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IntroductionMyeloid cells trafficking from the periphery to the central nervous system are key players in multiple sclerosis (MS) through antigen presentation, cytokine secretion and repair processes.MethodsCombination of mass cytometry on blood cells from 60 MS patients at diagnosis and 29 healthy controls, along with single cell RNA sequencing on paired blood and cerebrospinal fluid (CSF) samples from 5 MS patients were used for myeloid cells detailing.ResultsMyeloid compartment study demonstrated an enrichment of a peculiar classical monocyte population in 22% of MS patients at the time of diagnosis. Notably, this patients’ subgroup exhibited a more aggressive disease phenotype two years post-diagnosis. This monocytic population, detected in both the CSF and blood, was characterized by CD206, CD209, CCR5 and CCR2 expression, and was found to be more frequent in MS patients carrying the HLA-DRB1*15:01 allele. Furthermore, pathways analysis predicted that these cells had antigen presentation capabilities coupled with pro-inflammatory phenotype.DiscussionAltogether, these results point toward the amplification of a specific and pathogenic myeloid cell subset in MS patients with genetic susceptibilities.

IntroductionFollicular Lymphoma (FL) results from the malignant transformation of germinal center (GC) B cells. FL B cells display recurrent and diverse genetic alterations, some of them favoring their direct interaction with their cell microenvironment, including follicular helper T cells (Tfh). Although FL-Tfh key role is well-documented, the impact of their regulatory counterpart, the follicular regulatory T cell (Tfr) compartment, is still sparse.MethodsThe aim of this study was to characterize FL-Tfr phenotype by cytometry, gene expression profile, FL-Tfr origin by transcriptomic analysis, and functionality by in vitro assays.ResultsCD4+CXCR5+CD25hiICOS+ FL-Tfr displayed a regulatory program that is close to classical regulatory T cell (Treg) program, at the transcriptomic and methylome levels. Accordingly, Tfr imprinting stigmata were found on FL-Tfh and FL-B cells, compared to their physiological counterparts. In addition, FL-Tfr co-culture with autologous FL-Tfh or cytotoxic FL-CD8+ T cells inhibited their proliferation in vitro. Finally, although FL-Tfr shared many characteristics with Treg, TCR sequencing analyses demonstrated that part of them derived from precursors shared with FL-Tfh. DiscussionAltogether, these findings uncover the role and origin of a Tfr subset in FL niche and may be useful for lymphomagenesis knowledge and therapeutic management.

Multiple sclerosis (MS) is an immune-driven demyelinating disease of the central nervous system. Immune cell features are particularly promising as predictive biomarkers due to their central role in the pathogenesis but also as drug targets, even if nowadays, they have no impact in clinical practice. Recently, high-resolution approaches, such as mass cytometry (CyTOF), helped to better understand the diversity and functions of the immune system. In this study, we performed an exploratory analysis of blood immune response profiles in healthy controls and MS patients sampled at their first neurological relapse, using two large CyTOF panels including 62 markers exploring myeloid and lymphoid cells. An increased abundance of both a T-bet-expressing B cell subset and a CD206+ classical monocyte subset was detected in the blood of early MS patients. Moreover, T-bet-expressing B cells tended to be enriched in aggressive MS patients. This study provides new insights into understanding the pathophysiology of MS and the identification of immunological biomarkers. Further studies will be required to validate these results and to determine the exact role of the identified clusters in neuroinflammation.

Fibroblastic reticular cells (FRCs) are the specialized lymphoid stromal cells initially identified as triggering T-cell recruitment and dynamic motion in secondary lymphoid organs. Interestingly, FRCs also display antigen presentation capacities and support lymphocyte survival. CXCR5+CD4+ follicular T cells are important players of B-cell maturation and antibody response. Our study reported that in vitro-differentiated FRC-like cells enhanced the growth of the whole CXCR5+CD4+ T-cell compartment, while enhancing IL-4 secretion specifically by the PD1dimCXCR5+CD4+ cell subset, in a Notch- and ICAM1/LFA1-dependent manner. In addition, we revealed that in follicular lymphoma (FL) tissues, previously identified as enriched for PD1hiCXCR5hiCD4+ mature follicular helper T cells, PD1dimCXCR5+CD4+ T cells displayed an enrichment for Notch and integrin gene signatures, and a Notch and ICAM-1-dependent overexpression of IL-4 compared to their non-malignant counterparts. These findings suggest that the crosstalk between FRCs and CXCR5+PD1dimCD4+ T cells may contribute to the FL IL-4 rich environment, thus providing new insights in FL lymphomagenesis.

The notion of a classic education has been lost as technology continues to morph into the essential component of 21st Century and as educators also rise to the challenge of teaching the most diverse population of learners in American history. Literacy has shifted to include the vital “visual literacy”, the critical analysis of images, which in the past might have been an artistic pleasure as opposed to a fundamental educational skill. In this paper, I discuss this required change in the expectations of the English pedagogy. To encourage cross-curricular ties, I recommend that educators use the ancestors of today’s current magazine as a visual literacy genre, particularly political serials such as Labor Defender and New Pioneer to reach the high learning goals of visual literacy while strengthening cultural values and ideals of social action.

For more accurate estimation of the global burden of pregnancy associated disease, clarity is needed on definition and assessment of non-severe maternal morbidity. Our study aimed to define maternal morbidity with clear criteria for identification at primary care level and estimate the distribution of and evaluate associations between physical (infective and non-infective) and psychological morbidities in two different low-income countries.Cross sectional study with assessment of morbidity in early pregnancy (34%), late pregnancy (35%) and the postnatal period (31%) among 3459 women from two rural communities in Pakistan (1727) and Malawi (1732). Trained health care providers at primary care level used semi-structured questionnaires documenting signs and symptoms, clinical examination and laboratory tests which were bundled to reflect infectious, non-infectious and psychological morbidity.One in 10 women in Malawi and 1 in 5 in Pakistan reported a previous pregnancy complication with 1 in 10 overall reporting a previous neonatal death or stillbirth. In the index pregnancy, 50.1% of women in Malawi and 53% in Pakistan were assessed to have at least one morbidity (infective or non-infective). Both infective (Pakistan) and non-infective morbidity (Pakistan and Malawi) was lower in the postnatal period than during pregnancy. Multiple morbidities were uncommon ( 9. Complications during a previous pregnancy, infective morbidity (p

BackgroundAssessment of risk factors for preterm birth in a population with high incidence of preterm birth and HIV infection.MethodsSecondary analysis of data for 2,149 women included in a community based randomized placebo controlled trial for the prevention of preterm birth (APPLe trial (ISRCTN84023116) with gestational age at birth determined through ultrasound measurement in early pregnancy. Multivariate Logistic Regression analyses to obtain models for three outcome variables: all preterm, early preterm, and late preterm birth.FindingsNo statistical differences were noted for the prevalence of HIV infection (p = 0.30) or syphilis (p = 0.12) between women who delivered preterm versus term. BMI (Adjusted OR 0.91 (0.85-0.97); p = 0.005) and weight gain (Adjusted OR 0.89 (0.82-0.97); p = 0.006) had an independent, protective effect. Previous preterm birth doubled the odds of preterm birth (Adjusted OR 2.13 (1.198-3.80); p = 0.01). Persistent malaria (despite malaria prophylaxis) increased the risk of late preterm birth (Adjusted OR 1.99 (1.05-3.79); p = 0.04). Age ConclusionsDespite claims that HIV infection is an important cause of preterm birth in Africa, we found no evidence of an association in this population (unexposed to anti-retroviral treatment). Persistent malaria was associated with late preterm birth. Maternal undernourishment and anemia were independently associated with early preterm birth. The study did not assess whether the link was direct or whether a common precursor such as chronic infection was responsible for both maternal effects and early labour.