What Women With Disabilities Write in Personal Blogs About Pregnancy and Early Motherhood: Qualitative Analysis of Blogs.

BackgroundMore than 1 in 10 women of reproductive age identify as having some type of disability. Most of these women are able to become pregnant and have similar desires for motherhood as women without disability. Women with disability, however, face greater stigma and stereotyping, additional risk factors, and may be less likely to receive adequate reproductive health care compared with their peers without disability. More and more individuals, including those with disability, are utilizing the internet to seek information and peer support. Blogs are one source of peer-to-peer social media engagement that may provide a forum for women with disability to both share and obtain peer-to-peer information and support. Nevertheless, it is not clear what content about reproductive health and pregnancy and/or motherhood is featured in personal blogs authored by women with spinal cord injury (SCI), traumatic brain injury (TBI), spina bifida, and autism.ObjectiveThe objective of this study was twofold: (1) to examine the information being shared in blogs by women with 4 types of disabilities, namely, SCI, TBI, spina bifida, and autism, about reproductive health, disability, health care, pregnancy, and motherhood; and (2) to classify the content of reproductive health experiences addressed by bloggers to better understand what they viewed as important.MethodsPersonal blogs were identified by searching Google with keywords related to disabilities, SCI, TBI, spina bifida, and autism, and a variety of keywords related to reproductive health. The first 10 pages of each database search in Google, based on the relevance of the search terms, were reviewed and all blogs in these pages were included. Blog inclusion criteria were as follows: (1) written by a woman or care partner (ie, parent or spouse) of a woman with a self-identified diagnosis of SCI, TBI, spina bifida, or autism; (2) focused on the personal experience of health and health care during the prepregnancy, prenatal, antepartum, intrapartum, and/or postpartum periods; (3) written in English; and (4) published between 2013 and 2017. A descriptive and thematic qualitative analysis of blogs and corresponding comments was facilitated with NVivo software and matrix analysis.ResultsOur search strategy identified 125 blogs that met all the inclusion criteria; no blogs written by women with spina bifida were identified. We identified 4 reproductive health themes featured in the blog of women with disabilities: (1) (in)accessible motherhood, (2) (un)supportive others, (3) different, but not different, and (4) society questioning motherhood.ConclusionsThis analysis of personal blogs about pregnancy and health care written by women with SCI, TBI, and autism provides a glimpse into their experiences. The challenges faced by these women and the adaptations they made to successfully navigate pregnancy and early motherhood provide insights that can be used to shape future research

Mapping genomic and transcriptomic alterations spatially in epithelial cells adjacent to human breast carcinoma.

Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells. To address this we created a unique dataset of epithelial samples ductoscopically obtained from ducts leading to breast carcinomas and matched samples from ducts on the opposite side of the nipple. Here, we demonstrate that perturbations in mRNA abundance, with increasing proximity to tumour, cannot be explained by copy number aberrations. Rather, we find a possibility of field cancerization surrounding the primary tumour by constructing a classifier that evaluates where epithelial samples were obtained relative to a tumour (cross-validated micro-averaged AUC = 0.74). We implement a spectral co-clustering algorithm to define biclusters. Relating to over-represented bicluster pathways, we further validate two genes with tissue microarrays and in vitro experiments. We highlight evidence suggesting that bicluster perturbation occurs early in tumour development

Transitions in general practice training : quantifying epidemiological variation in trainees' experiences and clinical behaviours

Background: General Practice training in Australia is delivered through the apprenticeship model. General Practice supervisors support trainees transitioning from hospital-based work towards competent independent community-based practice. The timing and manner in which support should be provided is still not well understood. This study aimed to establish the variation in clinical and educational experiences and behaviours, and location, of general practice trainees’ consultations by stage of their vocational training. It was hypothesised that change is greater in earlier stages of training. Methods: A cross-sectional analysis of data (2010–2018) from the Registrar Clinical Encounters in Training (ReCEnT) study, an ongoing cohort study of Australian GP registrars’ in-consultation clinical and educational experience and behaviours. Multinomial logistic regression assessed the association of demographic, educational, and clinical factors in different stages of training. The outcome factor was the training term. Results: Two thousand four hundred sixteen registrars contributed data for 321,414 patient consultations. For several important variables (seeing patients with chronic disease; new patients; seeking in-consultation information or assistance; ordering pathology and imaging; and working in a small or regional practice), odds ratios were considerably greater for comparisons of Term 1 and 3, relative to comparisons of Term 2 and 3. Conclusion: Differences experienced in demographic, clinical and educational factors are significantly more pronounced earlier in registrars’ training. This funding has educational and training implications with respect to resource allocation, trainee supervision and curriculum design. Sociocultural learning theory enables an understanding of the impact of transitions on, and how to support, general practice trainees and supervisors

Objective physical activity and physical performance in middle-aged and older adults

Background: Older adults may have difficulty meeting the Physical Activity (PA) Guidelines. A favorable balance between PA and sedentary time (SED) is an important determinant of physical performance in older adults. Our objective was to explore associations of PA/SED with physical performance across mid-older age in adults without overt mobility disability. Methods: Framingham Offspring Study participants free of mobility disability with accelerometry and physical performance data (gait speed, chair stand time, and handgrip strength), were studied in cross-sectional analysis (n = 1352). We regressed physical performance on PA level, measured using steps, moderate to vigorous (MV)PA and SED. We stratified by age groups, adjusted for covariates, and modelled MVPA and SED separately and together as predictors. Results: Only 38% of adults 50–64 years and 15% of adults ≥75 years met the PA Guidelines (i.e., 150 min MVPA per week). Individuals achieving at least 5 min/day of MVPA had 0.062 ± 0.013 m/s greater gait speed and better chair stands and handgrip strength (in women) than those with 0.05). For adults ≥75 years, every 5000 more steps/day related to ~0.045 m/s greater gait speed (p = 0.006). Conclusion: Our cross-sectional study demonstrated that, across mid-older adulthood, MVPA related to better physical performance, but in adults ≥75 years, total steps walked associated with better gait speed. These data warrant future research on the impact of PA on physical performance and health outcomes in older age

Immunolocalization of NLRP3 Inflammasome in Normal Murine Airway Epithelium and Changes following Induction of Ovalbumin-Induced Airway Inflammation

Little is known about innate immunity and components of inflammasomes in airway epithelium. This study evaluated immunohistological evidence for NLRP3 inflammasomes in normal and inflamed murine (Balb/c) airway epithelium in a model of ovalbumin (OVA) induced allergic airway inflammation. The airway epithelium of control mice exhibited strong cytoplasmic staining for total caspase-1, ASC, and NLRP3, whereas the OVA mice exhibited strong staining for active caspase-1, with redistribution of caspase-1, IL-1β and IL-18, indicating possible activation of the NLRP3 inflammasome. Active caspase-1, NLRP3, and other inflammasome components were also detected in tissue eosinophils from OVA mice, and may potentially contribute to IL-1β and IL-18 production. In whole lung, inRNA expression of NAIP and procaspase-1 was increased in OVA mice, whereas NLRP3, IL-1β and IL-18 decreased. Some OVA-treated mice also had significantly elevated and tightly correlated serum levels of IL-1β and TNFα. In cultured normal human bronchial epithelial cells, LPS priming resulted in a significant increase in NLRP3 and II-lp protein expression. This study is the first to demonstrate NLRP3 inflammasome components in normal airway epithelium and changes with inflammation. We propose activation and/or luminal release of the inflammasome is a feature of allergic airway inflammation which may contribute to disease pathogenesis

Clinical and Molecular Features of Renal and Pheochromocytoma/Paraganglioma Tumor Association Syndrome (RAPTAS): Case Series and Literature Review.

CONTEXT: The co-occurrence of pheochromocytoma (PC) and renal tumors was linked to the inherited familial cancer syndrome von Hippel-Lindau (VHL) disease more than six decades ago. Subsequently, other shared genetic causes of predisposition to renal tumors and to PC, paraganglioma (PGL), or head and neck paraganglioma (HNPGL) have been described, but case series of non-VHL-related cases of renal tumor and pheochromocytoma/paraganglioma tumor association syndrome (RAPTAS) are rare. OBJECTIVE: To determine the clinical and molecular features of non-VHL RAPTAS by literature review and characterization of a case series. DESIGN: A review of the literature was performed and a retrospective study of referrals for investigation of genetic causes of RAPTAS. RESULTS: Literature review revealed evidence of an association, in addition to VHL disease, between germline mutations in SDHB, SDHC, SDHD, TMEM127, and MAX genes and RAPTAS [defined here as the co-occurrence of tumors from both classes (PC/PGL/HNPGL and renal tumors) in the same individual or in first-degree relatives]. In both the literature review and our case series of 22 probands with non-VHL RAPTAS, SDHB mutations were the most frequent cause of non-VHL RAPTAS. A genetic cause was identified in 36.3% (8/22) of kindreds. CONCLUSION: Renal tumors and PC/PGL/HNPGL tumors share common molecular features and their co-occurrence in an individual or family should prompt genetic investigations. We report a case of MAX-associated renal cell carcinoma and confirm the role of TMEM127 mutations with renal cell carcinoma predisposition

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

Metabolic Complementarity and Genomics of the Dual Bacterial Symbiosis of Sharpshooters

Mutualistic intracellular symbiosis between bacteria and insects is a widespread phenomenon that has contributed to the global success of insects. The symbionts, by provisioning nutrients lacking from diets, allow various insects to occupy or dominate ecological niches that might otherwise be unavailable. One such insect is the glassy-winged sharpshooter (Homalodisca coagulata), which feeds on xylem fluid, a diet exceptionally poor in organic nutrients. Phylogenetic studies based on rRNA have shown two types of bacterial symbionts to be coevolving with sharpshooters: the gamma-proteobacterium Baumannia cicadellinicola and the Bacteroidetes species Sulcia muelleri. We report here the sequencing and analysis of the 686,192–base pair genome of B. cicadellinicola and approximately 150 kilobase pairs of the small genome of S. muelleri, both isolated from H. coagulata. Our study, which to our knowledge is the first genomic analysis of an obligate symbiosis involving multiple partners, suggests striking complementarity in the biosynthetic capabilities of the two symbionts: B. cicadellinicola devotes a substantial portion of its genome to the biosynthesis of vitamins and cofactors required by animals and lacks most amino acid biosynthetic pathways, whereas S. muelleri apparently produces most or all of the essential amino acids needed by its host. This finding, along with other results of our genome analysis, suggests the existence of metabolic codependency among the two unrelated endosymbionts and their insect host. This dual symbiosis provides a model case for studying correlated genome evolution and genome reduction involving multiple organisms in an intimate, obligate mutualistic relationship. In addition, our analysis provides insight for the first time into the differences in symbionts between insects (e.g., aphids) that feed on phloem versus those like H. coagulata that feed on xylem. Finally, the genomes of these two symbionts provide potential targets for controlling plant pathogens such as Xylella fastidiosa, a major agroeconomic problem, for which H. coagulata and other sharpshooters serve as vectors of transmission

Transcriptomic evidence that von Economo neurons are regionally specialized extratelencephalic-projecting excitatory neurons.

von Economo neurons (VENs) are bipolar, spindle-shaped neurons restricted to layer 5 of human frontoinsula and anterior cingulate cortex that appear to be selectively vulnerable to neuropsychiatric and neurodegenerative diseases, although little is known about other VEN cellular phenotypes. Single nucleus RNA-sequencing of frontoinsula layer 5 identifies a transcriptomically-defined cell cluster that contained VENs, but also fork cells and a subset of pyramidal neurons. Cross-species alignment of this cell cluster with a well-annotated mouse classification shows strong homology to extratelencephalic (ET) excitatory neurons that project to subcerebral targets. This cluster also shows strong homology to a putative ET cluster in human temporal cortex, but with a strikingly specific regional signature. Together these results suggest that VENs are a regionally distinctive type of ET neuron. Additionally, we describe the first patch clamp recordings of VENs from neurosurgically-resected tissue that show distinctive intrinsic membrane properties relative to neighboring pyramidal neurons