Nonsexual Acute Genital Ulcerations as a Rare Presentation of Disseminated Lyme Disease in a Pediatric Patient.

Nonsexual acute genital ulcerations (NAGUs), also known as Lipschütz ulcers, are vulvar ulcers occurring predominantly in adolescent females. Although the pathogenesis is unknown, NAGUs are commonly associated with systemic infections. Here, we present a female child with NAGU along with disseminated Lyme disease. We believe this is the first reported pediatric case of this phenomenon.

Frontline therapy of ovarian cancer: trials and tribulations.

PURPOSE OF REVIEW: The current article reviews the advances and challenges in the fight with cancer and the hope for cure, with a focus on clinical trials, at the one time with the best outcomes; first-line therapy. RECENT FINDINGS: To date there have been four great stories that bridge inception to development of new drugs in ovarian cancer: Serendipitous insight into the role of platinum, discovery of taxanes, understanding the microenvironment and angiogenesis, and following the science in the development of Poly (ADP-Ribose) Polymerase (PARP) inhibitors. There is a fundamental difference between overall survival (OS), simply living longer; and eradicating disease, cure. The scientific underpinning of both our understanding and the recent developments encourages an optimistic view of the remaining hurdles. SUMMARY: There has been an unprecedented explosion in the number of new drugs approved for the treatment of ovarian cancer with three new classes of agent, and five new drugs receiving food and drug administration approval in the last 3 years (Fig. 2). Getting the right drug truly transforms patients' experience with the seminal event being the development of imatinib in CML. In 1980, an average patient would have lived only 3 years, and now they only live 3 years less than a full lifespan [Bower et al. (2016). J Clin Oncol 34:2851].

EGR1 Functions as a Potent Repressor of MEF2 Transcriptional Activity.

The myocyte enhancer factor 2 (MEF2) transcription factor requires interactions with co-factors for precise regulation of its target genes. Our lab previously reported that the mammalian MEF2A isoform regulates the cardiomyocyte costamere, a critical muscle-specific focal adhesion complex involved in contractility, through its transcriptional control of genes encoding proteins localized to this cytoskeletal structure. To further dissect the transcriptional mechanisms of costamere gene regulation and identify potential co-regulators of MEF2A, a bioinformatics analysis of transcription factor binding sites was performed using the proximal promoter regions of selected costamere genes. One of these predicted sites belongs to the early growth response (EGR) transcription factor family. The EGR1 isoform has been shown to be involved in a number of pathways in cardiovascular homeostasis and disease, making it an intriguing candidate MEF2 coregulator to further characterize. Here, we demonstrate that EGR1 interacts with MEF2A and is a potent and specific repressor of MEF2 transcriptional activity. Furthermore, we show that costamere gene expression in cardiomyocytes is dependent on EGR1 transcriptional activity. This study identifies a mechanism by which MEF2 activity can be modulated to ensure that costamere gene expression is maintained at levels commensurate with cardiomyocyte contractile activity.

Learner-controlled practice difficulty in the training of a complex task: cognitive and motivational mechanisms.

An inherent aspect of learner-controlled instructional environments is the ability of learners to affect the degree of difficulty faced during training. However, research has yet to examine how learner-controlled practice difficulty affects learning. Based on the notion of desirable difficulties (Bjork, 1994), this study examined the cognitive and motivational antecedents and outcomes of learner-controlled practice difficulty in relation to learning a complex task. Using a complex videogame involving both strong cognitive and psychomotor demands, 112 young adult males were given control over their practice difficulty, which was reflected in the complexity of the training task. Results show that general mental ability, prior experience, pre-training self-efficacy, and error encouragement were positively related to learner-controlled practice difficulty. In turn, practice difficulty was directly related to task knowledge and post-training performance, and it was related to adaptive performance through the mediating influences of task knowledge and post-training performance. In general, this study supports the notion that training difficulty operationalized in terms of task complexity is positively related to both knowledge and performance outcomes. Results are discussed with respect to the need for more research examining how task complexity and other forms of difficulty could be leveraged to advance learner-controlled instructional practices.