BAFF Index and CXCL13 levels in the cerebrospinal fluid associate respectively with intrathecal IgG synthesis and cortical atrophy in multiple sclerosis at clinical onset

Abstract Background B lymphocytes are thought to play a relevant role in multiple sclerosis (MS) pathology. The in vivo analysis of intrathecally produced B cell-related cytokines may help to clarify the mechanisms of B cell recruitment and immunoglobulin production within the central nervous system (CNS) in MS. Methods Paired cerebrospinal fluid (CSF) and serum specimens from 40 clinically isolated syndrome suggestive of MS or early-onset relapsing-remitting MS patients (CIS/eRRMS) and 17 healthy controls (HC) were analyzed for the intrathecal synthesis of IgG (quantitative formulae and IgG oligoclonal bands, IgGOB), CXCL13, BAFF, and IL-21. 3D-FLAIR, 3D-DIR, and 3D-T1 MRI sequences were applied to evaluate white matter (WM) and gray matter (GM) lesions and global cortical thickness (gCTh). Results Compared to HC, CIS/eRRMS having IgGOB (IgGOB+, 26 patients) had higher intrathecal IgG indexes ( p \u2009<\u20090.01), lower values of BAFF Index (11.9\u2009\ub1\u20096.1 vs 17.5\u2009\ub1\u20095.2, p \u2009<\u20090.01), and higher CSF CXCL13 levels (27.7\u2009\ub1\u200933.5 vs 0.9\u2009\ub1\u20091.5, p \u2009<\u20090.005). In these patients, BAFF Index but not CSF CXCL13 levels inversely correlated with the intrathecal IgG synthesis ( r \u2009>\u20090.5 and p \u2009<\u20090.05 for all correlations). CSF leukocyte counts were significantly higher in IgGOB+ compared to IgGOB\u2212 ( p \u2009<\u20090.05) and HC ( p \u2009<\u20090.01), and correlated to CSF CXCL13 concentrations ( r 0.77, p \u2009<\u20090.001). The gCTh was significantly lower in patients with higher CSF CXCL13 levels (2.41\u2009\ub1\u20090.1 vs 2.49\u2009\ub1\u20090.1\ua0mm, p \u2009<\u20090.05), while no difference in MRI parameters of WM and GM pathology was observed between IgGOB+ and IgGOB\u2212. Conclusions The intrathecal IgG synthesis inversely correlated with BAFF Index and showed no correlation with CSF CXCL13. These findings seem to indicate that intrathecally synthesized IgG are produced by long-term PCs that have entered the CNS from the peripheral blood, rather than produced by PCs developed in the meningeal follicle-like structures (FLS). In this study, CXCL13 identifies a subgroup of MS patients characterized by ..

Direct digital control of an efficient silicon+lequid crystal phase shifter

We demonstrate a phase shifter based on a silicon slot waveguide infiltrated with liquid crystal. We achieve a phase shift of 73 pi for a 5V drive voltage, with a voltage-length product of 0.022V.mm around 1V. We can drive the phase shifter directly with a 1V, duobinary pulse-width-modulated signal, allowing direct digital CMOS control of an analog optical phase shifter

Exposure to Ionizing Radiation Triggers Prolonged Changes in Circular RNA Abundance in the Embryonic Mouse Brain and Primary Neurons

The exposure of mouse embryos in utero and primary cortical neurons to ionizing radiation results in the P53-dependent activation of a subset of genes that is highly induced during brain development and neuronal maturation, a feature that these genes reportedly share with circular RNAs (circRNAs). Interestingly, some of these genes are predicted to express circular transcripts. In this study, we validated the abundance of the circular transcript variants of four P53 target genes (Pvt1, Ano3, Sec14l5, and Rnf169). These circular variants were overall more stable than their linear counterparts. They were furthermore highly enriched in the brain and their transcript levels continuously increase during subsequent developmental stages (from embryonic day 12 until adulthood), while no further increase could be observed for linear mRNAs beyond post-natal day 30. Finally, whereas radiation-induced expression of P53 target mRNAs peaks early after exposure, several of the circRNAs showed prolonged induction in irradiated embryonic mouse brain, primary mouse cortical neurons, and mouse blood. Together, our results indicate that the circRNAs from these P53 target genes are induced in response to radiation and they corroborate the findings that circRNAs may represent bioma

Early Immunotherapy and Longer Corticosteroid Treatment Are Associated With Lower Risk of Relapsing Disease Course in Pediatric MOGAD

Background and Objectives We sought to identify early factors associated with relapse and outcome in paediatric-onset myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD). Methods In a multicenter retrospective cohort of pediatric MOGAD (≤18 years), onset features and treatment were compared in patients with monophasic vs relapsing disease (including cases with follow-up ≥12 months after onset or relapse at any time) and in patients with final Expanded Disability Status Scale (EDSS) 0 vs ≥1 at last follow-up (including cases with followup >3 months after last event or EDSS0 at any time). Multivariable logistic regression models were used to evaluate factors associated with relapsing disease course and EDSS ≥ 1 at final follow-up. Results Seventy-five children were included (median onset age 7 years; median 30 months of follow-up). Presentation with acute disseminated encephalomyelitis was more frequent in children aged 8 years or younger (66.7%, 28/42) than in older patients (30.3%, 10/33) (p = 0.002), whereas presentation with optic neuritis was more common in children older than 8 years (57.6%, 19/33) than in younger patients (21.4%, 9/42) (p = 0.001). 40.0% (26/65) of patients relapsed. Time to first relapse was longer in children aged 8 years or younger than in older patients (median 18 vs 4 months) (p = 0.013). Factors at first event independently associated with lower risk of relapsing disease course were immunotherapy <7 days from onset (6.7-fold reduced odds of relapsing course, OR 0.15, 95% CI 0.03–0.61, p = 0.009), corticosteroid treatment for ≥5 weeks (6.7-fold reduced odds of relapse, OR 0.15, 95% CI 0.03–0.80, p = 0.026), and abnormal optic nerves on onset MRI (12.5-fold reduced odds of relapse, OR 0.08, 95% CI 0.01–0.50, p = 0.007). 21.1% (15/71) had EDSS ≥ 1 at final follow-up. Patients with a relapsing course had a higher proportion of final EDSS ≥ 1 (37.5%, 9/24) than children with monophasic disease (12.8%, 5/39) (p = 0.022, univariate analysis). Each 1-point increment in worst EDSS at onset was independently associated with 6.7-fold increased odds of final EDSS ≥ 1 (OR 6.65, 95% CI 1.33–33.26, p = 0.021). Discussion At first attack of pediatric MOGAD, early immunotherapy, longer duration of corticosteroid treatment, and abnormal optic nerves on MRI seem associated with lower risk of relapse, whereas higher disease severity is associated with greater risk of final disability (EDSS ≥ 1)

Cambio demográfico, migración y salud reproductiva : el papel de las mujeres senegalesas en la constitución de las familias

En aquest paper presentem en primer lloc els trets més característics de la transició de la nupcialitat i de la fecunditat a Senegal fent referència a alguns indicadors de la salut sexual i reproductiva de les dones. A continuació presentem els indicadors que resumeixen la biografia migratòria, nupcial i reproductiva d'un col·lectiu de dones senegaleses que han immigrat a Catalunya i que estan construint les seves famílies a cavall de dues cultures i de dos continents, fent referència entre altres coses a la poligamia, al lloc de naixement i residència dels seus fills i a la utilització de mètodes de planificació familiar. Acabem la comunicació amb algunes reflexions sobre el paper de les dones com agents actius en les decisions en materia de sexualitat i reproducció, en una societat que no és la seva, de la qual agraeixen els serveis de salut públics però sense deixar de banda la seva pròpia concepció de la família i de la salut.En este artículo presentamos en primer lugar los elementos más rellevantes de la transición de la nupcialidad y de la fecundidad en Senegal haciendo referencia a algunos indicadores de salud sexual y reproductiva de las mujeres. A continuación presentamos los indicadores que resumen la biografía migratoria, nupcial y reproductiva de un colectivo de mujeres de Senegal que han inmigrado a Cataluña y que están formando sus familias en el contexto de dos culturas y de dos continentes, haciendo referencia entre otras cosas a la poligamia, al lugar de nacimiento y residencia de sus hijos y a la utilización de métodos de planificación familiar. Finalizamos la comunicación con algunas reflexiones sobre el papel de las mujeres como agentes activos en las decisiones en materia de sexualidad y reproducción, en una sociedad que no es la suya propia, de la que agradecen los servicios de salud públicos pero sin olvidar su propia concepción de la familia y de la salud.In this paper we present the main characteristics from Senegal's nuptuality and fertility transition according to a group of measures related to women's sexual and reproductive health. We then show those indicators that summarise Senegal's women biography in terms of their migration, nuptuality and reproduction for those who have immigrated to Catalunya and have to raise a family between two cultures and two continents. In this way the article makes reference, among other things, to polygamy, the birthplace and residence of their offspring, as well as the existence of family planning. Lastly, we finish this paper with some ideas about the role of Senegal's women making sexual and reproduction decisions in a different society where they can obtain public health services while keeping their own approach to family and health issues

Multiple sclerosis epidemiological trends in Italy highlight the environmental risk factors

Italy is definitely a high-risk country for multiple sclerosis (MS). Over the last 50 years, several epidemiological studies, including longitudinal surveys, have disclosed that MS incidence and prevalence in Italy mainland and Islands (Sardinia and Sicily) have progressively increased, picturing a semi-parabolic curve. Based on the comprehensive scrutiny of 58 papers, we conclude that the latitude risk gradient does not fit to the Italian map of MS. The genetic heterogeneity of the Italian ethnicities, that likely forms the basis of MS predisposition, does not account for the dramatic increase of MS incidence and prevalence observed in Italy over the last half century that, rather, seems better explained by the effect of environmental factors