MicroRNA-330-5p as a putative modulator of neoadjuvant chemoradiotherapy sensitivity in oesophageal adenocarcinoma

Oesophageal adenocarcinoma (OAC) is the sixth most common cause of cancer deaths worldwide, and the 5-year survival rate for patients diagnosed with the disease is approximately 17%. The standard of care for locally advanced disease is neoadjuvant chemotherapy or, more commonly, combined neoadjuvant chemoradiation therapy (neo-CRT) prior to surgery. Unfortunately, ~60-70% of patients will fail to respond to neo-CRT. Therefore, the identification of biomarkers indicative of patient response to treatment has significant clinical implications in the stratification of patient treatment. Furthermore, understanding the molecular mechanisms underpinning tumour response and resistance to neo-CRT will contribute towards the identification of novel therapeutic targets for enhancing OAC sensitivity to CRT. MicroRNAs (miRNA/miR) function to regulate gene and protein expression and play a causal role in cancer development and progression. MiRNAs have also been identified as modulators of key cellular pathways associated with resistance to CRT. Here, to identify miRNAs associated with resistance to CRT, pre-treatment diagnostic biopsy specimens from patients with OAC were analysed using miRNA-profiling arrays. In pre-treatment biopsies miR-330-5p was the most downregulated miRNA in patients who subsequently failed to respond to neo-CRT. The role of miR-330 as a potential modulator of tumour response and sensitivity to CRT in OAC was further investigated in vitro. Through vector-based overexpression the E2F1/p-AKT survival pathway, as previously described, was confirmed as a target of miR-330 regulation. However, miR-330-mediated alterations to the E2F1/p-AKT pathway were insufficient to significantly alter cellular sensitivity to chemotherapy (cisplatin and 5-flurouracil). In contrast, silencing of miR-330-5p enhanced, albeit subtly, cellular resistance to clinically relevant doses of radiation. This study highlights the need for further investigation into the potential of miR-330-5p as a predictive biomarker of patient sensitivity to neo-CRT and as a novel therapeutic target for manipulating cellular sensitivity to neo-CRT in patients with OAC

Media Ecologies

In this chapter, we frame the media ecologies that contextualize the youth practices we describe in later chapters. By drawing from case studies that are delimited by locality, institutions, networked sites, and interest groups (see appendices), we have been able to map the contours of the varied social, technical, and cultural contexts that structure youth media engagement. This chapter introduces three genres of participation with new media that have emerged as overarching descriptive frameworks for understanding how youth new media practices are defi ned in relation and in opposition to one another. The genres of participation—hanging out, messing around, and geeking out—refl ect and are intertwined with young people’s practices, learning, and identity formation within these varied and dynamic media ecologies

Nest Site Characteristics of Great Blue Herons (Ardea herodias) in Northeast Ohio

Author Institution: Department of Biology, John Carroll UniversitySeventeen Great Blue Heronries were surveyed in nine counties of northeast Ohio during the 1993 breeding season to determine nest site characteristics. Herons nested in 15 species of deciduous trees, selecting the taller trees at each site. Crown integrity was not a requisite for tree usage; repaired (reoccupied) nests and new colonies were established in dead trees as well as in healthy ones

The Use of Electroacupuncture for Cervical Ripening in Pregnant Women

The purpose of this study was to compare cervical ripening outcomes, based on Bishop scoring methodology, of pregnant women receiving usual care treatment (UC) with those receiving electroacupuncture plus UC. A sample of 36 pregnant women completing their 39th week of gestation was randomized into one of the two groups. The women in the UC group continued to meet with their provider on a weekly basis until delivery. The women in the electroacupuncture plus usual care group met with their provider on a weekly basis and also received electroacupuncture treatments: three in the 39th gestational week and two in the 40th gestational week. Conceptual basis for the study was guided by and adapted from the Complementary and Alternative Medicine Model (Figure 1). An experimental research design was used for this pilot study with a sample size of 36 women; 18 in each group. The demographic data were analyzed using descriptive statistics. Means and standard deviations were calculated for the participant’s age, gestational age, parity, and Bishop score. Frequencies and percentages were calculated for ethnicity, use of induction methods, types of interventions and mode of delivery. A Mann-Whitney test was used to compare changes in the Bishop score and time in labor. Apgar scores below seven at 5 minutes were calculated using Chi Square methodology. Results from this study found that electroacupuncture plus UC positively influenced the timing of delivery (p = 0.051) and the method of delivery (94.4% vaginal delivery rate) compared to UC treatment alone (83.3% vaginal delivery rate). Electroacupuncture plus UC was not shown to be more effective for cervical ripening than UC treatment alone (p = .633); however, only 5.6% of participants in the lectroacupuncture plus UC group required induction with Cervidil® and Pitocin® compared to 22.2% of participants in the UC group. The use of electroacupuncture may be beneficial for cervical ripening, initiation of spontaneous labor, reduction of the time in active labor, and an increased potential for a vaginal birth

The neurochemical basis of photic entrainment of the circadian pacemaker

Circadian rhythmicity in mammals is controlled by the action of a light-entrainable hypothalamus, in association with two cell clusters known as the supra chiasmatic nuclei (SCN). In the absence of temporal environmental clues, this pacemaker continues to measure time by an endogenous mechanism (clock), driving biochemical, physiological, and behavioral rhythms that reflect the natural period of the pacemaker oscillation. This endogenous period usually differs slightly from 24 hours (i.e., circadian). When mammals are maintained under a 24 hour light-dark (LD) cycle, the pacemaker becomes entrained such that the period of the pacemaker oscillation matches that of the LD cycle. Potentially entraining photic information is conveyed to the SCN via a direct retinal projection, the retinohypothalamic tract (RHT). RHT neurotransmission is thought to be mediated by the release of excitatory amino acids (EAA) in the SCN. In support of this hypothesis, recent experiments using nocturnal rodents have shown that EAA antagonists block the effects of light on pacemaker-driven behavioral rhythms, and attenuate light induced gene expression in SCN cells. An understanding of the neurochemical basis of the photic entrainment process would facilitate the development of pharmacological strategies for maintaining synchrony among shift workers in environments, such as the Space Station, which provide unreliable or conflicting temporal photic clues

Using Medicare Part D Data for Research

Medical claims can be a primary data source for translational research. This presentation provides information on Medicare as a source of claims data, including a brief overview of Medicare Part D, brief overview of Part D data, and examples of Medicare Part D studies. This presentation was part of the retreat mini-symposium entitled: Big Data: Medical Claims Data for Translational Research

Book Review: Reflexive Narrative: Self-Inquiry Toward Self-Realization and Its Performance

Becky A. De Oliveira reviews Reflexive Narrative: Self-Inquiry Toward Self-Realization and Its Performance by Christopher Johns