Visual evoked potentials in multiple sclerosis: P100 latency and visual pathway damage including the lateral geniculate nucleus.

OBJECTIVE: To explore associations of the main component (P100) of visual evoked potentials (VEP) to pre- and postchiasmatic damage in multiple sclerosis (MS). METHODS: 31 patients (median EDSS: 2.5), 13 with previous optic neuritis (ON), and 31 healthy controls had VEP, optical coherence tomography and magnetic resonance imaging. We tested associations of P100-latency to the peripapillary retinal nerve fiber layer (pRNFL), ganglion cell/inner plexiform layers (GCIPL), lateral geniculate nucleus volume (LGN), white matter lesions of the optic radiations (OR-WML), fractional anisotropy of non-lesional optic radiations (NAOR-FA), and to the mean thickness of primary visual cortex (V1). Effect sizes are given as marginal R2 (mR2). RESULTS: P100-latency, pRNFL, GCIPL and LGN in patients differed from controls. Within patients, P100-latency was significantly associated with GCIPL (mR2 = 0.26), and less strongly with OR-WML (mR2 = 0.17), NAOR-FA (mR2 = 0.13) and pRNFL (mR2 = 0.08). In multivariate analysis, GCIPL and NAOR-FA remained significantly associated with P100-latency (mR2 = 0.41). In ON-patients, P100-latency was significantly associated with LGN volume (mR2 = -0.56). CONCLUSIONS: P100-latency is affected by anterior and posterior visual pathway damage. In ON-patients, damage at the synapse-level (LGN) may additionally contribute to latency delay. SIGNIFICANCE: Our findings corroborate post-chiasmatic contributions to the VEP-signal, which may relate to distinct pathophysiological mechanisms in MS.

Adding the Optic Nerve in Multiple Sclerosis Diagnostic Criteria: A Longitudinal, Prospective, Multicenter Study

BACKGROUND AND OBJECTIVES: The optic nerve is not one of the areas of the CNS that can be used to demonstrate dissemination in space (DIS) within the 2017 McDonald criteria for the diagnosis of multiple sclerosis (MS). Objectives were (1) to assess whether optic nerve-MRI (ON-MRI), optical coherence tomography (OCT), and visual evoked potentials (VEP) detect optic nerve involvement in clinically isolated syndrome (CIS) and (2) to evaluate the contribution of the optic nerve topography to the current diagnostic criteria in a prospective, multicenter cohort. METHODS: MAGNIMS centers were invited to provide prospective data on patients with CIS who underwent a visual assessment with at least 2 of 3 investigations (ON-MRI, OCT, or VEP) within 6 months of onset. Modified DIS criteria were constructed by adding the optic nerve topography, defined by each investigation separately and any combination of them, as the fifth area of the CNS. A risk assessment analysis and the performance of the different DIS criteria were analyzed using the diagnosis of MS according to the 2017 McDonald criteria as the primary outcome and new T2 lesions and/or a second relapse as the secondary outcome. RESULTS: We included 157 patients with CIS from 5 MAGNIMS centers; 60/157 (38.2%) patients presented with optic neuritis. Optic nerve involvement on ON-MRI was found in 40.2% patients at study entry and in 72.5% of those with optic neuritis.At follow-up (mean 27.9 months, SD 14.5), 111/157 patients (70.7%) were diagnosed with MS according to the 2017 McDonald criteria. Fulfilling either 2017 DIS or any modified DIS criteria conferred a similar high risk for reaching primary and secondary outcomes. The modified DIS criteria had higher sensitivity (92.5% [with ON-MRI] vs 88.2%), but slightly lower specificity (80.0% [with GCIPL IEA ≥4 µm] vs 82.2%), with overall similar accuracy (86.6% [with ON-MRI] vs 86.5%) than 2017 DIS criteria. Consistent results were found for secondary outcomes. DISCUSSION: In patients with CIS, the presence of an optic nerve lesion defined by MRI, OCT, or VEP is frequently detected, especially when presenting with optic neuritis. Our study supports the addition of the optic nerve as a fifth topography to fulfill DIS criteria.

Longitudinal analysis of new multiple sclerosis lesions with magnetization transfer and diffusion tensor imaging.

OBJECTIVE: The potential of magnetization transfer imaging (MTI) and diffusion tensor imaging (DTI) for the detection and evolution of new multiple sclerosis (MS) lesions was analyzed. METHODS: Nineteen patients with MS obtained conventional MRI, MTI, and DTI examinations bimonthly for 12 months and again after 24 months at 1.5 T MRI. MTI was acquired with balanced steady-state free precession (bSSFP) in 10 min (1.3 mm3 isotropic resolution) yielding both magnetization transfer ratio (MTR) and quantitative magnetization transfer (qMT) parameters (pool size ratio (F), exchange rate (kf), and relaxation times (T1/T2)). DTI provided fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). RESULTS: At the time of their appearance on MRI, the 21 newly detected MS lesions showed significantly reduced MTR/F/kf and prolonged T1/T2 parameters, as well as significantly reduced FA and increased AD/MD/RD. Significant differences were already observed for MTR 4 months and for qMT parameters 2 months prior to lesions' detection on MRI. DTI did not show any significant pre-lesional differences. Slightly reversed trends were observed for most lesions up to 8 months after their detection for qMT and less pronounced for MTR and three diffusion parameters, while appearing unchanged on MRI. CONCLUSIONS: MTI provides more information than DTI in MS lesions and detects tissue changes 2 to 4 months prior to their appearance on MRI. After lesions' detection, qMT parameter changes promise to be more sensitive than MTR for the lesions' evolutional assessment. Overall, bSSFP-based MTI adumbrates to be more sensitive than MRI and DTI for the early detection and follow-up assessment of MS lesions. CLINICAL RELEVANCE STATEMENT: When additionally acquired in routine MRI, fast bSSFP-based MTI can complement the MRI/DTI longitudinal lesion assessment by detecting MS lesions 2-4 months earlier than with MRI, which could implicate earlier clinical decisions and better follow-up/treatment assessment in MS patients. KEY POINTS: • Magnetization transfer imaging provides more information than DTI in multiple sclerosis lesions and can detect tissue changes 2 to 4 months prior to their appearance on MRI. • After lesions' detection, quantitative magnetization transfer changes are more pronounced than magnetization transfer ratio changes and therefore promise to be more sensitive for the lesions' evolutional assessment. • Balanced steady-state free precession-based magnetization transfer imaging is more sensitive than MRI and DTI for the early detection and follow-up assessment of multiple sclerosis lesions.

Novel Hybrid Silver-Silica Nanoparticles Synthesized by Modifications of the Sol-Gel Method and Their Theranostic Potential in Cancer.

Cancer is one of the leading causes of death worldwide. Conventional therapies lack selectivity and suffer from toxicity and drug resistance, leading to metastasis. To overcome these limitations, a new category of nanomaterials exploiting the tumor characteristics has been developed in cancer nanotherapeutics. Among them, pH, metabolism, and the disrupted architecture of cells can be exploited for theranostic applications. Such nanomaterials can be inorganic nanoparticles with silver ones and gain high attention as diagnostic, therapeutic, and antibacterial compounds. Silver has been linked with triggering the death of cancer cells via DNA damage due to the production of reactive oxygen species (ROS) during photodynamic therapy. Thus, improvement of biocompatibility, modification with targeted agents, and drug conjugation promote the use of silver nanoparticles. In this work, we managed to synthesize hybrid Ag@SiO2 core-shell nanoparticles via a modified sol-gel method by tackling the known etching of silver caused by ammonia by employing different bases of the sol-gel reaction. The bases used in the synthetic route were diethylamine (DEA) and triethylamine (TEA) and were monitored with silver nanoparticles individually from the absorbance peak of silver in the UV-vis region, showing no etching of silver in contrast with ammonia, which is usually used in the sol-gel method. Furthermore, we synthesized biocompatible nanoparticles with anticancer and diagnostic properties toward breast cancer cells and glioblastoma cells. The nanoparticles were characterized both structurally and morphologically. Their biological evaluation suggests minor toxicity toward healthy cells and red blood cells (RBCs). Also, the diagnostic potential of the hybrid nanoparticles was exploited by optical fluorescence microscopy. Therefore, we strongly suggest the investigation of such nanostructures as a dual platform for the diagnosis and therapy of cancer.

Ongoing Challenges in the Diagnosis of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

This cross-sectional study examines whether proposed myelin oligodendrocyte glycoprotein antibody­associated disease (MOGAD) diagnostic criteria can exclude other diseases, such as multiple sclerosis, and rely on results of cell-based assays.

Optical coherence tomography versus other biomarkers: Associations with physical and cognitive disability in multiple sclerosis.

BACKGROUND: Optical coherence tomography (OCT) is a biomarker of neuroaxonal loss in multiple sclerosis (MS). OBJECTIVE: The objective was to assess the relative role of OCT, next to magnetic resonance imaging (MRI) and serum markers of disability in MS. METHODS: A total of 100 patients and 52 controls underwent OCT to determine peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layers (GCIPL). Serum neurofilament light chain (sNfL), total lesion volume (TLV), and brain parenchymal fraction (BPF) were also assessed. The associations of OCT with disability were examined in linear regression models with correction for age, vision, and education. RESULTS: In patients, pRNFL was associated with the Symbol Digit Modalities Test (SDMT; p = 0.030). In the multivariate analysis including sNfL and MRI measures, pRNFL (ß = 0.19, p = 0.044) and TLV (ß = -0.24, p = 0.023) were the only markers associated with the SDMT. pRNFL (p < 0.001) and GCIPL (p < 0.001) showed associations with the Expanded Disability Status Scale (EDSS). In the multivariate analysis, GCIPL showed the strongest association with the EDSS (ß = -0.32, p < 0.001) followed by sNfL (ß = 0.18, p = 0.024). CONCLUSION: The associations of OCT measures with cognitive and physical disability were independent of serum and brain MRI markers of neuroaxonal loss. OCT can be an important tool for stratification in MS, while longitudinal studies using combinations of biomarkers are warranted.

Serum tau protein elevation in migraine: a cross-sectional case-control study.

BACKGROUND: Migraine is a disorder associated with neuropeptide release, pain and inflammation. Tau protein has recently been linked to inflammatory diseases and can be influenced by neuropeptides such as CGRP, a key neurotransmitter in migraine. Here, we report serum concentrations of total-tau protein in migraine patients and healthy controls. METHODS: In this cross-sectional study, interictal blood samples from n = 92 patients with episodic migraine (EM), n = 93 patients with chronic migraine (CM), and n = 42 healthy matched controls (HC) were studied. We assessed serum total-tau protein (t-tau) and for comparison neurofilament light chain protein (NfL), glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase L (UCH-L1) concentrations using the Neurology 4-plex kit, on a single molecule array HD-X Analyzer (Quanterix Corp Lexington, MA). Matched serum/cerebrospinal fluid (CSF) samples were used for post-hoc evaluations of a central nervous system (CNS) source of relevant findings. We applied non-parametric tests to compare groups and assess correlations. RESULTS: Serum t-tau concentrations were elevated in EM [0.320 (0.204 to 0.466) pg/mL] and CM [0.304 (0.158 to 0.406) pg/mL] patients compared to HC [0.200 (0.114 to 0.288) pg/mL] (p = 0.002 vs. EM; p = 0.025 vs. CM). EM with aura [0.291 (0.184 to 0.486 pg/mL); p = 0.013] and EM without aura [0.332 (0.234 to 0.449) pg/mL; p = 0.008] patients had higher t-tau levels than HC but did not differ between each other. Subgroup analysis of CM with/without preventive treatment revealed elevated t-tau levels compared to HC only in the non-prevention group [0.322 (0.181 to 0.463) pg/mL; p = 0.009]. T-tau was elevated in serum (p = 0.028) but not in cerebrospinal fluid (p = 0.760). In contrast to t-tau, all proteins associated with cell damage (NfL, GFAP, and UCH-L1), did not differ between groups. DISCUSSION: Migraine is associated with t-tau elevation in serum but not in the CSF. Our clinical study identifies t-tau as a new target for migraine research.

Immunoglobulin A Antibodies Against Myelin Oligodendrocyte Glycoprotein in a Subgroup of Patients With Central Nervous System Demyelination.

Importance: Differential diagnosis of patients with seronegative demyelinating central nervous system (CNS) disease is challenging. In this regard, evidence suggests that immunoglobulin (Ig) A plays a role in the pathogenesis of different autoimmune diseases. Yet little is known about the presence and clinical relevance of IgA antibodies against myelin oligodendrocyte glycoprotein (MOG) in CNS demyelination. Objective: To investigate the frequency of MOG-IgA and associated clinical features in patients with demyelinating CNS disease and healthy controls. Design, Setting, and Participants: This longitudinal study comprised 1 discovery and 1 confirmation cohort derived from 5 centers. Participants included patients with suspected or confirmed demyelinating diseases and healthy controls. MOG-IgA, MOG-IgG, and MOG-IgM were measured in serum samples and cerebrospinal fluid (CSF) of patients, who were assessed from September 2012 to April 2022. Main Outcomes and Measures: Frequency and clinical features of patients who were seropositive for MOG-IgA and double-seronegative for aquaporin 4 (AQP4) IgG and MOG-IgG. Results: After the exclusion of 5 participants with coexisting AQP4-IgG and MOG-IgA, MOG-IgG, and/or MOG-IgM, 1339 patients and 110 healthy controls were included; the median follow-up time was 39 months (range, 0-227 months). Of included patients with isolated MOG-IgA, 11 of 18 were female (61%), and the median age was 31.5 years (range, 3-76 years). Among patients double-seronegative for AQP4-IgG and MOG-IgG (1126/1339; 84%), isolated MOG-IgA was identified in 3 of 50 patients (6%) with neuromyelitis optica spectrum disorder, 5 of 228 patients (2%) with other CNS demyelinating diseases, and 10 of 848 patients (1%) with multiple sclerosis but in none of the healthy controls (0/110). The most common disease manifestation in patients seropositive for isolated MOG-IgA was myelitis (11/17 [65%]), followed by more frequent brainstem syndrome (7/16 [44%] vs 14/75 [19%], respectively; P = .048), and infrequent manifestation of optic neuritis (4/15 [27%] vs 46/73 [63%], respectively; P = .02) vs patients with MOG-IgG. Among patients fulfilling 2017 McDonald criteria for multiple sclerosis, MOG-IgA was associated with less frequent CSF-specific oligoclonal bands (4/9 [44%] vs 325/351 [93%], respectively; P < .001) vs patients with multiple sclerosis who were MOG-IgG/IgA seronegative. Further, most patients with isolated MOG-IgA presented clinical attacks after recent infection or vaccination (7/11 [64%]). Conclusion and Relevance: In this study, MOG-specific IgA was identified in a subgroup of patients who were double-seronegative for AQP4-/MOG-IgG, suggesting that MOG-IgA may be a novel diagnostic biomarker for patients with CNS demyelination.

Proposal for Investigating Self-Efficacy in Mathematics Using a Portable EEG System.

The present research proposal focuses on the search for the relation-ship between self-efficacy in mathematics, performance in mathematical tests, cognitive function during solving mathematical problems, and characteristics of the participants. The purpose of this study is to clarify the role of neurocognitive findings in the interpretation of perceived mathematical self-efficacy and, in addition, to investigate to what extent can neurophysiological data complement findings from socio-cognitive research and thus enrich general cognitive theories for mathematics education. The proposed research will use data from different datasets (questionnaire, neurophysiological, and biometric measurements). For the EEG measures the MUSE 2 portable EEG system will be used. The proposed study attempts to investigate (a) if there is a correlation between overall math self-efficacy scores and brain function during math problem-solving, (b) if there is a correlation between high self-efficacy and high math test performance, and (c) how math self-efficacy relates to participants' demographic characteristics and perceived math self-efficacy before and after the experiment.

Genetic differentiation following recent domestication events: A study of farmed Nile tilapia (Oreochromis niloticus) populations.

Nile tilapia (Oreochromis niloticus) is among the most farmed finfish worldwide, distributed across different environmental conditions. Its wide distribution has mainly been facilitated by several breeding programs and widespread dissemination of genetically improved strains. In the first Nile tilapia study exploiting a whole-genome pooled sequencing (Poolseq) approach, we identified the genetic structure and signatures of selection in diverse, farmed Nile tilapia populations, with a particular focus on the GIFT strain, developed in the 1980s, and currently managed by WorldFish (GIFTw). We also investigated important farmed strains from The Philippines and Africa. Using both SNP array data and Poolseq SNPs, we characterized the population structure of these samples. We observed the greatest separation between the Asian and African populations and greater admixture in the Asian populations than in the African ones. We also established that the SNP array data were able to successfully resolve relationships between these diverse Nile tilapia populations. The Poolseq data identified genomic regions with high levels of differentiation (F ST) between GIFTw and the other populations. Gene ontology terms associated with mesoderm development were significantly enriched in the genes located in these regions. A region on chromosome Oni06 was genetically differentiated in pairwise comparisons between GIFTw and all other populations. This region contains genes associated with muscle-related traits and overlaps with a previously published QTL for fillet yield, suggesting that these traits may have been direct targets for selection on GIFT. A nearby region was also identified using XP-EHH to detect genomic differentiation using the SNP array data. Genomic regions with high or extended homozygosity within each population were also identified. This study provides putative genomic landmarks associated with the recent domestication process in several Nile tilapia populations, which could help to inform their genetic management and improvement.

Leclercia adecarboxylata in Peritoneal Dialysis Patients: A Systematic Review.

Background:Leclercia adecarboxylata is a Gram-negative bacillus that can rarely cause infections in humans. We recently treated a case of peritonitis due to L. adecarboxylata in a peritoneal dialysis (PD) pediatric patient, and we systematically reviewed all the relevant reported cases in the literature. Methods: We searched the PubMed and Scopus databases, and we reviewed 13 such cases (2 children, 11 adults) that were reported, including our patient. Results: The mean (±SE) age was 53.2 ± 22.5 years, with a male-to-female ratio of approximately 1:1.6. Their mean vintage period on PD prior to L. adecarboxylata peritonitis was 37.5 ± 25.3 months. The VITEK card was the identification diagnostic tool in most cases (63%). The antimicrobial agent that was most frequently used was ceftazidime, which was implemented in 50% of cases as initial therapy, either as a monotherapy or combination therapy; in only two patients (15.3%) was the Tenkhoff catheter removed. The median duration of treatment was 18 days (range of 10-21 days), and all 13 patients that were reviewed were healed. Conclusions: Physicians should be aware that L. adecarboxylata is noted to rarely cause peritonitis in PD patients; however, this pathogen seems to be sensitive to most antimicrobial agents and can result in a favorable outcome with the selection of appropriate treatment.

Understanding host response to infectious salmon anaemia virus in an Atlantic salmon cell line using single-cell RNA sequencing.

BACKGROUND: Infectious Salmon Anaemia Virus (ISAV) is an Orthomixovirus that represents a large problem for salmonid aquaculture worldwide. Current prevention and treatment methods are only partially effective. Genetic selection and genome engineering have the potential to develop ISAV resistant salmon stocks. Both strategies can benefit from an improved understanding of the genomic regulation of ISAV pathogenesis. Here, we used single-cell RNA sequencing of an Atlantic salmon cell line to provide the first high dimensional insight into the transcriptional landscape that underpins host-virus interaction during early ISAV infection. RESULTS: Salmon head kidney (SHK-1) cells were single-cell RNA sequenced at 24, 48 and 96 h post-ISAV challenge. At 24 h post infection, cells showed expression signatures consistent with viral entry, with genes such as PI3K, FAK or JNK being upregulated relative to uninfected cells. At 48 and 96 h, infected cells showed a clear anti-viral response, characterised by the expression of IFNA2 or IRF2. Uninfected bystander cells at 48 and 96 h also showed clear transcriptional differences, potentially suggesting paracrine signalling from infected cells. These bystander cells expressed pathways such as mRNA sensing, RNA degradation, ubiquitination or proteasome; and up-regulation of mitochondrial ribosome genes also seemed to play a role in the host response to the infection. Correlation between viral and host genes revealed novel genes potentially key for this fish-virus interaction. CONCLUSIONS: This study has increased our understanding of the cellular response of Atlantic salmon during ISAV infection and revealed host-virus interactions at the cellular level. Our results highlight various potential key genes in this host-virus interaction, which can be manipulated in future functional studies to increase the resistance of Atlantic salmon to ISAV.

Evaluation of frequency, severity, and independent risk factors for recurrence of disease activity after fingolimod discontinuation in a large real-world cohort of patients with multiple sclerosis.

Background: Clinical and radiological signs of recurring disease activity (RDA) have been described in patients with multiple sclerosis (pwMS) after discontinuation of fingolimod (FGL). Objective: To describe frequency, severity and potential risk factors for RDA after FGL discontinuation in a large real-world cohort of pwMS. Methods: Post-FGL RDA was defined as evidence of clinical and/or radiological activity within 6 months after FGL discontinuation. Relapses with Expanded Disability Status Scale increase ⩾2 points and/or magnetic resonance imaging (MRI) activity with at least five cerebral gadolinium-enhancing lesions and/or ⩾6 cerebral new T2 lesions were defined as severe recurring disease activity (sRDA). Using a multivariate logistic model, we explored the influence of age, disease duration, sex, clinical, and MRI activity under FGL on the occurrence of RDA. Results: We identified 110 pwMS who discontinued FGL. Thirty-seven (33.6%) developed post-FGL RDA and 13 (11.8%) also fulfilled criteria for sRDA. Younger age at diagnosis [odds ratio (OR) = 1.10, p < 0.01], shorter disease duration (OR = 1.17, p < 0.01), and MRI activity under FGL (OR = 2.92, p = 0.046) were independent risk factors for the occurrence of post-FGL RDA. Conclusion: Individual risk assessment and optimal treatment sequencing can help to minimize the risk of post-FGL RDA. Early switch to highly effective disease-modifying therapy might reduce occurrence of post-FGL RDA.

Optical coherence tomography reflects clinically relevant gray matter damage in patients with multiple sclerosis.

BACKGROUND: Retinal degeneration leading to optical coherence tomography (OCT) changes is frequent in patients with multiple sclerosis (PwMS). OBJECTIVE: To investigate associations among OCT changes, MRI measurements of global and regional brain volume loss, and physical and cognitive impairment in PwMS. METHODS: 95 PwMS and 52 healthy controls underwent OCT and MRI examinations. Mean peripapillary retinal nerve fiber layer (pRNFL) thickness and ganglion cell/inner plexiform layer (GCIPL) volume were measured. In PwMS disability was quantified with the Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT). Associations between OCT, MRI, and clinical measures were investigated with multivariable regression models. RESULTS: In PwMS, pRNFL and GCIPL were associated with the volume of whole brain (p < 0.04), total gray matter (p < 0.002), thalamus (p ≤ 0.04), and cerebral cortex (p ≤ 0.003) -both globally and regionally-, but not white matter. pRNFL and GCIPL were also inversely associated with T2-lesion volume (T2LV), especially in the optic radiations (p < 0.0001). The brain volumes associated with EDSS and SDMT significantly overlapped with those correlating with pRNFL and GCIPL. CONCLUSIONS: In PwMS, pRNFL and GCIPL reflect the integrity of clinically-relevant gray matter structures, underling the value of OCT measures as markers of neurodegeneration and disability in multiple sclerosis.

Nasal eosinophilia as a preliminary discriminative biomarker of non-allergic rhinitis in every day clinical pediatric practice.

BACKGROUND: Non-allergic rhinitis (NAR) in children, named local allergic rhinitis (LAR) and non-allergic rhinitis with eosinophilia syndrome (NARES), are recently termed entities in childhood characterized by symptoms suggestive of allergic rhinitis in the absence of systemic atopy. Nasal eosinophils (nEo) are the principal cells involved in the allergy inflammation and nasal allergen provocation test is the gold standard method for the diagnosis, albeit with several limitations. The aim of this study was to validate the presence of nEo in combination with the therapeutic response to nasal steroids, as a preliminary discriminator of NAR in real life data. METHODS: In a prospective cohort study, 128 children (63.3% male, aged 72 ± 42 m) with history of NAR were enrolled and followed up for 52 ± 32 m. Nasal cytology was performed and nasal steroids trial was recommended initially in all and repeatedly in relapsing cases. Response to therapy was clinically evaluated using 10-VAS. RESULTS: Significant nEo was found in 59.3% of the cases and was related to reported dyspnea episodes. 23.4% had no response to therapy, whereas 51.5% were constantly good responders. Response to therapy was related to nEo and a cutoff point of 20% was defined as the most reliable biological marker with 94% sensitivity and 77% specificity. CONCLUSIONS: In children with symptoms of NAR, the presence of nEo > 20% constantly responding to nasal steroid therapy, is a clear indicator of atopy. In an everyday clinical setting, it emerged as an easy, preliminary, cell biomarker suggestive of further investigation such as NAPT, to discriminate LAR from NARES.

Transcriptomic response to ISAV infection in the gills, head kidney and spleen of resistant and susceptible Atlantic salmon.

BACKGROUND: Infectious Salmon Anaemia virus (ISAV) is an orthomyxovirus responsible for large losses in Atlantic salmon (Salmo salar) aquaculture. Current available treatments and vaccines are not fully effective, and therefore selective breeding to produce ISAV-resistant strains of Atlantic salmon is a high priority for the industry. Genomic selection and potentially genome editing can be applied to enhance the disease resistance of aquaculture stocks, and both approaches can benefit from increased knowledge on the genomic mechanisms of resistance to ISAV. To improve our understanding of the mechanisms underlying resistance to ISAV in Atlantic salmon we performed a transcriptomic study in ISAV-infected salmon with contrasting levels of resistance to this virus. RESULTS: Three different tissues (gills, head kidney and spleen) were collected on 12 resistant and 12 susceptible fish at three timepoints (pre-challenge, 7 and 14 days post challenge) and RNA sequenced. The transcriptomes of infected and non-infected fish and of resistant and susceptible fish were compared at each timepoint. The results show that the responses to ISAV are organ-specific; an important response to the infection was observed in the head kidney, with up-regulation of immune processes such as interferon and NLR pathways, while in gills and spleen the response was more moderate. In addition to immune related genes, our results suggest that other processes such as ubiquitination and ribosomal processing are important during early infection with ISAV. Moreover, the comparison between resistant and susceptible fish has also highlighted some interesting genes related to ubiquitination, intracellular transport and the inflammasome. CONCLUSIONS: Atlantic salmon infection by ISAV revealed an organ-specific response, implying differential function during the infection. An immune response was observed in the head kidney in these early timepoints, while gills and spleen showed modest responses in comparison. Comparison between resistance and susceptible samples have highlighted genes of interest for further studies, for instance those related to ubiquitination or the inflammasome.

Trace elements in edible tissues of elasmobranchs from the North Aegean Sea (Eastern Mediterranean) and potential risks from consumption.

Trace elements have the potential to bioaccumulate in marine organisms and to biomagnify towards the upper levels of marine trophic webs, resulting in a range of negative effects on organisms. Elasmobranchs are highly susceptible to bioaccumulation of trace metals, while their consumption by humans is increasing worldwide. Therefore, it is important to monitor the trace metal content in the edible tissues of elasmobranchs. This work reveals the content of 12 trace metals in the edible tissues of 10 elasmobranch species caught in Greek waters. Levels above the permissible limits for Hg and Pb were found in some species, while analysis of the lifetime consumption risk for adults and children using the Target Hazard Quotient (THQ), revealed a high risk for two of the most toxic substances on the priority list for substances, namely As and Hg. These are preliminary results, and further research is required to understand better the issue.

Normative Data and Conversion Equation for Spectral-Domain Optical Coherence Tomography in an International Healthy Control Cohort.

BACKGROUND: Spectral-domain (SD-) optical coherence tomography (OCT) can reliably measure axonal (peripapillary retinal nerve fiber layer [pRNFL]) and neuronal (macular ganglion cell + inner plexiform layer [GCIPL]) thinning in the retina. Measurements from 2 commonly used SD-OCT devices are often pooled together in multiple sclerosis (MS) studies and clinical trials despite software and segmentation algorithm differences; however, individual pRNFL and GCIPL thickness measurements are not interchangeable between devices. In some circumstances, such as in the absence of a consistent OCT segmentation algorithm across platforms, a conversion equation to transform measurements between devices may be useful to facilitate pooling of data. The availability of normative data for SD-OCT measurements is limited by the lack of a large representative world-wide sample across various ages and ethnicities. Larger international studies that evaluate the effects of age, sex, and race/ethnicity on SD-OCT measurements in healthy control participants are needed to provide normative values that reflect these demographic subgroups to provide comparisons to MS retinal degeneration. METHODS: Participants were part of an 11-site collaboration within the International Multiple Sclerosis Visual System (IMSVISUAL) consortium. SD-OCT was performed by a trained technician for healthy control subjects using Spectralis or Cirrus SD-OCT devices. Peripapillary pRNFL and GCIPL thicknesses were measured on one or both devices. Automated segmentation protocols, in conjunction with manual inspection and correction of lines delineating retinal layers, were used. A conversion equation was developed using structural equation modeling, accounting for clustering, with healthy control data from one site where participants were scanned on both devices on the same day. Normative values were evaluated, with the entire cohort, for pRNFL and GCIPL thicknesses for each decade of age, by sex, and across racial groups using generalized estimating equation (GEE) models, accounting for clustering and adjusting for within-patient, intereye correlations. Change-point analyses were performed to determine at what age pRNFL and GCIPL thicknesses exhibit accelerated rates of decline. RESULTS: The healthy control cohort (n = 546) was 54% male and had a wide distribution of ages, ranging from 18 to 87 years, with a mean (SD) age of 39.3 (14.6) years. Based on 346 control participants at a single site, the conversion equation for pRNFL was Cirrus = -5.0 + (1.0 × Spectralis global value). Based on 228 controls, the equation for GCIPL was Cirrus = -4.5 + (0.9 × Spectralis global value). Standard error was 0.02 for both equations. After the age of 40 years, there was a decline of -2.4 µm per decade in pRNFL thickness ( P < 0.001, GEE models adjusting for sex, race, and country) and -1.4 µm per decade in GCIPL thickness ( P < 0.001). There was a small difference in pRNFL thickness based on sex, with female participants having slightly higher thickness (2.6 µm, P = 0.003). There was no association between GCIPL thickness and sex. Likewise, there was no association between race/ethnicity and pRNFL or GCIPL thicknesses. CONCLUSIONS: A conversion factor may be required when using data that are derived between different SD-OCT platforms in clinical trials and observational studies; this is particularly true for smaller cross-sectional studies or when a consistent segmentation algorithm is not available. The above conversion equations can be used when pooling data from Spectralis and Cirrus SD-OCT devices for pRNFL and GCIPL thicknesses. A faster decline in retinal thickness may occur after the age of 40 years, even in the absence of significant differences across racial groups.