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The objective of the presented cross-sectional-evaluation-screening study is the clinical evaluation of high-risk(hr)HPVE7-protein detection as a triage method to colposcopy for hrHPV-positive women, using a newly developed sandwich-ELISA-assay. Between 2013-2015, 2424 women, 30-60 years old, were recruited at the Hippokratio Hospital, Thessaloniki/Greece and the Im Mare Klinikum, Kiel/Germany, and provided a cervical sample used for Liquid Based Cytology, HPV DNA genotyping, and E7 detection using five different E7-assays: "recomWell HPV16/18/45KJhigh", "recomWell HPV16/18/45KJlow", "recomWell HPV39/51/56/59", "recomWell HPV16/31/33/35/52/58" and "recomWell HPVHRscreen" (for 16,18,31,33,35,39,45,51,52,56,58,59 E7), corresponding to different combinations of hrHPVE7-proteins. Among 1473 women with eligible samples, those positive for cytology (ASCUS+ 7.2%), and/or hrHPV DNA (19.1%) were referred for colposcopy. Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+) was detected in 27 women (1.8%). For HPV16/18-positive women with no triage, sensitivity, positive predictive value (PPV) and the number of colposcopies needed to detect one case of CIN2+ were 100.0%, 11.11% and 9.0 respectively. The respective values for E7-testing as a triage method to colposcopy ranged from 75.0-100.0%, 16.86-26.08% and 3.83-5.93. Sensitivity and PPV for cytology as triage for hrHPV(non16/18)-positive women were 45.45% and 27.77%; for E7 test the respective values ranged from 72.72-100.0% and 16.32-25.0%. Triage of HPV 16/18-positive women to colposcopy with the E7 test presents better performance than no triage, decreasing the number of colposcopies needed to detect one CIN2+. In addition, triage of hrHPV(non16/18)-positive women with E7 test presents better sensitivity and slightly worse PPV than cytology, a fact that advocates for a full molecular screening approach.

Aim Age-related sleep changes have been associated with altered hypothalamic-pituitary-adrenal axis reactivity and impaired feedback inhibition at the glucocorticoid (GR) and mineralocorticoid (MR) receptor level. To further investigate the specific role of this binary receptor system in the elderly, sleep electroencephalogram (EEG) effects of the MR antagonist spironolactone and GR antagonist mifepristone in old-aged men were compared in this pilot study. Methods Old-aged healthy men (n = 6, 65–91 years) were treated on three occasions in a single-blinded design in random order with mifepristone, spironolactone and placebo, respectively, and nocturnal sleep EEG was recorded. Results Mifepristone led to increased wake time, decreased stage 2 and rapid eye movement (REM) sleep and prolonged REM sleep latency in the first half of the night, whereas spironolactone had no considerable effects on sleep EEG. Conclusion GR antagonism can potentiate age-related sleep pattern alterations and further support the role of impaired GR signaling in age-related changes in sleep architecture.

PURPOSE.: Brain thalami are important for a wide range of sensorimotor and neuropsychiatric functions. This study was carried out to calculate normative values for thalami volume during fetal life. METHODS.: Fetal thalami volumes were measured using 3D ultrasound in 122 normal, singleton fetuses at 20(+0) -34(+6) weeks' gestation. Virtual Organ Computer-aided AnaLysis (VOCAL) was used to obtain a sequence of six sections of each thalamus, starting from the transthalamic view of the brain at an axial plane. Thalamic contour was drawn manually. Volume contrast imaging was used to enhance image quality when needed. The volume of the thalamus distal to the transducer was also measured by a second operator in 30 randomly selected cases, blind to the measurements of the first, to calculate interobserver agreement. RESULTS.: Thalamic volume increased with gestational age, following a quadratic equation (R(2) = 0.83). There was no significant difference in volume between the right and left thalamus. The mean volume of each thalamus increased from 0.45 ml at 20(+0) weeks, to 1.39 ml at 28(+0) weeks, to 2.17 ml at 34(+0) weeks. The 95% limits of interobserver agreement for thalamic volume were -14.3% to +17.2%. CONCLUSIONS.: The increase in thalamic volume with gestation can be described adequately by a quadratic equation. The moderate interobserver repeatability is attributed to the similar echogenicity between the thalamus and its surrounding structures. (c) 2012 Wiley Periodicals, Inc. J Clin Ultrasound, 2012. J Clin Ultrasound

Summary Objective Apelin is an adipokine secreted from adipose and other tissues with increased expression in obesity, role in glucose metabolism and atherosclerosis, as well as in oxidative stress. Pregnancy is considered a state of hyperlipidemia, oxidative stress and decreased insulin sensitivity. The aim of the present study is to investigate the levels of apelin in human pregnancy and its relation to insulin sensitivity. Patients and measurements One hundred and six pregnant women (24th–28th week of gestation), aged 27·9 ± 0·4 years, were compared to 106 age-matched healthy, nonpregnant women (controls). Measured parameters included serum levels of glucose, insulin, apelin, adiponectin, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL), triglycerides and oxidized LDL (ox-LDL). The body mass index (BMI) and the quantitative insulin sensitivity check index (QUICKI) were calculated as well. Results BMI, serum lipids and insulin levels were significantly higher, whereas serum apelin and glucose levels were lower in the pregnancy group compared to the control group. There was a significant negative correlation between apelin and adiponectin, in both groups. Additionally, apelin was negatively correlated with ox-LDL and HDL-cholesterol in the pregnancy group. Conclusions Although strongly correlated with adiponectin, apelin cannot be used as a marker of insulin sensitivity, but it could serve as a marker of oxidative stress in pregnancy.

Glaucoma is a frequent ophthalmologic condition leading to chronic progressive optic neuropathy, which can result in visual impairment and blindness. In addition, glaucoma is associated with a dysregulation of circadian rhythms, as well as with a high incidence of sleep disorders, depression, and anxiety. However, because of their high comorbidity in older age, these conditions have not received much scientific attention and are often undertreated. In the current paper, we review the available literature on the role of melatonergic mechanisms in glaucoma, regulation of circadian rhythms, and depression. The literature is presented as a narrative review, providing an overview on the most important and clinically relevant publications. Recently, there has been evidence for a progressive loss of intrinsically photosensitive retinal ganglion cells (ipRGC) because of oxidative stress in glaucoma. As ipRGC are responsible for the photic transduction to the circadian system and subsequent melatonin secretion, and melatonin is involved in the pathophysiology of circadian desynchronization, sleep disorder, and depression, an impairment of photo-dependent melatonergic signaling may be a common pathway connecting glaucoma with these comorbidities. This fact, as well as the proven retinal neuroprotective role of melatonin, suggests that melatonergic drugs provide a potentially promising treatment strategy supplementing the management of intraocular pressure by pharmacological and surgical measures. Additionally, multidisciplinary treatment focusing on depression and normalization of circadian rhythms might be beneficial for glaucoma patients. Furthermore, glaucoma might be a useful model for studying the pathophysiological interactions between the melatonergic, circadian, and mood systems.

The most compelling question in evaluating the possible replacement of the conventional Papanicolaou smear from a high-risk HPV testing method is the balance between specificity and sensitivity for detection of cervical intraepithelial neoplasia grade ≥CIN 2 (CIN 2+). Multiple studies have shown that HPV testing has higher sensitivity than cytology for the detection of high-grade CIN. Positivity increases the test cut-off for HPV and may reduce false positive results without significantly compromising the sensitivity, potentially alleviating the concern of low specificity. Overall, available evidence convincingly shows that HPV testing is superior to traditional screening for the detection of high-grade cervical lesions, and efforts are focused on improving its sensitivity, either by increasing its cut-off for positivity or by selecting those subgroups where HPV testing is expected to have higher positive predictive value for cervical disease, or by seeking to optimize triage tests after a positive HPV result.

Aim: To investigate a possible relationship between tibolone therapy and recurrence or mortality in breast cancer survivors. Methods: In a retrospective study, data from files of 247 patients who had been treated for breast cancer were analyzed. Twenty women were treated with tibolone because of menopausal symptoms (Group 1: mean duration of tibolone use 37.1 months). One hundred and one women who did not take tibolone were selected as the control group (Group 2). All women were followed up in our Department on our standard protocol (mean follow up: 73.4 months in Group 1, 67.4 months in Group 2). Comparison of the survival curves was applied with the Wilcoxon (Gehan) statistic. Cox regression analysis was also applied in order to identify significant coefficients in the survival curve. Results: Recurrence of breast cancer was observed in two (10%) Group 1 women versus 21 (21%) Group 2 women (P = NS). Two Group 1 women died (one from breast cancer recurrence) versus 15 Group 2 women (14 from breast cancer recurrence). Conclusions: Despite of the inherent limitations of this small retrospective study, it seems that tibolone does not reveal an apparent negative impact on breast cancer outcome when given to breast cancer survivors.

The DNA ploidy of Feulgen-stained cell nuclei of in vivo preimplantation rabbit embryos was assayed by cytophotometry. DNA ploidy abnormalities were detected in single-cell nuclei readings by the criterion of ≥5C DNA. These hypermodal DNA contents are referred as to DNA aneuploidy. Two, 4 and 6 days old rabbit embryos, all of normal gross morphology, were investigated. The incidence of embryos with DNA ploidy abnormalities increased from 17% in 2-day-old cleavage stages to 51% in 6-day-old expanded blastocysts. All these embryos were mosaics and the percentage of DNA aneuploid nuclei per embryo did not usually exceed 9%. Fifteen percent of the expanded blastocysts, however, contained up to 23% abnormal nuclei. Throughout the embryonic stages studied, the DNA content of abnormal nuclei was remarkably constant and averaged 5.8C. DNA aneuploid and euploid blastocysts did not differ in size. A maternal FSH treatment did not influence the DNA ploidy. This is the first report on the DNA ploidy pattern in preimplantation rabbit embryos. Our results indicate that DNA aneuploidy of single blastomeres is common in this species and occurs more often than generally assumed. The embryonic viability does not seem to be affected by the presence of DNA aneuploid blastomeres supporting earlier findings that a limited number of abnormal blastomeres is compatible with normal preimplantation development. © 1993 Wiley-Liss, Inc.

The polymerase chain reaction (PCR) was applied for the detection of human papilloma virus (HPV) infection, in samples obtained from the uterine cervices of 202 asymptomatic women with normal cytology in Northern Greece. About 41.8% of the women with microscopically and cytologically normal cervices were found to be infected with HPV. Typing of HPV revealed that 6.9% and 1.5% of the women were infected with HPV16 and HPV18, respectively. © 1994 Wiiey-Liss, Inc.