkuk, a city in the Kurdistan region that voted for independence last month. Kirkuk also has 10% of Iraq’s known oil reserves. Washington Post’s Loveday Morris is in Baghdad covering this standoff joins me now via Skype. First of all the significance of this. Why is it so important?

LOVEDAY MORRIS: There’s been a longtime conflict between Baghdad and Kurdistan over these disputed territories. Most significant of which is Kirkuk because of the oil reserves. But the referendum last month has really sharpened these disputes because you have Baghdad opposing independence and so it feels like they have to restate its territorial claims these areas. So that’s why we’re seeing a lot of tension right now.

HARI SREENIVASAN: And just to give people a little bit of a brief timeline – Iraqi forces control this area for a while and then in June ISIS took over the area and now it’s kind of back in Kurdish hands?

LOVEDAY MORRIS: Right. So in June 2014 Iraq lost control of a lot of the areas and we have this huge collapse in the face of an ISIS offensive. Over 100,000 soldiers fled and Kurdish forces moved in some of these areas – some of them maybe took from ISIS and others just moved into into the vacuum. And so Iraqi forces have been in these areas since June 2014. And that’s their main demand that they return to the areas.

HARI SREENIVASAN: What’s the likelihood that this standoff right now turns violent? Into some sort of a civil war?

LOVEDAY MORRIS:: I think at this point both sides don’t want violence. Al-Abadi, the prime minister, is really trying to defuse the situation by saying there’s going to be no military attack. But at the same time there is this buildup of forces so that I think they are trying to, in a way, intimidate the Kurds to withdraw from some areas but they don’t want to see a fight per say. But in this really tense situation there can be a small spark and things can turn violent quite easily.

HARI SREENIVASAN: Thank you.

The post Iraqi, Kurdish forces in standoff, weeks after Kurdish vote for independence appeared first on PBS NewsHour.




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News Wrap: Dozens missing after deadly Mogadishu truck bombing

Watch Video | Listen to the Audio

JUDY WOODRUFF: And in the day’s other news: More than 300 people are now confirmed dead after Saturday’s massive truck bombing in Somalia, one of the world’s worst attacks in years.

Nearly 400 more were wounded. The government blamed the al-Qaida-linked Al-Shabaab group. Rescue crews today searched for survivors at the scene of the bombing, a crowded street in the capital, Mogadishu. With dozens still missing, officials say they expect the death toll to rise.

OSMAN LIBAH IBRAHIM, Deputy Minister for Natural Resources, Somalia (through interpreter): More bodies are gradually being found and removed from the rubble. There are other people who are under the rubble. We have heard them as they scream for help. My biggest worry is that even the wounded are succumbing to their injuries.

JUDY WOODRUFF: The attack happened two days after Somalia’s defense minister and army chief resigned for undisclosed reasons.

There’s been yet another shift to the right in European politics; 31-year-old conservative Sebastian Kurz, Austria’s foreign minister, is set to become that country’s next leader. But he’s short of a majority in Parliament and will likely form a coalition with the far-right Freedom Party. It was founded by ex-Nazis in the 1950s.

Kurz has called for the European Union to focus more on internal trade and securing borders. He celebrated in Vienna.

SEBASTIAN KURZ, Austrian People’s Party (through interpreter): I have a big request for you. Use today to celebrate. You all have earned it through hard work and dedication. At the same time, I need to tell you that tomorrow the work starts. We didn’t just run to win the elections. We did so to bring Austria back to the top. We ran in this election to achieve real change.

JUDY WOODRUFF: A final result in the election is likely to be decided on Thursday.

Wildfires that broke out over the weekend in Portugal have killed at least 35 people, including a one-month-old infant. Today, more than 5,300 firefighters with some 1,600 vehicles were battling the fires, some of which officials say were started by arsonists. Wildfires have also left at least four people dead in neighboring Spain.

Army Sergeant Bowe Bergdahl pleaded guilty today to desertion and misbehavior before the enemy. He was captured by the Taliban in 2009, after leaving his post in Afghanistan. It prompted an intense search and a prisoner swap. Bergdahl appeared before a military judge in Fort Bragg, North Carolina, today. The 31-year-old could be sentenced to life in prison. He said his actions were very inexcusable, adding he didn’t — quote — “think there’d be any reason to pull off a crucial mission to look for one guy.”

The truck driver in deadly immigrant smuggling run has pleaded guilty in court. San Antonio police found at least 39 immigrants, 10 of whom died, packed into a sweltering semi-trailer last year and died. The driver, James Matthew Bradley Jr., pleaded to conspiracy and transporting immigrants, resulting in death. He faces now up to life in prison.

A New Jersey man has been convicted of planting two pressure-cooker bombs on New York City streets last year. Ahmed Khan Rahimi faces a maximum sentence of life in prison for charges including using a weapon of mass destruction. One of the bombs exploded in Manhattan’s Chelsea neighborhood, wounding 30. The second didn’t detonate. Officials said Rahimi was inspired by ISIS and al-Qaida.

JOHN MILLER, Deputy Commissioner, NYPD Intelligence & Counterterrorism: Ahmed Khan Rahimi learned a lesson which we keep reminding people of. This is the wrong place to try and carry out an act of terrorism. Witnesses will come forward, evidence will be developed, arrests will be made, prosecutions will be brought forth, and they will be successful.

JUDY WOODRUFF: Prosecutors said Rahimi also planted a pipe bomb in Seaside Heights, New Jersey, but no one was injured.

Colin Kaepernick has filed a grievance against the national football league. The former San Francisco 49ers quarterback says that he remains unsigned due to collusion by team owners over his national anthem protests. Kaepernick sparked a debate when he kneeled during the anthem last year, protesting police mistreatment of African-Americans.

On Wall Street today, the Dow Jones industrial average gained 85 points to close at 22957. The Nasdaq rose 18. And the S&P 500 added four.

It was a milestone day in the world of astronomy. For the first time, researchers say they have detected gravitational waves with a flash of light from the same cosmic event. The dual observation supports Albert Einstein’s general theory of relativity. The ripples in space and the light burst were caused by the collision of two neutron stars. They were first detected in August.

The post News Wrap: Dozens missing after deadly Mogadishu truck bombing appeared first on PBS NewsHour.




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Beaten beasts to unleash: Tatafu

The beast was awakened. Indeed, it might have just stirred from a slumber but it was instantly on the alert.




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Smith lashes Daley’s ref bashing

Queensland captain Cameron Smith says Laurie Daley’s attack on the referees gave NSW an excuse they didn’t deserve.




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Taxman joins gold rush

The Bank of Mum and Dad has been a major sponsor of Olympic athletes for more than a century, but may be about to be superseded.




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Shorten: ‘Don’t underestimate Labor’

BILL Shorten believes Labor can still win next Saturday’s election despite new opinion polling predicting his party will struggle.




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Turnbull: ‘It is a big economic shock’

PM Malcolm Turnbull says Australians should vote to keep a stable majority government in uncertain economic times, as the fallout from Brexit continues.




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Turnbull and Shorten speak of mistakes

ROLLING UPDATES: Malcolm Turnbull and Bill Shorten have given candid interviews to Four Corners, where they reveal more about themselves and their hopes for winning the election.




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Shorten blasted for ‘treaty bomb’

LEADING Aboriginal academic Marcia Langton has blasted Bill Shorten over his claim Labor could sign a treaty with Indigenous Australians.




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‘Thrown under the bus’: Jones unleashes

RADIO shock jock fan Alan Jones unleashed on both sides of politics on Q&A last night — and came out in defence of Brexit.




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SNP MSP welcomes contest with Flynn as she declares bid to restand for seat

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




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Sarwar: Scottish Government must follow Chancellor and extend rates relief

Ministers must follow the UK Government and extend rates relief for businesses in Scotland, Anas Sarwar has said.




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Treasury stake in NatWest falls to 11.4% on £1bn shares buyback

NATWEST has moved to reduce the UK Government’s stake in the bank after buying back a significant tranche of shares from the Treasury in what it described as a “another important milestone”, it was announced this morning.




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Backlash after former Labour Spin Doctor's comment on Farmers and Thatcher

A former aid to Tony Blair has been criticised by the SNP after he said the Government "should do farmers what Thatcher did to the miners".




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First new homes on Scottish town's high street 'in living memory'

The flats are described as the first new homes on the Scottish town's High Street 'in living memory'




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Scottish family-run dairy wins major listing with world’s third largest retailer

Family business Graham’s Family Dairy has secured a multinational listing




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Accountancy firm opens new office in Scottish town

The accountancy firm has opened a new office in the Scottish town




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Scottish airport chief 'thrilled' as airline giant launches first advanced aircraft

The plane is hailed as 'one of the most advanced aircraft available on the market'




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Fire engine crashes with two cars while travelling under blue lights

A fire engine on its way to a callout has been involved in a collision with two cars on a road junction in Edinburgh.




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Steve Camley on ... Tam Shepherds closing

You can purchase Steven Camley's cartoons by calling 0141 302 7000 or visiting thepicturedesk.co.uk.




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Scottish family-owned distillery launches new ‘dining destination’

A Scottish distillery has hailed the opening of a new 'dining destination' amid an expansion push.




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Andy Murray announces Glasgow and Edinburgh stage shows as part of UK tour

Sir Andy Murray will swap Centre Court for the stage next summer as he embarks on a tour discussing his illustrious tennis career.




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Famous Doddie Weir trousers worn to promote charity's new Balmoral partnership

The concierge team at The Balmoral have helped raise awareness for a special event to raise money for charity in memory of Scotland legend Doddie Weir.




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Scottish investment group sells off software subsidiary

Scottish investment giant abrdn has sold its Focus Solutions software business and is said to be eyeing other potential disposals




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Major luxury lodge plans for shores of famous Scottish loch revealed

The site, on the shores of a famous Scottish loch, has been acquired for a luxury lodge development




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RPG Cast – Episode 544: “You Will NOT Bucket Shame Me”

Things are looking grim: we get thrown out cars, assassinated for our kingdoms, drowned underwater, and struck out. If you’re scratching your head, don’t worry! Everything will make sense once you listen to this week’s podcast.

The post RPG Cast – Episode 544: “You Will NOT Bucket Shame Me” appeared first on RPGamer.



  • News
  • RPG Cast
  • Bug Fables: The Everlasting Sapling
  • Grim Dawn
  • Phantasy Star Online 2
  • Titan Quest: Anniversary Edition
  • Trials of Mana
  • Utawarerumono: Prelude to the Fallen
  • XCOM: Chimera Squad
  • Xenoblade Chronicles

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RPG Cast – Episode 552: “Aw ***t, She’s Playing Diablo!”

This week we learn not to disturb Kelley's special demon slaying time, get too attached to dogs in games, or disturb the Harvest Moon plushie announcement. We also get your suggestions for series that need to be resurrected. Enjoy Action RPG August!

The post RPG Cast – Episode 552: “Aw ***t, She’s Playing Diablo!” appeared first on RPGamer.



  • News
  • RPG Cast
  • Blightbound
  • Divinity: Original Sin II
  • Fae Tactics
  • Knights of Pen & Paper
  • Phantasy Star Online 2
  • Story of Seasons: Friends of Mineral Town
  • The Legend of Heroes: Trails of Cold Steel III

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RPG Cast – Episode 562: “Don’t Disgaea Shame Me”

It's Extra Life 2020. Chris is dying in Hades. Anna Marie thinks orange is pretty sus. Kelley can't let go of Laharl. Josh is back on the Trails. And Alex is outta here to pursue his new racing career.

The post RPG Cast – Episode 562: “Don’t Disgaea Shame Me” appeared first on RPGamer.



  • News
  • Podcasts
  • RPG Cast
  • Solasta: Crown of the Magister
  • The Legend of Heroes: Trails of Cold Steel IV
  • World of Warcraft: Battle for Azeroth

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RPG Cast – Episode 580: “Marshmallow Is Canon”

It's just the core trio this week, as Chris tosses a coin to his hunting horn partner Kelley, and Anna Marie rolls her eyes as Chris cracks terrible jokes about what the Vita really means. We all consider MiHoYo's bottom line, as well as whether we're classified as normies.

The post RPG Cast – Episode 580: “Marshmallow Is Canon” appeared first on RPGamer.




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RPG Cast – Episode 593: “Banished to the Prince Dimension”

Chris snuggles his Teddy body pillow. Kelley signs up for rare Pokémon. Josh sacrifices children (what?!). Meanwhile Anna Marie is off celebrating her birthday by spreading the hork.

The post RPG Cast – Episode 593: “Banished to the Prince Dimension” appeared first on RPGamer.




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RPG Cast – Episode 596: “I’m Not Into Tails Unless I’m Shooting Them Out of a Cannon”

Josh wishes on a monkey paw and gets a new Shining Force game. Chris's body isn't ready for Death's Door. And no expects the shadow drop of Boyfriend Dungeon.

The post RPG Cast – Episode 596: “I’m Not Into Tails Unless I’m Shooting Them Out of a Cannon” appeared first on RPGamer.




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RPG Cast – Episode 610: “No One Should Learn Japanese from Super Robot Wars”

Chris embraces our cyberpunk subscription overlords. Josh kills the innkeeper (accidentally). Meanwhile Robert plunges down the .Hack hole.

The post RPG Cast – Episode 610: “No One Should Learn Japanese from Super Robot Wars” appeared first on RPGamer.



  • News
  • Podcasts
  • RPG Cast
  • Final Fantasy V
  • Final Fantasy XIV: Endwalker
  • Get in the Car Loser!
  • Persona 5 Strikers
  • Pokémon Sword / Shield
  • Shin Megami Tensei III: Nocturne

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RPG Cast – Episode 633: “Your Cat Sharts on the Rainbow Bridge”

Kelley is better at Elden Ring than Chris. Anna Marie shows off her deck. And Chris hates sand. Time to go play with the HD-2D you have at home.

The post RPG Cast – Episode 633: “Your Cat Sharts on the Rainbow Bridge” appeared first on RPGamer.