A five-microRNA model (pCaP) for predicting prostate cancer aggressiveness using cell-free urine

Improved biomarkers for prostate cancer (PC) risk stratification are urgently needed. Here, we aimed to develop a novel multimarker model for prediction of biochemical recurrence (BCR) after curatively intended radical prostatectomy (RP), based on minimally invasive sampling of blood and urine. We initially measured the levels of 45 selected miRNAs by RT-qPCR in exosome enriched cell-free urine samples collected prior to RP from 215 PC patients (Cohort 1, training). We trained a novel logistic regression model (pCaP), comprising five urine miRNAs (miR-151a-5p, miR-204-5p, miR-222-3p, miR-23b-3p and miR-331-3p) and serum prostate-specific antigen (PSA), which significantly predicted time to BCR in Cohort 1 (univariate Cox regression analysis: HR = 3.12, p < 0.001). Next, using the same exact numeric cutoff for dichotomization as trained in Cohort 1, we tested and successfully validated the prognostic potential of pCaP in two additional cohorts, including 199 (Cohort 2, HR = 2.24, p = 0.002) and 205 (Cohort 3, HR = 2.15, p = 0.004) RP patients, respectively. pCaP remained a significant predictor of BCR, also after adjustment for pathological T-stage, surgical margin status and Gleason grade group (p < 0.05 in multivariate Cox regression analysis: HR = 2.72, 1.94 and 1.83 for Cohorts 1, 2 and 3, respectively). Additionally, pCaP scores correlated positively with the established clinical risk stratification nomogram CAPRA in all three PC cohorts (Pearson's rho: 0.45, 0.39 and 0.44). Together, our results suggest that the minimally invasive pCaP model could potentially be used in the future to improve PC risk stratification and to guide more personalized treatment decisions. Further clinical validation studies are warranted.     

Work-related self-reported musculoskeletal injuries in Portuguese hypermarket cashiers

Background:Work-related musculoskeletal disorders are a group of painful disorders which arise from work situations with continuous repetitive movements, carried out with speed and without time for recovery. In the performance of their job tasks, supermarket cashiers are exposed to this type of ergonomic stress.Objectives:This study aimed to determine the incidence of self-reported injuries in Portuguese hypermarket cashiers and to identify the related factors.Methods:The sample included 176 hypermarket cashiers, aged between 18 and 65 years (39.57±11.11), 167 (94.9%) of them women. Symptoms and exposure of interest have been collected through an interview-based questionnaire. The presence of carpal tunnel syndrome was assessed by Phalen’s test.Results:One hundred and seventeen (66.5%) cashiers reported an injury during employment, 100 (56.8%) of them reporting an injury in the previous 6 months. A total of 166 injuries were reported, corresponding to 1.14 injuries per 1,000 hours of work. The most common injuries were non-specific pain (30.4%), located in the shoulder (23.2%), cervical (22%) and lumbar spine (22%). Part-time workers showed a 2.25 times greater risk of injury (95% CI: 1.17-4.32; p=0.015) than full-time workers. Cashiers with more than 6 years of employment length had a 3.59 times higher risk of injury (95% CI: 1.84-6.99; p≤0.001) than those who had been working for a shorter period.Conclusions:Our data showed a high rate of reported injuries among hypermarket cashiers, especially among part-time workers and those with the highest length of employment.Key words: Epidemiology, incidence, injury, prevalence, supermarket cashiers     

The presence of PIM3 increases hepatoblastoma tumorigenesis and tumor initiating cell phenotype and is associated with decreased patient survival

PurposeHepatoblastoma is the most common primary liver cancer of childhood and has few prognostic indicators. We have previously shown that Proviral Integration site for Moloney murine leukemia virus (PIM3) kinase decreased hepatoblastoma tumorigenicity. We sought to determine the effect of PIM3 overexpression on hepatoblastoma cells and whether expression of PIM3 correlated with patient/tumor characteristics or survival.MethodsThe hepatoblastoma cell line, HuH6, and patient-derived xenograft, COA67, were utilized. Viability, proliferation, migration, sphere formation, and tumor growth in mice were assessed in PIM3-overexpressing cells. Immunohistochemistry was performed for PIM3 on patient samples. Correlation between stain score and clinical/pathologic characteristics was assessed.ResultsPIM3 overexpression rescued the anti-proliferative effect observed with PIM3 knockdown. Sphere formation was increased in PIM3 overexpressing cells. Cells with PIM3 overexpression yielded larger tumors than those with empty vector. Seventy-four percent of samples expressed PIM3. There was no statistical difference in patient characteristics between subjects with strong versus weak PIM3 staining, but patients with strong PIM3 staining had decreased survival.ConclusionsPIM3 expression plays a role in hepatoblastoma tumorigenesis. PIM3 was present in the majority of hepatoblastomas and higher PIM3 expression correlated with decreased survival. PIM3 warrants investigation as a therapeutic target and prognostic marker for hepatoblastoma.     

La 8.ª edición de la clasificación AJCC-TNM: nuevas aportaciones a la estadificación del cáncer de la unión esofagogástrica

The new 8th edition of the TNM classification system for esophageal and cardia or esophagogastric junction cancer provides important innovations in the TNM stages. Two classifications are presented, updated by stages, clinical (cTNM) and pathological (pTNM) methods, together with another pathological classification applicable to cases receiving neoadjuvant treatment (ypTNM). There is a notable increase in complexity compared to previous versions, but it is still early to determine whether the current modifications will result in a clear improvement in the prognostic discrimination of survival among the patient groups (which is their main objective), although the initial expectations are favorable.     

The Effects of Publicized Suicide Deaths on Subsequent Suicide Counts in Israel

This study investigated associations between indiscriminate media reporting of suicides and later inflated suicide counts among Israel's general population between the years 2008 and 2012. Self-inflicted deaths that received post-suicide media exposure (referred to as “publicized suicides”) were selected via Google news search-hit appraisals. Distributions of suicides were inspected and risk ratios (RRs) estimated by comparing population suicide rates 4 weeks before and 4 weeks after each publicized suicide (“reference” vs. “affected” periods, respectively). Poisson time series regression was employed to account also for secular trends and seasonality. A total of 2,119 people died by suicide, 13 of whom received noticeable media attention throughout the study. No meaningful impact following the 13 deaths on subsequent suicide counts during the observation window (affected vs. reference phase) was found. Poisson regression confirmed that suicide counts following publicized suicides were independent of media coverage. Given the pronounced search hits following the publicized suicides developing regulation practices that constrain indiscreet media reporting should officially be included as part of suicide prevention practices. Future research should focus on imitation suicide effects as a function of post-suicide media exposure, while including both risk and protective factors.     

Protein kinase D1 induces G1-phase cell-cycle arrest independent of Checkpoint kinases by phosphorylating Cell Division Cycle Phosphatase 25

Protein Kinase D1 (PrKD1) functions as a tumor and metastasis suppressor in several human cancers by influencing cell-cycle progression. However, the exact mechanism of cell-cycle regulation by PrKD1 is unclear. Overexpression and ectopic expression of PrKD1 induces G1 arrest in cancer cell lines. Because checkpoint kinases (CHEKs) are known to play a role in progression through the G1 phase, we downregulated CHEK1, which did not overcome the G1 arrest induced by PrKD1. Using in vitro phosphorylation and Western blot assays, we showed that PrKD1 phosphorylates all CDC25 isoforms (known substrates of CHEK kinases), independent from CHEK kinases, suggesting that direct phosphorylation of CDC25 by PrKD1 may be an alternate mechanism of G1 arrest. The study has identified a molecular mechanism for the influence of PrKD1 in cell-cycle progression.     

A qualitative systematic review of published work on disclosure and help-seeking for domestic violence and abuse among women from ethnic minority populations in the UK

ABSTRACT

Introduction: Domestic violence and abuse has been recognised as an international public health problem. However, the pervasiveness of the problem is unknown due in part to underreporting, especially among women from ethnic minority populations. In relation to this group, this review seeks to explore: (1) the barriers to disclosure; (2) the facilitators of help-seeking; and (3) self-perceived impacts of domestic violence.

Design: We systematically identified published qualitative studies conducted among women from ethnic minority populations in the UK. Data analysis was completed using thematic analysis approach.

Result: 562 papers were identified and eight papers from four studies conducted among women from ethnic minority populations in the UK met the inclusion criteria and were reviewed. Barriers to disclosure include: Immigration status, community influences, problems with language and interpretation, and unsupportive attitudes of staff within mainstream services. Facilitators of help-seeking were: escalation of abuse and safety of children. Self-perceived impact of abuse includes: shame, denial, loss of identity and lack of choice.

Conclusion: There is an on-going need for staff from domestic violence services to be aware of the complexities within which women from ethnic minority populations experience domestic violence and abuse.