A single institution's long-term follow-up of patients with pathological complete response in locally advanced rectal adenocarcinoma following neoadjuvant chemoradiotherapy.

PURPOSE: This paper aimed to study the long term follow-up of patients with primary rectal adenocarcinoma receiving neoadjuvant chemoradiotherapy who obtained a pathological complete response (pCR) and identify factors predicting complete response. METHODS: Retrospective review of notes, histology, pre-operative full blood count and imaging of patients with primary rectal adenocarcinoma diagnosed in our institute from 2000 to 2012 from a prospectively maintained database were used. SPSS version 22.0 was used for statistical analysis. RESULTS: Three hundred eighty patients diagnosed with primary rectal adenocarcinoma were identified, 277 received neoadjuvant chemoradiotherapy followed by curative resection. Forty-six patients obtained a pCR (ypT0N0) with no local recurrence and two metastatic recurrences on follow-up. Patients with a pCR have a significantly improved overall survival and disease-free survival compared to a non-pCR (150.0 and 136.1 vs 77.5 and 84.7 months, p = 0.001). On univariate analysis, increased tumour height above anal verge, low lymph node yield, high pre-operative haemoglobin and a low neutrophil-lymphocyte ratio are significant factors identifying a pCR. Multivariable analysis of the above factors confirmed tumour height above anal verge as significant in obtaining a pCR. CONCLUSION: Patients with rectal adenocarcinoma who develop a pCR following neoadjuvant chemoradiotherapy have improved overall and disease-free survival. We have identified distance from anal verge, low lymph node yield, high pre-operative haemoglobin and low neutrophil-lymphocyte ratio as significant predictors of developing a pCR.

Increased absorption in autonomous sensory meridian response.

BACKGROUND: Autonomous sensory meridian response (ASMR) is a cross-sensory phenomenon characterised by a static-like sensation which typically originates on the scalp and spreads throughout the body leading to a state of deep relaxation. It can be triggered by visual and auditory stimuli in real life, incidentally by various media and via intentionally created ASMR videos. Previously ASMR has been linked to a specific personality profile and this study aimed to further elucidate individual differences associated with this phenomenon. METHODS: To this effect ASMR-Experiencers and age and gender matched controls were compared on measures of flow, absorption and mindfulness. RESULTS: This revealed that ASMR was associated with elevated absorption but no group differences were found with respect to the other constructs, suggesting that the ability to get deeply immersed with the current experience accompanied by loss of reflective awareness may be an important factor contributing to the experience of ASMR.

Development of a screening and recruitment registry to facilitate perinatal depression research in obstetrics settings in the USA.

OBJECTIVE: To create a multi-site registry to enable future large-scale studies of perinatal depression among women attending obstetrics clinics in the USA. METHODS: A screening and recruitment registry was developed that included women aged at least 18 years who attended seven obstetric clinics in the University of Michigan Health System (Ann Arbor, MI, USA) for prenatal care between September 8, 2008, and June 9, 2011. Participants completed depression screening and research recruitment materials. RESULTS: Of 4745 women who returned a screening form, 2983 had completed it, giving an overall agreement rate of 62.9%. A total of 630 participants were enrolled into ten research studies via the registry. Among the 2982 women for whom scores on the Edinburgh Postnatal Depression Scale were available, 494 (16.6%) fell within the at-risk range or had scores suggestive of clinical depression. CONCLUSION: The present registry could improve detection of perinatal depression symptoms and potentially serve as a model for dissemination and implementation at other sites with an interest in studying factors linked to perinatal depression.

Alternative splicing controls nuclear translocation of the cell cycle-regulated Nek2 kinase.

Nek2 is a cell cycle-regulated serine/threonine protein kinase that is up-regulated in human cancers. Functionally, it is implicated in control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Two major splice variants have been described in vertebrates, Nek2A and Nek2B, that differ in their non-catalytic C termini. Recently, a third splice variant, Nek2C, was identified that lacks an eight-amino acid internal sequence within the C-terminal domain of Nek2A. This excision occurs at the same position as the Nek2A/Nek2B splice point. As predicted from their high degree of similarity, we show here that Nek2C shares many properties with Nek2A including kinase activity, dimerization, protein phosphatase 1 interaction, mitotic degradation, microtubule binding, and centrosome localization. Unexpectedly, though, the non-centrosomal pool of protein exhibits a marked difference in distribution for the three splice variants. Nek2C is mainly nuclear, Nek2B is mainly cytoplasmic, and Nek2A is evenly distributed within nuclei and cytoplasm. Mutagenesis experiments revealed a functional bipartite nuclear localization sequence (NLS) that spans the splice site leading to Nek2C having a strong NLS, Nek2A having a weak NLS, and Nek2B having no NLS. Finally, we identified a 28-kDa protein in nuclear extracts as a potential novel substrate of Nek2. Thus, alternative splicing provides an unusual mechanism for modulating Nek2 localization, enabling it to have both nuclear and cytoplasmic functions.