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An empirical evaluation of guidelines on prostate-specific antigen velocity in prostate cancer detection

Background The National Comprehensive Cancer Network and American Urological Association guidelines on early detection of prostate cancer recommend biopsy on the basis of high prostate-specific antigen (PSA) velocity, even in the absence of other indications such as an elevated PSA or a positive digital rectal exam (DRE). Methods To evaluate the current guideline, we compared the area under the cu

Untangling the threads of cellulose mercerization

Naturally occurring plant cellulose, our most abundant renewable resource, consists of fibers of long polymer chains that are tightly packed in parallel arrays in either of two crystal phases collectively referred to as cellulose I. During mercerization, a process that involves treatment with sodium hydroxide, cellulose goes through a conversion to another crystal form called cellulose II, within

Mitochondrial biogenesis, telomere length and cellular senescence in Parkinson’s disease and Lewy body dementia

Progressive age is the single major risk factor for neurodegenerative diseases. Cellular aging markers during Parkinson’s disease (PD) have been implicated in previous studies, however the majority of studies have investigated the association of individual cellular aging hallmarks with PD but not jointly. Here, we have studied the association of PD with three aging hallmarks (telomere attrition, m

Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer : Preliminary analysis of the results of the IMPACT study

OBJECTIVE: To evaluate the role of targeted prostate cancer screening in men with BRCA1 or BRCA2 mutations, an international study, IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls), was established. This is the first multicentre screening study targeted at men with a known genetic predisposition to prostat

Individual excellence funding : effects on research autonomy and the creation of protected spaces

This article contributes to the emerging body of literature which investigates the mechanisms through which funding conditions affect research. It is an interview-based case study of the Distinguished Professor Grant (DPG); an excellence funding instrument aimed at individuals. The study uses the concept of “protected space” to explore the epistemic and organizational dynamics enabled by the DPG.

The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine

Background: Microseminoprotein-beta (MSMB) regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in

Prostate specific antigen concentration at age 60 and death or metastasis from prostate cancer : Case-control study

Objective: To determine the relation between concentrations of prostate specific antigen at age 60 and subsequent diagnosis of clinically relevant prostate cancer in an unscreened population to evaluate whether screening for prostate cancer and chemoprevention could be stratified by risk. Design: Case-control study with 1:3 matching nested within a highly representative population based cohort stu

Comparison of fractal and grid electrodes for studying the effects of spatial confinement on dissociated retinal neuronal and glial behavior

Understanding the impact of the geometry and material composition of electrodes on the survival and behavior of retinal cells is of importance for both fundamental cell studies and neuromodulation applications. We investigate how dissociated retinal cells from C57BL/6J mice interact with electrodes made of vertically-aligned carbon nanotubes grown on silicon dioxide substrates. We compare electrod

A panel of kallikrein markers can predict outcome of prostate biopsy following clinical work-up : An independent validation study from the European Randomized Study of Prostate Cancer screening, France

Background: We have previously shown that a panel of kallikrein markers - total prostate-specific antigen (PSA), free PSA, intact PSA and human kallikrein-related peptidase 2 (hK2) - can predict the outcome of prostate biopsy in men with elevated PSA. Here we investigate the properties of our panel in men subject to clinical work-up before biopsy.Methods: We applied a previously published predicti

The relationship between prostate-specific antigen and prostate cancer risk : The prostate biopsy collaborative group

Purpose: The relationship between prostate-specific antigen (PSA) level and prostate cancer risk remains subject to fundamental disagreements. We hypothesized that the risk of prostate cancer on biopsy for a given PSA level is affected by identifiable characteristics of the cohort under study. Experimental Design: We used data from five European and three U.S. cohorts of men undergoing biopsy for

Finasteride to prevent prostate cancer : Should all men or only a high-risk subgroup be treated?

Purpose: Finasteride has been shown to reduce the incidence of prostate cancer. Yet the use of finasteride remains low, likely because of the risk of adverse effects. We sought to determine whether prostate-specific antigen (PSA) levels could identify a high-risk subgroup for which the benefits of finasteride treatment outweigh the potential harms. Patients and Methods: Raw data from the Prostate

Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition

Background: Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations. Methods: We analysed targeted metabolomics data

Changes in the upper airway volume after orthognathic surgery: three-dimensional measurements in a supine body position

The objectives of this study were to analyse the changes in airway cross-sectional areas and volumes due to surgical movements of the jaws and to identify any possible correlation with the direction of the movements. Fifty-seven participants, aged 18–28 years (mean 20.8 years) at surgery, were followed up for 12 months postoperatively. Pre- and postoperative measurements of the facial region obtai

Frequent carbon input primes decomposition of decadal soil organic matter

Soil organic matter (SOM) decomposition in response to global change represents a critical uncertainty in coupled carbon (C) cycle-climate models. Much of this uncertainty arises from our limited mechanistic knowledge of the effects of organic C input frequency on SOM decomposition. Based on a three-source-partitioning isotopic approach (14C glucose addition to soil continuously labeled by C4 plan

Immunoreactivity of recombinant human glandular kallikrein using monoclonal antibodies raised against prostate-specific antigen

The gene encoding human glandular kallikrein (KLK2) was expressed in Escherichia coli, and the corresponding protein (hK2) was produced by fermentation. The hK2 was characterized by Western blotting and epitope map using monoclonal antibodies (MAbs) specific for another protease, prostate- specific antigen (PSA) with high structural identity (80%). MAbs that recognized three different epitopes wer

Cloning and characterization of the α1-antichymotrypsin produced by human prostate tissue

BACKGROUND. α1-antichymotrypsin (ACT) forms stable complexes with prostate-specific antigen (PSA), a serine protease, and this complex is the major form of PSA in the blood circulation. α1-antichymotrypsin occurs in the blood in approximately 105 molar excess to PSA, mainly due to hepatic production, but local prostatic production of ACT has been demonstrated by immunohistochemistry and in situ hy

Enzymatic activation of a doxorubicin-peptide prodrug by prostate- specific antigen

New approaches to target cytotoxic therapy specifically to metastatic prostate cancer sites are urgently needed. As such an approach, an inactive prodrug was synthesized by coupling the primary amine of doxorubicin to the COOH-terminal carboxyl of a seven-amino acid peptide carrier (i.e., Mu-His- Ser-Ser-Lys-Leu-Gln-Leu). The seven-amino acid peptide was documented to be hydrolyzable specifically

Biomarkers of cellular aging during a controlled human malaria infection

Cellular aging is difficult to study in individuals with natural infection, given the diversity of symptom duration and clinical presentation, and the high interference of aging-related processes with host and environmental factors. To address this challenge, we took advantage of the controlled human malaria infection (CHMI) model. This approach allowed us to characterize the relationship among ce

Silk scaffolding drives self-assembly of functional and mature human brain organoids

Human pluripotent stem cells (hPSCs) are intrinsically able to self-organize into cerebral organoids that mimic features of developing human brain tissue. These three-dimensional structures provide a unique opportunity to generate cytoarchitecture and cell-cell interactions reminiscent of human brain complexity in a dish. However, current in vitro brain organoid methodologies often result in intra

Specific and efficient peptide substrates for assaying the proteolytic activity of prostate-specific antigen

Prostate-specific antigen (PSA) is a serine protease secreted by hath normal prostate glandular celts and prostate cancer cells. The major proteolytic substrates for PSA are the gel-forming proteins in semen, semenogelin (Sg) I and II. On the basis of the PSA cleavage map for Sg I and II, a series of small peptides (ie., ≤ 7 amino acids) was synthesized and coupled at the COOH terminus to 7-amino-