Female genito-pelvic reflexes: an overview

The female reproductive system includes an active and responsive genital tract that shows involuntary activity triggered by sexual arousal, genital stimulation and/or orgasm. This pelvic and perineal somatic and autonomic reflex muscle activity ("genito-pelvic reflexes") may be an important constituent of the female sexual response. The aim of this study was to review the literature critically on female genito-pelvic reflexes. Only a small number of studies (15) have been published on this issue. More neurophysiological research is needed to search for the implications of these genito-pelvic reflexes for female sexual (dys)function

An overview of innovative techniques to improve cervical cancer screening

Although current cytomorphology-based cervical cancer screening has reduced the incidence of cervical cancer, Papsmears are associated with high false positive and false negative rates. This has spurred the search for new technologies to improve current screening. New methodologies are automation of Pap-smear analysis, addition of new biological or molecular markers to traditional cytology or using these new markers to replace the current screening method. In this overview we will summarize data on cervical cancer epidemiology and etiology and the current cervical cancer screening approach. Available data on new screening approaches, such as quantitative cytochemistry, detection of loss of heterozygosity (LOH) and hypermethylation analysis will be reviewed.We discuss the potential of these approaches to replace or augment current screening. When available, data on cost– effectiveness of certain approaches will be provided. In short, Human Papillomavirus (HPV) DNA detection stands closest to implementation in nation-wide screening programs of all markers reviewed. However, specificity is low in women aged <35 years and the psychological effects of knowledge of HPV positivity in absence of cervical (pre) malignant disease are important drawbacks. In our opinion the results of large clinical trials should be awaited before proceeding to implement HPV DNA detection. New technologies based on molecular changes associated with cervical carcinogenesis might result in comparable sensitivity, but improved specificity. Hypermethylation analysis is likely to be more objective to identify patients with high grade squamous intra-epithelial lesions (HSIL) or invasive cancer with a higher specificity than current cytomorphology based screening

Temperature-Dependent Coherent Tunneling across Graphene-Ferritin Biomolecular Junctions

Understanding the mechanisms of charge transport (CT) across biomolecules in solid-state devices is imperative to realize biomolecular electronic devices in a predictive manner. Although it is well-Accepted that biomolecule-electrode interactions play an essential role, it is often overlooked. This paper reveals the prominent role of graphene interfaces with Fe-storing proteins in the net CT across their tunnel junctions. Here, ferritin (AfFtn-AA) is adsorbed on the graphene by noncovalent amine-graphene interactions confirmed with Raman spectroscopy. In contrast to junctions with metal electrodes, graphene has a vanishing density of states toward its intrinsic Fermi level ("Dirac point"), which increases away from the Fermi level. Therefore, the amount of charge carriers is highly sensitive to temperature and electrostatic charging (induced doping), as deduced from a detailed analysis of CT as a function of temperature and iron loading. Remarkably, the temperature dependence can be fully explained within the coherent tunneling regime due to excitation of hot carriers. Graphene is not only demonstrated as an alternative platform to study CT across biomolecular tunnel junctions, but it also opens rich possibilities in employing interface electrostatics in tuning CT behavior

Radical Surgery in Patients With Residual Disease After (Chemo)Radiation for Cervical Cancer

Objective: The aim of this study was to determine possible impact of routinely scheduled biopsies and more radical surgery for residual central disease in locally advanced cervical cancer after (chemo) radiation. Methods/Materials: Data were analyzed of a consecutive series of cervical cancer patients (The International Federation of Gynecology and Obstetrics stages IB1-IVA) treated with (chemo) radiation between 1994 and 2011. Patients underwent gynecologic examination with biopsies 8 to 10 weeks after treatment. Since 2001, larger biopsies by electric loop excision were taken, and more radical surgery (type III hysterectomy or exenteration) was performed for central residual disease. Primary outcome was locoregional recurrence. Secondary outcomes were treatment-associated morbidity and disease-specific survival. Results: Primary (chemo) radiation was given to 491 cervical cancer patients; 345 patients had a posttreatment biopsy. Viable tumor cells were identified in 84 patients, and 61 patients were eligible for salvage surgery. Residual disease after (chemo) radiation was an independent poor prognostic factor (hazard ratio, 3.59; 95% confidence interval, 2.18-5.93; P <0.001). After 2001, larger biopsies were more frequently taken (29% vs 76%, P <0.001), and in patients without viable tumor cells, locoregional recurrence after 2001 decreased from 21% to 10% (P = 0.01). After 2001, more patients underwent more radical surgery (46% vs 90%) (P <0.001). Locoregional recurrence after surgery before 2001 occurred in 6 (46%) of the 13 patients, comparable with 19 (40%) of the 48 (P = 0.67) after 2001. More radical surgery was not associated with improved disease-specific survival (HR, 0.84; 95% CI, 0.20-3.46; P = 0.81) but did result in significantly more severe morbidity. Conclusion: More radical surgery in patients with (minimal) central residual disease identified by routine biopsy 8 to 10 weeks after (chemo) radiation does not improve survival and should not be recommended

Assessment of gene promoter hypermethylation for detection of cervical neoplasia

Current cervical cancer screening is based on morphological assessment of Pap smears and associated with significant false negative and false positive results. Previously, we have shown that detection of hypermethylated genes in cervical scrapings using quantitative methylation-specific PCR (QMSP) is a promising tool for identification of squamous cell cervical cancer. Aim of the present pilot-study was to evaluate presence of hypermethylated genes in cervical carcinogenesis, both in squamous cell as well as adenocarcinomas. Cervical scrapings were obtained from 30 patients diagnosed with cervical cancer (20 squamous cell carcinomas and 10 adenocarcinomas) and 19 women with histologically normal cervices. The scraped cells were used for, determination of promoter hypermethylation by QMSP for 12 genes and for morphological assessment. Overall, CALCA, DAPK, ESR1, TIMP3, APC and RAR-beta(2) promoters were significantly more often hypermethylated in cancers than in controls, while adenocarcinomas were more often hypermethylated above the highest control ratio for APC, TIMP3 and RASSF1A promoters. Combining 4 genes (CALCA, DAPK, ESR1 and APC) yielded a sensitivity of 89% (with all adenocarcinomas identified), equal to cytomorphology (89%) and high-risk human papilloma virus (Hr-HPV; 90%). The 4-gene QMSP proved theoretically superior to cytomorphology as well as Hr-HPV in specificity (100% vs. 83 and 68%, respectively), because cytology identified 3 controls as moderate or severe dyskaryosis and 6 controls were positive for Hr-HPV. In conclusions, QMSP of 4 gene promoters combined appears to have comparable sensitivity and potentially better specificity in comparison to "classic" cytomorphological assessment and Hr-HPV detection. QMSP holds promise as a new diagnostic tool for both squamous cell carcinoma and adenocarcinoma of the cervix. (c) 2006 Wiley-Liss, Inc

Radical surgery in patients with residual disease after (chemo)radiation for cervical cancer

Objective: The aim of this study was to determine possible impact of routinely scheduled biopsies and more radical surgery for residual central disease in locally advanced cervical cancer after (chemo) radiation. Methods/Materials: Data were analyzed of a consecutive series of cervical cancer patients (The International Federation of Gynecology and Obstetrics stages IB1-IVA) treated with (chemo) radiation between 1994 and 2011. Patients underwent gynecologic examination with biopsies 8 to 10 weeks after treatment. Since 2001, larger biopsies by electric loop excision were taken, and more radical surgery (type III hysterectomy or exenteration) was performed for central residual disease. Primary outcome was locoregional recurrence. Secondary outcomes were treatment-associated morbidity and disease-specific survival. Results: Primary (chemo) radiation was given to 491 cervical cancer patients; 345 patients had a posttreatment biopsy. Viable tumor cells were identified in 84 patients, and 61 patients were eligible for salvage surgery. Residual disease after (chemo) radiation was an independent poor prognostic factor (hazard ratio, 3.59; 95% confidence interval, 2.18-5.93; P <0.001). After 2001, larger biopsies were more frequently taken (29% vs 76%, P <0.001), and in patients without viable tumor cells, locoregional recurrence after 2001 decreased from 21% to 10% (P = 0.01). After 2001, more patients underwent more radical surgery (46% vs 90%) (P <0.001). Locoregional recurrence after surgery before 2001 occurred in 6 (46%) of the 13 patients, comparable with 19 (40%) of the 48 (P = 0.67) after 2001. More radical surgery was not associated with improved disease-specific survival (HR, 0.84; 95% CI, 0.20-3.46; P = 0.81) but did result in significantly more severe morbidity. Conclusion: More radical surgery in patients with (minimal) central residual disease identified by routine biopsy 8 to 10 weeks after (chemo) radiation does not improve survival and should not be recommended

Temperature-Dependent Coherent Tunneling across Graphene–Ferritin Biomolecular Junctions

Understanding the mechanisms of charge transport (CT) across biomolecules in solid-state devices is imperative to realize biomolecular electronic devices in a predictive manner. Although it is well-accepted that biomolecule–electrode interactions play an essential role, it is often overlooked. This paper reveals the prominent role of graphene interfaces with Fe-storing proteins in the net CT across their tunnel junctions. Here, ferritin (AfFtn-AA) is adsorbed on the graphene by noncovalent amine–graphene interactions confirmed with Raman spectroscopy. In contrast to junctions with metal electrodes, graphene has a vanishing density of states toward its intrinsic Fermi level (“Dirac point”), which increases away from the Fermi level. Therefore, the amount of charge carriers is highly sensitive to temperature and electrostatic charging (induced doping), as deduced from a detailed analysis of CT as a function of temperature and iron loading. Remarkably, the temperature dependence can be fully explained within the coherent tunneling regime due to excitation of hot carriers. Graphene is not only demonstrated as an alternative platform to study CT across biomolecular tunnel junctions, but it also opens rich possibilities in employing interface electrostatics in tuning CT behavior