Screening for Prostate Cancer: Digital rectal examination: outdated or still valuable?

Introduction and Objective: Digital rectal examination (DRE) is an important diagnostic tool of a urologist and it has been incorporated in screening programmes for prostate cancer (PC), such as the European Randomized Study of Screening for Prostate Cancer (ERSPC). In the Rotterdam section of this study, until 1997, a man with a PSA level ≥4.0 ng/ml or an abnormal result on DRE or TRUS (transrectal ultrasound) was offered a lateralised sextant prostate biopsy. After 1997 however, DRE and TRUS were discontinued as a biopsy indication and simultaneously the PSA threshold was lowered to 3.0 ng/ml. While TRUS clearly was not shown to be a valuable test for the early detection of PC, the value of DRE has been more controversial. In this study we summarise the evidence on the position of DRE in a PSA-based screening. Methods First, we assessed the variability in percentage of positive DRE between different physicians. Furthermore, we evaluated the additional effect of an abnormal DRE on the chance of a positive prostate biopsy result in men with an elevated PSA, the differences in characteristics between tumours detected in PSA range 2.0-4.0 ng/ml due to a positive DRE or due to a PSA cut-off, and the long-term effect of having an abnormal DRE. Finally, the effect of omitting DRE from the screening protocol was analysed. Results A positive result of a DRE is important subject to interobserver variability, varying from 4% to 28%. At very low PSA (<4.0 ng/ml), DRE has a poor PPV of approximately 10%. A suspicious DRE compared to normal findings, in addition to an elevated PSA, increased the chance of finding a positive biopsy at initial screening from 22.4% to 48.6%. This effect is independent of observer, but diminished with subsequent screening rounds. In the low PSA range of 2.0-4.0 ng/ml, DRE more selectively detects high-grade cancers when compared to biopsying all men, but still missed many of these. On long-term, however, an initially positive DRE with negative biopsy gives no worse outcomes regarding cancers detected later. Omitting DRE and TRUS, while lowering the PSA threshold to 3.0 ng/ml as a biopsy indication resulted in an overall decrease of 10% in the rate of biopsies, while the detection rate remained similar at 4.7%. On a relatively short-term follow-up, this neither resulted in an i! ncreased risk of interval cancers or PC detected in subsequent screening rounds. Conclusions At the first screening and when used in addition to an elevated PSA, DRE increases both the chance of finding PC and selectively detecting clinically significant disease. DRE could therefore be of use to optimise screening in subgroups of men. However, the predictive value of DRE is low in a screening setting, and therefore not suitable as a solitary screening tool in men with low PSA values

Расчет потерь давления воздуха в горных выработках с учетом равномерных и неравномерных утечек

Охарактеризовано метод розрахунку втрат тиску повітря у гірничих виробках за наявності витоків (притоків), який може бути використано під час проектування системи провітрювання шахти з метою вибору засобів місцевого керування повітряних потоків, розрахунку конфігурації ліній витоку у виробленому просторі та при оцінці зміни витоків у аварійній ситуації і розробці методів керування ними.The method of calculation losses of pressure of air in the mining workings at presence of leakages (inflows), which can be used for planning of the ventilation system of mine with the purpose of choice facilities of the local control of air blast, calculation of configuration lines of leakages in the worked out goaf and at estimation change of leakages in an emergency situation and development methods of control by them

ProCOC: The prostate cancer outcomes cohort study

BACKGROUND: Despite intensive research over the last several decades on prostate cancer, many questions particularly those concerning early diagnosis and the choice of optimal treatment for each individual patient, still remain unanswered. The goal of treating patients with localized prostate cancer is a curative one and includes minimizing adverse effects to preserve an adequate quality of life. Better understanding on how the quality of life is affected depending on the treatment modality would assist patients in deciding which treatment to choose; furthermore, the development of prognostic biomarkers that indicate the future course of the illness is a promising approach with potential and the focus of much attention. These questions can be addressed in the context of a cohort study. METHODS/DESIGN: This is a prospective, multi-center cohort study within the canton of Zurich, Switzerland. We will include patients with newly diagnosed localized prostate cancer independently of treatment finally chosen. We will acquire clinical data including quality of life and lifestyle, prostate tissue specimen as well as further biological samples (blood and urine) before, during and after treatment for setup of a bio-bank. Assessment of these data and samples in the follow up will be done during routine controls. Study duration will be at least ten years. Influence of treatment on morbidity and mortality, including changes in quality of life, will be identified and an evaluation of biomarkers will be performed. Further we intend to set up a bio-bank containing blood and urine samples providing research of various natures around prostate cancer in the future. DISCUSSION: We presume that this study will provide answers to pertinent questions concerning prognosis and outcomes of men with localised prostate cancer

Can we use intraoperative high-frequency oscillations to guide tumor-related epilepsy surgery?

Objective: In people with low-grade intrinsic brain tumors, an epileptic focus is often located close to the lesion. High-frequency oscillations (HFOs) in electrocorticography (ECoG) might help to delineate this focus. We investigated the relationship between HFOs and low-grade brain tumors and their potential value for tumor-related epilepsy surgery. Methods: We analyzed pre- and postresection intraoperative ECoG in 41 patients with refractory epilepsy and a low-grade lesion. Electrodes were designated as overlying the tumor, adjacent resected tissue (peritumoral), or outside the resection bed using magnetic resonance imaging (MRI) and intraoperative photographs. We then used a semiautomated approach to detect HFOs as either ripples (80–250 Hz) or fast ripples (250–500 Hz). Results: The rate of fast ripples was higher in electrodes covering tumor and peritumoral tissue than outside the resection (p =.04). Mesiotemporal tumors showed more ripples (p =.002), but not more fast ripples (p =.07), than superficial tumors. Rates of fast ripples were higher in glioma and extraventricular neurocytoma than in ganglioglioma or dysembryoplastic neuroepithelial tumor (DNET). The rate of ripples and fast ripples in postresection ECoG was not higher in patients with residual tumor tissue on MRI than those without. The rate of ripples in postresection ECoG was higher in patients with good than bad seizure outcome (p =.03). Fast ripples outside the resection and in post-ECoG seem related to seizure recurrence. Significance: Fast ripples in intraoperative ECoG can be used to help guide resection in tumor-related epilepsy surgery. Preresection fast ripples occur predominantly in epileptogenic tumor and peritumoral tissue. Fast ripple rates are higher in glioma and extraventricular neurocytoma than in ganglioglioma and DNET

Sharon Macdonald – Memorylands: Heritage and Identity in Europe Today

Memorylands: Heritage and Identity in Europe Today é um livro de síntese que assinala o culminar de anos de trabalho da antropóloga britânica Sharon Macdonald sobre os temas relacionados do património, da memória e da identidade em contextos europeus. Em Reimagining Culture: Histories, Identities and the Gaelic Renaissance, de 1997, situava o eixo analítico entre o local e o global, focando o seu olhar na questão dos muitos “renascimentos identitários” de escala local e regional que à época –..

Expression of Circ_Satb1 Is Decreased in Mesial Temporal Lobe Epilepsy and Regulates Dendritic Spine Morphology

Mesial temporal lobe epilepsy (mTLE) is a chronic disease characterized by recurrent seizures that originate in the temporal lobes of the brain. Anti-epileptic drugs (AEDs) are the standard treatment for managing seizures in mTLE patients, but are frequently ineffective. Resective surgery is an option for some patients, but does not guarantee a postoperative seizure-free period. Therefore, further insight is needed into the pathogenesis of mTLE to enable the design of new therapeutic strategies. Circular RNAs (circRNAs) have been identified as important regulators of neuronal function and have been implicated in epilepsy. However, the mechanisms through which circRNAs contribute to epileptogenesis remain unknown. Here, we determine the circRNA transcriptome of the hippocampus and cortex of mTLE patients by using RNA-seq. We report 333 differentially expressed (DE) circRNAs between healthy individuals and mTLE patients, of which 23 circRNAs displayed significant adjusted p-values following multiple testing correction. Interestingly, hippocampal expression of circ_Satb1, a circRNA derived from special AT-rich sequence binding protein 1 (SATB1), is decreased in both mTLE patients and in experimental epilepsy. Our work shows that circ_Satb1 displays dynamic patterns of neuronal expression in vitro and in vivo. Further, circ_Satb1-specific knockdown using CRISPR/CasRx approaches in hippocampal cultures leads to defects in dendritic spine morphology, a cellular hallmark of mTLE. Overall, our results identify a novel epilepsy-associated circRNA with disease-specific expression and previously unidentified cellular effects that are relevant for epileptogenesis

Epithelial cancers in the post-genomic era: should we reconsider our lifestyle?

The age-related epithelial cancers of the breast, colorectum and prostate are the most prevalent and are increasing in our aging populations. Epithelial cells turnover rapidly and mutations naturally accumulate throughout life. Most epithelial cancers arise from this normal mutation rate. All elderly individuals will harbour many cells with the requisite mutations and most will develop occult neoplastic lesions. Although essential for initiation, these mutations are not sufficient for the progression of cancer to a life-threatening disease. This progression appears to be dependent on context: the tissue ecosystem within individuals and lifestyle exposures across populations of individuals. Together, this implies that the seeds may be plentiful but they only germinate in the right soil. The incidence of these cancers is much lower in Eastern countries but is increasing with Westernisation and increases more acutely in migrants to the West. A Western lifestyle is strongly associated with perturbed metabolism, as evidenced by the epidemics of obesity and diabetes: this may also provide the setting enabling the progression of epithelial cancers. Epidemiology has indicated that metabolic biomarkers are prospectively associated with cancer incidence and prognosis. Furthermore, within cancer research, there has been a rediscovery that a switch in cell metabolism is critical for cancer progression but this is set within the metabolic status of the host. The seed may only germinate if the soil is fertile. This perspective brings together the different avenues of investigation implicating the role that metabolism may play within the context of post-genomic concepts of cancer