Simplified methods of acquisition and quantification would facilitate the use of synaptic density imaging in multicenter and longitudinal studies of Alzheimer disease (AD). We validated a simplified tissue-to-reference ratio method using SUV ratios (SUVRs) for estimating synaptic density with [¹¹C]UCB-J PET. Methods: Participants included 31 older adults with AD and 16 with normal cognition. The distribution volume ratio (DVR) using simplified reference tissue model 2 was compared with SUVR at short scan windows using a whole-cerebellum reference region. Results: Synaptic density was reduced in AD participants using DVR or SUVR. SUVR using later scan windows (60–90 or 70–90 min) was minimally biased, with the strongest correlation with DVR. Effect sizes using SUVR at these late time windows were minimally reduced compared with effect sizes with DVR. Conclusion: A simplified tissue-to-reference method may be useful for multicenter and longitudinal studies seeking to measure synaptic density in AD.

α-Synuclein (α-Syn) aggregation in Lewy bodies and Lewy neurites has emerged as a key pathogenetic feature in Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Various factors, including posttranslational modifications (PTMs), can influence the propensity of α-Syn to misfold and aggregate. PTMs are biochemical modifications of a protein that occur during or after translation and are typically mediated by enzymes. PTMs modulate several characteristics of proteins including their structure, activity, localization, and stability. α-Syn undergoes various posttranslational modifications, including phosphorylation, ubiquitination, SUMOylation, acetylation, glycation, O-GlcNAcylation, nitration, oxidation, polyamination, arginylation, and truncation. Different PTMs of a protein can physically interact with one another or work together to influence a particular physiological or pathological feature in a process known as PTMs crosstalk. The development of detection techniques for the cooccurrence of PTMs in recent years has uncovered previously unappreciated mechanisms of their crosstalk. This has led to the emergence of evidence supporting an association between α-Syn PTMs crosstalk and synucleinopathies. In this review, we provide a comprehensive evaluation of α-Syn PTMs, their impact on misfolding and pathogenicity, the pharmacological means of targeting them, and their potential as biomarkers of disease. We also highlight the importance of the crosstalk between these PTMs in α-Syn function and aggregation. Insight into these PTMS and the complexities of their crosstalk can improve our understanding of the pathogenesis of synucleinopathies and identify novel targets of therapeutic potential.

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:

Angioplasty and stent placement have been described as a bailout technique in individuals with failed thrombectomy. We aimed to investigate Stent retriever AssIsted Lysis (SAIL) with tirofiban before angioplasty and stent placement.

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.

Rare genetic conditions are challenging for the primary care provider to manage without proper guidelines. This clinical review is designed to assist the pediatrician, family physician, or internist in the primary care setting to manage the complexities of 16p11.2 deletion syndrome. A multidisciplinary medical home with the primary care provider leading the care and armed with up-to-date guidelines will prove most helpful to the rare genetic patient population. A special focus on technology to fill gaps in deficits, review of case studies on novel medical treatments, and involvement with the educational system for advocacy with an emphasis on celebrating diversity will serve the rare genetic syndrome population well.

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous group of lymphoid malignancies. Based on gene expression profiling, it has been subdivided into germinal center (GC)-derived and activated B-cell (ABC) types. Advances in molecular methodologies have further refined the subclassification of DLBCL, based on recurrent genetic abnormalities. Here, we describe a distinct case of DLBCL that presented in leukemic form. DNA sequencing targeting 275 genes revealed pathogenically relevant mutations of CD79B, MyD88, TP53, TBL1XR1, and PIM1 genes, indicating that this lymphoma would be best classified as MCD/C5 DLBCL, an ABC subtype. Despite an initial good clinical response to BTK inhibitor ibrutinib, anti-CD20 antibody rituxan, alkylating agent bendamustine, and hematopoietic stem-cell transplant, the lymphoma relapsed, accompanied by morphologic and molecular evidence of disease progression. Specifically, the recurrent tumor developed loss of TP53 heterozygosity (LOH) and additional chromosomal changes central to ABC DLBCL pathogenesis, such as PRDM1 loss. Acquired resistance to ibrutinib and rituxan was indicated by the emergence of BTK and FOXO1 mutations, respectively, as well as apparent activation of alternative cell-activation pathways, through copy-number alterations (CNAs), detected by high-resolution chromosomal microarrays. In vitro, studies of relapsed lymphoma cells confirmed resistance to standard BTK inhibitors but sensitivity to vecabrutinib, a noncovalent inhibitor active against both wild-type as well as mutated BTK. In summary, we provide in-depth molecular characterization of a de novo leukemic DLBCL and discuss mechanisms that may have contributed to the lymphoma establishment, progression, and development of drug resistance.

BackgroundDuring the COVID-19 pandemic, global trends of reduced healthcare-seeking behaviour were observed. This raises concerns about the consequences of healthcare avoidance for population health.AimTo determine the association between healthcare avoidance during the early stages of the COVID-19 pandemic and all-cause mortality.Design and settingThis was a 32-month follow-up within the population-based Rotterdam Study, after sending a COVID-19 questionnaire at the onset of the pandemic in April 2020 to all communty dwelling participants (n = 6241/8732, response rate 71.5%).MethodCox proportional hazards models assessed the risk of all-cause mortality among respondents who avoided health care because of the COVID-19 pandemic. Mortality status was collected through municipality registries and medical records.ResultsOf 5656 respondents, one-fifth avoided health care because of the COVID-19 pandemic (n = 1143). Compared with non-avoiders, those who avoided health care more often reported symptoms of depression (n = 357, 31.2% versus n = 554, 12.3%) and anxiety (n = 340, 29.7% versus n = 549, 12.2%), and more often rated their health as poor to fair (n = 336, 29.4% versus n = 457, 10.1%) . Those who avoided health care had an increased adjusted risk of all-cause mortality (hazard ratio [HR] 1.30, 95% confidence interval [CI] = 1.01 to 1.67), which remained nearly identical after adjustment for history of any non-communicable disease (HR 1.20, 95% CI = 0.93 to 1.54). However, this association attenuated after additional adjustment for mental and physical self-perceived health factors (HR 0.93, 95% CI = 0.71 to 1.20).ConclusionThis study found an increased risk of all-cause mortality among individuals who avoided health care during COVID-19. These individuals were characterised by poor mental and physical self-perceived health. Therefore, interventions should be targeted to these vulnerable individuals to safeguard their access to primary and specialist care to limit health disparities, inside and beyond healthcare crises.

BackgroundOrlistat is recommended as an adjunct to diet and exercise for weight loss in the treatment of type 2 diabetes mellitus (T2DM).AimTo explore associations between patient characteristics and orlistat prescribing, and to determine associations of orlistat with weight loss in T2DM and prediabetes.Design and settingCohort study using anonymised health records from a UK database of general practice.MethodThe UK Clinical Practice Research Datalink (CPRD) Aurum database was searched to compile a cohort of patients aged ≥18 years, first diagnosed with T2DM or prediabetes in 2016 or 2017. Once the data had been collated, multivariable logistic regression models were used to determine associations with starting orlistat and stopping it early (<12 weeks of prescriptions) and orlistat’s associations with weight loss in those who had not been prescribed second-line antidiabetic medications.ResultsOut of 100 552 patients with incident T2DM or prediabetes, 655 (0.8%) patients with T2DM and 128 (0.7%) patients with prediabetes were prescribed orlistat. Younger people, females, those in areas of deprivation, current smokers, those coprescribed metformin, and those recorded as having hypertension were statistically significantly more likely to be prescribed orlistat; higher baseline glycated haemoglobin levels were associated with early stopping. In comparison with patients not on orlistat, those who continued using it for ≥12 weeks were more likely to lose ≥5% weight (adjusted odds ratio [AOR] 1.69, 95% confidence interval [CI] = 1.07 to 2.67) but those who stopped orlistat early were less likely to lose ≥5% weight (AOR 0.56, 95% CI = 0.29 to 1.09).ConclusionOrlistat was significantly associated with weight loss in patients with T2DM and prediabetes when taken for at least 12 weeks; however, it was infrequently prescribed and often taken for <12 weeks. Orlistat may be a useful adjunct to lifestyle modifications for patients with T2DM and prediabetes, but barriers to continued use means it may not be effective for everyone in managing weight loss.

PURPOSE

We undertook a trial to test the efficacy of a technology-assisted health coaching intervention for weight management, called Goals for Eating and Moving (GEM), within primary care.

What does 2023's Scottish Health Survey tell us about Scotland's population - from smoking rates to obesity, and alcohol consumption?

The podcast trio is not at all ready for the flood of September releases. Anna Marie is kind of sick of the trigger, Chris insists Eclipse is owed an apology, and Kelley wants to know what is this garbage and how she can get more of it.

The post RPG Cast – Episode 599: “Serious Health Issues? No, Just a Cat” appeared first on RPGamer.

The Real Housewives of Salt Lake City is TV’s best soap opera, week after week offering twists more shocking than secret twins and characters returning from the dead. That’s because it’s all real, happening in the most haunted suburb in the continental United States.

Where else do two women connect over knowing the long-lost birth father of one’s child? Is there another city where women squabble over body positivity in a parking lot off the side of a snowy mountain? Surely, there’s no other place on Earth where Lisa Barlow could come across anywhere near a voice of reason.

But that all happens here in Salt Lake City. Five episodes in, Season 5 has continued to evolve into the most captivating season in modern Real Housewives history, carried by the ever-changing bonds between our OGs and a team of wonderfully bizarre newbies.

Read more at The Daily Beast.

In America, there’s a significant kind of public insistence that one’s “freedom” is fundamentally tied to one’s wealth.

Much of the country views America through an aspirational and transformative lens, a colorblind and bias-free utopia, wherein wealth conveys equality and acts as a panacea for social and racial ills. Once an individual achieves massive financial success, or so the message goes, he or she will “transcend” the scourge of economic and racial inequality, truly becoming “free.”

Working in parallel with this reverence for this colorblind version of the “American Dream” is the belief that economic privilege mandates patriotic gratitude. Across industries and disciplines, Americans are told to love their nation uncritically, be thankful that they are exceptional enough to live in a country that allows citizens the opportunity to reach astronomical heights of economic prosperity.

For the nation’s black citizens, there’s often an additional racialized presumption lurking under the surface of these concepts: the notion that black success and wealth demands public silence on systemic issues of inequality and oppression.

These are durable and fragile ideologies that prop up the concept of the American Dream – durable because they are encoded in the very fabric of American culture (most Americans, including African Americans, have readily embraced these ideologies as assumed facts); yet fragile because it’s all too easy to see that one’s economic privilege is a lousy barrier against both individual and systemic discrimination and oppression.

Consequently, black people have also been among the most vocal challengers of these ideologies, as we’ve seen most recently with the Colin Kaepernick and the NFL #TakeAKnee demonstrations. In a show of solidary with the free agent quarterback, professional football players – the vast majority of whom are black – have been kneeling during the National Anthem as a means of protesting racial injustice and police brutality.

WATCH: NFL players team up in defiance and solidarity

Over the past few weeks, the president of the United States has brought renewed attention to the inherent tensions that define the ideologies of the “American Dream” through his repeated public criticisms of these kneeling NFL players.

“If a player wants the privilege of making millions of dollars in the NFL, or other leagues,” Trump recently tweeted, he or she should not be allowed to kneel. Labeling the protestors actions “disrespectful” to the country, flag and anthem, President Donald Trump has called for players to be fired, encouraged a boycott of the NFL, insisted that the league pass a rule mandating that players stand for the anthem and derided the protestors as “sons of bitches.”

In a dramatic ploy more befitting of a scripted reality television show, the president gloated that he had instructed Vice President Mike Pence to walk out of an Indianapolis Colts game the moment any player kneeled. This was an orchestrated show of power and outrage, designed to send a flamboyant political message given that Trump and Pence knew in advance that on that particular day, the Colts were playing the San Francisco 49ers – the team that currently has the most protestors. The NFL’s announcement this week that the league has no plans to penalize protesting players is the most recent event to provoke the president’s fury; taking to social media during the early morning, he once again equated kneeling with “total disrespect” for our country.

As many have pointed out, the president’s moralizing outrage toward the NFL players is selective and deeply flawed – his apparent patriotic loyalty hasn’t stopped the billionaire politician from criticizing the removal of Confederate statues, or attacking a Gold Star family, or mocking Sen. John McCain’s military service.

The NFL players and their defenders have repeatedly stated that the protests are intended to highlight racial inequality and oppression. They’ve also explained that their decision to kneel emerged from a desire to protest peacefully and respectfully after a sustained conversation with military veterans.

Trump has chosen to ignore these rationales and the structural issues of inequality that motivate the protests and instead, advance a narrative exclusively concerned with overt displays of American patriotism and the “privilege” of the NFL players. As one of president’s advisors explained, by aggressively targeting the NFL players, Trump believes that he is “winning the cultural war,” having made black “millionaire sport athletes his new [Hillary Clinton].”

READ MORE: As ‘America’s sport,’ the NFL cannot escape politics

It’s a cynical statement, revealing the president’s perception of the jingoism of his base of supporters who envision him as a crusader for American values and symbols.

In casting the black protestors as the antithesis of all of this, Trump has marked the players as unpatriotic elites and enemies of the nation. For a president who has consistently fumbled his way through domestic and foreign policy since he was elected, a culture war between “hard-working” and “virtuous” working-class and middle-class white Americans and rich, ungrateful black football players is a welcome public distraction.

Trump’s attacks on the NFL protestors are rooted in those competing tensions inherent to the American Dream: that wealth equals freedom; that economic privilege demands patriotic gratitude; and most importantly, that black people’s individual economic prosperity invalidates their concerns about systemic injustice and requires their silence on racial oppression.

Among the protestors’ detractors, this has become a common line of attack, a means of disparaging the black NFL players’ activism by pointing to their apparent wealth. The fact that systemic racism is demonstrably real and that individual prosperity does not make one immune to racial discrimination appears to be lost on the protestors’ critics.

Theirs is a grievance that suggests that black athletes should be grateful to live in this country; that racism can’t exist in America since black professional athletes are allowed to play and sign contracts for considerable sums of money; that black players owe the nation their silence since America “gave” them opportunity and access; that black athletes have no moral authority on issues of race and inequality because of their individual success; and that black athletes’ success was never theirs to earn, but instead, was given to them and can just as easily be taken away.

This culture war being waged over black athletes is not new. Black athletes – and entertainers – have long been hyper-aware of their peculiar place in American society as individuals beloved for their athletic and artistic talents, yet reviled the moment they use their public platform to protest systemic racial inequality. The parallels between the #TakeAKnee protests and the protests of Muhammad Ali or John Carlos and Tommie Smith are readily apparent; so too are there important similarities to the case of Paul Robeson.

An outspoken civil rights activist, collegiate and professional football player, lawyer, opera singer and actor, Robeson had his passport revoked in 1950 because of his political activism and speech – actions that all but destroyed his career. The star athlete and entertainer, “who had exemplified American upward mobility” quickly “became public enemy number one” as institutions cancelled his concerts, the public called for his death and anti-Robeson mobs burned effigies of him.

During a 1956 congressional hearing, the chairman of the House Committee on Un-American Activities beat a familiar refrain with Robeson, challenging the entertainer’s accusations of American racism and racial oppression. He saw no sign of prejudice, he argued, since Robeson was privileged, having gone to elite universities and playing collegiate and professional football.

READ MORE: Poll: Americans divided on NFL protests

Black athletes, even the silent ones, largely understand that their economic privilege doesn’t insulate them from the realities of racial discrimination. They also understand that their wealth and success is precarious and is often dependent not only upon their athletic performance, but also upon them remaining silent on issues of racial injustice, especially those that appear to question the “American Dream” or implicate the American public by association.

It should come as no surprise then that Colin Kaepernick, whose protests turned him into a national pariah despite his on-the-field talents, has filed a grievance against the NFL, accusing the league and its teams of blackballing him because of his political beliefs. “Principled and peaceful political protest,” Kaepernick’s lawyers argued in a statement, “should not be punished and athletes should not be denied employment based on partisan political provocation by the Executive Branch of our government.” Whether the ostracized Kaepernick will win his grievance is unknown, but it is certainly telling that he and his lawyers have rooted their claims in contested definitions of freedom and the precarious economic privilege of outspoken NFL players.

For the loudest and most vocal critics of black protestors, in particular, outspokenness is tantamount to treason, grounds for the harshest of punishments. Perhaps they would benefit from a close reading of James Baldwin, who once argued: “I love America more than any other country in this world, and, exactly for this reason, I insist on the right to criticize her perpetually.”

The post Column: For black athletes, wealth doesn’t equal freedom appeared first on PBS NewsHour.

It has become trivially easy to use artificial intelligence to edit images or generate video to remove unwanted objects or beautify scenes, but doing so leads to people misremembering what they have seen

Google’s NotebookLM tool is billed as an AI-powered research assistant and can even turn your text history into a jovial fake podcast. But it could also tempt you into narcissism and nostalgia, says Jacob Aron

Ransomeware attacks against health care organizations are happening at an alarmingly high rate in 2024, putting patient health at risk.

Adam Peaty roared back at those writing him off after cruising through his 50 metres breaststroke semi-final – but was later accused of being disrespectful towards Commonwealth Games competitors.

Artificial intelligence can be the key to unlocking better relationships with work, HP revealed in its new Work Relationship Index (WRI) report. “AI represents a significant opportunity to transform our work dynamics and unlock a more positive and productive environment for all,” stated Dave Shull, president of HP Workforce Solutions at HP Inc.. “To foster […]

U.S.-based startup company Heliospect Genomics reportedly is offering wealthy couples embryo screening for IQ and other traits at $50,000 for 100 embryos.

Jay-yi Nah is an underwater archaeological site dating to the Early Classic Maya period (250-600 CE) that focused on salt production for local use or perhaps local production for down-the-line trading.

The post Earliest-Known Maya Salt Works Discovered in Belize appeared first on Sci.News: Breaking Science News.

I am one of millions of vapers in the UK, but growing evidence of the impact these e-cigarettes have on the environment means it may be time to quit, says Graham Lawton

Surrounding ourselves with greenery can do wonders for our physical and mental wellbeing. Kathy Willis reveals just what kinds of plants are best for our brains and bodies, and why

Despite the limitations of Alzheimer's drugs like lecanemab, this new class of treatments and a group of experimental vaccines are paving the way to a world without dementia

Drugs like Ozempic and Wegovy have unexpected effects on the brain, opening up potential new ways to treat depression, anxiety, addiction and Alzheimer’s

Loneliness was long thought to cause health conditions ranging from diabetes to cardiovascular disease, but new research paints a more nuanced picture

A flurry of studies has found microplastics in nearly every organ in the human body, from the brain to the testicles. But very few have revealed whether these tiny bits of plastic impact our health