Generalized,severe epidermolysis bullosa simplex caused by a Keratin 5 p.E477K mutation

Epidermolysis bullosa simplex (EBS) is a skin fragility disorder resulting from mutations of structural proteins in the epidermis. We provide a brief report of long‐term survival and reproduction in a mother with EBS due to keratin 5 (KRT5) c.1429G > A (p.E477K) mutation, which causes a particularly severe form of the disease.     

Alterations in Breast Cancer Biomarkers Following Neoadjuvant Therapy

Annals of Surgical Oncology - Biomarker changes in patients with residual disease (RD) after neoadjuvant systemic therapy (NAT) have unclear consequences. This study examined the prevalence of...     

Comparison of multiple oncotype DX® from the same patient

For women with breast cancer in whom multiple Oncotype DX^® Recurrence Scores (RS) are obtained, RS concordance utilizing current NCCN recommendations has not been evaluated. Patients with two or more RS were identified. RS were stratified by NCCN guidelines and compared for concordance. Twenty-four patients were evaluated. RS concordance varied by tumor type: 100% in the same tumor, 91.7% in multiple ipsilateral tumors, 71.4% in contralateral tumors, and 66.7% in in-breast recurrent tumors. RS concordance for multiple assays in the same patient is not high enough to omit Oncotype DX^® testing for each tumor.     

How do women interpret abortion information they find online?

ObjectiveWe sought to assess how women interpret the information they find online about the overall safety and risk of infertility associated with abortion and cesarean delivery (CD).MethodsWe conducted an exploratory, prospective study tracking the internet searches of 100 reproductive-aged individuals who identify as women. We directed participants to search for information about either (1) whether surgical abortion or CD is safe or (2) the risk of infertility following surgical abortion or CD. Our data collection had 3 phases: baseline survey, directed internet search, and a postsearch survey. We analyzed participants’ pre- and postsurvey responses using bivariate tests and analyzed within-subject changes. We evaluated the sites they visited based on expert ratings of site content based on trustworthiness and slant.ResultsWomen perceived abortion as safer and less likely to cause infertility after their web searches than before (70% perceived abortion in the United States as very/completely safe presearch vs 92% postsearch; p < 0.02). Women's perceptions about CD did not change. Participants sought information from web pages that experts largely deemed trustworthy and lacking in slant.ConclusionsWomen's perceptions about abortion safety and risk can be influenced by information they find online; perceptions about CD safety and risk may be less influenced by online information.ImplicationsDisseminating high quality, user-friendly abortion information on highly ranked and easily findable websites can help women find evidence-based information and influence knowledge about abortion.     

Evidence for regulatory diversity and auto-regulation at the TAC1 locus in sensory neurones

The neuropeptide substance-P (SP) is expressed from the TAC1 gene in sensory neurones where it acts as a key modulator of neurogenic inflammation. The promoter of TAC1 (TAC1prom) plays a central role in the regulation of the TAC1 gene but requires the presence of a second regulatory element; ECR2, to support TAC1 expression in sensory neurones and to respond appropriately to signalling pathways such as MAPkinases and noxious induction by capsaicin. We examined whether the effect of capsaicin on ECR2-TAC1prom activity in larger diameter neurones was cell autonomous or non- cell autonomous. We demonstrate that TRPV1 is not expressed in all the same cells as SP following capsaicin induction suggesting the presence of a non-cell autonomous mechanism for TAC1 up-regulation following capsaicin induction. In addition, we demonstrate that induction of SP and ECR1-TAC1prom activity in these larger diameter neurones can be induced by potassium depolarisation suggesting that, in addition to capsaicin induction, transgene activity may be modulated by voltage gated calcium channels. Furthermore, we show that NK1 is expressed in all SP- expressing cells after capsaicin induction and that an agonist of NK1 can activate both SP and the transgene in larger diameter neurones. These observations suggest the presence of an autocrine loop that controls the expression of the TAC1 promoter in sensory neurones. In contrast, induction of the TAC1 promoter by LPS was not dependent on ECR2 and did not occur in large diameter neurones. These studies demonstrate the diversity of mechanisms modulating the activity of the TAC1 promoter and provide novel directions for the development of new anti-inflammatory therapies.     

Capabilities Approach: Contextualizing Participants’ Perspectives on Systems Barriers to Recovery

Mental health resources are designed to facilitate recovery for adults with psychiatric disabilities. Two participants of an autovideography intervention described systems barriers to recovery. Researchers employed narrative analysis, guided by the capabilities approach, to evaluate how participants storied their experiences. Participants made meaning from encounters with barriers in ways that oppose the spirit and advancement of recovery while engendering adaptive preferences. Findings indicate that inadequate resources attenuate wellbeing by increasing barriers that actively oppose recovery, and positive reframing of unaccommodating environments reinforces adaptive preferences and incapacity. Adequate resources are essential for successful recovery transformation within the mental health system.     

T‐cell receptor profiling in cancer

Immunosequencing is a platform technology that allows the enumeration, specification and quantification of each and every B‐ and/or T‐cell in any biologic sample of interest. Thus, it provides an assessment of the level and distribution of all the clonal lymphocytes in any sample, and allows “tracking” of a single clone or multiple clones of interest over time or from tissue to tissue within a given patient. It is based on bias‐controlled multiplex PCR and high‐throughput sequencing, and it is highly accurate, standardized, and sensitive. In this review, we provide evidence that immunosequencing is becoming an important analytic tool for the emerging field of immune‐oncology, and describe several applications of this approach, including the assessment of residual disease post therapy in lymphoid malignancies, the prediction of response to immunotherapeutics of solid tumors containing tumor infiltrating lymphocytes, the identification of clonal responses in vaccination, infectious disease, bone marrow reconstitution, and autoimmunity, and the exploration of whether there are population‐based stereotyped responses to certain exposures or interventions.