Active surveillance in males with low- to intermediate-risk localized prostate cancer: A modern prospective cohort study

Purpose: To compare the clinical outcome of males with low-risk and favorable intermediate-risk prostate cancer managed within a standardized modern protocol of active surveillance. Materials and methods: This was a prospective cohort study with strict and expanded active surveillance criteria in males with prostate cancer. Baseline assessment included multiparametric magnetic resonance imaging (mpMRI), extended systematic biopsy, and software-based MR-targeted biopsy. Follow-up included biannual prostate-specific antigen (PSA) check, mpMRI, and control biopsy once a year for the first 2 years, and afterward mpMRI every 2 years with additional tests as clinically indicated. The primary outcome was the transition rate to active treatment. Results: A total of 51 patients were included: 17 (33%) and 34 (67%) followed protocols of strict (study arm 1) and expanded (study arm 2) active surveillance criteria, respectively. Median age and PSA were 65 years (IQR, 60-69 years) and 5.3 ng/mL (IQR, 4.5-7.7 ng/mL), respectively. At baseline, a median of 2 (IQR, 1-3) cores were positive out of 13 (IQR, 12-14) cores; 22 males (43%) had visible mpMRI lesions. Eight males (24%) in study arm 2 had Gleason score 3+4. After a median follow-up of 36 months (IQR, 24-48 mo), no patient in study arm 1 compared with 17 patients (33%) in arm 2 underwent active treatment (p<0.0005). Conclusions: Although expanding eligibility criteria leads to a greater transition rate to active treatment, active surveillance should be contemplated in well-selected males with favorable intermediate-risk prostate cancer as the curability window seems to be maintained

Magnetoresistance through a single molecule

The use of single molecules to design electronic devices is an extremely challenging and fundamentally different approach to further downsizing electronic circuits. Two-terminal molecular devices such as diodes were first predicted [1] and, more recently, measured experimentally [2]. The addition of a gate then enabled the study of molecular transistors [3-5]. In general terms, in order to increase data processing capabilities, one may not only consider the electron's charge but also its spin [6,7]. This concept has been pioneered in giant magnetoresistance (GMR) junctions that consist of thin metallic films [8,9]. Spin transport across molecules, i.e. Molecular Spintronics remains, however, a challenging endeavor. As an important first step in this field, we have performed an experimental and theoretical study on spin transport across a molecular GMR junction consisting of two ferromagnetic electrodes bridged by a single hydrogen phthalocyanine (H2Pc) molecule. We observe that even though H2Pc in itself is nonmagnetic, incorporating it into a molecular junction can enhance the magnetoresistance by one order of magnitude to 52%.Comment: To appear in Nature Nanotechnology. Present version is the first submission to Nature Nanotechnology, from May 18th, 201

Age and growth of the smooth hammerhead, Sphyrna zygaena, in the Atlantic Ocean: comparison with other hammerhead species

The smooth hammerhead Sphyrna zygaena (Sphyrnidae) is a pelagic shark occasionally caught as bycatch in pelagic longline fisheries, but is one of the least studied of all pelagic sharks. Age and growth of S. zygaena was studied along a wide Atlantic region covering both the northern and southern hemispheres. Data from 304 specimens, caught between October 2009 and September 2014, ranging in size from 126 to 253 cm fork length (FL), were analysed. Growth models were fitted using the three-parameter von Bertalanffy growth function (VBGF) re-parameterized to calculate L0 (size at birth). Growth models were fitted to the sample data and data from several back-calculation models. The model fit to the quadratic modified Dahl-Lea back-calculated data seems to be the most appropriate to describe growth in this species, with resulting growth parameters of Linf = 285 cm FL, k = 0.09 year−1 for males and Linf = 293 cm FL, k = 0.09 year−1 for females. Compared with other species of the same genus, estimated growth coefficients for S. zygaena seem to fall in the low to middle range. Although further work is still needed, this study adds to knowledge of the vital life-history parameters of smooth hammerheads in the Atlantic Ocean, which can be used in the management and conservation of this species.Programa Operacional Potencial Humano: IF/00253/2014info:eu-repo/semantics/publishedVersio

Loss of 5'-Methylthioadenosine Phosphorylase (MTAP) is Frequent in High-Grade Gliomas; Nevertheless, it is Not Associated with Higher Tumor Aggressiveness.

The 5'-methylthioadenosine phosphorylase (MTAP) gene is located in the chromosomal region 9p21. MTAP deletion is a frequent event in a wide variety of human cancers; however, its biological role in tumorigenesis remains unclear. The purpose of this study was to characterize the MTAP expression profile in a series of gliomas and to associate it with patients' clinicopathological features. Moreover, we sought to evaluate, through glioma gene-edited cell lines, the biological impact of MTAP in gliomas. MTAP expression was evaluated in 507 glioma patients by immunohistochemistry (IHC), and the expression levels were associated with patients' clinicopathological features. Furthermore, an in silico study was undertaken using genomic databases totalizing 350 samples. In glioma cell lines, MTAP was edited, and following MTAP overexpression and knockout (KO), a transcriptome analysis was performed by NanoString Pan-Cancer Pathways panel. Moreover, MTAP's role in glioma cell proliferation, migration, and invasion was evaluated. Homozygous deletion of 9p21 locus was associated with a reduction of MTAP mRNA expression in the TCGA (The Cancer Genome Atlas) - glioblastoma dataset (p < 0.01). In addition, the loss of MTAP expression was markedly high in high-grade gliomas (46.6% of cases) determined by IHC and Western blotting (40% of evaluated cell lines). Reduced MTAP expression was associated with a better prognostic in the adult glioblastoma dataset (p < 0.001). Nine genes associated with five pathways were differentially expressed in MTAP-knockout (KO) cells, with six upregulated and three downregulated in MTAP. Analysis of cell proliferation, migration, and invasion did not show any significant differences between MTAP gene-edited and control cells. Our results integrating data from patients as well as in silico and in vitro models provide evidence towards the lack of strong biological importance of MTAP in gliomas. Despite the frequent loss of MTAP, it seems not to have a clinical impact in survival and does not act as a canonic tumor suppressor gene in gliomas

Work satisfaction of the self-employed: The roles of work autonomy, working hours, gender and sector of self-employment

Studies on segregation in employment are suggestive of higher levels of job satisfaction in female-dominated occupational settings. This research investigates whether this effect is replicated in self-employment. We explore whether satisfaction differentials are related to differences in autonomy and working hours. Our hypotheses are tested using data from the European Social Survey. The final sample consists of 1079 males and 326 females. Our research suggests that differences in job satisfaction among self-employed men and women should not be attributed to gender but to gender composition of sector. Our study contributes to our understanding of gender within a sectoral perspective and the significance of work autonomy and level of working hours to improve work satisfaction of the self-employed

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Biodegradable starch-based composites: effect of micro and nanoreinforcements on composite properties

Thermoplastic starch (TPS) matrix was reinforced with various kenaf bast cellulose nanofiber loadings (0–10 wt%). Thin films were prepared by casting and evaporating the mixture of aqueous suspension of nanofibers (NFs), starch, and glycerol which underwent gelatinization process at the same time. Moreover, raw fibers (RFs) reinforced TPS films were prepared with the same contents and conditions. The effects of filler type and loading on different characteristics of prepared materials were studied using transmission and scanning electron microscopies, X-ray diffractometry, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and moisture absorption analysis. Obtained results showed a homogeneous dispersion of NFs within the TPS matrix and strong association between the filler and matrix. Moreover, addition of nanoreinforcements decreased the moisture sensitivity of the TPS film significantly. About 20 % decrease in moisture content at equilibrium was observed with addition of 10 wt% NFs while this value was only 5.7 % for the respective RFs reinforced film

Lack of MHC class I surface expression on neoplastic cells and poor activation of the secretory pathway of cytotoxic cells in oral squamous cell carcinomas

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells use the secretory pathway of perforin/granzymes to kill their target cells. In contrast to NK cells, CTL responses are MHC class I restricted. In this study we analysed the relative activation of CTL and NK cells in relation with MHC class I expression on oral squamous cell carcinomas (OSCCs). MHC class I expression was investigated in 47 OSCCs by immunohistochemistry using HCA2, HC10 and β2-m antibodies. The presence of CTLs, NK cells, and its activation, was investigated in 21 of these OSCCs using respectively, CD8, CD57 and GrB7 antibodies. The Q-Prodit measuring system was used for quantification of cytotoxic cells. All OSCCs showed weak or absent staining of β2-m on the cell surface. The absence of β2-m was significantly associated with absent expression of MHC class I heavy chain as detected by HC10 antibody (P = 0.004). In tumour infiltrates CTLs always outnumbered NK cells, as reflected by the ratio CD57/CD8 being always inferior to one (mean: 0.19; SD: 0.15). The proportion of activated cytotoxic cells as detected by granzyme B expression was generally low (mean: 8.6%; SD 8.9). A clear correlation between MHC class I expression and the relative proportion of NK cells/CTLs was not found. This study shows that the majority of OSCCs show weak or absent expression of MHC class I molecules on the cell surface, possibly due to alterations in the normal β2-m pathway. The low proportion of granzyme B-positive CTLs/NK cells indicates that the secretory pathway of cytotoxicity is poor in these patients. The lack of correlation between MHC class I expression and CTL/NK cell activation as detected by granzyme B expression suggests that, next to poor antigen presentation, also local factors seem to determine the final outcome of the cytotoxic immune response. © 1999 Cancer Research Campaig