Altered gene expression and spongiotrophoblast differentiation in placenta from a mouse model of diabetes in pregnancy

Aims/hypothesis  

Pregnancies complicated by diabetes have a higher risk of adverse outcomes for mothers and children, including predisposition to disease later in life, e.g. metabolic syndrome and hypertension. We hypothesised that adverse outcomes from diabetic pregnancies may be linked to compromised placental function, and sought to identify cellular and molecular abnormalities in diabetic placenta.     

The majority of infiltrating CD8 T lymphocytes in multiple sclerosis lesions is insensitive to enhanced PD-L1 levels on CNS cells

Central nervous system (CNS) cells locally modulate immune responses using numerous molecules that are not fully elucidated. Engagement of programmed death-1 (PD-1), expressed on activated T cells, by its ligands (PD-L1 or PD-L2) suppresses T-cell responses. Enhanced CNS PD-1 and PD-L1 expression has been documented in inflammatory murine models; however, human CNS data are still incomplete. We determined that human primary cultures of astrocytes, microglia, oligodendrocytes, or neurons expressed low or undetectable PD-L1 under basal conditions, but inflammatory cytokines significantly induced such expression, especially on astrocytes and microglia. Blocking PD-L1 expression in astrocytes using specific siRNA led to significantly increased CD8 T-cell responses (proliferation, cytokines, lytic enzyme). Thus, our results establish that inflamed human glial cells can express sufficient and functional PD-L1 to inhibit CD8 T cell responses. Extensive immunohistochemical analysis of postmortem brain tissues demonstrated a significantly greater PD-L1 expression in multiple sclerosis (MS) lesions compared with control tissues, which colocalized with astrocyte or microglia/macrophage cell markers. However, more than half of infiltrating CD8 T lymphocytes in MS lesions did not express PD-1, the cognate receptor. Thus, our results demonstrate that inflamed human CNS cells such as in MS lesions express significantly elevated PD-L1, providing a means to reduce CD8 T cell responses, but most of these infiltrating immune cells are devoid of PD-1 and thus insensitive to PD-L1/L2. Strategies aimed at inducing PD-1 on deleterious activated human CD8 T cells that are devoid of this receptor could provide therapeutic benefits since PD-L1 is already increased in the target organ.     

Association of non‐syndromic macrocephaly with autism

Harlequin ichthyosis, (MIM 242500), is a rare, autosomal recessive skin disorder due to an inborn error of epidermal keratinization. The gene for this condition has not been localized. We present a case of HI in which there was a de novo deletion of chromosome 18q: the karyotype was 46, XY, del(18)(q21.3). We postulate that the gene for HI may lie at, or distal to 18q21.3 and that the deletion observed in this case may have unmasked this autosomal recessive disorder. © 2001 Wiley‐Liss, Inc.     

Paradoxical nasal obstruction.

The phenomenon of paradoxical nasal obstruction is described. An understanding of this phenomenon is made possible by the knowledge of the nasal cycle and of the concept of total nasal airway resistance. These topics are reviewed and two patients with paradoxical nasal obstruction are described. Direct observation, rhinomanometric tests and serial tomograms were utilized to substantiate these findings.     

3D printed versus conventionally cured provisional crown and bridge dental materials

Objectives

To optimize the 3D printing of a dental material for provisional crown and bridge restorations using a low-cost stereolithography 3D printer; and compare its mechanical properties against conventionally cured provisional dental materials.

Innovative Uses of Technology in Online Midwifery Education

Women's health care in the United States is at a critical juncture. There is increased demand for primary care providers, including women's health specialists such as certified nurse‐midwives/certified midwives, women's health nurse practitioners, and obstetrician‐gynecologists, yet shortages in numbers of these providers are expected. This deficit in the number of women's health care providers could have adverse consequences for women and their newborns when women have to travel long distances to access maternity health care. Online education using innovative technologies and evidence‐based teaching and learning strategies have the potential to increase the number of health care providers in several disciplines, including midwifery. This article reviews 3 innovative uses of online platforms for midwifery education: virtual classrooms, unfolding case studies, and online return demonstrations of clinical skills. These examples of innovative teaching strategies can promote critical and creative thinking and enhance competence in skills. Their use in online education can help enhance the student experience. More students, including those who live in rural and underserved regions and who otherwise might be unable to attend a traditional onsite campus, are provided the opportunity to complete quality midwifery education through online programs, which in turn may help expand the women's health care provider workforce. This article is part of a special series of articles that address midwifery innovations in clinical practice, education, interprofessional collaboration, health policy, and global health.     

Stillbirth in Canada: anachronistic definition and registration processes impede public health surveillance and clinical care

The archaic definition and registration processes for stillbirth currently prevalent in Canada impede both clinical care and public health. The situation is fraught because of definitional problems related to the inclusion of induced abortions at ≥20 weeks’ gestation as stillbirths: widespread uptake of prenatal diagnosis and induced abortion for serious congenital anomalies has resulted in an artefactual temporal increase in stillbirth rates in Canada and placed the country in an unfavourable position in international (stillbirth) rankings. Other problems with the Canadian stillbirth definition and registration processes extend to the inclusion of fetal reductions (for multi-fetal pregnancy) as stillbirths, and the use of inconsistent viability criteria for reporting stillbirth. This paper reviews the history of stillbirth registration in Canada, provides a rationale for updating the definition of fetal death and recommends a new definition and improved processes for fetal death registration. The recommendations proposed are intended to serve as a starting point for reformulating issues related to stillbirth, with the hope that building a consensus regarding a definition and registration procedures will facilitate clinical care and public health.