Oxidative stress, fibrosis, and inflammasome activation from advanced glycation end product (AGE)–receptor of advanced glycation end product (RAGE) interaction contribute to diabetic cardiomyopathy (DCM) formation and progression. Our study revealed the impact of β-caryophyllene (BCP) on activating cannabinoid type 2 receptors (CB2Rs) against diabetic complication, mainly cardiomyopathy and investigated the underlying cell signaling pathways in mice. The murine model of DCM was developed by feeding a high-fat diet with streptozotocin injections. After the development of diabetes, the animals received a 12-week oral BCP treatment at a dose of 50 mg/kg/body weight. BCP treatment showed significant improvement in glucose tolerance and insulin resistance and enhanced serum insulin levels in diabetic animals. BCP treatment effectively reversed the heart remodeling and restored the phosphorylated troponin I and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a expression. Ultrastructural examination showed reduced myocardial cell injury in DCM mice treated with BCP. The preserved myocytes were found to be associated with reduced expression of AGE/RAGE in DCM mice hearts. BCP treatment mitigated oxidative stress by inhibiting expression of NADPH oxidase 4 and activating phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid 2–related factor 2 (Nrf2) signaling. Also, BCP suppressed cardiac fibrosis and endothelial-to-mesenchymal transition in DCM mice by inhibiting transforming growth factor β (TGF-β)/suppressor of mothers against decapentaplegic (Smad) signaling. Further, BCP treatment suppressed nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome activation in DCM mice and alleviated cellular injury to the pancreatic tissues evidenced by significant elevation of the number of insulin-positive cells. To demonstrate a CB2R-dependent mechanism of BCP, another group of DCM mice were pretreated with AM630, a CB2R antagonist. AM630 was observed to abrogate the beneficial effects of BCP in DCM mice. Taken together, BCP demonstrated the potential to protect the myocardium and pancreas of DCM mice mediating CB2R-dependent mechanisms.

Cannabis and its products have been used for centuries for both medicinal and recreational purposes. The recent widespread legalization of cannabis has vastly expanded its use in the United States across all demographics except for adolescents. Meanwhile, decades of research have advanced our knowledge of cannabis pharmacology and particularly of the endocannabinoid system with which the components of cannabis interact. This research has revealed multiple targets and approaches for manipulating the system for therapeutic use and to ameliorate cannabis toxicity or cannabis use disorder. Research has also led to new questions that underscore the potential risks of its widespread use, particularly the enduring consequences of exposure during critical windows of brain development or for consumption of large daily doses of cannabis with high content ⁹-tetrahydrocannabinol. This article highlights current neuroscience research on cannabis that has shed light on therapeutic opportunities and potential adverse consequences of misuse and points to gaps in knowledge that can guide future research.

Chronic hypertension leads to injury and fibrosis in major organs. Fibroblast activation protein (FAP) is one of key molecules in tissue fibrosis, and ⁶⁸Ga-labeled FAP inhibitor-46 (FAPI46) PET is a recently developed method for evaluating FAP. The aim of this study was to evaluate FAP expression and fibrosis in a hypertension model and to test the feasibility of ⁶⁸Ga-FAPI46 PET in hypertension. Methods: Hypertension was induced in mice by angiotensin II infusion for 4 wk. ⁶⁸Ga-FAPI46 biodistribution studies and PET scanning were conducted at 1, 2, and 4 wk after hypertension modeling, and uptake in the major organs was measured. The FAP expression and fibrosis formation of the heart and kidney tissues were analyzed and compared with ⁶⁸Ga-FAPI46 uptake. Subgroups of the hypertension model underwent angiotensin receptor blocker administration and high-dose FAPI46 blocking, for comparison. As a preliminary human study, ⁶⁸Ga-FAPI46 PET images of lung cancer patients were analyzed and compared between hypertension and control groups. Results: Uptake of ⁶⁸Ga-FAPI46 in the heart and kidneys was significantly higher in the hypertension group than in the sham group as early as week 1 and decreased after week 2. The uptake was specifically blocked in the high-dose blocking study. Immunohistochemistry also revealed FAP expression in both heart and kidney tissues. However, overt fibrosis was observed in the heart, whereas it was absent from the kidneys. The angiotensin receptor blocker–treated group showed lower uptake in the heart and kidneys than did the hypertension group. In the pilot human study, renal uptake of ⁶⁸Ga-FAPI46 significantly differed between the hypertension and control groups. Conclusion: In hypertension, FAP expression is increased in the heart and kidneys from the early phases and decreases over time. FAP expression appears to represent fibrosis activity preceding or underlying fibrotic tissue formation. ⁶⁸Ga-FAPI46 PET has potential as an effective imaging method for evaluating FAP expression in progressive fibrosis by hypertension.

The role of gastrin-releasing peptide receptor (GRPR) in various diseases, including cancer, has been extensively studied and has emerged as a promising therapeutic target. In this study, we successfully achieved the use of [²¹²Pb]Pb-DOTAM-GRPR1, comprising the α-particle generator, ²¹²Pb, combined with a GRPR-targeting peptide, GRPR1, in a prostate cancer model. Methods: Pharmacokinetics, toxicity, radiation dosimetry, and efficacy were assessed in GRPR-positive prostate tumor–bearing mice after intravenous administration of [²¹²Pb]Pb-DOTAM-GRPR1 (where DOTAM is 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane). Results: Preclinical studies have shown tumor targeting of up to 5 percent injected dose per gram over 24 h, and optimization of the drug formulation and quantity has led to minimized oxidation and off-target binding, respectively. Particularly, an increase in peptide amount from 28 to 280 ng was shown to reduce off-target uptake, especially at the level of the pancreas, by about 30%. Furthermore, dosimetry studies confirmed the kidney as the dose-limiting organ, and toxicity studies revealed that a nontoxic dose of up to 1,665 kBq could be injected into mice. Efficacy studies indicated a median survival time of 9 wk in the control group, which received only a buffer solution, compared with 19 wk in the group that received 4 injections of 370 kBq at 3-wk intervals. Conclusion: Taken together, these combined data demonstrate the safety, tolerability, and efficacy of [²¹²Pb]Pb-DOTAM-GRPR1, thus warranting further exploration in clinical trials.

Neuroendocrine tumor (NET) metastases to the heart are found in 1%–4% of NET patients and have been reported primarily in the form of individual cases. We investigated the prevalence, clinical characteristics, imaging features, and outcomes of NET patients with cardiac metastases on ⁶⁸Ga-DOTATATE PET/CT. Methods: ⁶⁸Ga-DOTATATE PET/CT of 490 consecutive patients from a single institution were retrospectively reviewed for sites of metastases. The cumulative cardiovascular event rate and overall survival of patients with cardiac NET metastases (CNMs) were compared with those of a control group of metastatic NET patients without cardiac metastases. In patients with CNMs, the cardiac SUV_max with and without normalization to the myocardial background uptake was compared with a separate cohort of 11 patients with active cardiac sarcoidosis who underwent ⁶⁸Ga-DOTATATE PET/CT for research purposes. Results: In total, 270 patients with metastatic NETs were identified, 9 (3.3%) of whom had CNMs. All 9 patients had grade 1–2 gastroenteropancreatic NETs, most commonly from the small intestine (7 patients). The control group consisted of 140 patients with metastatic grade 1–2 gastroenteropancreatic NETs. On Kaplan–Meier analysis, there was no significant difference in the risk of cardiovascular adverse events (P = 0.91 on log-rank test) or mortality (P = 0.83) between the metastatic NET patients with and without cardiac metastases. The degree of cardiac DOTATATE uptake was significantly higher in CNMs than in patients with cardiac sarcoidosis without overlap, in terms of both cardiac SUV_max (P = 0.027) and SUV_max–to–myocardial background ratio (P = 0.021). Conclusion: Routine ⁶⁸Ga-DOTATATE PET/CT can be used to identify CNMs in 3% of patients with metastatic NETs. CNMs do not confer added cardiovascular or mortality risk. A distinguishing feature of CNMs is their high degree of DOTATATE uptake compared with focal myocardial inflammation.

In several malignancies, only a limited number of patients respond to immune checkpoint inhibitors. Predicting and monitoring responses to these inhibitors represent an unmet clinical need. Here, we developed a PET/CT probe targeting granzyme B, [⁶⁸Ga]Ga-NOTA-Gly-Gly-Gly-Ile-Glu-Pro-Asp-CHO (GSI), and aimed to investigate whether it can be used to monitor the effects of immune checkpoint inhibitors early in the course of therapy. Methods: Seventy-two patients with gastric cancer (stages III–IV) were recruited for [⁶⁸Ga]Ga-NOTA-GSI PET/CT imaging after 2 or 3 cycles of the immunotherapy, and 40 patients were included in the final analysis. The SUV_max of primary tumors (SUV_max-t), SUV_max of metastatic lymph nodes (SUV_max-LN), and SUV_max of normal tissues (liver and blood pool) were measured, and their target-to-liver background ratio (TLR) and target-to-blood background ratio (TBR) were denoted for primary tumors as TLR_tumor and TBR_tumor and for metastatic lymph nodes as TLR_LN and TBR_LN, respectively. The treatment responses were assessed within 1 wk after full-course treatment according to RECIST version 1.1. Wilcoxon rank-sum tests were used to compare the PET/CT parameters between responders and nonresponders. Receiver operating characteristic curve analysis was used to assess the diagnostic efficacy of [⁶⁸Ga]Ga-NOTA-GSI PET/CT parameters in identifying responders. Two-tailed P value of less than 0.05 was considered statistically significant. Results: We found that SUV_max-t, TLR_tumor, TBR_tumor, SUV_max-LN, and TBR_LN were higher in responders than in nonresponders (2.49 ± 0.58 vs. 1.55 ± 0.48, P = 0.000; 2.24 ± 0.48 vs. 1.74 ± 0.67, P = 0.007; 1.38 ± 0.43 vs. 0.90 ± 0.23, P = 0.000; 2.24 ± 0.99 vs. 1.42 ± 0.55, P = 0.003; and 1.28 ± 0.68 vs. 0.83 ± 0.32, P = 0.012, respectively). According to receiver operating characteristic curve analysis, the area under the curve for SUV_max-t, TBR_tumor, TLR_tumor, SUV_max-LN, TLR_LN, and TBR_LN was 0.886, 0.866, 0.746, 0.772, 0.648, and 0.731, respectively. The threshold of SUV_max-t was 2.05, and its sensitivity and specificity were 81.0% and 84.2%, respectively. In addition, multivariate logistic regression indicated that TBR_tumor was an independent predictor of treatment response (P = 0.03). Conclusion: Our results indicated that [⁶⁸Ga]Ga-NOTA-GSI PET/CT is a promising tool for predicting early response to combined immunotherapy in gastric cancer patients.

BACKGROUND AND PURPOSE:

World Health Organization (WHO) grade 2 and 3 diffuse gliomas account for approximately 5% of primary brain tumors. They are invasive and infiltrative tumors and have considerable morbidity, causing progressive neurologic deterioration. The mean survival time is <10 years from diagnosis. Surgical debulking represents first-line management. The extent of resection is associated with progression-free and overall survival. Radiologic assessment of the extent of resection is challenging. This can be underestimated on early postoperative MRI, meaning that accurate assessment may be achieved only on delayed follow-up imaging. We hypothesized that DWI may help facilitate more reliable estimates of the extent of resection on early postoperative MRI. This study aimed to assess the utility of DWI in early postoperative MRI to evaluate the extent of resection.

BACKGROUND AND PURPOSE:

Gadolinium-based contrast agents are widely used for meningioma imaging; however, concerns exist regarding their side effects, cost, and environmental impact. At the standard gadolinium dose, most meningiomas show avid contrast enhancement, suggesting that administering a smaller dose may be feasible. The purpose of this study was to evaluate the impact of a lower gadolinium dose on the differentiation between meningiomas and adjacent intracranial tissues.

SUMMARY:

The 2021 World Health Organization Classification of Tumors of the Central Nervous System (CNS5), introduced significant changes, impacting tumors ranging from glial to ependymal neoplasms. Ependymal tumors were previously classified and graded based on histopathology, which had limited clinical and prognostic utility. The updated CNS5 classification now divides ependymomas into 10 subgroups based on anatomic location (supratentorial, posterior fossa, and spinal compartment) and genomic markers. Supratentorial tumors are defined by zinc finger translocation associated (ZFTA) (formerly v-rel avian reticuloendotheliosis viral oncogene [RELA]), or yes-associated protein 1 (YAP1) fusion; posterior fossa tumors are classified into groups A (PFA) and B (PFB), spinal ependymomas are defined by MYCN amplification. Subependymomas are present across all these anatomic compartments. The new classification kept an open category of "not elsewhere classified" or "not otherwise specified" if no pathogenic gene fusion is identified or if the molecular diagnosis is not feasible. Although there is significant overlap in the imaging findings of these tumors, a neuroradiologist needs to be familiar with updated CNS5 classification to understand tumor behavior, for example, the higher tendency for tumor recurrence along the dural flap for ZFTA fusion-positive ependymomas. On imaging, supratentorial ZFTA-fused ependymomas are preferentially located in the cerebral cortex, carrying predominant cystic components. YAP1-MAMLD1-fused ependymomas are intra- or periventricular with prominent multinodular solid components and have significantly better prognosis than ZFTA-fused counterparts. PFA ependymomas are aggressive paramedian masses with frequent calcification, seen in young children, originating from the lateral part of the fourth ventricular roof. PFB ependymomas are usually midline, noncalcified solid-cystic masses seen in adolescents and young adults arising from the fourth ventricular floor. PFA has a poorer prognosis, higher recurrence, and higher metastatic rate than PFB. Myxopapillary spinal ependymomas are now considered grade II due to high recurrence rates. Spinal-MYCN ependymomas are aggressive tumors with frequent leptomeningeal spread, relapse, and poor prognosis. Subependymomas are noninvasive, intraventricular, slow-growing benign tumors with an excellent prognosis. Currently, the molecular classification does not enhance the clinicopathologic understanding of subependymoma and myxopapillary categories. However, given the molecular advancements, this will likely change in the future. This review provides an updated molecular classification of ependymoma, discusses the individual imaging characteristics, and briefly outlines the latest targeted molecular therapies.

Anorectal malformations (ARMs) constitute a group of congenital defects of the gastrointestinal and urogenital systems. They affect males and females, with an estimated worldwide prevalence of 1 in 5000 live births. These malformations are clinically heterogeneous and can be part of a syndromic presentation (syndromic ARM) or as a nonsyndromic entity (nonsyndromic ARM). Despite the well-recognized heritability of nonsyndromic ARM, the genetic etiology in most patients is unknown. In this study, we describe three siblings with diverse congenital anomalies of the genitourinary system, anemia, delayed milestones, and skeletal anomalies. Genome sequencing identified a novel, paternally inherited heterozygous Caudal type Homeobox 2 (CDX2) variant (c.722A > G (p.Glu241Gly)), that was present in all three affected siblings. The variant identified in this family is absent from population databases and predicted to be damaging by most in silico pathogenicity tools. So far, only two other reports implicate variants in CDX2 with ARMs. Remarkably, the individuals described in these studies had similar clinical phenotypes and genetic alterations in CDX2. CDX2 encodes a transcription factor and is considered the master regulator of gastrointestinal development. This variant maps to the homeobox domain of the encoded protein, which is critical for interaction with DNA targets. Our finding provides a potential molecular diagnosis for this family's condition and supports the role of CDX2 in anorectal anomalies. It also highlights the clinical heterogeneity and variable penetrance of ARM predisposition variants, another well-documented phenomenon. Finally, it underscores the diagnostic utility of genomic profiling of ARMs to identify the genetic etiology of these defects.

Sleep is a fundamental feature of life for virtually all multicellular animals, but many questions remain about how sleep is regulated by circadian rhythms, homeostatic sleep drive that builds up with wakefulness, and modifying factors such as hunger or social interactions, as well as about the biological functions of sleep. Substantial headway has been made in the study of both circadian rhythms and sleep in the fruit fly Drosophila melanogaster, much of it through studies of individual fly activity using Drosophila activity monitors (DAMs). Here, we describe approaches for the activation of specific neurons of interest using optogenetics (involving genetic modifications that allow for light-based neuronal activation) and thermogenetics (involving genetic modifications that allow for temperature-based neuronal activation) so that researchers can evaluate the roles of those neurons in controlling rest and activity behavior. In this protocol, we describe how to set up a rig for simultaneous optogenetic or thermogenetic stimulation and activity monitoring for analysis of sleep and circadian rhythms in Drosophila, how to raise appropriate flies, and how to perform the experiment. This protocol will allow researchers to assess the causative role in the regulation of sleep and activity rhythms of any genetically tractable subset of cells.

Sleep is important for survival, and the need for sleep is conserved across species. In the past two decades, the fruit fly Drosophila melanogaster has emerged as a promising system in which to study the genetic, neural, and physiological bases of sleep. Through significant advances in our understanding of the regulation of sleep in flies, the field is poised to address several open questions about sleep, such as how the need for sleep is encoded, how molecular regulators of sleep are situated within brain networks, and what the functions of sleep are. Here, we describe key findings, open questions, and commonly used methods that have been used to inform existing theories and develop new ways of thinking about the function, regulation, and adaptability of sleep behavior.

PURPOSE

HIV pre-exposure prophylaxis (PrEP) may increase rates of bacterial sexually transmitted infections (STIs) among gay, bisexual, and other men who have sex with men (GBM) through risk compensation (eg, an increase in condomless sex or number of partners); however, longitudinal studies exploring the time-dependent nature of PrEP uptake and bacterial STIs are limited. We used marginal structural models to estimate the effect of PrEP uptake on STI incidence.

Netflix's mega-violent mega-hit series returns December 26.

Video game workers face challenges from employers in their efforts to unionize in Canada.

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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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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.

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JUDY WOODRUFF: But first: Sunday’s elections Austria were the latest ample of a shift to the right Europe’s politics, as 31-year-old Christian Kurz was elected chancellor on an anti-immigration platform.

He may now form a government with a far-right party founded in the 1950s by former Nazis.

That follows recent elections in Germany, where a far-right party roiled the race and dealt a blow to returning leader Angela Merkel.

In Sweden, too, there is a strong challenge from the right and a neo-Nazi group that looks stand in elections next year.

Special correspondent Malcolm Brabant ha been surveying the political landscape in Germany and Sweden, and he begins his report in Scandinavia.

MALCOLM BRABANT, Special Correspondent: In a Gothenburg parking lot, supporters of the Nordic Resistance Movement form up for what they hope will be their biggest-ever march, to propagate an ideology espoused by mother of eight Paulina Forslund.

PAULINA FORSLUND, Nordic Resistance Movement: When white becomes the minority, they will be destroyed. I want my children to have a secure future. I want them not only for them to have a secure Sweden. I want them to have a secure world. And I want other people to fight for the same thing.

MALCOLM BRABANT: When addressing her fellow neo-Nazis, Forslund’s rhetoric sharpens.

PAULINA FORSLUND (through interpreter): I’m the welder’s daughter, the forester’s grandchild. My line consists of hardworking men and women. It’s people like them we can thank for the welfare system that our lying politicians are now giving away to imported scum.

MALCOLM BRABANT: Clearly expecting trouble, the movement’s leaders have a muscular protection detail, marching past a silent protest. The sign reads “No Nazis on our streets.”

This protester would only give her name as Johanna.

JOHANNA, Anti-Nazi Protester: They are racist people. They are people who think that certain people are better than others, and I will not stand for that. It’s not something I think has a place in a modern society.

MALCOLM BRABANT: Experts say the resistance movement is recruiting aggressively, and believe this demonstration is emblematic of the rise of the far right.

It took place on Yom Kippur, the Jewish day of atonement.

Allan Stutzinky is leader of Gothenburg’s Jewish community.

ALLAN STUTZINKY, Jewish Community Leader (through interpreter): Nazism has returned. The descendants of the murderers are organizing the same marches today, waving the same flags, shouting the same slogans, and have the same racist agenda.

MALCOLM BRABANT: Anna Johansson is a member of the governing Social Democrat Party. It’s considering outlawing the Nordic Resistance Movement.

ANNA JOHANSSON, Swedish Social Democratic Party: In Sweden and in Denmark, and in other countries, extreme parties are growing, and the hatred is spreading around.

MALCOLM BRABANT: “Go home to mama,” he shouts. “Nazi pigs,” chant the anti- fascist protesters, as a bottle flies through the air.

DAMON, Nordic Resistance Movement: If someone calls themselves a Nazi, most of us would dissociate with that person. That’s nothing we stand for ourselves. I never call myself a Nazi. I’m a national socialist.

MALCOLM BRABANT: Hitler’s party was also called National Socialist, but Damon, a 40-year-old welder, insists he’s a nonviolent family man.

DAMON: The demographic landscape of our — of the whole of Europe is changing, so, basically, it’s a concern on preserving my heritage for my family and our kin.

MALCOLM BRABANT: This demonstration has been stopped short of its destination. The Nordic Resistance Movement is currently trapped between a line of police and anti-fascist protesters. And it looks as though this demonstration isn’t going any further.

Violence briefly erupts as the resistance movement tries to break through police lines, and several marchers are arrested.

PAULINA FORSLUND: We are not your enemy. We are the government’s enemy.

They say we live in a democracy, but we have never had an election about if we want to take all these people in.

MALCOLM BRABANT: When Europe’s refugee crisis began in 2015, Sweden copied Germany’s open-door policy, and 160,000 migrants entered the country. Two years on, Sweden has tighter borders and has begun deporting some of the newcomers.

The new atmosphere alarms Floid Gumbo, entertaining an anti-Nazi rally.

FLOID GUMBO, Singer Originally from Zimbabwe: I came to Sweden over 20 years ago. The climate in Sweden, the people were so friendly, and things were completely different, more welcoming. And I feel like things have sort of gradually changed.

I’m very concerned, because I have children, because I’m thinking what I experienced here is not the same kind of climate, atmosphere that they are going to experience here.

ANNA JOHANSSON: It’s not so long ago that the Nazis ruined Europe. And that makes me very worried. The German elections were terrifying, I think.

MALCOLM BRABANT: Johansson is referring to last month’s success of the right-wing Alternative For Germany Party, or AFD, when it entered Parliament for the first time with 13 percent of the vote.

HUGH BRONSON, Alternative For Germany Party: The AFD only came into existence because Merkel deserted the traditional conservative Christian voters. They were looking for a home, and the AFD has offered them a safe place.

MALCOLM BRABANT: Hugh Bronson is deputy leader of the AFD in Berlin.

Now his party, the third largest in Parliament, is demanding that Angela Merkel imposes tougher immigration rules.

Your opponents claim that you are a party of hate. What’s your response to that?

HUGH BRONSON: We embrace foreigners who respect our laws, pay their taxes, send their children to school, and go about their normal life. The problem is with people who abuse the system to have a better life, or let others pay for their better lives, or who are criminals.

MALCOLM BRABANT: Outside the opera house in Dresden, former East Germany, singer Luca Bergelt is dismayed by the political landscape shifting to the right.

LUCA BERGELT, Singer: My fear is that they will tear Europe apart. They are going to raise up the walls again. They’re going to build new walls between the countries, and that Europe will get more close into itself.

MALCOLM BRABANT: Anti-immigrant sentiment is strong in Dresden. The city was the birthplace of a pan-European anti-Islamic movement, and it delivered the largest number of votes for the right-wing party.

On a holiday to celebrate German unification after the fall of communism, retired engineer Wilfried Schmidt explained why he sent a message to Angela Merkel.

WILFRIED SCHMIDT, Retired Engineer (through interpretor): Let’s put it this way. We all need to recognize that Germany is undergoing social changes that are becoming harder to control. For one, there is mass immigration from difficult regions that is increasingly uncontrollable, of people with entirely different concepts of life, from fundamental differently structured societies that are problematic.

MALCOLM BRABANT: About one million migrants poured into Germany in 2015. Chancellor Merkel consistently defended her pro-refugee policies, but now she has been punished by voters who believe she ignored their concerns.

Chancellor Merkel has promised to listen to the people who voted for the AFD, and she says she’s going to try to win them over with what she calls good politics. But she will not countenance having the party in her coalition.

But the chancellor needs to find new partners who are prepared to be tough on immigration.

As she tries to forge a coalition, the chancellor has agreed to put an annual cap of 200,000 on the number of immigrants, something she previously refused to do. But will it be enough to woo back people who deserted her at the election?

A question for Werner Patzelt, a political scientist at Dresden University.

WERNER PATZELT, Dresden University: Since Chancellor Merkel has made so many U-turns in German domestic politics, it wouldn’t be a surprise if she would try to do a U-turn, also winning back AFD voters.

But this is a really hard political task, because so many of them are so much disappointed by the Christian Democratic Union in general, and by Chancellor Merkel in particular, that they will do anything to avoid going back.

MALCOLM BRABANT: Back in Sweden, the governing party is horrified at the concept of conceding ground to right-wingers, and is trying to isolate them.

ANNA JOHANSSON: Experience shows that, when you adopt the ideas from these right-wing parties, they spread. These parties have their agenda implemented by other parties. And I wouldn’t want to see that happen in Sweden.

FLOID GUMBO: We’re all human beings. We share this world. We’re all here. There’s enough space for us all.

MALCOLM BRABANT: But that’s an appeal that an increasing number of Swedes are rejecting, as the country and much of Europe go through a crisis of identity.

For the PBS NewsHour, I’m Malcolm Brabant in Gothenburg.

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The man who helped Justin Hodges escape a charge before last year’s grand final will try to save Wade Graham.

Two thirds of Celtic fans believe the club should have an independently elected Fan Advisory Board according to new research from the University of Glasgow.

Human rights campaigners are calling on SNP ministers to do all they can to “mitigate” Prevent, the UK Government's controversial anti-terror strategy.

A new Nordic-style Open Kindergarten will be trialled in part of Scotland ahead of a potential roll-out across the country.

Campaigners in Argyll and Bute are demanding a proposed tourist tax is rejected when it goes to a council vote next month.

Health Secretary Neil Gray will address concerns around his use of a ministerial car to attend football games at Hampden.

A new digital-first Gaelic language production will be launched in Scotland after a joint agreement between BBC Alba and BBC Scotland.

With many media events getting pushed back, the news is a little trim this week. But we still manage to pull together our basket of zany personalities for a podcast we hope brings a smile to your face.

The post RPG Cast – Episode 545: “Did You Infect My Game With Harvest Moon?” appeared first on RPGamer.

Before we go pre-order all the games from Steve, we get a podcast up for you. Chris and Kelley complain about Civ 6 on Switch. Johnathan rages in some streets. And Josh is trying to find where to turn all his sidequests into. Ok, we're off to go be feline couriers.

The post RPG Cast – Episode 546: “Sugar Coated Turd” appeared first on RPGamer.

The last two weeks have had an interesting mix of news, and it just might break Chris by the end of the show. Anna Marie is hijacking the Question of the Week, but it's definitely a unique question! Alex stealths his way into the cast alongside Kelley and Peter. How is it still only July?

The post RPG Cast – Episode 550: “Gamer Girl Glue” appeared first on RPGamer.

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.

We can't believe we have to say this, but this week Chris tries to understand water vapor. Anna Marie takes a week off to go date some demons. Josh frequents a sex shop to pick up some weapons. Pascal starts vaping in his Xbox. And Robert and Kelley are testing the jiggle physics of sacks in World of Warcraft.

The post RPG Cast – Episode 563: “Isn’t Compile Heart Jail Against the Geneva Convention?” appeared first on RPGamer.

Anna Marie spends the whole show looking for her holes. Jonathan Stringer is off singing Sakuna Matata. Josh Carpenter has all the sinks. Kelley Ryan cleans her entire house with a broom. And Chris has issues with Wil Wheaton.

The post RPG Cast – Episode 568: “What Popcorn Is Disgaea?” appeared first on RPGamer.

From beefcakes to thirsty NPCs, we cover the gamut of the most important awards of the year. Wheels finally gets his due. And everyone comes to terms with their feelings about visual novels.

The post RPG Cast – Episode 573: “Game of the Year 2020” appeared first on RPGamer.

Kelley ruins Warcraft by including Conker. Chris mortgages his Xbox. Josh's cat won't let him control his Xbox. And Microsoft has announced their new Candy Crush themed Windows 12.

The post RPG Cast – Episode 615: “The New Dialga Looks Like My Brother’s Broken Vacuum Cleaner” appeared first on RPGamer.

Jonathan Stringer joins us in an attempt to sell his copy of Mugen Souls. Josh is launching his Kickstarter for his new documentary, Legacy of the Bitcoins. And Chris has lost his Epic Games launcher, thanks Windows 11.

The post RPG Cast – Episode 616: “Garland Does It His Way” appeared first on RPGamer.

Kelley goes down the Sega Strategy Game Rabbit Hole. Chris becomes a doily shill. And Josh wants Sega to release Valkyria Chronicles as many times as it takes until people like it!

The post RPG Cast – Episode 629: “Legally Distinct Ghost Rider” appeared first on RPGamer.

Tragedy strikes Kelley on the Beetle core. Phil doesn't expect the balloon inquisition. Chris brings his standard issue cat. And you all get to just sit there and wonder when the next Persona will come out.

The post RPG Cast – Episode 653: “What Really Sank Sega?” appeared first on RPGamer.

Chris gets trolled by the bear cave. Jason sets optics to stun. Josh is hiding in a rest stop bathroom. Kelley stretches harder than she did for The Witch and the Hundred Knight. Also, find out how to increase your poop by 10 and express your opinions about Dragon Quest Soundtracks.

The post RPG Cast – Episode 664: “We Need to Talk About Gambit” appeared first on RPGamer.

Chris suffers from "The Curse of the Steam Deck." Kelley can't pickpocket, so she mugs people at night. And Ryan likes practical grave robbers. Curl up in your clothmap quilt and enjoy our cozy '60s demon world.

The post RPG Cast – Episode 681: “Ganon Is Afraid of Homemade Apple Pie” appeared first on RPGamer.

Josh explains that all Genesis music is bad. Robert only has sub-standards for video games. Chris arm-chair quarterbacks the Persona 3 remake. Not the ramp!

The post RPG Cast – Episode 696: “Have You Met Video Game Fans?” appeared first on RPGamer.

Josh enjoys the important things, like a hot springs mini-game. Kelley purchased Legos; sacrifices were made. Bethesda tells Chris it's his fault for not enjoying Starfield. Meanwhile, we just can't quit Kiryu.

The post RPG Cast – Episode 701: “Allergic to Good Games” appeared first on RPGamer.

Chris kink-shames Red XIII. Kelley violates the time space continuum with cat cafes. Josh is better at keeping things afloat than Embracer Group. Robert fails at being family friendly.

The post RPG Cast – Episode 711: “I’ve Always Wanted a Gaming Napkin” appeared first on RPGamer.

Ryan, Ryan, Ryan, and Kelley Ryan join Pascal and Chris as they go through the best and worst of 2023. See how many categories Baldur's Gate 3 wins and Diablo 4 loses.

The post RPG Cast – Episode 713: “Game Awards 2023” appeared first on RPGamer.

Chris is hunting bears, because of course that's what you do. Kelley hangs out with Chadley and the massively annoying individual. Robert is all about that exquisite fraisier cake.

The post RPG Cast – Episode 716: “Canadian Telephone Game” appeared first on RPGamer.

World-building, identity and decolonising spaces in the digital and offline realms.

The post Interview: Gabriel Massan & LYZZA appeared first on Fact Magazine.

THE Federal Bureau of Investigation is probing a possible computer hacking attack on J.P. Morgan Chase & Co.

Sega has sold Humankind and Endless developer Amplitude Studios to members of its internal team, announced the developer in a community post. This means the studio is now independent.

"Our studio is backed by strong and meaningful franchises and our team is committed to creating the best games possible," said Amplitude Studios founder Romain de Waubert de Genlis.

"With our extensive experiences in strategy game development and two exciting titles currently in progress, we are confident in our ability to deliver outstanding experience to players. This decision allows us to be more agile in our approach while continuing to shape the vision that has been ours from the very beginning, empowering us to push boundaries and be closer as ever of our community."

Sega in its own statement said: "Sega Europe has today announced the sale of Amplitude Studios following a management buyout from senior leaders and employees at the Parisian studio. The move will see Amplitude go back to its roots as an independent organisation and concludes the structural reforms that have been taking place in Sega’s European business.  

"The decision to part ways follows a period of close consultation between Sega Europe and Amplitude. As an independent studio once more, Amplitude will focus on its in-development projects and growing its own franchises, while Sega will continue to advance its strong and diverse stable of Japanese and Western IP. 

“Sega Europe acquired Amplitude in 2016, and together have released epic strategy titles like Endless Space 2 and Humankind, along with Endless Dungeon, the successor to 2014’s indie hit, Dungeon of the Endless.

"While Amplitude is no longer a part of the Sega family of studios, the two entities will continue to work together on the smooth transition of services and operations, ensuring minimum disruption for Amplitude employees and continuity of service for players of Amplitude games."

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463024/sega-sells-humankind-developer-amplitude-studios/

ublisher Bethesda Softworks and developer MachineGames have released a gameplay deep dive video for Indiana Jones and the Great Circle that is nearly 15 minutes in length.

"From locations and puzzles to gear and combat, MachineGames Audio Director, Pete Ward, takes us on a whirlwind journey through the world of The Great Circle," reads the description to the video. "Get ready for launch with this look at Indy’s grand adventure."

View the gameplay deep dive below:

Indiana Jones and the Great Circle will launch for the Xbox Series X|S, PC via Steam and Microsoft Store, and Xbox Game Pass on December 9.

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463033/indiana-jones-and-the-great-circle-gets-gameplay-deep-dive/