Correlation analysis of p53 protein isoforms with NPM1/FLT3 mutations and therapy response in acute myeloid leukemia

The wild-type tumor-suppressor gene TP53 encodes several isoforms of the p53 protein. However, while the role of p53 in controlling normal cell cycle progression and tumor suppression is well established, the clinical significance of p53 isoform expression is unknown. A novel bioinformatic analysis of p53 isoform expression in 68 patients with acute myeloid leukemia revealed distinct p53 protein biosignatures correlating with clinical outcome. Furthermore, we show that mutated FLT3, a prognostic marker for short survival in AML, is associated with expression of full-length p53. In contrast, mutated NPM1, a prognostic marker for long-term survival, correlated with p53 isoforms β and γ expression. In conclusion, p53 biosignatures contain useful information for cancer evaluation and prognostication.     

p53 mutation, deprivation and poor prognosis in primary breast cancer

Background:

The deprivation gap for breast cancer survival remains unexplained by stage at presentation, treatment, or co-morbidities. We hypothesised that p53 mutation might contribute to the impaired outcome observed in patients from deprived communities.

Methods:

p53 mutation status was determined using the Roche Amplichip research test in 246 women with primary breast cancer attending a single cancer centre and related to deprivation, pathology, overall, and disease-free survival.

Results:

p53 mutation, identified in 64/246 (26%) of cancers, was most common in 10 out of 17 (58.8%) of the lowest (10th) deprivation decile. Those patients with p53 mutation in the 10th decile had a significantly worse disease-free survival of only 20% at 5 years (Kaplan–Meier logrank χ²=6.050, P=0.014) and worse overall survival of 24% at 5 years (Kaplan–Meier logrank χ²=6.791, P=0.009) than women of deciles 1–9 with p53 mutation (c.f. 56% and 72%, respectively) or patients in the 10th decile with wild-type p53 (no disease relapse or deaths).

Conclusion:

p53 mutation in breast cancer is associated with socio-economic deprivation and may provide a molecular basis, with therapeutic implications, for the poorer outcome in women from deprived communities.     

Blood and tissue zinc levels in spontaneously hypertensive rats.

Zinc (Zn) determinations were performed on blood plasma and red cells, liver, heart, adrenals, and spleen of spontaneously hypertensive (SHR) and control normotensive (WKY) male rats, 20 weeks of age. SHR revealed higher red cell (p = 2 × 10(?5)) and heart (p = 0.007) Zn levels than WKY rats. The water content of organs was the same in the two strains. When compared with published data, these results suggest an association between high cell Zn levels and hypertension, the meaning of which is briefly discussed.     

Mothering in the Wake of Childhood Violence Experiences: Reweaving a Self and a World at the Intersection of History and Context

We examined the stories of 12 women mothering growing children at the intersection of personal history (childhood violence experiences) and symbolic, structural, and ideological forces and conditions. Women revealed their determination to reweave a self and a world, that is, to continually reconstruct and reconfigure their lives to change the story for themselves and their children. Women's ability to reweave, however, was facilitated or challenged through intersections with family, networks, single stories, and prescribed rules and routines. We propose that reweaving work is a significant phenomenon to consider as deeper understandings of the dynamic experience of adult resilience are sought.     

Effect of measuring blood lactate concentrations using different automated lactate analysers on blood lactate transition thresholds

This study investigated the effect of using three automated blood lactate analysers (Accusport, Lactate Pro, YSI 1500 Sport) on blood lactate transition thresholds (BLTT). Blood lactate concentrations were measured using the three analysers in rowers (n = 17) and kayakers (n = 6) during incremental exercise. The BLTT determined were: 1) ADAPT lactate threshold (data point preceding lactate increase of > or = 0.4 mmol x l(-1)), 2) log-log lactate threshold (point of lactate increase when log lactate plotted against log of relevant exercise parameter), 3) DMAX anaerobic threshold, 4) ADAPT anaerobic threshold (modified DMAX method), 5) Onset of blood lactate accumulation (OBLA, fixed blood lactate concentration of 4 mmol x l(-1)). Measurements of blood lactate concentration differed between analysers (p < 0.0001), resulting in BLTT differing between analysers when expressed as a blood lactate concentration (p < 0.0001), or when the BLTT was defined as a fixed blood lactate concentration (e.g. OBLA) (p < 0.0001). When expressed as a power output or heart rate using BLTT based on relative changes in lactate concentration (log-log, ADAPT and DMAX thresholds) the values were similar between analysers (p > 0.05), except the Accusport provided higher values for the log-log lactate threshold (p < 0.0001). We concluded that, despite providing significantly different lactate concentrations, unless the Accusport was used to determine the log-log lactate threshold, or values were expressed as a blood lactate concentration, the use of different analysers had little effect on the BLTT.     

Criminal harassment by patients with mental disorders.

OBJECTIVE: To assess whether there is a subgroup of persons with mental disorders who engage in criminal harassment and to determine whether substance abuse is a cofactor in this behaviour. METHOD: A cross-sectional casenote study was used to examine incidents of harassment by patients prior to admission to acute and forensic wards (n = 106) at a provincial psychiatric hospital. RESULTS: Of 106 patients, 8 (7.5%) were found to have engaged in behaviour defined as criminal harassment prior to admission. Only 1 was charged under Section 264 of the Criminal Code. Alcohol was a cofactor in only 1 case. CONCLUSIONS: The number of persons with a mental disorder who engage in criminal harassment prior to admission is relatively small. The behaviour is not usually identified at any stage of the admission as criminal harassment. Although substance-abuse problems were prevalent, substance use was not a concomitant risk factor for behaviour defined as criminal harassment.     

Extended culture of poor-quality supernumerary embryos improves ART outcomes

Purpose

The aims of this study were to investigate the possible benefits of extending the culture of poor-quality day-2 embryos (PQE) versus good-quality embryos (GQE) and to identify factors associated with pregnancy and live birth when transferring frozen-thawed blastocysts originating from GQE and PQE.

Methods

This is a retrospective cohort follow-up study performed between November 2012 and February 2015 at the IVF Laboratory Unit of Cochin University Hospital (Paris, France) including 3108 day-2 supernumerary embryos resulting from 1237 IVF/ICSI cycles.

Results

Total blastulation rate was 67.2% from GQE and 48.7% from PQE. Percentage of good-quality blastocysts was 60.7 and 47.9% respectively including 14.7 and 7.3% top-quality blastocysts. A total of 150 blastocysts originating from GQE and 729 from PQE were frozen, and then, 37 and 164 were thawed and transferred respectively resulting in 19 (51.4%) and 61 (37.9%) clinical pregnancies with 13 (35.1%) deliveries from GQE and 32 (19.9%) from PQE (p = 0.046) without any difference in neonatal outcomes. Quality of blastocysts that resulted in live birth was similar in the two groups. Women < 35 years old and day-5 blastocyst expansion were predictive of pregnancy and live birth.

Conclusions

(i) PQE are able to reach the blastocyst stage, to implant, and to give healthy babies and (ii) women age and day of blastocyst expansion are predictive of pregnancy and live birth.