Screening for pre-eclampsia by maternal serum glycosylated fibronectin and angiogenic markers at 36 weeks' gestation.

OBJECTIVES: First, to examine the predictive performance of maternal serum glycosylated fibronectin (GlyFn) at 35 + 0 to 36 + 6 weeks' gestation in screening for delivery with pre-eclampsia (PE) and delivery with gestational hypertension (GH) at ≥ 37 weeks' gestation, both within 3 weeks and at any time after the examination. Second, to compare the predictive performance for delivery with PE and delivery with GH of various combinations of biomarkers, including GlyFn, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Third, to compare the predictive performance for delivery with PE and delivery with GH by serum PlGF concentration, sFlt-1/PlGF concentration ratio and the competing-risks model with different combinations of biomarkers as above. Fourth, to compare the predictive performance of screening at 11 + 0 to 13 + 6 weeks vs 35 + 0 to 36 + 6 weeks for delivery with PE and delivery with GH at ≥ 37 weeks' gestation. METHODS: This was a case-control study in which maternal serum GlyFn was measured in stored samples from a non-intervention screening study in singleton pregnancies at 35 + 0 to 36 + 6 weeks' gestation using a point-of-care device. We used samples from women who delivered at ≥ 37 weeks' gestation, including 100 who developed PE, 100 who developed GH and 600 controls who did not develop PE or GH. In all cases, MAP, UtA-PI, PlGF and sFlt-1 were measured during the routine visit at 35 + 0 to 36 + 6 weeks. We used samples from patients that had been examined previously at 11 + 0 to 13 + 6 weeks' gestation. Levels of GlyFn were transformed to multiples of the expected median (MoM) values after adjusting for maternal demographic characteristics and elements from the medical history. Similarly, the measured values of MAP, UtA-PI, PlGF and sFlt-1 were converted to MoM. The competing-risks model was used to combine the prior distribution of the gestational age at delivery with PE, obtained from maternal risk factors, with various combinations of biomarker MoM values to derive the patient-specific risks of delivery with PE. The performance of screening of different strategies was estimated by examining the detection rate (DR) at a 10% fixed false-positive rate (FPR) and McNemar's test was used to compare the DRs between the different methods of screening. RESULTS: The DR, at 10% FPR, of screening by the triple test (maternal risk factors plus MAP, PlGF and sFlt-1) was 83.7% (95% CI, 70.3-92.7%) for delivery with PE within 3 weeks of screening and 80.0% (95% CI, 70.8-87.3%) for delivery with PE at any time after screening, and this performance was not improved by the addition of GlyFn. The performance of screening by a combination of maternal risk factors, MAP, PlGF and GlyFn was similar to that of the triple test, both for delivery with PE within 3 weeks and at any time after screening. The performance of screening by a combination of maternal risk factors, MAP, UtA-PI and GlyFn was similar to that of the triple test, and they were both superior to screening by low PlGF concentration (PE within 3 weeks: DR, 65.3% (95% CI, 50.4-78.3%); PE at any time: DR, 56.0% (95% CI, 45.7-65.9%)) or high sFlt-1/PlGF concentration ratio (PE within 3 weeks: DR, 73.5% (95% CI, 58.9-85.1%); PE at any time: DR, 63.0% (95% CI, 52.8-72.4%)). The predictive performance of screening at 35 + 0 to 36 + 6 weeks' gestation for delivery with PE and delivery with GH at ≥ 37 weeks' gestation was by far superior to screening at 11 + 0 to 13 + 6 weeks. CONCLUSION: GlyFn is a potentially useful biomarker in third-trimester screening for term PE and term GH, but the findings of this case-control study need to be validated by prospective screening studies. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

BRCA1 and BRCA2 mutation testing in Cyprus; a population based study.

This paper presents the largest study in Cyprus evaluating the frequency and distribution of BRCA1/2 mutations in a high risk patient cohort. Deleterious mutations in the BRCA1/2 genes were identified in 68 of the 527 patients tested (13%). It is of interest that a quarter of those tested positive, did not have an extensive family history of breast/ovarian cancer but were diagnosed with early onset breast cancer, ovarian cancer under the age of 60 or triple negative breast cancer. The spectrum of mutations identified in our patient cohort is different compared to other Mediterranean countries. Furthermore, several of the mutations detected are novel and have not been identified in other ethnic populations. This highlights the importance of operating a national reference center for cancer genetic diagnosis which offers services tailored to the needs of the Cypriot population.

Mycotoxin contamination of cereal grain commodities in relation to climate in North West Europe.

This study aimed to investigate mycotoxin contamination of cereal grain commodities for feed and food production in North Western Europe during the last two decades, including trends over time and co-occurrence between toxins, and to assess possible effects of climate on the presence of mycotoxins. For these aims, analytical results related to mycotoxin contamination of cereal grain commodities, collected in the course of national monitoring programmes in Finland, Sweden, Norway and the Netherlands during a 20-year period, were gathered. Historical observational weather data, including daily relative humidity, rainfall and temperature, were obtained from each of these four countries. In total 6382 records, referring to individual sample results for mycotoxin concentrations (one or more toxins) in cereal grains were available. Most records referred to wheat, barley, maize and oats. The most frequently analysed mycotoxins were deoxynivalenol, 3-acetyl-deoxynivalenol, nivalenol, T-2 toxin, HT-2 toxin and zearalenone. Deoxynivalenol had the highest overall incidence of 46%, and was mainly found in wheat, maize and oats. Mycotoxins that showed co-occurrence were: deoxynivalenol and 3-acetyl-deoxynivalenol in oats; deoxynivalenol and zearalenone in maize and wheat; and T-2 toxin and HT-2 toxin in oats. The presence of both deoxynivalenol and zearalenone in wheat increased with higher temperatures, relative humidity and rainfall during cultivation, but the presence of nivalenol was negatively associated with most of these climatic factors. The same holds for both nivalenol and deoxynivalenol in oats. This implies that climatic conditions that are conducive for one toxin may have a decreasing effect on the other. The presence of HT-2 toxin in oats showed a slight decreasing trends over time, but significant trends for other toxins showed an increasing presence during the last two decades. It is therefore useful to continue monitoring of mycotoxins. Obtained results can be used for development of predictive models for presence of mycotoxins in cereal grains.

Expression of Smad4 and TGF-beta2 in colorectal carcinoma.

BACKGROUND: TGF-beta, a potent natural antiproliferative agent, is believed to play an important role in suppressing tumorigenicity. This effect is mediated through Smad4, a tumour-suppressor gene, at chromosome 18q21, which affects gene transcription and controls cell growth. The aim of the study was to investigate the expression of Smad4 and TGF-beta2 in colorectal carcinomas and to correlate them with pathological parameters and patient survival. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded tissue from 49 cases of colon carcinoma was stained by immunohistochemistry for TGF-beta2 and Smad4 protein. RESULTS: Smad4 nuclear and cytoplasmic staining was absent in 9/49 (18.3%) or reduced in 18/49 (36. 7%) colorectal carcinoma, while in the remaining 22 (44.8%) Smad4 expression comparable with colonic mucosa was observed. TGF-P2 cytoplasmic staining was expressed in all cases and was overexpressed in 24/49 (48.9%) carcinoma. A statistically significant correlation was found between Smad4 expression and tumour grade (p =0.02) and between TGF-beta2 expression and Dukes' stage (p=0.03). A slight tendency for a relationship between Smad4 and TGF-beta2 (p=0.25) was also observed. No statistically significant relationship between the above markers and survival was detected. CONCLUSION: In poorly-differentiated carcinoma, Smad4 protein expression was retained and may be linked to TGF-beta2 overexpression, due to the activation or deregulation of the TGF-fl signalling pathway. Inactivation of the TGF-beta gene occurs at an early stage of colorectal carcinogenesis, while inactivation of Smad4 is probably a late event.

Surveillance and control of aflatoxins B1, B2, G1, G2, and M1 in foodstuffs in the Republic of Cyprus: 1992-1996.

Aflatoxins (AFs) B1, B2, G1, and G2 in locally produced and imported foodstuffs (nuts, cereals, oily seeds, pulses, etc.) were monitored and controlled systematically and effectively from 1992-1996. Samples (peanuts, pistachios, etc.) with total AFs above the Cyprus maximum level (ML) of 10 micrograms/kg fluctuated between 0.7 and 6.9%. The results indicate the effectiveness of monitoring, as well as the need for constant surveillance and control, especially at critical control points (sites of import, primary storage, etc.), to prevent unfit products from entering the Cyprus market. The control included sampling, retainment, analysis, and destruction of foodstuff lots with AF levels above MLs. The highest incidence of aflatoxin contamination was observed in peanut butter (56.7%) and the highest level of AF B1 was found in peanuts (700 micrograms/kg). Levels of AF M1 in raw and pasteurized milk analyzed in 1993, 1995, and 1996 were within both the Cyprus ML (0.5 microgram/L) and the lower ML (0.05 microgram/L) of some European countries. Only 12% of samples had detectable levels of AF M1. Analyses were performed by immunochemical methods. When recoveries were lower than 80%, the AF levels were corrected for recovery.

Multi-focal, multi-centric angiosarcoma of bone.

A multi-focal multi-centric, malignant tumour of vascular origin arising in bone in a 55-year-old man is described. The presenting symptoms were pain and weight loss. Radiologically, multiple lytic lesions were demonstrated in the long bones of both legs and throughout the pelvis. Histological examination demonstrated an angiosarcoma which was predominantly low grade in nature but with focal areas of intermediate grade. Turnout cells expressed the endothelial markers CD31, CD34 and von Willebrand's factor. There was rapid radiological progression of disease with no response to radiotherapy. Pain abated within a few days of institution of doxorubicin, 75 mg m(-2), but the patient died of massive pulmonary thromboembolism 14 days later, 11 months after the first symptoms.