Microscopic fractional anisotropy outperforms multiple sclerosis lesion assessment and clinical outcome associations over standard fractional anisotropy tensor.

We aimed to compare the ability of diffusion tensor imaging and multi-compartment spherical mean technique to detect focal tissue damage and in distinguishing between different connectivity patterns associated with varying clinical outcomes in multiple sclerosis (MS). Seventy-six people diagnosed with MS were scanned using a SIEMENS Prisma Fit 3T magnetic resonance imaging (MRI), employing both conventional (T1w and fluid-attenuated inversion recovery) and advanced diffusion MRI sequences from which fractional anisotropy (FA) and microscopic FA (µFA) maps were generated. Using automated fiber quantification (AFQ), we assessed diffusion profiles across multiple white matter (WM) pathways to measure the sensitivity of anisotropy diffusion metrics in detecting localized tissue damage. In parallel, we analyzed structural brain connectivity in a specific patient cohort to fully grasp its relationships with cognitive and physical clinical outcomes. This evaluation comprehensively considered different patient categories, including cognitively preserved (CP), mild cognitive deficits (MCD), and cognitively impaired (CI) for cognitive assessment, as well as groups distinguished by physical impact: those with mild disability (Expanded Disability Status Scale [EDSS] <=3) and those with moderate-severe disability (EDSS >3). In our initial objective, we employed Ridge regression to forecast the presence of focal MS lesions, comparing the performance of µFA and FA. µFA exhibited a stronger association with tissue damage and a higher predictive precision for focal MS lesions across the tracts, achieving an R-squared value of .57, significantly outperforming the R-squared value of .24 for FA (p-value <.001). In structural connectivity, µFA exhibited more pronounced differences than FA in response to alteration in both cognitive and physical clinical scores in terms of effect size and number of connections. Regarding cognitive groups, FA differences between CP and MCD groups were limited to 0.5% of connections, mainly around the thalamus, while µFA revealed changes in 2.5% of connections. In the CP and CI group comparison, which have noticeable cognitive differences, the disparity was 5.6% for FA values and 32.5% for µFA. Similarly, µFA outperformed FA in detecting WM changes between the MCD and CI groups, with 5% versus 0.3% of connections, respectively. When analyzing structural connectivity between physical disability groups, µFA still demonstrated superior performance over FA, disclosing a 2.1% difference in connectivity between regions closely associated with physical disability in MS. In contrast, FA spotted a few regions, comprising only 0.6% of total connections. In summary, µFA emerged as a more effective tool than FA in predicting MS lesions and identifying structural changes across patients with different degrees of cognitive and global disability, offering deeper insights into the complexities of MS-related impairments.

A metabolic readout of the urine metabolome of COVID-19 patients.

Analysis of urine samples from COVID-19 patients by 1H NMR reveals important metabolic alterations due to SAR-CoV-2 infection. Previous studies have identified biomarkers in urine that reflect metabolic alterations in COVID-19 patients. We have used 1H NMR to better define these metabolic alterations since this technique allows us to obtain a broad profile of the metabolites present in urine. This technique offers the advantage that sample preparation is very simple and gives us very complete information on the metabolites present. To detect these alterations, we have compared urine samples from COVID-19 patients (n = 35) with healthy people (n = 18). We used unsupervised (Robust PCA) and supervised (PLS-LDA) multivariate analysis methods to evaluate the differences between the two groups: COVID-19 and healthy controls. The differences focus on a group of metabolites related to energy metabolism (glucose, ketone bodies, glycine, creatinine, and citrate) and other processes related to bacterial flora (TMAO and formic acid) and detoxification (hippuric acid). The alterations in the urinary metabolome shown in this work indicate that SARS-CoV-2 causes a metabolic change from a normal situation of glucose consumption towards a gluconeogenic situation and possible insulin resistance.

Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study.

OBJECTIVE: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). METHODS: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. RESULTS: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. CONCLUSION: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS.

Risk factors for potentially avoidable readmissions following gynecologic oncology surgery.

OBJECTIVE: Determine the incidence and identify factors associated with potentially avoidable hospital readmissions due to uncontrolled symptoms or minor complications after surgery for gynecologic cancers. METHODS: Women who underwent major abdominal or pelvic surgery for a gynecologic malignancy between 2015 and 2017 were identified from the National Surgical Quality Improvement Program targeted hysterectomy dataset. Hospital readmissions within 30 days of surgery were categorized as indicated readmissions or potentially avoidable readmissions by three independent reviewers. Demographic, clinical, and operative covariates were evaluated to determine their association with type of readmission using bivariable tests and adjusted multinomial logistic regression models. RESULTS: A total of 20,986 women were identified. 19,814 (94.4%) were not readmitted, 894 (4.3%) were indicated readmissions, and 278 (1.3%) were potentially avoidable readmissions. Among those readmitted, 24% were potentially avoidable readmissions. Presence of ascites, increasing length of stay, and discharge to facility were associated with an increased risk of indicated and potentially avoidable readmissions. Age < 60 years old (RR 1.4, 95%CI 1.1-1.8), BMI ≥ 30 (RR 1.7, 95%CI 1.3-2.3), history of abdominal/pelvic surgery (RR 1.6, 95%CI 1.2-2.1), cervical cancer (RR 2.1, 95%CI 1.4-3.1), and open surgery (RR 2.1, 95%CI 1.4-3.2) were associated with an increased risk of a potentially avoidable readmission but not with increased risk of an indicated readmission. Median time to readmission did not differ between the two readmission groups (indicated = 8 days; avoidable = 7 days; p = .72). CONCLUSIONS: Among women with gynecologic cancer, 24% of all unplanned readmissions were attributed to uncontrolled symptoms or minor complications that were potentially avoidable. Age <60 years old, history of previous abdominal/pelvic surgery, obesity, cervical cancer, and open surgery were associated with an increase in risk of a potentially avoidable readmission.

No association between migraine frequency, white matter lesions and silent brain infarctions: a study in a series of women with chronic migraine.

BACKGROUND AND PURPOSE: It has been suggested that silent infarctions (SIs) and hyperintense white matter lesions (WMLs) are related to migraine frequency. We studied their prevalence and anatomical distribution in patients with chronic migraine (CM). METHODS: A total of 96 women with CM [mean age 43 (range 16-65) years] and 29 women with episodic migraine (EM) [mean age 36 (range 16-58) years] underwent 1.5-T magnetic resonance imaging following the CAMERA protocol. The number, size and location of SIs and deep WMLs were recorded and a modified Fazekas scale was applied to assess periventricular WMLs. RESULTS: White matter lesions were found in 59 (61.5%) women with CM and 17 (58.6%) women with EM (odds ratio, 1.13; 95% confidence intervals, 0.48-2.62; P = 0.784). The majority (63% CM and 71% EM) were small deep WMLs. Exclusive periventricular WMLs were exceptional. Of the 739 WMLs seen in patients with CM, 734 (99.3%) were hemispheric and mostly frontal (81%). Posterior fossa WMLs were seen in only five (5.2%) women with CM (always in the pons) and two (6.9%) women with EM. Age >45 years was the only vascular risk factor associated with a higher WML number (median: 0 < 45 years and 3 > 45 years; P = 0.004). We found seven SIs in six women with CM (6.3%). CONCLUSIONS: As compared with the expected prevalence at this age, this study confirms that the prevalence of WMLs, in most cases small, deep and frontal, was increased in CM and EM. However, our results do not support an association of WMLs or SIs with a higher frequency of attacks, but with the presence of vascular risk factors and mainly age >45 years.

Influence of microbiology on endodontic failure. Literature review.

BACKGROUND: The main cause of endodontic failure is the persistence of microorganisms that cause an intraradicular or extratradicular infection and that become resistant to disinfection measures. The objective of this review is to identify the microbiota associated with endodontic failure, as well as the reasons why these microorganisms are capable of surviving basic disinfection measures. MATERIAL AND METHODS: Systematic search of scientific articles in the databases PubMed with the following keywords "Endodontic Infections", "Endodontic Microbiology", "Endodontic Failure", "Enterococcus Faecalis", "Endodontics Retreatment" was carried out. Case reports and articles with publication date prior to 2000 were not included in this review. RESULTS: Most authors highlight E. faecalis as the main microorganism associated with endodontic failure, nevertheless there are recent studies that isolate, to a greater extent, other bacteria such as Fusobacterium nucleatum and Propionibacterium. DISCUSSION: These microorganisms have in common the following proprieties, which make them able to escape the disinfection measures: the ability to form a biofilm, to locate in areas unreachable to root canal instrumentation techniques, synergism, the ability to express survival genes and activate alternative metabolic pathways.

MOG encephalomyelitis: international recommendations on diagnosis and antibody testing.

Over the past few years, new-generation cell-based assays have demonstrated a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations. Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). Owing to a substantial overlap in clinicoradiological presentation, MOG-EM was often unwittingly misdiagnosed as MS in the past. Accordingly, increasing numbers of patients with suspected or established MS are currently being tested for MOG-IgG. However, screening of large unselected cohorts for rare biomarkers can significantly reduce the positive predictive value of a test. To lessen the hazard of overdiagnosing MOG-EM, which may lead to inappropriate treatment, more selective criteria for MOG-IgG testing are urgently needed. In this paper, we propose indications for MOG-IgG testing based on expert consensus. In addition, we give a list of conditions atypical for MOG-EM ("red flags") that should prompt physicians to challenge a positive MOG-IgG test result. Finally, we provide recommendations regarding assay methodology, specimen sampling and data interpretation.

[MOG encephalomyelitis: international recommendations on diagnosis and antibody testing]. / MOG-Enzephalomyelitis: Internationale Empfehlungen zu Diagnose und Antikörpertestung.

Over the past few years, new-generation cell-based assays have demonstrated a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations. Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). Owing to a substantial overlap in clinicoradiological presentation, MOG-EM was often unwittingly misdiagnosed as MS in the past. Accordingly, increasing numbers of patients with suspected or established MS are currently being tested for MOG-IgG. However, screening of large unselected cohorts for rare biomarkers can significantly reduce the positive predictive value of a test. To lessen the hazard of overdiagnosing MOG-EM, which may lead to inappropriate treatment, more selective criteria for MOG-IgG testing are urgently needed. In this paper, we propose indications for MOG-IgG testing based on expert consensus. In addition, we give a list of conditions atypical for MOG-EM ("red flags") that should prompt physicians to challenge a positive MOG-IgG test result. Finally, we provide recommendations regarding assay methodology, specimen sampling and data interpretation, and propose for the first time diagnostic criteria for MOG-EM.

Marginal and Internal Gap of Handmade, Milled and 3D Printed Additive Manufactured Patterns for Pressed Lithium Disilicate Onlay Restorations.

STATEMENT OF THE PROBLEM: On a pressed lithium disilicate restoration, the building up of a wax pattern of the future restoration is a necessary step on the fabrication process. Conventionally, a wax pattern can be produced by handmade or milled procedures; however, the development of additive manufacturing technologies allows a new fabrication method. PURPOSE: The present study measured the marginal and internal gap of handmade, milled and additive manufactured patterns for an onlay restoration. MATERIAL AND METHODS: A preparation of an onlay restoration was made on an extracted mandibular tooth. A definitive cast was fabricated from a conventional silicone impression of the prepared tooth. Three groups were established: handmade (HM), milled (ML) and additive manufactured (AM); 4 specimens per group were obtained. The marginal and internal gap of each pattern was measured on the extracted molar through a computed tomography test. Sixty measurements were done to measure the marginal gap and another 60 measurements were calculated to analyze the internal gap on each pattern on the prepared tooth. A total of 1.440 measurements were completed. Mann-Whitney and Turkey statistical tests were used for pairwise comparison. RESULTS: The mean of the marginal and internal gap was of 67.56 ± 6.08 µm and 80.62 ± 3.26 µm for the HM group, 85.28 ± 2.17 µm and 96 ± 1.97 µm for the ML group and 86.49 ± 1.74 µm and 91.86 ± 2.88 µm for the AM group, respectively. The HM group presented significantly lower marginal (p=0.029) and internal (p=0.029) gap compared to the ML and AM groups. There was no statistical significant difference (p=0.486) on the marginal gap between the ML and the AM groups, but the AM group, showed significantly (p=0.029) smaller internal gap than the ML group. CONCLUSIONS: All the groups presented less than 100 µm marginal and internal gap, which is a considered clinically acceptable. CLINICAL IMPLICATIONS: The three fabrication processes are viable option for manufacturing patterns for lithium disilicate onlay restorations, but the best marginal and internal fit was still obtained by the conventional handmade procedures.

Phase Transition, Dielectric Properties, and Ionic Transport in the [(CH3)2NH2]PbI3 Organic-Inorganic Hybrid with 2H-Hexagonal Perovskite Structure.

In this work, we focus on [(CH3)2NH2]PbI3, a member of the [AmineH]PbI3 series of hybrid organic-inorganic compounds, reporting a very easy mechanosynthesis route for its preparation at room temperature. We report that this [(CH3)2NH2]PbI3 compound with 2H-perovskite structure experiences a first-order transition at ≈250 K from hexagonal symmetry P63/mmc (HT phase) to monoclinic symmetry P21/c (LT phase), which involves two cooperative processes: an off-center shift of the Pb2+ cations and an order-disorder process of the N atoms of the DMA cations. Very interestingly, this compound shows a dielectric anomaly associated with the structural phase transition. Additionally, this compound displays very large values of the dielectric constant at room temperature because of the appearance of a certain conductivity and the activation of extrinsic contributions, as demonstrated by impedance spectroscopy. The large optical band gap displayed by this material (Eg = 2.59 eV) rules out the possibility that the observed conductivity can be electronic and points to ionic conductivity, as confirmed by density functional theory calculations that indicate that the lowest activation energy of 0.68 eV corresponds to the iodine anions, and suggests the most favorable diffusion paths for these anions. The obtained results thus indicate that [(CH3)2NH2]PbI3 is an electronic insulator and an ionic conductor, where the electronic conductivity is disfavored because of the low dimensionality of the [(CH3)2NH2]PbI3 structure.

Effectiveness of an intervention to prevent frailty in pre-frail community-dwelling older people consulting in primary care: a randomised controlled trial.

Background: evidence on the effectiveness of interventions to prevent frailty is scarce. Objective: to assess the effect of an intervention in preventing frailty progression in pre-frail older people. Study design: a randomised, open label, controlled trial with two parallel arms. Population: community-dwelling pre-frail older people (≥70 years) consulting in primary care. Intervention: nutritional assessment (and derivation to a Nutritional Unit for usual care in the event of nutritional risk) and a physical activity programme including aerobic exercise and a set of mixed strengthening, balance and coordination exercises. Control group: patients receiving the usual care. Main outcome measure: prevalence of frailty (Fried criteria) at 12 months. Secondary outcomes measures: functional capacity (Barthel index), falls and nutritional status (Short-Form Mini Nutritional Assessment) on follow-up at 12 months. Results: one hundred and seventy-two participants were recruited and randomised (mean age: 78.3 years; mean number of Fried criteria: 1.45). Thirty-nine participants (22.6%) were dropped out during the study. At follow-up, 4.9% of the intervention group and 15.3% of the control group had evolved to frailty, for a crude odds ratio (OR) of 0.29 (95% confidence interval [CI]: 0.08-1.08; P = 0.052) and an adjusted (by age, gender and number of co-morbidities) OR of 0.19 (95% CI: 0.04-0.95; P = 0.044). Intervention group showed a higher outdoors walking hour per day (0.97 versus 0.73; P = 0.019) but no difference was observed in muscle strength, gait speed or other functional indicators. Conclusion: an intervention focused on physical exercise and maintaining good nutritional status may be effective in preventing frailty in community-dwelling pre-frail older individuals. ClinicalTrials.gov identifier: NCT02138968.

Similar biological effect of high-dose oral versus intravenous methylprednisolone in multiple sclerosis relapses.

UNLABELLED: Our aim was to investigate differences in immune mechanisms in multiple sclerosis (MS) relapse, after high-dose oral methylprednisolone (oMP) or intravenous methylprednisolone (ivMP). We measured serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and IFN-γ) in 39 of 49 MS patients with moderate-severe relapse, whom were treated with ivMP or oMP in a placebo-controlled, non-inferiority clinical trial. We assessed these cytokine levels at baseline and at 1 and 4 weeks post-treatment. The cytokine levels between oMP and ivMP were similar at any time. Proinflammatory cytokines (IL-6 and IFN-γ) were significantly decreased in both groups at week 1 (p = 0.05 / p = 0.03) and at week 4 (p = 0.04 / p = 0.05). This study provides further confirmatory evidence that oMP is not inferior to ivMP. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00753792.

Neuromyelitis optica and multiple sclerosis: Seeing differences through optical coherence tomography.

Neuromyelitis optica (NMO) is an inflammatory autoimmune disease of the central nervous system that preferentially targets the optic nerves and spinal cord. The clinical presentation may suggest multiple sclerosis (MS), but a highly specific serum autoantibody against the astrocytic water channel aquaporin-4 present in up to 80% of NMO patients enables distinction from MS. Optic neuritis may occur in either condition resulting in neuro-anatomical retinal changes. Optical coherence tomography (OCT) has become a useful tool for analyzing retinal damage both in MS and NMO. Numerous studies showed that optic neuritis in NMO typically results in more severe retinal nerve fiber layer (RNFL) and ganglion cell layer thinning and more frequent development of microcystic macular edema than in MS. Furthermore, while patients' RNFL thinning also occurs in the absence of optic neuritis in MS, subclinical damage seems to be rare in NMO. Thus, OCT might be useful in differentiating NMO from MS and serve as an outcome parameter in clinical studies.

Therapeutic compliance of first line disease-modifying therapies in patients with multiple sclerosis. COMPLIANCE Study.

INTRODUCTION: Non-adherence to disease-modifying therapies (DMTs) in multiple sclerosis may be associated with reduced efficacy. We assessed compliance, the reasons for non-compliance, treatment satisfaction, and quality of life (QoL) of patients treated with first-line therapies. METHODS: A cross-sectional, multicenter study was conducted that included relapsing multiple sclerosis patients. Compliance in the past month was assessed using Morisky-Green test. Seasonal compliance and reasons for non-compliance were assessed by an ad-hoc questionnaire. Treatment satisfaction and QoL were evaluated by means of TSQM and PRIMUS questionnaires. RESULTS: A total of 220 patients were evaluated (91% relapsing-remitting); the mean age was 39.1 years, 70% were female, and the average time under treatment was 5.4 years. Subcutaneous interferon (IFN) ß-1b was used in 23% of the patients, intramuscular IFN ß-1a in 21%, subcutaneous IFN ß-1a in 37%, and with glatiramer acetate in 19%. The overall compliance was 75%, with no significant differences related to the therapy, and 81% did not report any seasonal variation. Compliant patients had significantly lower disability scores and time of diagnosis, and greater satisfaction with treatment and its effectiveness. Discomfort and flu-like symptoms were the most frequent reasons for non-compliance. The satisfaction and QoL were associated with less disability and number of therapeutic switches. CONCLUSIONS: The rate of compliance, satisfaction and QoL in multiple sclerosis patients under DMTs is high, especially for those newly diagnosed, less disabled, and with fewer therapeutic switches. Discomfort and flu-like symptoms associated with injected therapies significantly affect adherence.

Changes in B and T-cell subsets and NMO-IgG levels after immunoglobulins and rituximab treatment for an acute attack of neuromyelitis optica.

BACKGROUND: There is increasing evidence supporting that neuromyelitis optica (NMO) is an inflammatory humoral mediated disorder associated with NMO-IgG/AQP-4 antibodies. However, little is known about the subsets of B cells and T cells that contribute to the pathogenesis or therapy response. OBJECTIVES: To describe the clinical and immunological changes associated with intravenous immunoglobulins (IV-Igs) plus rituximab (RTX) in a patient with a severe acute attack of NMO and intrathecal synthesis of NMO-IgG/AQP-4, who previously did not respond to intravenous methylprednisolone and plasma exchange. METHODS: We sequentially analysed the levels of NMO-IgG/AQP-4 by immunohistochemistry, and B and T cells subsets by multiparametric flow-cytometry, in the CSF and peripheral blood (PB), before and alter IV-Igs plus RTX therapy. RESULTS: In the CSF before treatment, and compared with PB, there was a higher percentage of CD4(+) T cells and a lower percentage of CD8(+) T cells and CD19(+) B cells. After therapy, the percentage of CD4(+) T cells remained high, and that of CD8(+) T cells increased. The observed decrease in the percentage of CD19(+) B cells was lower than in the PB. When the CSF was compared, it was found that the percentage of effector-memory and effector CD8(+) T cells had increased after therapy, and that of IgM memory B cells and switched-memory B cells decreased. The observed changes paralleled the decrease of NMO-IgG/AQP-4 results to negative and the clinical improvement. CONCLUSIONS: Our findings confirm that, besides intrathecal humoral immune response against AQP4, B and T cell subsets are involved in the modulation of inflammation within and outside the central nervous system.

Spanish consensus on the use of natalizumab (Tysabri®)-2013.

INTRODUCTION: Natalizumab treatment has been shown to be very efficacious in clinical trials and very effective in clinical practice in patients with relapsing-remitting multiple sclerosis, by reducing relapses, slowing disease progression, and improving magnetic resonance imaging patterns. However, the drug has also been associated with a risk of progressive multifocal leukoencephalopathy (PML). The first consensus statement on natalizumab use, published in 2011, has been updated to include new data on diagnostic procedures, monitoring for patients undergoing treatment, PML management, and other topics of interest including the management of patients discontinuing natalizumab. MATERIAL AND METHODS: This updated version followed the method used in the first consensus. A group of Spanish experts in multiple sclerosis (the authors of the present document) reviewed all currently available literature on natalizumab and identified the relevant topics would need updating based on their clinical experience. The initial draft passed through review cycles until the final version was completed. RESULTS AND CONCLUSIONS: Studies in clinical practice have demonstrated that changing to natalizumab is more effective than switching between immunomodulators. They favour early treatment with natalizumab rather than using natalizumab in a later stage as a rescue therapy. Although the drug is very effective, its potential adverse effects need to be considered, with particular attention to the patient's likelihood of developing PML. The neurologist should carefully explain the risks and benefits of the treatment, comparing them to the risks of multiple sclerosis in terms the patient can understand. Before treatment is started, laboratory tests and magnetic resonance images should be available to permit proper follow-up. The risk of PML should be stratified as high, medium, or low according to presence or absence of anti-JC virus antibodies, history of immunosuppressive therapy, and treatment duration. Although the presence of anti-JC virus antibodies is a significant finding, it should not be considered an absolute contraindication for natalizumab. This update provides general recommendations, but neurologists must use their clinical expertise to provide personalised follow-up for each patient.

A randomized clinical trial of oral versus intravenous methylprednisolone for relapse of MS.

BACKGROUND: Steroids improve multiple sclerosis (MS) relapses but therapeutic window and dose, frequency and administration route remain uncertain. OBJECTIVE: The objective of this paper is to compare the clinical and radiologic efficacy, tolerability and safety of intravenous methylprednisolone (ivMP) vs oral methylprednisolone (oMP), at equivalent high doses, for MS relapse. METHODS: Forty-nine patients with moderate or severe relapse within the previous 15 days were randomized in a double-blind, noninferiority, multicenter trial to receive ivMP or oMP and their matching placebos. Expanded Disability Status Scale (EDSS) scores were determined at baseline and weeks 1, 4 and 12. Brain MRI were assessed at baseline and at weeks 1 and 4. Primary endpoint was a noninferiority assessment of EDSS improvement at four weeks (noninferiority margin of one point), with further key efficacy assessments of number and volume of T1 gadolinium-enhancing (Gd+), and new or enlarged T2 lesions at four weeks' post-treatment initiation. Secondary outcomes were safety and tolerability. RESULTS: The study achieved the main outcome of noninferiority at four weeks for improved EDSS score. No differences were found between ivMP and oMP in the number of Gd+ lesions (0 (0-1) vs 0 (0-0.5), p = 0.630), volume of Gd+ lesions (0 (0-88.0) vs 0 (0-32.9) mm(3), p = 0.735), or new or enlarged T2 lesions (0 (0-194) vs 0 (0-123), p = 0.769). MP was well tolerated, and no serious adverse events were reported. CONCLUSIONS: This study provides confirmatory evidence that oMP is not inferior to ivMP in reducing EDSS, similar in MRI lesions at four weeks for MS relapses and is equally well tolerated and safe. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00753792.

[Neuroimaging follow-up of cerebral aneurysms treated with endovascular techniques]. / Seguimiento mediante técnicas de neuroimagen de los aneurismas cerebrales tratados por vía endovascular.

There are no specific recommendations in clinical guidelines about the best time, imaging tests, or intervals for following up patients with intracranial aneurysms treated with endovascular techniques. We reviewed the literature, using the following keywords to search in the main medical databases: cerebral aneurysm, coils, endovascular procedure, and follow-up. Within the Cerebrovascular Disease Group of the Spanish Society of Neuroradiology, we aimed to propose recommendations and an orientative protocol based on the scientific evidence for using neuroimaging to monitor intracranial aneurysms that have been treated with endovascular techniques. We aimed to specify the most appropriate neuroimaging techniques, the interval, the time of follow-up, and the best approach to defining the imaging findings, with the ultimate goal of improving clinical outcomes while optimizing and rationalizing the use of available resources.

Investigating the effectiveness of a new indoor ventilation model in reducing the spread of disease: A case of sports centres amid the COVID-19 pandemic.

The ventilation of buildings is crucial to ensure indoor health, especially when demanding physical activities are carried out indoors, and the pandemic has highlighted the need to develop new management methods to ensure adequate ventilation. In Spain, there are no specific ventilation regulations to prevent the spread of pathogens such as the coronavirus. Therefore, it is necessary to have a theoretical tool for calculating occupancy to maintain sports facilities in optimal safety conditions. The proposed theoretical method is based on the analysis of mathematical expressions from European standardisation documents and uses the concentration of CO2 as a bioeffluent. It is also based on the concept of background and critical concentration, which allows its application to be extrapolated to future crises caused by pathogens. This study presents a unique and novel dataset for sports centres. For this purpose, the calculation methods were applied to the data set provided by Mostoles City Council, Spain, during the pandemic years with the highest incidence of COVID-19, when the government introduced the assimilation of COVID-19 sick leave to occupational accidents. The data on this type of sick leave provided by the City Council correspond to the period between March 2020 and February 2022. Similarly, the data on the average use of sports facilities by activity, provided by the Sports Department, correspond to the years 2020 and 2021. In this way, it was possible to verify the effectiveness in preventing the spread of any type of coronavirus. In conclusion, the implementation of a theoretical occupancy calculation method based on the concentration of carbon dioxide as a bioeffluent can be an effective tool for the management of future crises caused by pathogens or hazardous chemicals in the air, and demonstrated its effectiveness in sports centres such as gyms, sports fields, and indoor swimming pools during the COVID-19 pandemic.

Magnetic ionic plastic crystal: choline[FeCl4].

A novel organic ionic plastic crystal (OIPC) based on a quaternary ammonium cation and a tetrachloroferrate anion has been synthesized with the intention of combining the properties of the ionic plastic crystal and the magnetism originating from the iron incorporated in the anion. The thermal analysis of the obtained OIPC showed a solid-solid phase transition below room temperature and a high melting point above 220 °C, indicating their plastic crystalline behaviour over a wide temperature range, as well as thermal stability up to approximately 200 °C. The magnetization measurements show the presence of three-dimensional antiferromagnetic ordering below 4 K. The results from electrochemical characterization display a solid-state ionic conduction sufficiently high and stable (between 10(-2.7) and 10(-3.6) S cm(-1) from 20 to 180 °C) for electrochemical applications.