The intercellular adhesion molecule-1 (ICAM-1) gene polymorphism K469E in end-stage renal disease patients with cardiovascular disease

The intercellular adhesion molecule-1 (ICAM-1) mediates interaction of activated endothelial cells with leukocytes. It plays an important role in the pathogenesis of atherosclerosis. A functionally important polymorphism of the ICAM-1 gene, K469E, has been described. We investigated whether this polymorphism influences the risk of CVD in end-stage renal disease (ESRD) patients. The groups of 1016 ESRD patients and 824 healthy individuals were genotyped by PCR and allele specific oligonucleotide technique. The T allele of the K469E polymorphism was significantly more frequent in ESRD CVD+ patients than CVD- and controls (OR 2.26, 95% CI 1.87-2.72 and 1.82, 95% CI 1.55-2.11, respectively). The TT genotype was also more frequent in CVD+ patients (OR 9.90, 95% CI 6.17-15.88 vs. CVD- subgroup). When patients were stratified according to clinical outcome of CVD, there was a tendency towards higher frequencies of the T allele and TT genotype in patients with myocardial infarction (OR for T allele 1, 57, 95% CI 1.12-2.18 vs. patients without MI). In the multivariate regression analysis the carrier status of T allele of K469E was an independent risk factor of susceptibility to CVD. Our data suggest that the ICAM-1 K469E polymorphism is associated with CVD in ESRD patients.     

Temporal order memory assessed during spatiotemporal navigation as a behavioral cognitive marker for differential Alzheimer's disease diagnosis

Episodic memory impairment is a hallmark for early diagnosis of Alzheimer's disease. Most actual tests used to diagnose Alzheimer's disease do not assess the spatiotemporal properties of episodic memory and lead to false-positive or -negative diagnosis. We used a newly developed, nonverbal navigation test for Human, based on the objective experimental testing of a spatiotemporal experience, to differentially Alzheimer's disease at the mild stage (N = 16 patients) from frontotemporal lobar degeneration (N = 11 patients) and normal aging (N = 24 subjects). Comparing navigation parameters and standard neuropsychological tests, temporal order memory appeared to have the highest predictive power for mild Alzheimer's disease diagnosis versus frontotemporal lobar degeneration and normal aging. This test was also nonredundant with classical neuropsychological tests. As a conclusion, our results suggest that temporal order memory tested in a spatial navigation task may provide a selective behavioral marker of Alzheimer's disease.     

Predictors of environmental exposure to polycyclic aromatic hydrocarbons among pregnant women — Prospective cohort study in Poland

Objectives  

The aim of the study was to characterize the PAH exposure level based on 1-hydroxypyrene (1-HP) in urine of Polish pregnant women and to assess the relationship between PAH and factors such as smoking, environmental tobacco smoke exposure, place of residence, heating and cooking method.     

The relationship between exposure to air pollution and sperm disomy

The causes of the chromosome abnormalities have been studied for decades. It has been suggested that exposure to various environmental agents can induce chromosomal abnormalities in germ cells. This study was designed to address the hypothesis that exposure to specific air pollutants increases sperm disomy. The study population consisted of 212 men who were attending an infertility clinic for diagnostic purposes. They represented a subset of men in a multicenter parent study conducted in Poland to evaluate environmental factors and male fertility. Sperm aneuploidy for chromosomes 13, 18, 21, X, and Y was assessed using multicolor fluorescence in situ hybridization. Air quality data were obtained from the AirBase database. After adjusting for age, smoking, alcohol consumption, temperature (90 days), season, past diseases, abstinence interval, distance from the monitoring station, concentration, motility and morphology, positive associations were observed between exposure to PM_2.5 and disomy Y (P = 0.001), sex chromosome disomy (P = 0.05) and disomy 21 (P = 0.03). Exposure to PM₁₀ was associated with disomy 21 (P = 0.02). Conversely, exposure to ozone, CO, SO₂, and NOx did not affect sperm aneuploidy. A separate analysis conducted among men who were nonsmokers (n = 117) showed that the relationship between PM_2.5 and disomy Y and disomy 21 remained significant (P = 0.01, P = 0.05, respectively). The present findings indicate that exposure to air pollution induces sperm aneuploidy. Environ. Mol. Mutagen. 56:50–59, 2015. © 2014 Wiley Periodicals, Inc.     

Risk preferences and attitudes to surgery in decision making

Background and purpose — There is increasing evidence that several commonly performed surgical procedures provide little advantage over nonoperative treatment, suggesting that doctors may sometimes be inappropriately optimistic about surgical benefit when suggesting treatment for individual patients. We investigated whether attitudes to risk influenced the choice of operative treatment and nonoperative treatment.

Methods — 946 Swedish orthopedic surgeons were invited to participate in an online survey. A radiograph of a 4-fragment proximal humeral fracture was presented together with 5 different patient characteristics, and the surgeons could choose between 3 different operative treatments and 1 nonoperative treatment. This was followed by an economic risk-preference test, and then by an instrument designed to measure 6 attitudes to surgery that are thought to be hazardous. We then investigated if choice of non-operative treatment was associated with risk aversion, and thereafter with the other variables, by regression analysis.

Results — 388 surgeons responded. Nonoperative treatment for all cases was suggested by 64 of them. There was no significant association between risk aversion and tendency to avoid surgery. However, there was a statistically significant association between suggesting to operate at least 1 of the cases and a "macho" attitude to surgery or resignation regarding the chances of influencing the outcome of surgery. Choosing nonoperative treatment for all cases was associated with long experience as a surgeon.

Interpretation — The discrepancy between available evidence for surgery and clinical practice does not appear to be related to risk preference, but relates to hazardous attitudes. It appears that choosing nonoperative treatment requires experience and a feeling that one can make a difference (i.e. a low score for resignation). There is a need for better awareness of available evidence for surgical indications.     

Ovarian cancer-derived ascitic fluids induce a senescence-dependent pro-cancerogenic phenotype in normal peritoneal mesothelial cells

Purpose

After the seeding ovarian cancer cells into the peritoneal cavity, ascitic fluid creates a microenvironment in which these cells can survive and disseminate. The exact nature of the interactions between malignant ascitic fluids and peritoneal mesothelial cells (HPMCs) in ovarian cancer progression has so far remained elusive. Here we assessed whether malignant ascitic fluids may promote the senescence of HPMCs and, by doing so, enhance the acquisition of their pro-cancerogenic phenotype.

Methods

Primary omentum-derived HPMCs, ovarian cancer-derived cell lines (A2780, OVCAR-3, SKOV-3), malignant ascitic fluids and benign ascitic fluids from non-cancerous patients were used in this study. Ovarian cancer cell proliferation, as well as HPMC proliferation and senescence, were determined using flow cytometry and β-galactosidase assays, respectively. Ovarian cancer cell migration was quantified using a Transwell assay. The concentrations of soluble agents in ascitic fluids, conditioned media and cell lysates were measured using DuoSet® Immunoassay Development kits.

Results

We found that HPMCs, when exposed to malignant ascitic fluids, exhibited decreased proliferation and increased senescence rates. The malignant ascitic fluids were found to contain elevated levels of HGF, TGF-β1 and GRO-1, of which HGF and GRO-1 were able to induce senescence in HPMCs. We also found that HPMCs subjected to malignant ascitic fluids or exogenously added HGF and GRO-1 stimulated ovarian cancer cell progression, which was manifested by an increased production of HA (adhesion), uPA (proliferation), IL-8 and MCP-1 (migration).

Conclusion

Our results indicate that malignant ascitic fluids may contribute to ovarian cancer progression by accelerating the senescence of HPMCs.