Pharmacological validation of Trypanosoma brucei phosphodiesterases as novel drug targets.

The development of drugs for neglected infectious diseases often uses parasite-specific enzymes as targets. We here demonstrate that parasite enzymes with highly conserved human homologs may represent a promising reservoir of new potential drug targets. The cyclic nucleotide-specific phosphodiesterases (PDEs) of Trypanosoma brucei, causative agent of the fatal human sleeping sickness, are essential for the parasite.

Increased non-prostate cancer death risk in clinically diagnosed prostate cancer.

Unlabelled: Study Type - Prognosis (case control). Level of Evidence 3a. What's known on the subject? and What does the study add? Treatment of advanced PC might put patients at an increased risk of cardiovascular events.

Sexual function with localized prostate cancer: active surveillance vs radical therapy.

Unlabelled: Study Type - Outcomes (cohort sample) Level of Evidence 2b. What's known on the subject? and What does the study add? The study compares the sexual function of men with low-risk prostate cancer who chose active surveillance (expectant management) with similar men who received radiation therapy or radical prostatectomy. The first group appeared to be sexually active more frequently and had less erectile dysfunction.

Validation of novel fluorescence assays for the routine screening of drug susceptibilities of Trichomonas vaginalis.

Objectives: To evaluate existing protocols, based on Alamar blue (resazurin), for the routine determination of drug susceptibility in trichomonads, develop new ones and validate these by screening small antiprotozoal libraries.

Methods: The resazurin-based assay was evaluated by determining fluorescence development in Trichomonas media with various cell densities after various intervals and in the presence of metronidazole. Similar investigations were performed with the alternative fluorophores propidium iodide (PI) and resorufin.

A different approach to treatment-resistant tinnitus: pulsed radiofrequency to the ganglion C2.

Tinnitus represents one of the most common and distressing otologic problems, and it causes various somatic and psychological disorders that interfere with the quality of life. Treatments for tinnitus include pharmacotherapy, cognitive and behavioral therapy, sound therapy, music therapy, tinnitus retraining therapy, massage and stretching, and electrical suppression. In this case report we present a potential treatment, namely pulsed radiofrequency to the ganglion C2.

NELSON lung cancer screening study.

The Dutch-Belgian Randomized Lung Cancer Screening Trial (Dutch acronym: NELSON study) was designed to investigate whether screening for lung cancer by low-dose multidetector computed tomography (CT) in high-risk subjects will lead to a decrease in 10-year lung cancer mortality of at least 25% compared with a control group without screening. Since the start of the NELSON study in 2003, 7557 participants underwent CT screening, with scan rounds in years 1, 2, 4 and 6. In the current review, the design of the NELSON study including participant selection and the lung nodule management protocol, as well as results on validation of CT screening and first results on lung cancer screening are described.

Synthesis of marine-derived 3-alkylpyridinium alkaloids with potent antiprotozoal activity.

Given the pressing need for new antiprotozoal drugs without cross-resistance with current (failing) chemotherapy, we have explored 3-tridecylpyridinium alkaloids (3TPAs), derivatives of viscosamine, as antiparasitic agents. We have developed a simple synthetic route toward viscosamine and related cyclic and linear monomers and oligomers. Evaluation for cytotoxicity on the protozoan parasites Trypanosoma brucei, Leishmania spp.

Mammography screening and risk of breast cancer death: a population-based case-control study.

Background: Because the efficacy of mammography screening had been shown in randomized controlled trials, the focus has turned on its effectiveness within the daily practice. Using individual data of women invited to screening, we conducted a case-control study to assess the effectiveness of the Dutch population-based program of mammography screening.

Methods: Cases were women who died from breast cancer between 1995 and 2003 and were closely matched to five controls on year of birth, year of first invitation, and number of invitations before case's diagnosis.

No benefit for consensus double reading at baseline screening for lung cancer with the use of semiautomated volumetry software.

Purpose: To retrospectively evaluate the performance of consensus double reading compared with single reading at baseline screening of a lung cancer computed tomography (CT) screening trial.

Materials And Methods: The study was approved by the Dutch Minister of Health and ethical committees. Written informed consent was obtained from all participants.

The effectiveness of a computer-tailored smoking cessation intervention for participants in lung cancer screening: a randomised controlled trial.

Background: Lung cancer screening might be a teachable moment for smoking cessation intervention. The objective was to investigate whether a tailored self-help smoking cessation intervention is more effective in inducing smoking cessation compared to a standard brochure in male smokers who participate in the Dutch-Belgian randomised controlled lung cancer screening trial (NELSON trial).

Methods: Two random samples of male smokers who had received either a standard brochure (n=642) or a tailoring questionnaire for computer-tailored smoking cessation information (n=642) were sent a questionnaire to measure smoking behaviour two years after randomisation.

Modeling the impact of population screening on breast cancer mortality in the United States.

Objective: Optimal US screening strategies remain controversial. We use six simulation models to evaluate screening outcomes under varying strategies.

Methods: The models incorporate common data on incidence, mammography characteristics, and treatment effects.

The provision of information and informed decision-making on prenatal screening for Down syndrome: a questionnaire- and register-based survey in a non-selected population.

Objective: Evaluating the information provision procedure about prenatal screening for Down syndrome, using informed decision-making as a quality-indicator.

Methods: Questionnaire- and register-based surveys. Midwives associated with 59 midwifery practices completed process data for 6435 pregnancies.

Identification of chronic obstructive pulmonary disease in lung cancer screening computed tomographic scans.

Context: Smoking is a major risk factor for both cancer and chronic obstructive pulmonary disease (COPD). Computed tomography (CT)-based lung cancer screening may provide an opportunity to detect additional individuals with COPD at an early stage.

Objective: To determine whether low-dose lung cancer screening CT scans can be used to identify participants with COPD.

Characterization of protocadherin-1 expression in primary bronchial epithelial cells: association with epithelial cell differentiation.

Protocadherin-1 (PCDH1) is a novel susceptibility gene for asthma that is expressed in airway epithelium. We aimed to characterize PCDH1 mRNA transcripts and protein expression in primary bronchial epithelial cells and to determine regulation of PCDH1 during mucociliary differentiation. Total RNA and protein were isolated from human primary bronchial epithelial cells.

Protocadherin-1 polymorphisms are associated with eczema in two Dutch birth cohorts.

Background:   Eczema and asthma share a common genetic background and show linkage to chromosome 5q31-33. Protocadherin-1 (PCDH1) is located in this region and was identified as a susceptibility gene for bronchial hyper-responsiveness (BHR), a hallmark of asthma. PCDH1 encodes an adhesion molecule, expressed in airway and skin epithelium.

The role of the ¹⁸f-fluorodeoxyglucose-positron emission tomography scan in the Nederlands Leuvens Longkanker screenings Onderzoek lung cancer screening trial.

Background: In computed tomography lung cancer screening programs, up to 30% of all resections are futile.

Objective: To investigate whether a preoperative positron emission tomography (PET) after a conclusive or inconclusive nonsurgical workup will reduce the resection rate for benign disease in test-positive participants of a lung cancer screening program.

Methods: ¹⁸F-Fluorodeoxyglucose-PET scans were made in 220 test positives.

Prediction of higher mortality reduction for the UK Breast Screening Frequency Trial: a model-based approach on screening intervals.

Background: The optimal interval between two consecutive mammograms is uncertain. The UK Frequency Trial did not show a significant difference in breast cancer mortality between screening every year (study group) and screening every 3 years (control group). In this study, the trial is simulated in order to gain insight into the results of the trial and to predict the effect of different screening intervals on breast cancer mortality.

Asthma-like symptoms in the first year of life and health-related quality of life at age 12 months: the Generation R study.

Purpose: This study compares HRQOL among subgroups of infants with asthma-like symptoms to a subgroup without such symptoms and examines independent associations between asthma-like symptoms during the first year of life and HRQOL at age 12 months.

Methods: Our study sample included 5,000 infants participating in the Generation R study. Their parents completed structured questionnaires to obtain information on asthma-like symptoms, HRQOL, infants', and maternal characteristics.

Determinants and outcome of unsuccessful referral after positive screening in a large birth-cohort study of population-based vision screening.

Purpose: The efficacy of population-based vision screening is hampered by unsuccessful referral after a positive screening test. We studied the nature and causes of unsuccessful referral in a 7-year birth cohort study of vision screening in Rotterdam, the Netherlands.

Methods: All parents of children who had been unsuccessfully referred were asked whether they recalled the referral.

Digital mammography screening: weighing reduced mortality against increased overdiagnosis.

Objective: Digital mammography has been shown to increase the detection of ductal carcinoma in situ (DCIS) compared to screen-film mammography. The benefits and risks of such an increase were assessed.

Methods: Breast cancer detection rates were compared between 502,574 screen-film and 83,976 digital mammograms performed between 2004 and 2006 among Dutch screening participants.

Interpreting overdiagnosis estimates in population-based mammography screening.

Estimates of overdiagnosis in mammography screening range from 1% to 54%. This review explains such variations using gradual implementation of mammography screening in the Netherlands as an example. Breast cancer incidence without screening was predicted with a micro-simulation model.

Meningitis after invasive treatment of the trigeminal ganglion: two case reports and a review of the literature.

Objectives: The objective of this case is to report the rare complication of a meningitis after an invasive treatment of the trigeminal ganglion.

Methods: In this case report, two cases of meningitis due to oral streptococci are reported and a review of literature is presented.

Results And Discussion: This complication should be recognized as early as possible to prevent deterioration of the situation.

Therapeutic potential of phosphodiesterase inhibitors in parasitic diseases.

Protozoan parasites of the order kinetoplastida are the causative agents of three of the world's most important neglected human diseases: African trypanosomiasis, American trypanosomiasis, and leishmaniasis. Current therapies are limited, with some treatments having serious and sometimes lethal side effects. The growing number of cases that are refractory to treatment is also of concern.

Disease-specific survival of men with prostate cancer detected during the screening interval: results of the European randomized study of screening for prostate cancer-Rotterdam after 11 years of follow-up.

Background: In a screening program, interval cancers are cancers diagnosed between two screening visits.

Objective: To assess the disease-specific survival (DSS) of men with prostate cancer (PCa) detected during the screening interval.

Design, Setting, And Participants: Within the European Randomized Study of Screening for Prostate Cancer section Rotterdam, 42 376 men identified from population registries (55-74 yr of age) were randomized to a screening or control arm.