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Education Generative Adversarial Sites through Stochastic Nash Online games.
OBJECTIVE This study explored the availability and perception of Global Health (GH) training opportunities in US-based Neonatal-Perinatal Medicine (NPM) fellowship programs. STUDY DESIGN Electronic surveys, containing discrete choice and open-ended questions, were distributed to current and recent fellows and to Program Directors (PDs). RESULTS Fifty-eight PDs and ninety-eight fellows completed the survey. Fellows reported declining GH participation from 48% in medical school to 21% in fellowship. Among the 42% of fellows reporting GH opportunities at their programs, 30% personally participated. Fewer than 30% of these programs offer structured classroom or online learning; 10% offer research opportunities. 72% of fellows stated that GH availability is moderately to extremely important, compared with 58% of PDs. PDs cited cost, scheduling, mentorship, and lack of suitable global partners as barriers to supporting fellows in GH. CONCLUSION NPM fellows place high importance on GH opportunities during fellowship, but only a minority engage in GH work.OBJECTIVE To compare skin-to-skin care (SSC) and oral sucrose for preterm neonatal pain control. METHODS Preterm neonates (28-36 weeks gestation) requiring heel-stick were eligible. Lapatinib concentration In group-A, SSC was given 15-min before first heel-stick, and sucrose was given 2-min before second heel-stick. In group-B, the sequence was reversed. Blinded premature infant pain profile (PIPP) score assessment was done at 0, 1, and 5-min of heel-stick by two assessors. RESULTS A hundred neonates were enrolled. The inter-rater agreement for the PIPP score was good. The behavior state component was significantly lower in the sucrose group at all assessment points. The mean (SD) difference between 1-min and 0 min was similar [SSC 3.58(3.16) vs. sucrose 4.09(3.82), p = 0.24] between groups. The PIPP score attained baseline values at 5-min in both groups. CONCLUSION Albeit sucrose indicated instantaneous action, SSC and sucrose have comparable clinical efficacy for preterm neonatal pain control. Multisensory stimulation with SSC may result in a higher behavioral state component of the PIPP score.Angelman syndrome (AS) is a rare neurogenetic imprinting disorder caused by the loss of function of UBE3A. In ~3-5% of AS patients, the disease is due to an imprinting defect (ID). These patients lack DNA methylation of the maternal SNRPN promotor so that a large SNRPN sense/UBE3A antisense transcript (SNHG14) is expressed, which silences UBE3A. In very rare cases, the ID is caused by a deletion of the AS imprinting centre (AS-IC). To search for sequence alterations, we sequenced this region in 168 patients without an AS-IC deletion, but did not detect any sequence alteration. However, the AS-IC harbours six common variants (five single nucleotide variants and one TATG insertion/deletion variant), which constitute five common haplotypes. To determine if any of these haplotypes is associated with an increased risk for an ID, we investigated 119 informative AS-ID trios with the transmission disequilibrium test, which is a family-based association test that measures the over-transmission of an allele or haplotype from heterozygous parents to affected offspring. By this we observed maternal over-transmission of haplotype H-AS3 (p = 0.0073). Interestingly, H-AS3 is the only haplotype that includes the TATG deletion allele. We conclude that this haplotype and possibly the TATG deletion, which removes a SOX2 binding site, increases the risk for a maternal ID and AS. Our data strengthen the notion that the AS-IC is important for establishing and/or maintaining DNA methylation at the SNRPN promotor and show that common genetic variation can affect genomic imprinting.Lineage plasticity, the ability of cells to transition from one committed developmental pathway to another, has been proposed as a source of intratumoural heterogeneity and of tumour adaptation to an adverse tumour microenvironment including exposure to targeted anticancer treatments. Tumour cell conversion into a different histological subtype has been associated with a loss of dependency on the original oncogenic driver, leading to therapeutic resistance. A well-known pathway of lineage plasticity in cancer - the histological transformation of adenocarcinomas to aggressive neuroendocrine derivatives - was initially described in lung cancers harbouring an EGFR mutation, and was subsequently reported in multiple other adenocarcinomas, including prostate cancer in the presence of antiandrogens. Squamous transformation is a subsequently identified and less well-characterized pathway of adenocarcinoma escape from suppressive anticancer therapy. The increased practice of tumour re-biopsy upon disease progression has increased the recognition of these mechanisms of resistance and has improved our understanding of the underlying biology. In this Review, we provide an overview of the impact of lineage plasticity on cancer progression and therapy resistance, with a focus on neuroendocrine transformation in lung and prostate tumours. We discuss the current understanding of the molecular drivers of this phenomenon, emerging management strategies and open questions in the field.Folate receptor α (FRα) came into focus as an anticancer target many decades after the successful development of drugs targeting intracellular folate metabolism, such as methotrexate and pemetrexed. Binding to FRα is one of several methods by which folate is taken up by cells; however, this receptor is an attractive anticancer drug target owing to the overexpression of FRα in a range of solid tumours, including ovarian, lung and breast cancers. Furthermore, using FRα to better localize effective anticancer therapies to their target tumours using platforms such as antibody-drug conjugates, small-molecule drug conjugates, radioimmunoconjugates and, more recently, chimeric antigen receptor T cells could further improve the outcomes of patients with FRα-overexpressing cancers. FRα can also be harnessed for predictive biomarker research. Moreover, imaging FRα radiologically or in real time during surgery can lead to improved functional imaging and surgical outcomes, respectively. In this Review, we describe the current status of research into FRα in cancer, including data from several late-phase clinical trials involving FRα-targeted therapies, and the use of new technologies to develop FRα-targeted agents with improved therapeutic indices.
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