Surface proteomics on nanoparticles: a step to simplify the rapid prototyping of nanoparticles.

Engineered nanoparticles for biomedical applications require increasing effectiveness in targeting specific cells while preserving non-target cells' safety. We developed a surface proteomics method for a rapid and systematic analysis of the interphase between the nanoparticle protein corona and the targeted cells that could implement the rapid prototyping of nanomedicines. Native nanoparticles entering in a protein-rich liquid medium quickly form a macromolecular structure called protein corona. This protein structure defines the physical interaction between nanoparticles and target cells. The surface proteins compose the first line of interaction between this macromolecular structure and the cell surface of a target cell. We demonstrated that SUSTU (SUrface proteomics, Safety, Targeting, Uptake) provides a qualitative and quantitative analysis from the protein corona surface. With SUSTU, the spatial dynamics of the protein corona surface can be studied. Data from SUSTU would ascertain the nanoparticle functionalized groups exposed at a destiny that could circumvent preliminary in vitro experiments. Therefore, this method could implement in the analysis of nanoparticle targeting and uptake capability and could be integrated into a rapid prototyping strategy which is a major challenge in nanomaterials science. Data are available via ProteomeXchange with the identifier PXD004636.

Pharmaceutical industry interactions of psychiatric trainees from 20 European countries.

BACKGROUND: Interactions between the pharmaceutical industry (PI) and psychiatrists have been under scrutiny recently, though there is little empirical evidence on the nature of the relationship and its intensity at psychiatry trainee level. We therefore studied the level of PI interactions and the underlying beliefs and attitudes in a large sample of European psychiatric trainees. METHODS: One thousand four hundred and forty-four psychiatric trainees in 20 European countries were assessed cross-sectionally, with a 62-item questionnaire. RESULTS: The total number of PI interactions in the preceding two months varied between countries, with least interactions in The Netherlands (M (Mean)=0.92, SD=1.44, range=0-12) and most in Portugal (M=19.06, SD=17.44, range=0-100). Trainees were more likely to believe that PI interactions have no impact on their own prescribing behaviour than that of other physicians (M=3.30, SD=1.26 vs. M=2.39, SD=1.06 on a 5-point Likert scale: 1 "completely disagree" to 5 "completely agree"). Assigning an educational role to the pharmaceutical industry was associated with more interactions and higher gift value (IRR (incidence rate ratio)=1.21, 95%CI=1.12-1.30 and OR=1.18, 95%CI=1.02-1.37). CONCLUSIONS: There are frequent interactions between European psychiatric trainees and the PI, with significant variation between countries. We identified several factors affecting this interaction, including attribution of an educational role to the PI. Creating alternative educational opportunities and specific training dedicated to PI interactions may therefore help to reduce the impact of the PI on psychiatric training.

Absolute quantification of free tumor cells in the peripheral blood of gastric cancer patients.

Gastric cancer remains the third most common cancer in the world. Metastatic disease is a major cause of death in about half of the patients; therefore, early diagnosis is crucial for successful outcome. This study applied a sensitive method for the detection of circulating tumor cells using specific tumor markers for early detection. A total of 80 blood samples from 40 patients and 40 age-matched healthy controls were collected for the study. Circulating mRNA levels of two tumor markers, tumor endothelial marker 8 (TEM-8) and carcinoembryogenic antigen (CEA) were evaluated using absolute quantitative real-time PCR assay in the Stratagene Mx-3000P real-time PCR system. GAPDH was used to normalize the data. TEM-8 and CEA were detected in patients' blood more than in controls, 22/40 vs 9/40, P=0.005, and 30/40 vs 11/40, P=0.008, respectively. The mRNA level of these markers in patients was significantly higher in comparison to normal controls (P=0.018, 0.01). This panel showed an overall sensitivity of 64% and specificity of 73%. Statistical analysis for demographic variants did not show any significant differences. Both markers were detected more frequently and in significantly higher levels in blood samples of patients compared to samples from normal individuals. Copy number of CEA and TEM-8 mRNA, as detected by real-time quantitative PCR, appears to be a promising marker to evaluate the risk of tumor spread.

Prevalence of high DNA fragmentation index in male partners of unexplained infertile couples.

The sperm chromatin structure assay (SCSA) parameter DNA fragmentation Index (DFI) is a valuable tool for prediction of fertility in vivo. Clinical data show that a DFI above 30% is associated with very low chance for achieving pregnancy by natural conception or by insemination. Already when DFI is above 20% the chance of natural pregnancy is reduced, this despite normal conventional semen parameters. The aim of the present study was to investigate the prevalence of high DFI in male partners of unexplained infertile couples to further identification of male factors contributing to subfertility. Among 212 consecutive men under infertility investigation, 122 cases with the diagnosis 'unexplained infertility' were identified. For all but three, SCSA data were available. The percentage of couples with diagnosis 'unexplained infertility' in which the male partner has DFI >20% or DFI >30% was calculated. In the group diagnosed with 'unexplained infertility' 17.7% of the men (95% CI 10.8-24.5) presented with 20 ≤DFI <30 and 8.4% (95% CI 3.40-13.4) had DFI ≥30%. A significant part of men diagnosed as unexplained infertile according to traditional diagnostic methods has remarkably high degrees of fragmented sperm DNA. Apart from adding to our understanding of biology of infertility our finding has clinical implications. Couples in which the DFI of the male partner is high can avoid prolonged attempts to become spontaneously pregnant or referral for intrauterine insemination, both having low chances of leading to conception.

Seroepidemiology of crimean congo hemorrhagic Fever in slaughterhouse workers in north eastern iran.

BACKGROUND: Crimean Congo Hemorrhagic Fever (CCHF) is an acute febrile haemorrhagic disease. This study was conducted to ascertain the infection status amongst slaughterhouse workers in Iran's north-eastern provinces (Razavi and northern and southern Khorasan), so that analysis of the results could help clarification of the epidemiology of this disease in the aforementioned provinces and eastern regions of Iran. METHODS: In this cross-sectional study, conducted in 2004 and 2005, 108 slaughterhouse workers from 24 cities of the three previously mentioned provinces were randomly entered into the study. An IgG specific ELISA test was carried out on the participants' serum samples. RESULTS: Sixteen out of 108 (14.8%) participants under study were shown to have IgG against CCHF. The highest rate of infection was seen in Razavi Khorasan and southern Khorasan at 17.5% and 16.7%, respectively. CONCLUSION: The study showed a relatively high frequency of this disease amongst slaughterhouse workers in these provinces. Taking into account the small number of reported cases from these provinces, it would seem that more focus is required on primary diagnosis and on referral of suspected patients.

Bone mineral density changes within 11 months of renal transplantation in Iranian patients.

BACKGROUND AND AIM: We studied bone mineral density (BMD) changes in Iranian patients with end-stage renal disease (ESRD) within 11 months after renal transplantation. METHODS: Among 68 ESRD candidates for renal transplantation, the BMD at the femur and the spine were assessed using a DEXA Norland scanner. Linear regression analysis was used to identify risk factors associated with low bone density. RESULTS: Mean BMD, T-score and Z-score of femur and spine were significantly reduced (at femur, 0.78 +/- 0.14, -2.4 +/- 1.1, -1.6 +/- 1.0; at spine, 142.25 +/- 105, -1.09 +/- 1.1, -1.07 +/- 0.9). Osteoporosis and osteopenia were found 55.2% and 36.2% at the femur and 8.6% and 58.6% at the spine, respectively. The BMD showed a significant negative association with age (r=0.615), female gender (r=0.394), and corticosteroid intake (r=0.286), and a positive association with weight (r=0.394) and body mass index (r=0.626). There was no significant association between BMD measurements and calcium, phosphorous, or parathyroid hormone levels. At 11 months follow-up, in 20 patients, the subject had lost a mean of 2.4% T-score and 2.8% Z-score at spine (P=.027 and .13, respectively), but did not experience significant declines at the femur. BMD showed a decrease in 80% of recipients in the spine area; there was a 15% BMD increase at the hip. CONCLUSION: Low bone density is common among ESRD Iranian patients. Early screening and treatment of this group is recommended. Significant loss in lumbar density occurred within 11 months of transplantation in more than one third of a prospective cohort of renal transplant recipients.