Match and Mismatch between Lived Experiences of Daytime Sleepiness and Diagnostic Instruments: A Qualitative Study amongst Patients with Sleep Disorders.

Excessive daytime sleepiness is a common symptom of sleep disorders. Despite its prevalence, it remains difficult to define, detect, and address. The difficulties surrounding sleepiness have been linked to an ambiguous conceptualization, a large variety of scales and measures, and the overlap with other constructs, such as fatigue.

Optimising follow-up strategy based on cytology and human papillomavirus after fertility-sparing surgery for early stage cervical cancer: a nationwide, population-based, retrospective cohort study.

Background: The optimal follow-up strategy to detect recurrence after fertility-sparing surgery for early stage cervical cancer is unknown. Tailored surveillance based on individual risks could contribute to improved efficiency and, subsequently, reduce costs in health care. The aim of this study was to establish the predictive value of cervical cytology and high-risk human papillomavirus (HPV) testing to detect recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+; including recurrent cervical cancer) after fertility-sparing surgery.

Psychophysiological dynamics of emotional reactivity: Interindividual reactivity characterization and prediction by a machine learning approach.

The fast reaction of the autonomic nervous system (ANS) to an emotional challenge (EC) is the result of a functional coupling between parasympathetic (PNS) and sympathetic (SNS) branches. This coupling can be characterized by measures of cross-correlations between electrodermal activity (EDA) (under the influence of the SNS) and the RR interval (the interval between R peaks) (under the influence of the PNS and the SNS). Significant interindividual variability has previously been reported in SNS-PNS coupling in emotional situations, and the present study aimed to identify interindividual cross-correlation variability in ANS reactivity.

Evaluation of p16/Ki-67 dual-stained cytology as triage test for high-risk human papillomavirus-positive women.

The aim of this study was to evaluate the clinical utility of p16/Ki-67 dual staining, for the identification of CIN in high-risk HPV-positive women from a non-responder screening cohort. P16/Ki-67 dual staining, Pap cytology, and HPV16/18 genotyping were performed on physician-taken liquid-based samples from 495 women who tested high-risk HPV positive on self-sampled material (PROHTECT-3B study). Different triage strategies involving p16/Ki-67 dual staining were evaluated for sensitivity, specificity, and predictive value for ≥CIN2 and ≥CIN3, and compared to Pap cytology with a threshold of atypical cells of undetermined significance.

The clinical value of HPV genotyping in triage of women with high-risk-HPV-positive self-samples.

Cytology alone, or combined with HPV16/18 genotyping, might be an acceptable method for triage in hrHPV-cervical cancer screening. Previously studied HPV-genotype based triage algorithms are based on cytology performed without knowledge of hrHPV status. The aim of this study was to explore the value of hrHPV genotyping combined with cytology as triage tool for hrHPV-positive women.

Validation of the FAM19A4/mir124-2 DNA methylation test for both lavage- and brush-based self-samples to detect cervical (pre)cancer in HPV-positive women.

Objectives: DNA methylation analysis of cancer-related genes is a promising tool for HPV-positive women to identify those with cervical (pre)cancer (CIN3+) in need of treatment. However, clinical performance of methylation markers can be influenced by the sample type utilized. We describe a multiplex quantitative methylation-specific PCR that targets FAM19A4 and mir124-2 loci, to detect CIN3+ using both HPV-positive lavage- and brush self-samples.

Follow-up of high-risk HPV positive women by combined cytology and bi-marker CADM1/MAL methylation analysis on cervical scrapes.

Objectives: Triage of HPV screen-positive women is needed to identify those with underlying cervical intraepithelial neoplasia grade 2/3 or worse (CIN2/3+). Presently, cytology on a physician-taken cervical scrape is mostly accepted as triage test, but needs follow-up testing in order not to miss severe disease. Here, we evaluated the performance of combined cytology and bi-marker CADM1/MAL-methylation analysis as triage test on physician-taken cervical scrapes of HPV positive women.

Methylation marker analysis and HPV16/18 genotyping in high-risk HPV positive self-sampled specimens to identify women with high grade CIN or cervical cancer.

Objectives: Methylation marker analysis using bi-marker panel MAL/miR-124-2 is a promising triage test for identifying cervical (pre)cancer in high-risk human papillomavirus (hrHPV) positive women. Bi-marker panel MAL/miR-124-2 can be applied directly on self-sampled cervico-vaginal material and its sensitivity is non-inferior to that of cytology, yet at the cost of more colposcopy referrals. Our objective was to increase specificity of MAL/miR-124-2 methylation analysis by varying the assay thresholds and adding HPV16/18 genotyping.

DNA methylation analysis in self-sampled brush material as a triage test in hrHPV-positive women.

Background: Primary high-risk human papillomavirus (hrHPV) testing in cervical cancer screening shows relatively low specificity, which makes triage testing necessary. In this study, DNA methylation analysis was compared with cytology for triage testing in hrHPV-positive women. Moreover, feasibility of DNA methylation analysis directly on brush-based self-sampled specimens was assessed.

Comparative performance of novel self-sampling methods in detecting high-risk human papillomavirus in 30,130 women not attending cervical screening.

We determined whether the participation rate for a brush-based cervicovaginal self-sampling device is noninferior to the participation rate for a lavage-based one for testing for hrHPV (high-risk human papillomavirus). Additionally, positivity rates for hrHPV, the detection rates for cervical intraepithelial neoplasia grades 2 and 3 or worse (CIN2+/3+), and user comfort were compared. A total of 35,477 non-responders of the regular cervical screening program aged 33-63 years were invited to participate.

Reasons for non-attendance to cervical screening and preferences for HPV self-sampling in Dutch women.

Objectives: High attendance rates in cervical screening are essential for effective cancer prevention. Offering HPV self-sampling to non-responders increases participation rates. The objectives of this study were to determine why non-responders do not attend regular screening, and why they do or do not participate when offered a self-sampling device.

Arguments in favor of HPV testing for cervical screening and post-treatment CIN2+ monitoring.

Several studies have shown that the human papilloma virus (HPV) test is a more sensitive and objective primary cervical cancer screening tool than cytology. Therefore, conversion of cytology into HPV screening (as is planned in The Netherlands and some other European regions) will result in a better protection against cervical cancer and high-grade precursor lesions. Moreover, offering self-sampling for HPV testing will increase screening attendance by re-attracting former non-attendees.

Triage by methylation-marker testing versus cytology in women who test HPV-positive on self-collected cervicovaginal specimens (PROHTECT-3): a randomised controlled non-inferiority trial.

Background: Cytology is a widely used method of triaging women who test positive for human papillomavirus (HPV). However, self-sampled specimens, which can substantially increase participation in screening programmes, are not suitable for accurate cytological assessment. We investigated whether direct DNA methylation-based molecular triage on self-sampled cervicovaginal specimens was non-inferior to cytology triage on additional physician-collected cervical samples in the detection of cervical intraepithelial neoplasia grade 2 (CIN2) or worse in women who did not attend cervical screening programmes.

Accuracy of human papillomavirus testing on self-collected versus clinician-collected samples: a meta-analysis.

Background: Screening for human papillomavirus (HPV) infection is more effective in reducing the incidence of cervical cancer than screening using Pap smears. Moreover, HPV testing can be done on a vaginal sample self-taken by a woman, which offers an opportunity to improve screening coverage. However, the clinical accuracy of HPV testing on self-samples is not well-known.

A second generation cervico-vaginal lavage device shows similar performance as its preceding version with respect to DNA yield and HPV DNA results.

Background: Attendance rates of cervical screening programs can be increased by offering HPV self-sampling to non-attendees. Acceptability, DNA yield, lavage volumes and choice of hrHPV test can influence effectiveness of the self-sampling procedures and could therefore play a role in recruiting non-attendees. To increase user-friendliness, a frequently used lavage sampler was modified.

High-risk HPV testing on self-sampled versus clinician-collected specimens: a review on the clinical accuracy and impact on population attendance in cervical cancer screening.

This review elaborates on the accuracy and feasibility of human papillomavirus (HPV) self-sampling, i.e., offering self-sampling of (cervico-)vaginal cell material by women themselves in nonclinical settings for high-risk HPV (hrHPV) detection in the laboratory, for cervical screening.

NOX5 expression is increased in intramyocardial blood vessels and cardiomyocytes after acute myocardial infarction in humans.

Reactive oxygen species producing NADPH oxidases play important roles under different (patho)physiological conditions. NOX1, NOX2, and NOX4 are important sources of reactive oxygen species in the heart, but knowledge of the calcium-dependent NOX5 in the heart is lacking. The presence of NOX5 was studied via RT-PCR in heart tissue from patients with end-stage heart failure; the tissue was obtained during cardiac transplantation surgery.

Myelotoxicity of rifabutin and 3'-azido-3'-deoxythymidine, alone and in combination, to human hematopoietic progenitor cells in vitro.

Mycobacterial infection is a common complication of acquired immunodeficiency syndrome (AIDS) frequently requiring antimycobacterial medication. It was of interest to determine if one such agent, rifabutin, could be tolerated by AIDS patients in conjunction with 3'-azido-3'-deoxythymidine (AZT) therapy. We evaluated the in vitro myelotoxic effects of rifabutin on human hematopoietic progenitor cells, alone and in combination with AZT (rifabutin: AZT, 1:10 ratio) over a range of concentrations in a microcapillary assay.

Regulation of purine deoxynucleoside phosphorylation by deoxycytidine kinase from human leukemic blast cells.

The kinetics and regulation of nucleoside phosphorylation by highly purified human deoxycytidine kinase from leukemic lymphoblasts were studied. The phosphorylation of purine nucleosides by this enzyme showed sensitivity to the endogenous inhibitors dCTP and UDP three times greater than the phosphorylation of dCyd. Examination of nucleotide pools in human T and B lymphoblasts disclosed that the levels of dCTP and UDP in these cells were sufficient to regulate kinase activity.

Mono and bis(bioreductive) alkylating agents: synthesis and antitumor activities in a B16 melanoma model.

Several potentially bis(alkylating) bis(quinones) (3-5) and 1,4- and 1,3-bis(alkylating) monoquinones (6-13) belonging to general structure 2,2'-ethylenebis[5-[(leaving group)methyl]-1,4-benzoquinone] (3-5) and 2,5- and 2,6-bis[(leaving group)methyl]-1,4-benzoquinone water-soluble and -insoluble classes were prepared by oxidative demethylation of the corresponding tetramethoxydiphenylethanes (17-19) and dimethoxybenzenes (24, 27, 36-39), respectively. Methods employed for the preparation of tetramethoxydiphenylethane intermediates involved (1) arylmethyl bromide coupling and (2) catalytic hydrogenation of stilbene intermediates derived via Wittig reaction of (arylmethyl)phosphonium salts with aryl aldehydes. However, in biological investigations using a subcutaneous B16 (hypoxic) melanoma tumor in BDF1 hybrid mice with cyclophosphamide as positive control the most interesting series of structurally related analogues were the potentially monoalkylating monoquinones of the 2-[(leaving group)methyl]-1,4-benzoquinone type (i.

Rhodamine 123 and flow cytometry to monitor the cytotoxic actions of nucleoside analogues in nondividing human lymphocytes.

We used human lymphocytes from the peripheral blood of normal individuals to compare the cytolytic actions of 2-chloro-2'-deoxyadenosine (2-Cl-dAdo) and 9-beta-D-arabinofuranosylguanine (ara-G). Membrane integrity was ascertained by flow cytometric quantification of the cells' uptake of the fluorescent mitochondria-specific probe rhodamine 123. Addition of 10 microM ara-G to lymphocyte cultures led to a progressive decline in the number of cells that could assimilate rhodamine 123, and after 2 days exposure to drug less than 50% of the cells showed normal staining compared to untreated cells.

Metabolism and selectivity of arabinonucleoside in human lymphoid cells.

The selective toxicity of purine deoxynucleosides against lymphoid cells appears to be mediated by a preferential accumulation of the corresponding triphosphates in these cells. We report a study of the metabolism and toxicity of arabinonucleosides of guanine and cytosine toward human T- and B-lymphoblastoid-cell lines. Both compounds inhibited the growth of T lymphoblasts at concentrations less than 2 microM.

Metabolic basis of arabinonucleoside selectivity for human leukemic T- and B-lymphoblasts.

Purine analogues are potentially useful agents for selective chemotherapy of lymphoproliferative diseases. We compared the toxic effects of various arabinonucleosides against eight human T- and B-lymphoblastoid lines. The arabinosides of cytosine (ara-C), 2-fluoroadenine (F-ara-A), adenine (ara-A) and guanine (ara-G) all inhibited the growth of T-lymphoblasts at concentrations below 2 microM.

Adenosine phosphorylase activity in mycoplasma-free growth media for mammalian cells.

Mammalian cells have enzymes that deaminate adenosine to inosine, which can readily be phosphorolysed to hypoxanthine. They do not, however, possess enzymes to form adenine by the cleavage of adenosine. For this reason, the release of adenine from adenosine by mammalian cell cultures has usually been interpreted as indicating the presence of mycoplasma, a frequent microbial contaminant that contains high levels of adenosine phosphorylase.