Long-dominant global supply chains look less tenable in the light of pressures ranging from pandemics to disasters, trade tensions and protectionism.

The UK is the top country, but Dublin is leading city, for foreign companies setting up headquarters in Europe, according to fDi’s ranking.

FDI project numbers from China into the EU are on a downward trend, but Europe is still a popular destination for Chinese investment.

Europe’s most well-known digital disruptor banks have been expanding across the globe, but not without some controversy. Alex Irwin-Hunt reports.

Over the past three years, the UK has led Europe for financial services FDI, with the US as top investor. Emma McCoy reports.

The Yamal-Europe pipeline that usually delivers Russian gas to Western Europe was sending the fuel back to Poland for a ninth straight day yesterday, as per data from German network operator Gascade.

warsaw, poland — Polish President Andrzej Duda marked Independence Day on Monday with a call for sustained U.S. commitment to Europe's security in view of Russian aggression in the region and argued that Ukraine's pre-2014 borders should be restored. Weighing on the minds of many is the war across Poland's border in Ukraine, and an expectation that Donald Trump's return to the White House will bring a change in the security situation in the region. Some fear Trump could end the U.S. commitment to NATO or make a deal with Russian President Vladimir Putin that could result in a permanent loss of territory for Ukraine and encourage Russia to attack other nations. Others believe Trump could persuade Putin to stop the fighting. Duda, who has had friendly relations with Trump, said in a speech in Warsaw that Europe will continue to need U.S. protection. “It is a pipe dream — as some people think — that Europe can ensure its own security today,” Duda said. He emphasized that the security guarantees of successive U.S. presidents are extremely important in times of resurgent Russian imperialism. “Today we have no doubts that for the security of Europe and the world, it is necessary to strengthen Euro-Atlantic ties,” Duda said. He said the territorial integrity of all countries, especially Ukraine, should be respected and it “must return to its borders from before the Russian attack, not only the one in 2022 but also the first one, in 2014." Russia annexed Ukraine's Crimean Peninsula in 2014 and launched its full-scale invasion in 2022. Later in a news conference, Duda said he had spoken to Trump and that they would meet before the inauguration in January. Duda spoke as Poland marked the 106th anniversary of its restored independence at the end of World War I after more than a century of being partitioned and ruled by Russia, Germany and Austro-Hungary. The date of Nov. 11 carries powerful weight for a nation where the trauma of losing national sovereignty endures. In Warsaw, tens of thousands of people took part in a march organized by nationalist groups that has sometimes seen violent clashes in past years but passed without major incident Monday. Organizers estimated turnout at 250,000 while city hall put it at 90,000. Police said they detained 75 people and seized banned items from participants, including pyrotechnic materials, knives, telescopic batons and brass knuckles. Jaroslaw Kaczynski, leader of the conservative Law and Justice party, which governed Poland from 2015-2023 and is seeking a comeback, joined the march with other party members.

Terrorist acts in Algeria and surrounding countries spell trouble for the debt-racked European countries that depend on the region for energy supply.

While the Catholic Church confronts contemporary issues with a modern face, the Orthodox Church remains stubbornly entrenched in its Byzantine heritage.

Furious about its government cowing to Russia and mishandling economic challenges, Ukrainian citizens have taken to the streets in record force.

The rise of a right-wing coalition in Denmark reflects a trend across Europe of political parties stoking anti-immigrant sentiment and Islamophobia.

Past observations have indicated that the icy moon of Jupiter has a vast subsurface ocean. Launching in October, NASA’s Europa Clipper will go there in search of evidence that it could support life

DNA from bones found in a cave in Germany has been identified as from Homo sapiens, showing that our species endured frigid conditions there as they expanded across the continent

A stone wall nearly a kilometre long found under the Baltic Sea may have been built by ancient hunters to channel deer into a confined space

Korolevo, a site in Ukraine where early humans made stone tools, has been dated to 1.4 million years ago, suggesting early humans moved from Ukraine into the rest of Europe

Most people are too risk-averse when it comes to life's biggest choices. Learning how to overcome the cognitive biases at play can help you make better decisions - with no looking back

DNA evidence from tombs in Sweden and Denmark suggests major plague outbreaks were responsible for the Neolithic decline in northern Europe

The use of cocaine only took off in Europe during the 19th century, after the drug was chemically isolated from coca leaves, but new evidence suggests much earlier use

Title: Kids With Neurological Conditions at Higher Risk of Flu Death: CDC
Category: Health News
Created: 8/29/2012 10:05:00 AM
Last Editorial Review: 8/29/2012 12:00:00 AM

Title: European MRSA Originated in Sub-Saharan Africa, Study Finds
Category: Health News
Created: 8/29/2014 9:35:00 AM
Last Editorial Review: 8/29/2014 12:00:00 AM

Title: 'Dramatic Resurgence' of Measles in Europe: WHO
Category: Health News
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Title: What Does a Neurologist Do for a Vestibular Migraine?
Category: Diseases and Conditions
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Title: Monkeypox Cases May Finally Be Ebbing, With Declines Seen in Europe, WHO Says
Category: Health News
Created: 8/25/2022 12:00:00 AM
Last Editorial Review: 8/25/2022 12:00:00 AM

Retrotransposable elements (RTEs) are common mobile genetic elements comprising ~42% of the human genome. RTEs play critical roles in gene regulation and function, but how they are specifically involved in complex diseases is largely unknown. Here, we investigate the cellular heterogeneity of RTEs using 12 single-cell transcriptome profiles covering three neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease, and multiple sclerosis. We identify cell type marker RTEs in neurons, astrocytes, oligodendrocytes, and oligodendrocyte precursor cells that are related to these diseases. The differential expression analysis reveals the landscape of dysregulated RTE expression, especially L1s, in excitatory neurons of multiple neurodegenerative diseases. Machine learning algorithms for predicting cell disease stage using a combination of RTE and gene expression features suggests dynamic regulation of RTEs in AD. Furthermore, we construct a single-cell atlas of retrotransposable elements in neurodegenerative disease (scARE) using these data sets and features. scARE has six feature analysis modules to explore RTE dynamics in a user-defined condition. To our knowledge, scARE represents the first systematic investigation of RTE dynamics at the single-cell level within the context of neurodegenerative diseases.

The neuronal nucleus houses a meticulously organized genome. Within this structure, genetic material is not simply compacted but arranged into a precise and functional 3D chromatin landscape essential for cellular regulation. This mini-review highlights the importance of this chromatin landscape in healthy neurodevelopment, as well as the diseases that occur with aberrant chromatin architecture. We discuss insights into the fundamental mechanistic relationship between histone modifications, DNA methylation, and genome organization. We then discuss findings that reveal how these epigenetic features change throughout normal neurodevelopment. Finally, we highlight single-gene neurodevelopmental disorders that illustrate the interdependence of epigenetic features, showing how disruptions in DNA methylation or genome architecture can ripple across the entire epigenome. As such, we emphasize the importance of measuring multiple chromatin architectural aspects, as the disruption of one mechanism can likely impact others in the intricate epigenetic network. This mini-review underscores the vast gaps in our understanding of chromatin structure in neurodevelopmental diseases and the substantial research needed to understand the interplay between chromatin features and neurodevelopment.

Neural reflexes occupy a central role in physiological homeostasis. The vagus nerve is a major conduit for transmitting afferent and efferent signals in homeostatic reflex arcs between the body and the brain. Recent advances in neuroscience, immunology, and physiology have revealed important vagus nerve mechanisms in suppressing inflammation and treating rheumatoid arthritis and other autoimmune conditions. Numerous clinical trials indicate that there is significant benefit to vagus nerve stimulation therapy. Although many questions are still unanswered, it will be important, even necessary, to pursue answers that will be useful in guiding interventions to modulate immunological and physiological homeostasis.

Our approaches toward understanding cancer have evolved beyond cell-intrinsic and local microenvironmental changes within the tumor to encompass how the cancer interfaces with the entire host organism. The nervous system is uniquely situated at the interface between the brain and body, constantly receiving and sending signals back and forth to maintain homeostasis and respond to salient stimuli. It is becoming clear that various cancers disrupt this dialog between the brain and body via both neuronal and humoral routes, leading to aberrant brain activity and accelerated disease. In this outlook, I discuss this view of cancer as a homeostatic challenge, emphasize cutting-edge work, and provide outstanding questions that need to be answered to move the field forward.

Memory formation is contingent on molecular and structural changes in neurons in response to learning stimuli—a process known as neuronal plasticity. The initiation step of mRNA translation is a gatekeeper of long-term memory by controlling the production of plasticity-related proteins in the brain. The mechanistic target of rapamycin complex 1 (mTORC1) controls mRNA translation, mainly through phosphorylation of the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BPs) and ribosomal protein S6 kinases (S6Ks). mTORC1 signaling decreases throughout brain development, starting from the early postnatal period. Here, we discovered that in mice, the age-dependent decrease in mTORC1 signaling occurs selectively in excitatory but not inhibitory neurons. Using a gene conditional knockout (cKO) strategy, we demonstrate that either up- or downregulating the mTORC1-4E-BP2 axis in GAD65 inhibitory interneurons, but not excitatory neurons, results in long-term object recognition and object location memory deficits. Our data indicate that the mTORC1 pathway in inhibitory but not excitatory neurons plays a key role in memory formation.

Extract

It is of utmost importance that medicines are available at all times for our patients. Historically, medication unavailability has typically, if not exclusively, affected low- and middle-income countries [1]. More recently however, drug shortages have also been reported in high-income European countries [2]. Drug shortages have negative health consequences for patients [3], and a profound economic impact, with the need to resort to more expensive alternatives and demands on healthcare professionals’ time to find, prescribe and dispense alternatives [4].

The -aminobutyric acid type A (GABA_A) receptor is modulated by a number of neuroactive steroids. Sulfated steroids and 3β-hydroxy steroids inhibit, while 3α-hydroxy steroids typically potentiate the receptor. Here, we have investigated inhibition of the α1β32L GABA_A receptor by the endogenous neurosteroid 3α-hydroxy-5β-pregnan-20-one (3α5βP) and the synthetic neuroactive steroid 3α-hydroxy-5α-androstane-17β-carbonitrile (ACN). The receptors were expressed in Xenopus oocytes. All experiments were done using two-electrode voltage-clamp electrophysiology. In the presence of low concentrations of GABA, 3α5βP and ACN potentiate the GABA_A receptor. To reveal inhibition, we conducted the experiments on receptors activated by the combination of a saturating concentration of GABA and propofol to fully activate the receptors and mask potentiation, or on mutant receptors in which potentiation is ablated. Under these conditions, both steroids inhibited the receptor with IC₅₀s of ~13 μM and maximal inhibitory effects of 70–90%. Receptor inhibition by 3α5βP was sensitive to substitution of the α1 transmembrane domain (TM) 2-2' residue, previously shown to ablate inhibition by pregnenolone sulfate. However, results of coapplication studies and the apparent lack of state dependence suggest that pregnenolone sulfate and 3α5βP inhibit the GABA_A receptor independently and through distinct mechanisms. Mutations to the neurosteroid binding sites in the α1 and β3 subunits statistically significantly, albeit weakly and incompletely, reduced inhibition by 3α5βP and ACN.

The orexigenic gut peptide ghrelin is an endogenous ligand for the growth hormone secretagogue receptor type 1a (GHSR1a). Systemic ghrelin administration has previously been shown to increase gastric motility and emptying. While these effects are known to be mediated by the vagus nerve, the cellular mechanism underlying these effects remains unclear. Therefore, the purpose of the present study was to investigate the signaling mechanism by which GHSR1a inhibits voltage-gated Ca²⁺ channels in isolated rat gastric vagal afferent neurons using whole-cell patch-clamp electrophysiology. The ghrelin pharmacological profile indicated that Ca²⁺ currents were inhibited with a log (Ic₅₀) = –2.10 ± 0.44 and a maximal inhibition of 42.8 ± 5.0%. Exposure to the GHSR1a receptor antagonist (D-Lys3)-GHRP-6 reduced ghrelin-mediated Ca²⁺ channel inhibition (29.4 ± 16.7% vs. 1.9 ± 2.5%, n = 6, P = 0.0064). Interestingly, we observed that activation of GHSR1a inhibited Ca²⁺ currents through both voltage-dependent and voltage-independent pathways. We also treated the gastric neurons with either pertussis toxin (PTX) or YM-254890 to examine whether the Ca²⁺ current inhibition was mediated by the Gα_i/o or Gα_q/11 family of subunits. Treatment with both PTX (Ca²⁺ current inhibition = 15.7 ± 10.6%, n = 8, P = 0.0327) and YM-254890 (15.2 ± 11.9%, n = 8, P = 0.0269) blocked ghrelin’s effects on Ca²⁺ currents, as compared with control neurons (34.3 ± 18.9%, n = 8). These results indicate GHSR1a can couple to both Gα_i/o and Gα_q/11 in gastric vagal afferent neurons. Overall, our findings suggest GHSR1a-mediated inhibition of Ca²⁺ currents occurs through two distinct pathways, offering necessary insights into the cellular mechanisms underlying ghrelin’s regulation of gastric vagal afferents.

Mitochondrial dysfunction is a hallmark of many genetic neurodegenerative diseases, but therapeutic options to reverse mitochondrial dysfunction are limited. While recent studies support the possibility of improving mitochondrial fusion/fission dynamics and motility to correct mitochondrial dysfunction and resulting neurodegeneration in Charcot-Marie-Tooth disease (CMT) and other neuropathies, the clinical utility of reported compounds and relevance of preclinical models are uncertain. Here, we describe motor and sensory neuron dysfunction characteristic of clinical CMT type 2 A in a CRISPR/Casp-engineered Mfn2 Thr105Met (T105M) mutant knock-in mouse. We further demonstrate that daily oral treatment with a novel mitofusin activator derived from the natural product piperine can reverse these neurologic phenotypes. Piperine derivative 8015 promoted mitochondrial fusion and motility in Mfn2-deficient cells in a mitofusin-dependent manner and reversed mitochondrial dysfunction in cultured fibroblasts and reprogrammed motor neurons from a human CMT2A patient carrying the MFN2 T105M mutation. Like previous mitofusin activators, 8015 exhibited stereospecific functionality, but the more active stereoisomer, 8015-P2, is unique in that it has subnanomolar potency and undergoes entero-hepatic recirculation which extends its in vivo half-life. Daily administration of 8015-P2 to Mfn2 T105M knock-in mice for 6 weeks normalized neuromuscular and sensory dysfunction and corrected histological/ultrastructural neurodegeneration and neurogenic myoatrophy. These studies describe a more clinically relevant mouse model of CMT2A and an improved mitofusin activator derived from piperine. We posit that 8015-P2 and other piperine derivatives may benefit CMT2A or other neurodegenerative conditions wherein mitochondrial dysdynamism plays a contributory role.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy treatment, routinely manifesting as increased pain sensitivity (allodynia) in distal extremities. Despite its prevalence, effective treatment options are limited. Cannabinoids are increasingly being evaluated for their ability to treat chronic pain conditions, including CIPN. While previous studies have revealed sex differences in cannabinoid-mediated antinociception in acute and chronic pain models, there is a paucity of studies addressing potential sex differences in the response of CIPN to cannabinoid treatment. Therefore, we evaluated the long-term antiallodynic efficacy of cannabinoid receptor type 1 (CB₁)-selective, cannabinoid receptor type 2 (CB₂)-selective, and CB₁/CB₂ mixed agonists in the cisplatin CIPN model, using both male and female mice. CB₁ selective agonism was observed to have sex differences in the development of tolerance to antiallodynic effects, with females developing tolerance more rapidly than males, while the antiallodynic effects of selective CB₂ agonism lacked tolerance development. Compound-specific changes to the female estrous cycle and female plasma estradiol levels were noted, with CB₁ selective agonism decreasing plasma estradiol while CB₂ selective agonism increased plasma estradiol. Chronic administration of a mixed CB₁/CB₂ agonist resulted in increased mRNA expression of proinflammatory cytokines and endocannabinoid regulatory enzymes in female spinal cord tissue. Ovarian tissue was noted to have proinflammatory cytokine mRNA expression following administration of a CB₂ acting compound while selective CB₁ agonism resulted in decreased proinflammatory cytokines and endocannabinoid regulatory enzymes in testes. These results support the need for further investigation into the role of sex and sex hormones signaling in pain and cannabinoid-mediated antinociceptive effects.

Neuropathic pain is a form of chronic pain that develops because of damage to the nervous system. Treatment of neuropathic pain is often incompletely effective, and most available therapeutics have only moderate efficacy and present side effects that limit their use. Opioids are commonly prescribed for the management of neuropathic pain despite equivocal results in clinical studies and significant abuse potential. Thus, neuropathic pain represents an area of critical unmet medical need, and novel classes of therapeutics with improved efficacy and safety profiles are urgently needed. The cannabidiol structural analog and novel antagonist of GPR55, KLS-13019, was screened in rat models of neuropathic pain. Tactile sensitivity associated with chemotherapy exposure was induced in rats with once-daily 1-mg/kg paclitaxel injections for 4 days or 5 mg/kg oxaliplatin every third day for 1 week. Rats were then administered KLS-13019 or comparator drugs on day 7 in an acute dosing paradigm or days 7–10 in a chronic dosing paradigm, and mechanical or cold allodynia was assessed. Allodynia was reversed in a dose-dependent manner in the rats treated with KLS-13019, with the highest dose reverting the response to prepaclitaxel injection baseline levels with both intraperitoneal and oral administration after acute dosing. In the chronic dosing paradigm, four consecutive doses of KLS-13019 completely reversed allodynia for the duration of the phenotype in control animals. Additionally, coadministration of KLS-13019 with paclitaxel prevented the allodynic phenotype from developing. Together, these data suggest that KLS-13019 represents a potential new drug for the treatment of neuropathic pain.

Chronic pain conditions affect nearly 20% of the population in the United States. Current medical interventions, such as opioid drugs, are effective at relieving pain but are accompanied by many undesirable side effects. This is one reason increased numbers of chronic pain patients have been turning to Cannabis for pain management. Cannabis contains many bioactive chemical compounds; however, current research looking into lesser-studied minor cannabinoids in Cannabis lacks uniformity between experimental groups and/or excludes female mice from investigation. This makes it challenging to draw conclusions between experiments done with different minor cannabinoid compounds between laboratories or parse out potential sex differences that could be present. We chose five minor cannabinoids found in lower quantities within Cannabis: cannabinol (CBN), cannabidivarin (CBDV), cannabigerol (CBG), 8-tetrahydrocannabinol (8-THC), and 9-tetrahydrocannabivarin (THCV). These compounds were then tested for their cannabimimetic and pain-relieving behaviors in a cannabinoid tetrad assay and a chemotherapy-induced peripheral neuropathy (CIPN) pain model in male and female CD-1 mice. We found that the minor cannabinoids we tested differed in the cannabimimetic behaviors evoked, as well as the extent. We found that CBN, CBG, and high-dose 8-THC evoked some tetrad behaviors in both sexes, while THCV and low-dose 8-THC exhibited cannabimimetic tetrad behaviors only in females. Only CBN efficaciously relieved CIPN pain, which contrasts with reports from other researchers. Together these findings provide further clarity to the pharmacology of minor cannabinoids and suggest further investigation into their mechanism and therapeutic potential.

The role of somatostatin receptor (SSTR) PET/CT, using ⁶⁸Ga-based tracers or [⁶⁴Cu]Cu-DOTATATE (⁶⁴Cu-DOTATATE), in the management of patients with neuroendocrine neoplasm (NEN) is guided by appropriate use criteria (AUC). In this study, we performed systematic analyses of referral patterns and image findings of routine ⁶⁴Cu-DOTATATE PET/CT scans to support AUC development. Methods: We included all clinical routine ⁶⁴Cu-DOTATATE PET/CT scans performed between April 10, 2018 (start of clinical use), and May 2, 2022, at Copenhagen University Hospital–Rigshospitalet. We reviewed the referral text and image report of each scan and classified the indication according to clinical scenarios as listed in the AUC. Results: In total, 1,290 patients underwent 2,249 ⁶⁴Cu-DOTATATE PET/CT scans. Monitoring of patients with NEN seen both on conventional imaging and on SSTR PET without clinical evidence of progression was the most common indication (defined as "may be appropriate" in the AUC) and accounted for 703 (31.3%) scans. Initial staging after NEN diagnosis ("appropriate" in the AUC) and restaging after curative-intent surgery ("may be appropriate" in the AUC) accounted for 221 (9.8%) and 241 (10.7%) scans, respectively. Selection of patients eligible for peptide receptor radionuclide therapy ("appropriate" in the AUC) and restaging after peptide receptor radionuclide therapy completion ("appropriate" in the AUC) accounted for 95 (4.2%) and 115 (5.1%) scans, respectively. The number of scans performed for indications not defined in the AUC was 371 (16.5%). Image result analysis revealed no disease in 669 scans (29.7%), stable disease in 582 (25.9%), and progression in 461 (20.5%). In 99 of the 461 (21.5%) scans, progression was detected on PET but not on CT. Conclusion: Our study provided real-life data that may contribute to support development of ⁶⁴Cu-DOTATATE/SSTR PET/CT guidelines including AUC. Some scenarios listed as "may be appropriate" in the current AUC were frequent in our data. Monitoring of patients with NEN without clinical evidence of progression was the most frequent indication for ⁶⁴Cu-DOTATATE PET/CT, in which disease progression was detected in more than one third, and a large proportion was visible by PET only. We therefore conclude that this scenario could potentially be classified as appropriate.

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.

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.

Both preclinical and clinical studies implicate functional impairments of several neuroactive metabolites of the kynurenine pathway (KP), the major degradative cascade of the essential amino acid tryptophan in mammals, in the pathophysiology of neurologic and psychiatric diseases. A number of KP enzymes, such as tryptophan 2,3-dioxygenase (TDO2), indoleamine 2,3-dioxygenases (IDO1 and IDO2), kynurenine aminotransferases (KATs), kynurenine 3-monooxygenase (KMO), 3-hydroxyanthranilic acid oxygenase (3-HAO), and quinolinic acid phosphoribosyltransferase (QPRT), control brain KP metabolism in health and disease and are therefore increasingly considered to be promising targets for the treatment of disorders of the nervous system. Understanding the distribution, cellular expression, and regulation of KP enzymes and KP metabolites in the brain is therefore critical for the conceptualization and implementation of successful therapeutic strategies.

BACKGROUND AND PURPOSE:

Previous studies have reported metal accumulation and microstructure changes in deep gray nuclei (DGN) in Wilson disease (WD). However, there are limited studies that investigate whether there is metal accumulation and microstructure changes in DGN of patients with WD with normal-appearing routine MRI. This study aimed to evaluate multiparametric changes in DGN of WD and whether the findings correlate with clinical severity in patients with WD.

BACKGROUND AND PURPOSE:

Brain atrophy occurs in the late stage of dementia, yet structural MRI is widely used in the work-up. Atrophy patterns can suggest a diagnosis of Alzheimer disease (AD) or frontotemporal dementia (FTD) but are difficult to assess visually. We hypothesized that the availability of a quantitative volumetric brain MRI report would increase neuroradiologists’ accuracy in diagnosing AD, FTD, or healthy controls compared with visual assessment.

BACKGROUND AND PURPOSE:

Overuse of CT-based cerebrovascular imaging in the emergency department and inpatient settings, notably CTA of the head and neck for minor and nonfocal neurologic presentations, stresses imaging services and exposes patients to radiation and contrast. Furthermore, such CT-based imaging is often insufficient for definitive diagnosis, necessitating additional MR imaging. Recent advances in fast MRI may allow timely assessment and a reduced need for head and neck CTA in select populations.

BACKGROUND AND PURPOSE:

Physician-industry relationships can be useful for driving innovation and technologic progress, though little is known about the scale or impact of industry involvement in neuroradiology. The purpose of this study was to assess the trends and distributions of industry payments to neuroradiologists.

SUMMARY:

The ASNR Neuroradiology Division Chief Working Group's 2023 survey, with responses from 62 division chiefs, provides insights into turnaround times, faculty recruitment, moonlighting opportunities, and academic funds. In emergency cases, 61% aim for a turnaround time of less than 45–60 minutes, with two-thirds meeting this expectation more than 75% of the time. For inpatient CT and MR imaging scans, 54% achieve a turnaround time of 4–8 hours, with three-quarters meeting this expectation at least 50% of the time. Outpatient scans have an expected turnaround time of 24–48 hours, which is met in 50% of cases. Faculty recruitment strategies included 35% offering sign-on bonuses, with a median of $30,000. Additionally, 23% provided bonuses to fellows during fellowship to retain them in the practice upon completion of their fellowship. Internal moonlighting opportunities for faculty were offered by 70% of divisions, with a median pay of $250 per hour. The median annual academic fund for a full-time neuroradiology faculty member was $6000, typically excluding license fees but including American College of Radiology and American Board of Radiology membership, leaving $4000 for professional expenses. This survey calls for further dialogue on adapting and innovating academic institutions to meet evolving needs in neuroradiology.

Spinal CSF leak care has evolved during the past several years due to pivotal advances in its diagnosis and treatment. To the reader of the American Journal of Neuroradiology (AJNR), it has been impossible to miss the exponential increase in groundbreaking research on spinal CSF leaks and spontaneous intracranial hypotension (SIH). While many clinical specialties have contributed to these successes, the neuroradiologist has been instrumental in driving this transformation due to innovations in noninvasive imaging, novel myelographic techniques, and image-guided therapies. In this editorial, we will delve into the exciting advancements in spinal CSF leak diagnosis and treatment and celebrate the vital role of the neuroradiologist at the forefront of this revolution, with particular attention paid to CSF leak–related work published in the AJNR.

Electron transport chain (ETC) disorders are a group of rare, multisystem diseases caused by impaired oxidative phosphorylation and energy production. Deficiencies in complex III (CIII), also known as ubiquinol–cytochrome c reductase, are particularly rare in humans. Ubiquinol–cytochrome c reductase core protein 2 (UQCRC2) encodes a subunit of CIII that plays a crucial role in dimerization. Several pathogenic UQCRC2 variants have been identified in patients presenting with metabolic abnormalities that include lactic acidosis, hyperammonemia, hypoglycemia, and organic aciduria. Almost all previously reported UQCRC2-deficient patients exhibited neurodevelopmental involvement, including developmental delays and structural brain anomalies. Here, we describe a girl who presented at 3 yr of age with lactic acidosis, hyperammonemia, and hypoglycemia but has not shown any evidence of neurodevelopmental dysfunction by age 15. Whole-exome sequencing revealed compound heterozygosity for two novel variants in UQCRC2: c.1189G>A; p.Gly397Arg and c.437T>C; p.Phe146Ser. Here, we discuss the patient's clinical presentation and the likely pathogenicity of these two missense variants.

We identified a de novo heterozygous transient receptor potential cation channel subfamily M (melastatin) member 3 (TRPM3) missense variant, p.(Asn1126Asp), in a patient with developmental delay and manifestations of cerebral palsy (CP) using phenotype-driven prioritization analysis of whole-genome sequencing data with Exomiser. The variant is localized in the functionally important ion transport domain of the TRPM3 protein and predicted to impact the protein structure. Our report adds TRPM3 to the list of Mendelian disease–associated genes that can be associated with CP and provides further evidence for the pathogenicity of the variant p.(Asn1126Asp).

T-lymphoblastic lymphoma (T-LLy) is the most common lymphoblastic lymphoma in children and often presents with a mediastinal mass. Lymphomatous suprarenal masses are possible but rare. Here, we discuss the case of a previously healthy 3-yr-old male who presented with mediastinal T-LLy with bilateral suprarenal masses. Following initial treatment, surgical biopsy of persisting adrenal masses revealed bilateral neuroblastoma (NBL). A clinical genetics panel for germline cancer predisposition did not identify any pathogenic variants. Combination large panel (864 genes) profiling analysis in the context of a precision oncology study revealed two novel likely pathogenic heterozygous variants: SMARCA4 c.1420-1G > T p.? and EZH2 c.1943G > C p.(Ile631Phefs*44). Somatic analysis revealed potential second hits/somatic variants in EZH2 (in the T-LLy) and a segmental loss in Chromosome 19p encompassing SMARCA4 (in the NBL). Synchronous cancers, especially at a young age, warrant genetic evaluation for cancer predisposition; enrollment in a precision oncology program assessing germline and tumor DNA can fulfill that purpose, particularly when standard first-line genetic testing is negative and in the setting of tumors that are not classic for common cancer predisposition syndromes.