Interplay between endocannabinoids and dopamine in the basal ganglia: implications for pain in Parkinson's disease.

Pain is a complex phenomenon, and basal ganglia circuitry integrates many aspects of pain including motor, emotional, autonomic, and cognitive responses. Perturbations in dopamine (DA) signaling are implicated in the pathogenesis of chronic pain due to its involvement in both pain perception and relief. Several lines of evidence support the role of endocannabinoids (eCBs) in the regulation of many electrical and chemical aspects of DAergic neuron function including excitability, synaptic transmission, integration, and plasticity. However, eCBs play an even more intricate and intimate relationship with DA, as indicated by the adaptive changes in the eCB system following DA depletion. Although the precise mechanisms underlying DA control on pain are not fully understood, given the high correlation of eCB and DAergic system, it is conceivable that eCBs may be part of these mechanisms.In this brief survey, we describe the reciprocal regulation of eCB-DA neurotransmission with a particular emphasis on the actions of eCBs on ionic and synaptic signaling in DAergic neurons mediated by CB receptors or independent on them. Furthermore, we analyze the eCB-DA imbalance which characterizes pain condition and report the implications of reduced DA levels for pain in Parkinson's disease. Lastly, we discuss the potential of the eCB-DA system in the development of future therapeutic strategies for the treatment of pain.

DEep LearnIng-based QuaNtification of epicardial adipose tissue predicts MACE in patients undergoing stress CMR.

BACKGROUND AND AIMS: This study investigated the additional prognostic value of epicardial adipose tissue (EAT) volume for major adverse cardiovascular events (MACE) in patients undergoing stress cardiac magnetic resonance (CMR) imaging. METHODS: 730 consecutive patients [mean age: 63 ± 10 years; 616 men] who underwent stress CMR for known or suspected coronary artery disease were randomly divided into derivation (n = 365) and validation (n = 365) cohorts. MACE was defined as non-fatal myocardial infarction and cardiac deaths. A deep learning algorithm was developed and trained to quantify EAT volume from CMR. EAT volume was adjusted for height (EAT volume index). A composite CMR-based risk score by Cox analysis of the risk of MACE was created. RESULTS: In the derivation cohort, 32 patients (8.7 %) developed MACE during a follow-up of 2103 days. Left ventricular ejection fraction (LVEF) < 35 % (HR 4.407 [95 % CI 1.903-10.202]; p<0.001), stress perfusion defect (HR 3.550 [95 % CI 1.765-7.138]; p<0.001), late gadolinium enhancement (LGE) (HR 4.428 [95%CI 1.822-10.759]; p = 0.001) and EAT volume index (HR 1.082 [95 % CI 1.045-1.120]; p<0.001) were independent predictors of MACE. In a multivariate Cox regression analysis, adding EAT volume index to a composite risk score including LVEF, stress perfusion defect and LGE provided additional value in MACE prediction, with a net reclassification improvement of 0.683 (95%CI, 0.336-1.03; p<0.001). The combined evaluation of risk score and EAT volume index showed a higher Harrel C statistic as compared to risk score (0.85 vs. 0.76; p<0.001) and EAT volume index alone (0.85 vs.0.74; p<0.001). These findings were confirmed in the validation cohort. CONCLUSIONS: In patients with clinically indicated stress CMR, fully automated EAT volume measured by deep learning can provide additional prognostic information on top of standard clinical and imaging parameters.

Wolbachia strain wAlbB shows favourable characteristics for dengue control use in Aedes aegypti from Burkina Faso.

Dengue represents an increasing public health burden worldwide. In Africa, underreporting and misdiagnosis often mask its true epidemiology, and dengue is likely to be both more widespread than reported data suggest and increasing in incidence and distribution. Wolbachia-based dengue control is underway in Asia and the Americas but has not to date been deployed in Africa. Due to the genetic heterogeneity of African Aedes aegypti populations and the complexity of the host-symbiont interactions, characterization of key parameters of Wolbachia-carrying mosquitoes is paramount for determining the potential of the system as a control tool for dengue in Africa. The wAlbB Wolbachia strain was stably introduced into an African Ae. aegypti population by introgression, and showed high intracellular density in whole bodies and different mosquito tissues; high intracellular density was also maintained following larval rearing at high temperatures. No effect on the adult lifespan induced by Wolbachia presence was detected. Moreover, the ability of this strain to strongly inhibit DENV-2 dissemination and transmission in the host was also demonstrated in the African background. Our findings suggest the potential of harnessing Wolbachia for dengue control for African populations of Ae. aegypti.

Oxytocin Modifies the Excitability and the Action Potential Shape of the Hippocampal CA1 GABAergic Interneurons.

Oxytocin (OT) is a neuropeptide that modulates social-related behavior and cognition in the central nervous system of mammals. In the CA1 area of the hippocampus, the indirect effects of the OT on the pyramidal neurons and their role in information processing have been elucidated. However, limited data are available concerning the direct modulation exerted by OT on the CA1 interneurons (INs) expressing the oxytocin receptor (OTR). Here, we demonstrated that TGOT (Thr4,Gly7-oxytocin), a selective OTR agonist, affects not only the membrane potential and the firing frequency but also the neuronal excitability and the shape of the action potentials (APs) of these INs in mice. Furthermore, we constructed linear mixed-effects models (LMMs) to unravel the dependencies between the AP parameters and the firing frequency, also considering how TGOT can interact with them to strengthen or weaken these influences. Our analyses indicate that OT regulates the functionality of the CA1 GABAergic INs through different and independent mechanisms. Specifically, the increase in neuronal firing rate can be attributed to the depolarizing effect on the membrane potential and the related enhancement in cellular excitability by the peptide. In contrast, the significant changes in the AP shape are directly linked to oxytocinergic modulation. Importantly, these alterations in AP shape are not associated with the TGOT-induced increase in neuronal firing rate, being themselves critical for signal processing.

Population-specific responses to developmental temperature in the arboviral vector Aedes albopictus: Implications for climate change.

The increase of environmental temperature due to current global warming is not only favouring the expansion of the distribution range of many insect species, but it is also changing their phenology. Insect phenology is tightly linked to developmental timing, which is regulated by environmental temperatures. However, the degree to which the effects of developmental temperatures extend across developmental stages and their inter-stage relationships have not been thoroughly quantified in mosquitoes. Here, we used the mosquito Aedes albopictus, which is an aggressive invasive species and an arboviral vector, to study how developmental temperature influences fitness across developmental stages, thermal traits, energy reserves, transcriptome and Wolbachia prevalence in laboratory-reared populations originally collected from either temperate or tropical regions. We show that hatchability, larval and pupal viability and developmental speed are strongly influenced by temperature, and these effects extend to wing length, body mass, longevity and content of water, protein and lipids in adults in a population-specific manner. On the contrary, neither adult thermal preference nor heat resistance significantly change with temperature. Wolbachia density was generally lower in adult mosquitoes reared at 18°C than at other tested temperatures, and transcriptome analysis showed enrichment for functions linked to stress responses (i.e. cuticle proteins and chitin, cytochrome p450 and heat shock proteins) in mosquitoes reared at both 18 and 32°C. Our data showed an overall reduced vector fitness performance when mosquitoes were reared at 32°C, and the absence of isomorphy in the relationship between developmental stages and temperature in the laboratory population deriving from larvae collected in northern Italy. Altogether, these results have important implications for reliable model projections of the invasion potentials of Ae. albopictus and its epidemiological impact.

Ex vivo drug testing of patient-derived lung organoids to predict treatment responses for personalized medicine.

Lung cancer is the leading cause of global cancer-related mortality resulting in âˆ¼ 1.8 million deaths annually. Systemic, molecular targeted, and immune therapies have provided significant improvements of survival outcomes for patients. However, drug resistance usually arises and there is an urgent need for novel therapy screening and personalized medicine. 3D patient-derived organoid (PDO) models have emerged as a more effective and efficient alternative for ex vivo drug screening than 2D cell culture and patient-derived xenograft (PDX) models. In this review, we performed an extensive search of lung cancer PDO-based ex vivo drug screening studies. Lung cancer PDOs were successfully established from fresh or bio-banked sections and/or biopsies, pleural effusions and PDX mouse models. PDOs were subject to ex vivo drug screening with chemotherapy, targeted therapy and/or immunotherapy. PDOs consistently recapitulated the genomic alterations and drug sensitivity of primary tumors. Although sample sizes of the previous studies were limited and some technical challenges remain, PDOs showed great promise in the screening of novel therapy drugs. With the technical advances of high throughput, tumor-on-chip, and combined microenvironment, the drug screening process using PDOs will enhance precision care of lung cancer patients.

Predictors of adverse cardiac events of coronary myocardial bridging diagnosed with computed tomography angiography.

AIMS: Myocardial bridging (MB) is a frequent congenital anomaly of the epicardial coronary arteries commonly considered a benign condition. However, in some cases a complex interplay between anatomical, clinical and physiology factors may lead to adverse events, including sudden cardiac death. Coronary CT angiography (CCTA) emerged as the gold standard noninvasive imaging technique for the evaluation of MB. Aim of the study was to evaluate MB prevalence and anatomical features in a large population of patients who underwent CCTA for suspected CAD and to identify potential anatomical and clinical predictors of adverse cardiac events at long-term follow-up. METHODS AND RESULTS: Two-hundred and six patients (mean age 60.3 ± 11.8 years, 128 male) with MB diagnosed at CCTA were considered. A long MB was defined as ≥25 mm of overlying myocardium, whereas a deep MB as ≥2 mm of overlying myocardium. The study endpoint was the sum of the following adverse events: cardiac death, bridge-related acute coronary syndrome, hospitalization for angina or bridge-related ventricular arrhythmias and MB surgical treatment. Of the 206 patients enrolled in the study, 9 were lost to follow-up, whereas 197 (95.6%) had complete follow-up (mean 7.01 ± 3.0 years) and formed the analytic population. Nineteen bridge-related events occurred in 18 patients (acute coronary syndrome in 7, MB surgical treatment in 2 and hospitalization for bridge-related events in 10). Typical angina at the time of diagnosis and long MB resulted as significant independent predictors of adverse outcome. CONCLUSIONS: Typical angina and MB length ≥ 25 mm were independent predictors of cardiac events.

Analysis of Clinical Samples of Pancreatic Cyst's Lesions with A Multi-Analyte Bioelectronic Simot Array Benchmarked Against Ultrasensitive Chemiluminescent Immunoassay.

Pancreatic cancer, ranking as the third factor in cancer-related deaths, necessitates enhanced diagnostic measures through early detection. In response, SiMoT-Single-molecule with a large Transistor multiplexing array, achieving a Technology Readiness Level of 5, is proposed for a timely identification of pancreatic cancer precursor cysts and is benchmarked against the commercially available chemiluminescent immunoassay SIMOA (Single molecule array) SP-X System. A cohort of 39 samples, comprising 33 cyst fluids and 6 blood plasma specimens, undergoes detailed examination with both technologies. The SiMoT array targets oncoproteins MUC1 and CD55, and oncogene KRAS, while the SIMOA SP-X planar technology exclusively focuses on MUC1 and CD55. Employing Principal Component Analysis (PCA) for multivariate data processing, the SiMoT array demonstrates effective discrimination of malignant/pre-invasive high-grade or potentially malignant low-grade pancreatic cysts from benign non-mucinous cysts. Conversely, PCA analysis applied to SIMOA assay reveals less effective differentiation ability among the three cyst classes. Notably, SiMoT unique capability of concurrently analyzing protein and genetic markers with the threshold of one single molecule in 0.1 mL positions it as a comprehensive and reliable diagnostic tool. The electronic response generated by the SiMoT array facilitates direct digital data communication, suggesting potential applications in the development of field-deployable liquid biopsy.

Loss-of-function of GNAL dystonia gene impairs striatal dopamine receptors-mediated adenylyl cyclase/ cyclic AMP signaling pathway.

Loss-of-function mutations in the GNAL gene are responsible for DYT-GNAL dystonia. However, how GNAL mutations contribute to synaptic dysfunction is still unclear. The GNAL gene encodes the Gαolf protein, an isoform of stimulatory Gαs enriched in the striatum, with a key role in the regulation of cAMP signaling. Here, we used a combined biochemical and electrophysiological approach to study GPCR-mediated AC-cAMP cascade in the striatum of the heterozygous GNAL (GNAL+/-) rat model. We first analyzed adenosine type 2 (A2AR), and dopamine type 1 (D1R) receptors, which are directly coupled to Gαolf, and observed that the total levels of A2AR were increased, whereas D1R level was unaltered in GNAL+/- rats. In addition, the striatal isoform of adenylyl cyclase (AC5) was reduced, despite unaltered basal cAMP levels. Notably, the protein expression level of dopamine type 2 receptor (D2R), that inhibits the AC5-cAMP signaling pathway, was also reduced, similar to what observed in different DYT-TOR1A dystonia models. Accordingly, in the GNAL+/- rat striatum we found altered levels of the D2R regulatory proteins, RGS9-2, spinophilin, Gß5 and ß-arrestin2, suggesting a downregulation of D2R signaling cascade. Additionally, by analyzing the responses of striatal cholinergic interneurons to D2R activation, we found that the receptor-mediated inhibitory effect is significantly attenuated in GNAL+/- interneurons. Altogether, our findings demonstrate a profound alteration in the A2AR/D2R-AC-cAMP cascade in the striatum of the rat DYT-GNAL dystonia model, and provide a plausible explanation for our previous findings on the loss of dopamine D2R-dependent corticostriatal long-term depression.

High promiscuity among females of the invasive pest species Drosophila suzukii.

Drosophila suzukii (Matsumura, 1931), the spotted-wing drosophila, is a highly invasive fruit fly that spread from Southern Asia across most regions of Asia and, in the last 15 years, has invaded Europe and the Americas. It is an economically important pest of small fruits such as berries and stone fruits. Drosophila suzukii speciated by adapting to cooler, mountainous, and forest environments. In temperate regions, it evolved seasonal polyphenism traits which enhanced its survival during stressful winter population bottlenecks. Consequently, in these temperate regions, the populations undergo seasonal reproductive dynamics. Despite its economic importance, no data are available on the behavioural reproductive strategies of this fly. The presence of polyandry, for example, has not been determined despite the important role it might play in the reproductive dynamics of populations. We explored the presence of polyandry in an established population in Trentino, a region in northern Italy. In this area, D. suzukii overcomes the winter bottleneck and undergoes a seasonal reproductive fluctuation. We observed a high remating frequency in females during the late spring demographic explosion that led to the abundant summer population. The presence of a high degree of polyandry and shared paternity associated with the post-winter population increase raises the question of the possible evolutionary adaptive role of this reproductive behaviour in D. suzukii.

Circulating Small Extracellular Vesicles Reflect the Severity of Myocardial Damage in STEMI Patients.

Circulating small extracellular vesicles (sEVs) contribute to inflammation, coagulation and vascular injury, and have great potential as diagnostic markers of disease. The ability of sEVs to reflect myocardial damage assessed by Cardiac Magnetic Resonance (CMR) in ST-segment elevation myocardial infarction (STEMI) is unknown. To fill this gap, plasma sEVs were isolated from 42 STEMI patients treated by primary percutaneous coronary intervention (pPCI) and evaluated by CMR between days 3 and 6. Nanoparticle tracking analysis showed that sEVs were greater in patients with anterior STEMI (p = 0.0001), with the culprit lesion located in LAD (p = 0.045), and in those who underwent late revascularization (p = 0.038). A smaller sEV size was observed in patients with a low myocardial salvage index (MSI, p = 0.014). Patients with microvascular obstruction (MVO) had smaller sEVs (p < 0.002) and lower expression of the platelet marker CD41-CD61 (p = 0.039). sEV size and CD41-CD61 expression were independent predictors of MVO/MSI (OR [95% CI]: 0.93 [0.87-0.98] and 0.04 [0-0.61], respectively). In conclusion, we provide evidence that the CD41-CD61 expression in sEVs reflects the CMR-assessed ischemic damage after STEMI. This finding paves the way for the development of a new strategy for the timely identification of high-risk patients and their treatment optimization.

Early Biological Valve Failure: Structural Valve Degeneration, Thrombosis, or Endocarditis?

Biological valve failure (BVF) is an inevitable condition that compromises the durability of biological heart valves (BHVs). It stems from various causes, including rejection, thrombosis, and endocarditis, leading to a critical state of valve dysfunction. Echocardiography, cardiac computed tomography, cardiac magnetic resonance, and nuclear imaging play pivotal roles in the diagnostic multimodality workup of BVF. By providing a comprehensive overview of the pathophysiology of BVF and the diagnostic approaches in different clinical scenarios, this review aims to aid clinicians in their decision-making process. The significance of early detection and appropriate management of BVF cannot be overstated, as these directly impact patients' prognosis and their overall quality of life. Ensuring timely intervention and tailored treatments will not only improve outcomes but also alleviate the burden of this condition on patients' life. By prioritizing comprehensive assessments and adopting the latest advancements in diagnostic technology, medical professionals can significantly enhance their ability to manage BVF effectively.

Occurrence of a New Variant of Salmonella Infantis Lacking Somatic Antigen.

Salmonella Infantis is one of the most frequent serovars reported in broilers and is also regularly identified in human salmonellosis cases, representing a relevant public health problem. In the laboratories of the Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata (IZSPB), six Salmonella Infantis strains with antigenic formula -:r:1,5 have been isolated from the litter and carcass of broilers between 2018 and 2022. The strains were investigated to evaluate their phenotype, antibiotic resistance and genomic profiles. Genomic analysis confirmed that the isolates belonged to the Infantis serotype and to the sequence type ST32. Moreover, all strains showed a multidrug-resistant (MDR) profile and were characterised by the presence of the IncFIB plasmid incompatibility group. Three strains had the blaCTX-M-1 gene, and one of them carried IncX1. The presence of this new variant of S. Infantis is particularly relevant because it could expand the landscape of the S. Infantis population. The absence of the somatic antigen could pose a problem in both isolation and serotyping and a consequent public health concern due to the spread of Salmonella infection.

EU-27 ecological footprint was primarily driven by food consumption and exceeded regional biocapacity from 2004 to 2014.

The European Union (EU) plans to decarbonize the region by 2050. As highlighted by the Green Deal and Farm to Fork Strategy, food systems are essential for this transition. Here we investigate the resource dependence and carbon emissions of the EU-27's food systems from 2004 to 2014 via an ecological footprint (EF)-extended multi-regional input-output approach, accounting for demand and supply (including trade), and considering multiple externalities. Food contributes towards almost a third of the region's EF, and appropriates over half of its biocapacity. Average reliance on biocapacity within national borders decreased, while reliance on intra-EU biocapacity increased; yet a quarter of the biocapacity for food consumption originates from non-EU countries. Despite a reduction in both total EF and food EF over the study period, EU-27 residents demand more from nature than the region's ecosystems can regenerate-highlighting the need for new or strengthened food and trade policies to enable a transformation to sustainable EU food systems.

Pre-TAVI aortic annulus sizing: comparison between manual and semi-automated new generation software measurements in operators with different experience.

OBJECTIVES: Aim of the study is to compare manual and semi-automatic measurements for aortic annulus assessment among different operators. METHODS: Eighty patients who underwent TAVI were retrospectively enrolled. The measurements manually performed by an experienced reader for aortic annulus (minimum and maximum diameters, perimeter, area), annulus-to-coronary ostia distance and time needed for the whole evaluation, were collected. The same operator (observer 1) and two less experienced readers (observer 2 and 3, with >5 years and 1 year of experience, respectively) assessed the same measurements using a semi-automatic software. Differences between manual and semi-automatic measurements, reading time and suggested valves size derived by CT were compared. RESULTS: Very good correlations were found between manual and software-aided measurements for aortic annulus area and perimeter in comparison with standard measurements for the three readers (ICC range 0.81-0.98). Good correlations were found for the distance with coronary ostia(0.75-0.79). The same area-derived prosthesis size for manual and semi-automatic measurements was selected in 96% of cases for observer 1; very good correlations were also found for observer 2 and 3 (ICC = 0.89 and 0.88, respectively). Using semi-automatic measurements, the mean time needed for CT images was significantly lower for observers 1 and 2 (1.50 and 1.72versus 3.14 min), respectively. CONCLUSIONS: Pre-TAVI CT using semi-automatic software allows accurate and reproducible measurements, reducing reconstruction time up to 50% and is reliable even for operators with different experience. ADVANCES IN KNOWLEDGE: The use of semi-automatic dedicated software for CT in TAVI planning is reliable even for operators without long time experience and allows accurate and reproducible measurements improving pre-TAVI workflow.

A Single-Molecule Bioelectronic Portable Array for Early Diagnosis of Pancreatic Cancer Precursors.

A cohort of 47 patients is screened for pancreatic cancer precursors with a portable 96-well bioelectronic sensing-array for single-molecule assay in cysts fluid and blood plasma, deployable at point-of-care (POC). Pancreatic cancer precursors are mucinous cysts diagnosed with a sensitivity of at most 80% by state-of-the-art cytopathological molecular analyses (e.g., KRASmut DNA). Adding the simultaneous assay of proteins related to malignant transformation (e.g., MUC1 and CD55) is deemed essential to enhance diagnostic accuracy. The bioelectronic array proposed here, based on single-molecule-with-a-large-transistor (SiMoT) technology, can assay both nucleic acids and proteins at the single-molecule limit-of-identification (LOI) (1% of false-positives and false-negatives). It comprises an enzyme-linked immunosorbent assay (ELISA)-like 8 × 12-array organic-electronics disposable cartridge with an electrolyte-gated organic transistor sensor array, and a reusable reader, integrating a custom Si-IC chip, operating via software installed on a USB-connected smart device. The cartridge is complemented by a 3D-printed sensing gate cover plate. KRASmut , MUC1, and CD55 biomarkers either in plasma or cysts-fluid from 5 to 6 patients at a time, are multiplexed at single-molecule LOI in 1.5 h. The pancreatic cancer precursors are classified via a machine-learning analysis resulting in at least 96% diagnostic-sensitivity and 100% diagnostic-specificity. This preliminary study opens the way to POC liquid-biopsy-based early diagnosis of pancreatic-cancer precursors in plasma.

Synaptic mechanisms underlying onset and progression of memory deficits caused by hippocampal and midbrain synucleinopathy.

Cognitive deficits, including working memory, and visuospatial deficits are common and debilitating in Parkinson's disease. α-synucleinopathy in the hippocampus and cortex is considered as the major risk factor. However, little is known about the progression and specific synaptic mechanisms underlying the memory deficits induced by α-synucleinopathy. Here, we tested the hypothesis that pathologic α-Synuclein (α-Syn), initiated in different brain regions, leads to distinct onset and progression of the pathology. We report that overexpression of human α-Syn in the murine mesencephalon leads to late onset memory impairment and sensorimotor deficits accompanied by reduced dopamine D1 expression in the hippocampus. In contrast, human α-Syn overexpression in the hippocampus leads to early memory impairment, altered synaptic transmission and plasticity, and decreased expression of GluA1 AMPA-type glutamate receptors. These findings identify the synaptic mechanisms leading to memory impairment induced by hippocampal α-synucleinopathy and provide functional evidence of the major neuronal networks involved in disease progression.

Quantification of extracellular volume with cardiac computed tomography in patients with dilated cardiomyopathy.

BACKGROUND: Cardiac computed tomography (CCT) was recently validated to measure extracellular volume (ECV) in the setting of cardiac amyloidosis, showing good agreement with cardiovascular magnetic resonance (CMR). However, no evidence is available with a whole-heart single source, single energy CT scanner in the clinical context of newly diagnosed left ventricular dysfunction. Therefore, the aim of this study was to test the diagnostic accuracy of ECVCCT in patients with a recent diagnosis of dilated cardiomyopathy, having ECVCMR as the reference technique. METHODS: 39 consecutive patients with newly diagnosed dilated cardiomyopathy (LVEF <50%) scheduled for clinically indicated CMR were prospectively enrolled. Myocardial segment evaluability assessment with each technique, agreement between ECVCMR and ECVCCT, regression analysis, Bland-Altman analysis and interclass correlation coefficient (ICC) were performed. RESULTS: Mean age of enrolled patients was 62 â€‹± â€‹11 years, and mean LVEF at CMR was 35.4 â€‹± â€‹10.7%. Overall radiation exposure for ECV estimation was 2.1 â€‹± â€‹1.1 â€‹mSv. Out of 624 myocardial segments available for analysis, 624 (100%) segments were assessable by CCT while 608 (97.4%) were evaluable at CMR. ECVCCT demonstrated slightly lower values compared to ECVCMR (all segments, 31.8 â€‹± â€‹6.5% vs 33.9 â€‹± â€‹8.0%, p â€‹< â€‹0.001). At regression analysis, strong correlations were described (all segments, r â€‹= â€‹0.819, 95% CI: 0.791 to 0.844). On Bland-Altman analysis, bias between ECVCMR and ECVCCT for global analysis was 2.1 (95% CI: -6.8 to 11.1). ICC analysis showed both high intra-observer and inter-observer agreement for ECVCCT calculation (0.986, 95%CI: 0.983 to 0.988 and 0.966, 95%CI: 0.960 to 0.971, respectively). CONCLUSIONS: ECV estimation with a whole-heart single source, single energy CT scanner is feasible and accurate. Integration of ECV measurement in a comprehensive CCT evaluation of patients with newly diagnosed dilated cardiomyopathy can be performed with a small increase in overall radiation exposure.

Dopamine Transmission Imbalance in Neuroinflammation: Perspectives on Long-Term COVID-19.

Dopamine (DA) is a key neurotransmitter in the basal ganglia, implicated in the control of movement and motivation. Alteration of DA levels is central in Parkinson's disease (PD), a common neurodegenerative disorder characterized by motor and non-motor manifestations and deposition of alpha-synuclein (α-syn) aggregates. Previous studies have hypothesized a link between PD and viral infections. Indeed, different cases of parkinsonism have been reported following COVID-19. However, whether SARS-CoV-2 may trigger a neurodegenerative process is still a matter of debate. Interestingly, evidence of brain inflammation has been described in postmortem samples of patients infected by SARS-CoV-2, which suggests immune-mediated mechanisms triggering the neurological sequelae. In this review, we discuss the role of proinflammatory molecules such as cytokines, chemokines, and oxygen reactive species in modulating DA homeostasis. Moreover, we review the existing literature on the possible mechanistic interplay between SARS-CoV-2-mediated neuroinflammation and nigrostriatal DAergic impairment, and the cross-talk with aberrant α-syn metabolism.