Abnormal large-scale resting-state functional networks in anti-N-methyl-D-aspartate receptor encephalitis.

Background: Patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis often experience severe symptoms. Resting-state functional MRI (rs-fMRI) has revealed widespread impairment of functional networks in patients. However, the changes in information flow remain unclear. This study aims to investigate the intrinsic functional connectivity (FC) both within and between resting-state networks (RSNs), as well as the alterations in effective connectivity (EC) between these networks. Methods: Resting-state functional MRI (rs-fMRI) data were collected from 25 patients with anti-NMDAR encephalitis and 30 healthy controls (HCs) matched for age, sex, and educational level. Changes in the intrinsic functional connectivity (FC) within and between RSNs were analyzed using independent component analysis (ICA). The functional interaction between RSNs was identified by granger causality analysis (GCA). Results: Compared to HCs, patients with anti-NMDAR encephalitis exhibited lower performance on the Wisconsin Card Sorting Test (WCST), both in terms of correct numbers and correct categories. Additionally, these patients demonstrated decreased scores on the Montreal Cognitive Assessment (MoCA). Neuroimaging studies revealed abnormal intra-FC within the default mode network (DMN), increased intra-FC within the visual network (VN) and dorsal attention network (DAN), as well as increased inter-FC between VN and the frontoparietal network (FPN). Furthermore, aberrant effective connectivity (EC) was observed among the DMN, DAN, FPN, VN, and somatomotor network (SMN). Conclusion: Patients with anti-NMDAR encephalitis displayed noticeable deficits in both memory and executive function. Notably, these patients exhibited widespread impairments in intra-FC, inter-FC, and EC. These results may help to explain the pathophysiological mechanism of anti-NMDAR encephalitis.

The impact of histopathological criteria for definite vasculitis in giant cell arteritis: retrospective analysis of temporal artery biopsies.

Histopathological findings associated with definite vasculitis in temporal artery biopsy (TAB) defined in 2022 ACR/EULAR classification criteria for Giant Cell Arteritis (GCA) was published in 2022. We aimed to evaluate the TAB of our GCA patients for histopathological findings associated with definite vasculitis. Patients who were diagnosed with GCA by clinicians and underwent TAB between January 2012 and May 2022 were included. Hospital electronic records and patients' files were reviewed retrospectively. A total of 90 patients' pathology reports were evaluated by a pathologist and a rheumatologist. In cases where microscopic findings were not specified in the pathology reports, histopathologic specimens were re-evaluated (n = 36). A standard checklist was used for histopathological findings of definite vasculitis. Patients were divided into two groups; (i) definite vasculitis-GCA and (ii) non-definite-GCA group, and the clinical and demographic characteristics for all patients were compared. The mean age of patients was 69.8 (± 8.5) years and 52.2% were female. In the first evaluation, 66 (73.3%) patients had a diagnosis of vasculitis according to pathology reports. In the re-evaluation of biopsy specimens, at least one definite finding of vasculitis was observed in TAB of 10/24 (41.6%) patients whose microscopic findings were not specified in the pathology reports. The ROC analysis showed that biopsy length had diagnostic value in predicting the diagnosis of definite vasculitis (AUC: 0.778, 95% CI: 0.65-0.89, p < 0.001). In those with a biopsy length of ≥ 1 cm, sensitivity was 76.5%, specificity was 64.3%, and PPV value was 92. In multivariate analysis, the most significant factor associated with definite vasculitis was biopsy length (OR: 1.18 (1.06-1.31), p = 0.002). Microscopic findings were reported in over 70% of patients. Reinterpretation of results according to a standard check-list improved the impact of TAB in the diagnosis of GCA. A biopsy length ≥ 1 cm was found to contribute towards a definitive histopathological vasculitis diagnosis.

Retrospective Analysis of Specimen Quality in Temporal Artery Biopsies for Giant Cell Arteritis and Disease Association in North Midlands, England.

Background Temporal artery biopsy (TAB) is the recommended index diagnostic method for giant cell arteritis (GCA). Per the British Society for Rheumatology (BSR) guidelines, we assessed our procedural performance. Additionally, we evaluated the occurrence of GCA diagnosis in immunosuppressed patients and other comorbidities. Methods Following the audit registration, a retrospective analysis of prospectively collected data was conducted from 2017 to 2022 at a large university hospital in North Midlands, England. Data on demographics and comorbidities were gathered. The study's primary outcome was adherence to BSR guidelines and our service provisions. Secondary outcomes included examining the relationship between biopsy-confirmed GCA and other comorbidities. Statistical analysis was carried out using SPSS version 29 (IBM Corporation, Armonk, New York, United States of America). Two-sample t-test and Chi-square/Fisher exact test were used for continuous and categorical variables, respectively. Holm-Bonferroni method was incorporated to adjust for multiple comparisons. Results A total of 156 patients who underwent temporal artery biopsy (TAB) were included in the study, with a male-to-female ratio of 0.44:1. The median age was 73. Among the patients, 19% were smokers. The procedures were performed by either a vascular surgeon (119, 76%) or by an ophthalmologist (37, 24%). Two-thirds of the patients underwent TAB within seven days of referral. In 73, 47% of cases, the post-fixation biopsy sample size exceeded 10 mm. Positive biopsy results were found in 45 patients (29%). GCA was confirmed in 39% of patients with polymyalgia rheumatica (PMR), 24% with diabetics, 20% with hypothyroidism, 29% with hypertension, 32% with hyperlipidaemia, and 26% with other inflammatory diseases. However, the p-value was below the statistically significant threshold. The biopsy outcome was also not dependent on the speciality, time from referral to biopsy, nor on the length of the post-fixation specimen. Conclusions Temporal artery biopsy remains a valuable and crucial diagnostic tool in challenging equivocal cases of giant cell arteritis (GCA), although it is limited by its sensitivity, but there is also room for improvement. There is still uncertainty regarding the relationship between biopsy positivity, post-fixation sample size, and the interval between referral and procedure. Additionally, the speciality of the clinician performing the biopsy does not appear to significantly influence the likelihood of a positive result. We still do not fully understand why this is, but the association of the GCA with other comorbidities was unpredictably insignificant.

Vascular-adhesion protein 1 in giant cell arteritis and polymyalgia rheumatica.

Vascular adhesion protein-1 (VAP-1) is a type 2 transmembrane sialoglycoprotein with oxidative deamination functionality, encoded by the amine oxidase copper-containing 3 (AOC3) gene. VAP-1 is widely expressed across various tissues, particularly in highly vascularized tissues and organs essential for lymphocyte circulation. In the vascular system, VAP-1 is predominantly found in vascular smooth muscle cells and endothelial cells, with higher expression levels in vascular smooth muscle cells. Under inflammatory conditions, VAP-1 rapidly translocates to the endothelial cell surface, facilitating leukocyte adhesion and migration through interactions with specific ligands, such as sialic acid-binding immunoglobulin-type lectins (Siglec)-9 on neutrophils and monocytes, and Siglec-10 on B cells, monocytes, and eosinophils. This interaction is crucial for leukocyte transmigration into inflamed tissues. Furthermore, VAP-1's enzymatic activity generates hydrogen peroxide and advanced glycation end-products, contributing to cytotoxic damage and vascular inflammation. In this context, the soluble form of VAP-1 (sVAP-1), produced by matrix metalloproteinase cleavage from its membrane-bound counterpart, also significantly influences leukocyte migration. This review aims to elucidate the multifaceted pathophysiological roles of VAP-1 in vascular inflammation, particularly in giant cell arteritis (GCA) and associated polymyalgia rheumatica (PMR). By exploring its involvement in immune cell adhesion, migration, and its enzymatic contributions to oxidative stress and tissue damage, we investigate the importance of VAP-1 in GCA. Additionally, we discuss recent advancements in imaging techniques targeting VAP-1, such as [68Ga]Ga-DOTA-Siglec-9 PET/CT, which have provided new insights into VAP-1's role in GCA and PMR. Overall, understanding VAP-1's comprehensive roles could pave the way for improved strategies in managing these conditions.

Giant Cell Arteritis with Intracranial and Extracranial Aneurysms: A Case Report and Brief Review of the Literature.

Giant cell arteritis (GCA) is a relatively rare, auto-immune vasculitis, more common in women over age 50. It is important to recognize and treat the disease early to prevent late complications of permanent vision loss. Inflammation-associated weakening of vessel walls involved by GCA may also represent a potential etiology for intracranial aneurysm development. In this report, we describe an atypical presentation of GCA confirmed with temporal artery biopsy with associated manifestations including intracranial right posterior communicating artery aneurysm and extracranial right internal carotid aneurysm. Our patient in a 78-year-old female who presented with progressively worsening headaches that began 10 days prior to admission. These were described as global, non-pulsatile, and located over her occiput. She reported associated jaw soreness while chewing or claudication. Her erythrocyte sedimentation rate (ESR) was elevated at 74 mm/hr. Magnetic resonance angiogram showed a right posterior communicating artery aneurysm measuring 5 mm and a right cervical carotid lengthwise dissecting aneurysm measuring 12 mm. Left temporal artery biopsy confirmed the diagnosis of GCA. High-dose steroid therapy was initiated and was continued for treatment of GCA with resolution of symptoms at her one month follow-up. This case highlights a rare instance of cervical internal carotid aneurysm and intracranial aneurysm associated with GCA, emphasizing the systemic nature of this vasculitis.

Single-cell transcriptomic analysis to identify endomembrane regulation of metalloproteins and motor proteins in autoimmunity.

TMEM230 promotes antigen processing, trafficking, and presentation by regulating the endomembrane system of membrane bound organelles (lysosomes, proteosomes and mitochondria) and phagosomes. Activation of the immune system requires trafficking of various cargos between the endomembrane system and cell plasma membrane. The Golgi apparatus is the hub of the endomembrane system and essential for the generation, maintenance, recycling, and trafficking of the components of the endomembrane system itself and immune system. Intracellular trafficking and secretion of immune system components depend on mitochondrial metalloproteins for ATP synthesis that powers motor protein transport of endomembrane cargo. Glycan modifying enzyme genes and motor proteins are essential for the activation of the immune system and trafficking of antigens between the endomembrane system and the plasma membrane. Recently, TMEM230 was identified as co-regulated with RNASET2 in lysosomes and with metalloproteins in various cell types and organelles, including mitochondria in autoimmune diseases. Aberrant metalloproteinase secretion by motor proteins is a major contributor to tissue remodeling of synovial membrane and joint tissue destruction in rheumatoid arthritis (RA) by promoting infiltration of blood vessels, bone erosion, and loss of cartilage by phagocytes. In this study, we identified that specific glycan processing enzymes are upregulated in certain cell types (fibroblast or endothelial cells) that function in destructive tissue remodeling in rheumatoid arthritis compared to osteoarthritis (OA). TMEM230 was identified as a regulator in the secretion of metaloproteinases and heparanase necessary tissue remodeling in OA and RA. In dendritic (DC), natural killer and T cells, TMEM230 was expressed at low or no levels in RA compared to OA. TMEM230 expression in DC likely is necessary for regulatory or helper T cells to maintain tolerance to self-antigens and prevent susceptibility to autoimmune disease. To identify how TMEM230 and the endomembrane system contribute to autoimmunity we investigated, glycan modifying enzymes, metalloproteinases and motor protein genes co-regulated with or regulated by TMEM230 in synovial tissue by analyzing published single cell transcriptomic datasets from RA patient derived synovial tissue.

Nitro fatty acids: A comprehensive review on analytical methods and levels in health and disease.

Nitro fatty acids (NO2-FAs) are biologically active compounds produced from the reaction of unsaturated fatty acids with reactive nitrogen species (RNS). Due to their electrophilic nature, these endogenously produced metabolites can react with nucleophilic targets, producing a spectrum of modulatory and protective effects. Determination of NO2-FAs in biological samples is challenging due to their low nanomolar to picomolar endogenous concentrations, indistinct metabolism, and distribution in many tissues and biofluids. Several attempts have been made to develop precise, standardized, and efficient methodologies for assessing physiological and pathophysiological processes to overcome the difficulties associated with their measurement. This review discusses those approaches utilizing liquid chromatography tandem mass spectrometry (LC‒MS/MS) and gas chromatography tandem mass spectrometry (GC‒MS/MS) for the quantification of NO2-FAs, in addition to a summary of their laboratory synthesis and extraction from biological samples. Clinical associations with different pathological conditions, including hyperlipidaemia, cardiac ischemia and herpes simplex type 2 viral infection (HSV-2), are also discussed.

Polymyalgia rheumatica is a risk factor for more recalcitrant disease in giant cell arteritis: A retrospective cohort study.

OBJECTIVES: To evaluate differences in presentation and outcome of giant cell arteritis (GCA) patients with and without polymyalgia rheumatica (PMR) symptoms. METHODS: Consecutive patients diagnosed with GCA between 2000 and 2020 and followed for ≥12 months at the University Hospitals Leuven (Belgium), were included retrospectively. RESULTS: We included 398 GCA patients, of which 181 (45%) with PMR symptoms. Patients with PMR symptoms had a longer symptom duration (11 vs 6 weeks, p < 0.001). They less frequently reported fever (19% vs 28%, p = 0.030) and fatigue (52% vs 64%, p = 0.015) and tended to have less permanent vision loss (12% vs 19%, p = 0.052). There was no difference in the cumulative oral GC dose at 2 years (4.4 vs 4.3 g methylprednisolone, p = 0.571). However, those with PMR symptoms were treated with higher GC doses during subsequent follow-up (p < 0.05 from 38 months after diagnosis) and had a lower probability of stopping GC (62% vs 71%, HR 0.74 [95%CI 0.58-0.94], p = 0.018) with a longer median duration of GC treatment (29 vs 23 months, p = 0.021). In addition, presence of PMR symptoms was associated with an increased risk of relapse (64% vs 51%, HR 1.38 [95%CI 1.06-1.79], p = 0.017) with a higher number of relapses (1.47 [95%CI 1.30-1.65] vs 1.16 relapses [95%CI 1.02-1.31], p = 0.007). Patients with PMR symptoms less frequently developed thoracic aortic aneurysms during follow-up (3% vs 11%, p = 0.005). CONCLUSION: GCA patients with PMR symptoms had more recalcitrant disease with a higher risk of relapse and longer duration of GC treatment with need for higher GC doses.

Downregulation of tRF-Cys-GCA-029 by hyperglycemia promotes tumorigenesis and glycolysis of diabetic breast cancer through upregulating PRKCG translation.

BACKGROUND: Diabetes mellitus (DM) affects up to one-third of breast cancer (BC) patients. Patients with co-existing BC and DM (BC-DM) have worsened BC prognosis. Nevertheless, the molecular mechanisms orchestrating BC-DM prognosis remain poorly understood. tRNA-derived fragments (tRFs) have been shown to regulate cancer progression. However, the biological role of tRFs in BC-DM has not been explored. METHODS: tRF levels in tumor tissues and cells were detected by tRF sequencing and qRT-PCR. The effects of tRF on BC cell malignancy were assessed under euglycemic and hyperglycemic conditions in vitro. Metabolic changes were assessed by lactate, pyruvate, and extracellular acidification rate (ECAR) assays. Diabetic animal model was used to evaluate the impacts of tRF on BC tumor growth. RNA-sequencing (RNA-seq), qRT-PCR, Western blot, polysome profiling, luciferase reporter assay, and rescue experiments were performed to explore the regulatory mechanisms of tRF in BC-DM. RESULTS: We identified that tRF-Cys-GCA-029 was downregulated in BC-DM tissues and under hyperglycemia conditions in BC cells. Functionally, downregulation of tRF-Cys-GCA-029 promoted BC cell proliferation and migration in a glucose level-dependent manner. tRF-Cys-GCA-029 knockdown also enhanced glycolysis metabolism in BC cells, indicated by increasing lactate/pyruvate production and ECAR levels. Notably, injection of tRF-Cys-GCA-029 mimic significantly suppressed BC tumor growth in diabetic-mice. Mechanistically, tRF-Cys-GCA-029 regulated BC cell malignancy and glycolysis via interacting with PRKCG in two ways: binding to the coding sequence (CDS) of PRKCG mRNA to regulate its transcription and altering polysomal PRKCG mRNA expression to modify its translation. CONCLUSIONS: Hyperglycemia-downregulated tRF-Cys-GCA-029 enhances the malignancy and glycolysis of BC cells. tRF-Cys-GCA-029-PRKCG-glycolysis axis may be a potential therapeutic target against BC-DM.

Predictive Factors for Biopsy-Negative Giant Cell Arteritis and Alternative Diagnoses in a Neuro-Ophthalmology Context.

Giant cell arteritis is a challenging diagnosis for patients given the high prevalence of negative temporal artery biopsies (TAB). Despite the lack of histopathological evidence of giant cell arteritis in the TAB, patients can still have TAB-negative giant cell arteritis. The purpose of this paper is to analyse the predictors for TAB-negative giant cell arteritis and the alternative diagnosis of biopsy-negative patients without a giant cell arteritis diagnosis. A retrospective electronic database review of all TABs performed at the Royal Victorian Eye and Ear Hospital from February 2015 to May 2020. Logistic regression analysis was performed to determine predictive factors for a diagnosis of TAB-negative giant cell arteritis. In all cases, a clinical diagnosis of TAB-negative giant cell arteritis was determined by a neuro-ophthalmologist. Alternative diagnoses for negative TABs were identified and explored. A total of 368 TABs were analysed with 287 (78%) negative for histopathological evidence of GCA. Twenty-seven (9.4%) patients were diagnosed and treated as TAB-negative giant cell arteritis. The clinical predictors of a TAB-negative giant cell arteritis diagnosis were the presence of jaw claudication (OR 2.77, 95% CI 1.10-6.98) and CRP (OR 1.02, 95% CI 1.00-1.03). Alternative diagnoses included non-specific headache, non-arteritic anterior ischaemic optic neuropathy, retinal vessel occlusions, and ocular nerve palsies. Predictive factors for a diagnosis of TAB-negative giant cell arteritis were jaw claudication and an elevated CRP. Several alternative diagnoses can be considered for patients with a negative TAB in a neuro-ophthalmology context.

Investigational agents for polymyalgia rheumatica treatment: assessing the critical needs for future development.

INTRODUCTION: Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disorder characterized by pain and stiffness in the shoulder and pelvic girdles, constitutional symptoms, and elevated acute-phase reactants. Glucocorticoids (GCs) remain the first-choice treatment for PMR, but relapses are common. Identification of steroid-sparing agents is therefore of utmost importance. AREAS COVERED: The efficacy of conventional immunosuppressive drugs is controversial. The use of interleukin (IL)-6 receptor inhibitors proved to be effective and safe in treating PMR patients. Currently, there are 12 ongoing clinical trials exploring potential treatments such as leflunomide, low-dose IL-2, rituximab, abatacept, secukinumab, Janus kinase inhibitors, and selective inhibitors like SPI-62 and ABBV 154. EXPERT OPINION: The high efficacy of IL-6 R receptor inhibitors as well as the numerous drug trials currently recruiting suggest that several therapeutic options will be available in the near future. Accurate diagnosis and early stratification of PMR patients according to the giant cell arteritis-PMR Spectrum Disease 'GPSD' and potential risk factors for relapsing disease or GC-related adverse events are crucial to identify patients who would benefit most from GC-sparing agents. The development of internationally accepted definitions for remission and relapse is urgently needed. Early referral strategies to specialist settings would improve disease stratification and personalized treatment.

A Case of Large Vessel Giant Cell Arteritis Presenting With Cough and Diagnosed Using an FDG-PET Scan.

Giant-cell arteritis (GCA) is a type of vasculitis characterised by the presence of granulomas. It is the predominant form of systemic vasculitis in adults and primarily affects the larger arteries in individuals aged ≥ 50 years. GCA affects the major arteries, such as the aorta and its branches, particularly the outer branches of the external carotid artery. Signs and symptoms can be categorised into cranial, extracranial, and systemic manifestations. Patients with headaches, jaw claudication, and vision disturbances usually have extracranial branches of the external carotid artery. Aside from being the prevailing manifestation of GCA, our primary concern regarding this variant is the potential for irreversible vision loss if not properly identified and addressed. Conversely, the GCA can also affect other major blood vessels such as the aorta. Here, we present the case of a 70-year-old Caucasian female patient with cranial GCA who had experienced a temporal headache three years prior. The patient was successfully treated with prednisolone, which was gradually reduced to a very low level with the assistance of methotrexate. Recently, the patient presented with a dry cough that lasted for two months and elevated inflammatory markers. After thorough research, it was determined that there was no evidence of infection, including atypical infections, and that no abnormalities were found in the lungs. Ultimately, via an 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan, the patient was diagnosed with large vessel giant cell arteritis (LV-GCA). This impacted the aorta, carotid arteries, and subclavian arteries. The patient experienced notable improvement in her cough and a reduction in inflammatory markers after receiving a high dosage of oral prednisolone. This case exemplifies the unusual manifestation of LV-GCA and verifies that recurring symptoms may differ from the original presentation. While dry cough is not commonly listed as a symptom of LV-GCA, it can be present as a manifestation or the sole presentation in certain patients, particularly when inflammatory markers are consistently high and there is no pulmonary disease.

Impaired effective functional connectivity in the social preference of children with autism spectrum disorder.

Background: The medial prefrontal cortex (mPFC), amygdala (Amyg), and nucleus accumbens (NAc) have been identified as critical players in the social preference of individuals with ASD. However, the specific pathophysiological mechanisms underlying this role requires further clarification. In the current study, we applied Granger Causality Analysis (GCA) to investigate the neural connectivity of these three brain regions of interest (ROIs) in patients with ASD, aiming to elucidate their associations with clinical features of the disorder. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from the ABIDE II database, which included 37 patients with ASD and 50 typically developing (TD) controls. The mPFC, Amyg, and NAc were defined as ROIs, and the differences in fractional amplitude of low-frequency fluctuations (fALFF) within the ROIs between the ASD and TD groups were computed. Subsequently, we employed GCA to investigate the bidirectional effective connectivity between the ROIs and the rest of the brain. Finally, we explored whether this effective connectivity was associated with the social responsiveness scale (SRS) scores of children with ASD. Results: The fALFF values in the ROIs were reduced in children with ASD when compared to the TD group. In terms of the efferent connectivity from the ROIs to the whole brain, the ASD group exhibited increased connectivity in the right cingulate gyrus and decreased connectivity in the right superior temporal gyrus. Regarding the afferent connectivity from the whole brain to the ROIs, the ASD group displayed increased connectivity in the right globus pallidus and decreased connectivity in the right cerebellar Crus 1 area and left cingulate gyrus. Additionally, we demonstrated a positive correlation between effective connectivity derived from GCA and SRS scores. Conclusion: Impairments in social preference ASD children is linked to impaired effective connectivity in brain regions associated with social cognition, emotional responses, social rewards, and social decision-making. This finding further reveals the potential neuropathological mechanisms underlying ASD.

Giant Cell Arteritis Masquerading as Tooth Pain: A Case Report.

Giant cell arteritis (GCA) is a form of vasculitis characterized by symptoms that often lead a patient to consult a general dentist. Its rarity in the dental setting and serious life-altering effects make it a formidable diagnosis. We discuss a case of a 60-year-old female with GCA presenting with primary symptoms of excruciating tooth and jaw pain on the left side. We also report secondary symptoms of headache and partial vision loss and engage in a review of the relevant literature. Jaw pain, unexplained toothache, or tissue necrosis in patients aged over 50 years can be misdiagnosed as joint arthritis or temporomandibular disease (TMD), which could lead to severe consequences. Accurately diagnosing this ophthalmic emergency is critical for implementing therapy promptly and preventing ischemic complications. Dentists should maintain a high index of suspicion about its signs and symptoms, which will aid in making an early diagnosis and prompt referral.

Uncovering spatiotemporal dynamics of the corticothalamic network at ictal onset.

OBJECTIVE: Although the clinical efficacy of deep brain stimulation targeting the anterior nucleus (AN) and centromedian nucleus (CM) of the thalamus has been actively investigated for the treatment of medication-resistant epilepsy, few studies have investigated dynamic ictal changes in corticothalamic connectivity in human electroencephalographic (EEG) recording. This study aims to establish the complex spatiotemporal dynamics of the ictal corticothalamic network associated with various seizure foci. METHODS: We analyzed 10 patients (aged 2.7-28.1 years) with medication-resistant focal epilepsy who underwent stereotactic EEG evaluation with thalamic sampling. We examined both undirected and directed connectivity, incorporating coherence and spectral Granger causality analysis (GCA) between the diverse seizure foci and thalamic nuclei (AN and CM) at ictal onset. RESULTS: In our analysis of 36 seizures, coherence between seizure onset and thalamic nuclei increased across all frequencies, especially in slower bands (delta, theta, alpha). GCA showed increased information flow from seizure onset to the thalamus across all frequency bands, but outflows from the thalamus were mainly in slower frequencies, particularly delta. In the subgroup analysis based on various seizure foci, the delta coherence showed a more pronounced increase at CM than at AN during frontal lobe seizures. Conversely, in limbic seizures, the delta coherence increase was greater at AN compared to CM. SIGNIFICANCE: It appears that the delta frequency plays a pivotal role in modulating the corticothalamic network during seizures. Our results underscore the significance of comprehending the spatiotemporal dynamics of the corticothalamic network at ictal onset, and this knowledge could guide personalized responsive neuromodulation treatment strategies.

Association between vascular FDG uptake during follow-up and the development of thoracic aortic aneurysms in giant cell arteritis.

Background: A positive PET scan at diagnosis was associated with a greater yearly increase in ascending and descending aortic diameter and thoracic aortic volume in patients with giant cell arteritis (GCA). Radiologic and histopathologic vascular abnormalities persist in a subset of treated patients despite clinical remission. The aim of this study was to evaluate the association between vascular FDG uptake during follow-up and the development of thoracic aortic aneurysms. Methods: We recently performed a prospective cohort study of 106 GCA patients, who underwent FDG PET and CT imaging at diagnosis and CT imaging yearly for a maximum of 10 years. In this post hoc analysis, GCA patients who also have had FDG PET imaging during follow-up were included. PET scans were visually scored (0-3) at 7 vascular areas. PET scans were considered positive in case of FDG uptake ≥grade 2 in any large vessel. Results: Eighty-eight repeat PET scans were performed in 52 out of 106 GCA patients, who were included in the original prospective cohort. Fifty-five (63%) PET scans were done at the time of a relapse and 33 (38%) were done while in remission. Nine out of ten patients with an incident thoracic aortic aneurysm had both a positive PET scan at diagnosis and during follow-up. Conclusion: In addition to the intensity and extent of the initial vascular inflammation, ongoing aortic inflammation may contribute to the development of thoracic aortic aneurysms in GCA. However, this hypothesis should be confirmed in a large prospective trial with repeat PET scans at predefined time points during follow-up.

The minimum energy required to build a cell.

Understanding the energy requirements for cell synthesis accurately and comprehensively has been a longstanding challenge. We introduce a computational model that estimates the minimum energy necessary to build any cell from its constituent parts. This method combines omics and internal cell compositions from various sources to calculate the Gibbs Free Energy of biosynthesis independently of specific metabolic pathways. Our public tool, Synercell, can be used with other models for minumum species-specific energy estimations in any well-sequenced species. The energy for synthesising the genome, transcriptome, proteome, and lipid bilayer of four cell types: Escherichia coli, Saccharomyces cerevisiae, an average mammalian cell and JCVI-syn3A were estimated. Their modelled minimum synthesis energies at 298 K were 9.54 × 10 - 11 J/cell, 4.99 × 10 - 9 J/cell, 3.71 × 10 - 7 J/cell and 3.69 × 10 - 12 respectively. Gram-for-gram synthesis of lipid bilayers requires the most energy, followed by the proteome, genome, and transcriptome. The average per gram cost of biomass synthesis is in the 300s of J/g for all four cells. Implications for the generalisability of cell construction and applications to biogeosciences, cellular biology, biotechnology, and astrobiology are discussed.

Low incidence of malignancy in patients with suspected polymyalgia rheumatica or giant cell arteritis, examined with FDG-PET/CT.

Introduction: The need to systematically examine patients suspected of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) for malignancy is controversial. The aim of this study was to assess the frequency of malignancy in patients with suspected PMR and/or GCA who have been referred to a 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography with computed tomography (FDG-PET/CT) as part of the diagnostic investigation. Method: The records of all patients referred to FDG-PET/CT from Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup with the suspicion of PMR and/or GCA during a two-year period, were retrospectively reviewed. Data was analyzed with descriptive statistics, and a standard incidence ratio was calculated based on background cancer incidences extracted from the NORDCAN database. Results: 220 patients were included in the study. Findings suspicious of malignancy were found in 19 of the examinations, and in seven cases (3.2%), malignancy was confirmed. In three out of the seven cases the patients were diagnosed with PMR concomitantly with malignancy. The estimated standardized incidence ratio (SIR) for cancer compared to the background incidence of cancer in Denmark was 1.58 (95% CI 0.63-2.97), i.e., not statistically significant. There were no statistically significant differences in characteristics of the patients that were diagnosed with malignancy compared with those that were not. Conclusion: The frequency of malignancy in this cohort of patients with suspected PMR/GCA who underwent PET/CT was low. Our results, though based on a small cohort, do not suggest that all patients with suspected PMR/GCA should systematically be examined with FDG-PET/CT for excluding malignancy.