Inhibition of the BMP Signaling Pathway Ameliorated Established Clinical Symptoms of Experimental Autoimmune Encephalomyelitis

Bone morphogenetic proteins (BMPs) are secreted growth factors that belong to the transforming growth factor beta superfamily. BMPs have been implicated in physiological processes, but they are also involved in many pathological conditions. Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS); however, its etiology remains elusive. Some evidence points to BMPs as important players in the pathogenesis of inflammatory and autoimmune disorders. In the present work, we studied the expression of BMP2, BMP4, BMP5, BMP6, BMP7, BMP type II receptor, and noggin in the immune system during different phases of experimental autoimmune encephalomyelitis (EAE). Major changes in the expression of BMPs took place in the initial phases of EAE. Indeed, those changes mainly affected BMP6 (whose expression was abrogated), BMP2, and BMP7 (whose expression was increased). In addition, we showed that in vivo inhibition of the BMP signaling pathway with small molecules ameliorated the already established clinical symptoms of EAE, as well as the CNS histopathological features. At the immune level, we observed an expansion of plasmacytoid dendritic cells (pDCs) in mice treated with small molecules that inhibit the BMP signaling pathway. pDCs could play an important role in promoting the expansion of antigen-specific regulatory T cells. Altogether, our data suggest a role for BMPs in early immune events that take place in myelin oligodendrocyte glycoprotein (MOG)-induced EAE. In addition, the clinical outcome of the disease was improved when the BMP signaling pathway was inhibited in mice that presented established EAE symptoms.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00885-8) contains supplementary material, which is available to authorized users.     

Left‐handed musicians show a higher probability of atypical cerebral dominance for language

Music processing and right hemispheric language lateralization share a common network in the right auditory cortex and its frontal connections. Given that the development of hemispheric language dominance takes place over several years, this study tested whether musicianship could increase the probability of observing right language dominance in left‐handers. Using a classic fMRI language paradigm, results showed that atypical lateralization was more predominant in musicians (40%) than in nonmusicians (5%). Comparison of left‐handers with typical left and atypical right lateralization revealed that: (a) atypical cases presented a thicker right pars triangularis and more gyrified left Heschl's gyrus; and (b) the right pars triangularis of atypical cases showed a stronger intra‐hemispheric functional connectivity with the right angular gyrus, but a weaker interhemispheric functional connectivity with part of the left Broca's area. Thus, musicianship is the first known factor related to a higher prevalence of atypical language dominance in healthy left‐handed individuals. We suggest that differences in the frontal and temporal cortex might act as shared predisposing factors to both musicianship and atypical language lateralization.     

Geometrical Measurement of Central Tumor Location in cT1N0M0 NSCLC Predicts N1 but Not N2 Upstaging

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Molecular profiling refines minimal residual disease‐based prognostic assessment in adults with Philadelphia chromosome‐negative B‐cell precursor acute lymphoblastic leukemia

Minimal residual disease (MRD) assessment is an essential tool in contemporary acute lymphoblastic leukemia (ALL) protocols, being used for therapeutic decisions such as hematopoietic stem cell transplantation in high‐risk patients. However, a significant proportion of adult ALL patients with negative MRD still relapse suggesting that other factors (ie, molecular alterations) must be considered in order to identify those patients with high risk of disease progression. We have identified partial IKZF1 gene deletions and CDKN2A/B deletions as markers of disease recurrence and poor survival in a series of uniformly treated adolescent and adult Philadelphia chromosome‐negative B‐cell progenitor ALL patients treated according to the Programa Español de Tratamientos en Hematología protocols. Importantly, CDKN2A/B deletions showed independent significance of MRD at the end of induction, which points out the need for treatment intensification in these patients despite being MRD‐negative after induction therapy.     

Bilateral bifid mandibular condyle: case report and literature review

Bifid mandibular condyle is an infrequent and normally asymptomatic morphological alteration of the mandibular condyle. Although the underlying cause is not clear, a number of theories have been proposed, including teratogenic effects in the embryo, vascular alterations during condyle development, and condylar remodeling following fracture. Since Schier first described this anomaly in 1948 in live individuals, further cases have been documented in the literature. We present a new case of bilateral bifid condyle. The disorder was asymptomatic and constituted a casual finding in a young male presenting for the surgical extraction of two impacted molars.     

Rationale and Methodology of the SARAH Trial: Long-Term Cardiovascular Outcomes in Patients With Resistant Hypertension and Obstructive Sleep Apnea

Introduction

Patients with resistant hypertension (RH) have a high risk of developing cardiovascular events; therefore, new therapeutic approaches to better control blood pressure may be useful in improving cardiovascular outcomes. The prevalence of obstructive sleep apnea (OSA) is very high among patients with RH. Continuous positive airway pressure (CPAP) has been shown to be an effective treatment for reducing blood pressure in patients with RH. Nevertheless, the long-term effect of CPAP treatment on cardiovascular outcomes has not been explored.The main objective of the SARAH study is to assess the impact of OSA and its treatment on cardiovascular outcomes (morbidity and mortality) in patients with RH.