Prostate Indeterminate Lesions on Magnetic Resonance Imaging-Biopsy Versus Surveillance: A Literature Review

CONTEXT: The indeterminate multiparametric prostate magnetic resonance image (mpMRI) lesion is one which cannot be classified as "positive" or "negative" for suspected cancer. Currently, there is no consensus on how to manage patients with indeterminate mpMRIs where areas cannot be classified as positives or negatives (Prostate Imaging Reporting and Data System [PI-RADS] 3 or Likert 3). OBJECTIVE: To define the concept of indeterminate lesion and describe the management strategies that may be adopted for these patients. EVIDENCE ACQUISITION: A literature search of the PubMed database was performed including the search terms "prostate indeterminate lesions", "PI-RADS 3", "Likert 3", "magnetic resonance imaging", and "prostate cancer". EVIDENCE SYNTHESIS: There is no universally accepted definition of what constitutes an indeterminate lesion on mpMRI. This is partly due to the experience of the reporting radiologist and their willingness to call a lesion indeterminate, knowing that this may have consequences for biopsy decisions. This is also partly due to the significant variation in mpMRI acquisition parameters used between different sites. Strategies for managing the indeterminate lesion include: (1) biopsy, where there is a highly variable prevalence of prostate cancer (PCa), reflecting the differences in clinically significant PCa definitions, mpMRI protocols and interobserver variability in characterization of indeterminate lesions and (2) surveillance, where early results suggest that this strategy may be of value for some selected patients with prostate-specific antigen (PSA) monitoring and/or interval mpMRI. The use of prebiopsy MRI, in conjunction with traditional clinical parameters and secondary biomarkers-nomograms, may allow a more accurate selection of patients who can avoid biopsy. CONCLUSIONS: A strategy of close surveillance based on PSA monitoring and interval mpMRI is a feasible management option for motivated patients with indeterminate mpMRI. This surveillance strategy could result in fewer men needing to undergo biopsy, and although early results are promising, long-term results for such a strategy are awaited. PATIENT SUMMARY: In some patients who have an MRI scan of their prostate, the scan may identify an area which may or may not contain cancer. This area is typically called the "indeterminate" lesion. In this report, we attempted to define the concept of indeterminate lesion on multiparametric magnetic resonance (mpMRI) and described the strategies that may be performed for these patients. The use of mpMRI in conjunction with traditional clinical parameters may allow more accurate risk stratification and assessment of the need for prostate biopsy

Detection of active hepatitis C in a single visit and linkage to care among marginalized people using a mobile unit in Madrid, Spain

Background: The burden of hepatitis C virus (HCV) infection among marginalized people in Spain is high, despite the fact that HCV prevalence has decreased in recent years. We aimed to assess the effectiveness of a simplified point-of-care (PoC) model for screening for active HCV infection via a mobile unit and subsequent linkage to care with the assistance of navigators. Methods: We carried out a prospective study on 2001 participants from Madrid, Spain. A nurse and a navigator/educator screened for hepatitis C in a mobile unit, using the OraQuick HCV Rapid Antibody Test and Xpert HCV VL Fingerstick assay. Participants with active HCV were referred to the hospital the same day with a navigator for evaluation and treatment of HCV. Results: Overall, 1621 (81%) participants had not been exposed to HCV, 380 (18.9%) were positive for HCV antibodies, and 136 (6.8%) had active hepatitis C. Among the latter, 134 (98.5%) received the HCV screening results, 133 (97.8%) had an appointment at the hospital, 126 (92.8%) were seen by a physician once they were at the hospital, and 105 (77.2%) started HCV treatment. Being over 50 years old and a person who uses drugs, particularly people who inject drugs (PWID), was directly associated with active hepatitis C (p<0.05). PWID were the only patients with HCV reinfection (4.3% in people without recent injecting drug use and 5.9% in people with recent injecting drug use). Among PWID, no income and daily alcohol intake were also directly associated with active hepatitis C. People with recent injecting drug use showed the lowest rates of attendance at the hospital (91.8%) and starting HCV treatment (70.4%). Conclusion: HCV screening using a two-step PoC-based strategy and its linkage to care was extremely efficient for identifying and treating marginalized people with active hepatitis C, thanks to the use of a mobile unit with personnel and technical equipment, an interdisciplinary team, and collaboration between institutions.This work was funded by a research grant from Gilead Science (IN-ES-987-5391 and GLD20_0144) and Instituto de Salud Carlos III (ISCII; grant numbers PI20CIII/00004 and RD16CIII/0002/0002 to SR). It also received funding from AbbVie, Asociación Española para Estudio del Higado (AEEH), and Madrid Positivo Association.S

Optimizing DDRADseq in non-model species: A Case Study in Eucalyptus dunnii Maiden

Restriction site-associated DNA sequencing (RADseq) and its derived protocols, such as double digest RADseq (ddRADseq), offer a flexible and highly cost-effective strategy for efficient plant genome sampling. This has become one of the most popular genotyping approaches for breeding, conservation, and evolution studies in model and non-model plant species. However, universal protocols do not always adapt well to non-model species. Herein, this study reports the development of an optimized and detailed ddRADseq protocol in Eucalyptus dunnii, a non-model species, which combines different aspects of published methodologies. The initial protocol was established using only two samples by selecting the best combination of enzymes and through optimal size selection and simplifying lab procedures. Both single nucleotide polymorphisms (SNPs) and simple sequence repeats (SSRs) were determined with high accuracy after applying stringent bioinformatics settings and quality filters, with and without a reference genome. To scale it up to 24 samples, we added barcoded adapters. We also applied automatic size selection, and therefore obtained an optimal number of loci, the expected SNP locus density, and genome-wide distribution. Reliability and cross-sequencing platform compatibility were verified through dissimilarity coefficients of 0.05 between replicates. To our knowledge, this optimized ddRADseq protocol will allow users to go from the DNA sample to genotyping data in a highly accessible and reproducible way.Instituto de BiotecnologíaFil: Aguirre, Natalia Cristina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Filippi, Carla Valeria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zaina, Giusi. University of Udine. Department of Agricultural, Food, Environmental and Animal Sciences; ItaliaFil: Rivas, Juan Gabriel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Acuña, Cintia Vanesa. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Villalba, Pamela Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garcia, Martin Nahuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gonzalez, Sergio Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rivarola, Maximo Lisandro. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martinez, Maria Carolina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Puebla, Andrea Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Morgante, Michele. University of Udine. Department of Agricultural, Food, Environmental and Animal Sciences; ItaliaFil: Hopp, Horacio Esteban. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paniego, Norma Beatriz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marcucci Poltri, Susana Noemi. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Measurement of Atmospheric Neutrino Oscillations with the ANTARES Neutrino Telescope

The data taken with the ANTARES neutrino telescope from 2007 to 2010, a total live time of 863 days, are used to measure the oscillation parameters of atmospheric neutrinos. Muon tracks are reconstructed with energies as low as 20 GeV. Neutrino oscillations will cause a suppression of vertical upgoing muon neutrinos of such energies crossing the Earth. The parameters determining the oscillation of atmospheric neutrinos are extracted by fitting the event rate as a function of the ratio of the estimated neutrino energy and reconstructed flight path through the Earth. Measurement contours of the oscillation parameters in a two-flavour approximation are derived. Assuming maximum mixing, a mass difference of $\Delta m_{32}^2=(3.1\pm 0.9)\cdot 10^{-3}$ eV$^2$ is obtained, in good agreement with the world average value.Comment: 9 pages, 5 figure

Acoustic and optical variations during rapid downward motion episodes in the deep north-western Mediterranean Sea

An Acoustic Doppler Current Profiler (ADCP) was moored at the deep-sea site of the ANTARES neutrino telescope near Toulon, France, thus providing a unique opportunity to compare high-resolution acoustic and optical observations between 70 and 170 m above the sea bed at 2475 m. The ADCP measured downward vertical currents of magnitudes up to 0.03 m s-1 in late winter and early spring 2006. In the same period, observations were made of enhanced levels of acoustic reflection, interpreted as suspended particles including zooplankton, by a factor of about 10 and of horizontal currents reaching 0.35 m s-1. These observations coincided with high light levels detected by the telescope, interpreted as increased bioluminescence. During winter 2006 deep dense-water formation occurred in the Ligurian subbasin, thus providing a possible explanation for these observations. However, the 10-20 days quasi-periodic episodes of high levels of acoustic reflection, light and large vertical currents continuing into the summer are not direct evidence of this process. It is hypothesized that the main process allowing for suspended material to be moved vertically later in the year is local advection, linked with topographic boundary current instabilities along the rim of the 'Northern Current'.Comment: 30 pages, 7 figure

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.&lt;p&gt;&lt;/p&gt; Methods: Sixty-six non-HLA SNPs showing a P value &#60;10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.&lt;p&gt;&lt;/p&gt; Conclusion: Our results suggest a role of PPARG gene in the development of SSc

Connecting Network Properties of Rapidly Disseminating Epizoonotics

To effectively control the geographical dissemination of infectious diseases, their properties need to be determined. To test that rapid microbial dispersal requires not only susceptible hosts but also a pre-existing, connecting network, we explored constructs meant to reveal the network properties associated with disease spread, which included the road structure.Using geo-temporal data collected from epizoonotics in which all hosts were susceptible (mammals infected by Foot-and-mouth disease virus, Uruguay, 2001; birds infected by Avian Influenza virus H5N1, Nigeria, 2006), two models were compared: 1) 'connectivity', a model that integrated bio-physical concepts (the agent's transmission cycle, road topology) into indicators designed to measure networks ('nodes' or infected sites with short- and long-range links), and 2) 'contacts', which focused on infected individuals but did not assess connectivity.THE CONNECTIVITY MODEL SHOWED FIVE NETWORK PROPERTIES: 1) spatial aggregation of cases (disease clusters), 2) links among similar 'nodes' (assortativity), 3) simultaneous activation of similar nodes (synchronicity), 4) disease flows moving from highly to poorly connected nodes (directionality), and 5) a few nodes accounting for most cases (a "20:80" pattern). In both epizoonotics, 1) not all primary cases were connected but at least one primary case was connected, 2) highly connected, small areas (nodes) accounted for most cases, 3) several classes of nodes were distinguished, and 4) the contact model, which assumed all primary cases were identical, captured half the number of cases identified by the connectivity model. When assessed together, the synchronicity and directionality properties explained when and where an infectious disease spreads.Geo-temporal constructs of Network Theory's nodes and links were retrospectively validated in rapidly disseminating infectious diseases. They distinguished classes of cases, nodes, and networks, generating information usable to revise theory and optimize control measures. Prospective studies that consider pre-outbreak predictors, such as connecting networks, are recommended

Expression of the Ebola Virus VP24 Protein Compromises the Integrity of the Nuclear Envelope and Induces a Laminopathy- Like Cellular Phenotype

ABSTRACT Ebola virus (EBOV) VP24 protein is a nucleocapsid-associated protein that inhibits interferon (IFN) gene expression and counteracts the IFN-mediated antiviral response, preventing nuclear import of signal transducer and activator of transcription 1 (STAT1). Proteomic studies to identify additional EBOV VP24 partners have pointed to the nuclear membrane component emerin as a potential element of the VP24 cellular interactome. Here, we have further studied this interaction and its impact on cell biology. We demonstrate that VP24 interacts with emerin but also with other components of the inner nuclear membrane, such as lamin A/C and lamin B. We also show that VP24 diminishes the interaction between emerin and lamin A/C and compromises the integrity of the nuclear membrane. This disruption is associated with nuclear morphological abnormalities, activation of a DNA damage response, the phosphorylation of extracellular signal-regulated kinase (ERK), and the induction of interferon-stimulated gene 15 (ISG15). Interestingly, expression of VP24 also promoted the cytoplasmic translocation and downmodulation of barrier-to-autointegration factor (BAF), a common interactor of lamin A/C and emerin, leading to repression of the BAF-regulated CSF1 gene. Importantly, we found that EBOV infection results in the activation of pathways associated with nuclear envelope damage, consistent with our observations in cells expressing VP24. In summary, here we demonstrate that VP24 acts at the nuclear membrane, causing morphological and functional changes in cells that recapitulate several of the hallmarks of laminopathy diseases. IMPORTANCE The Ebola virus (EBOV) VP24 protein is a nucleocapsid-associated protein with multiple functions. Proteomic studies have identified the cellular nuclear membrane component emerin as a potential VP24 interactor. Here, we demonstrate that VP24 not only interacts with emerin but also with lamin A/C and lamin B, prompting nuclear membrane disruption. This disruption is associated with nuclear morphological abnormalities, activation of a DNA damage response, the phosphorylation of extracellular signal-regulated kinase (ERK), and the induction of interferon-stimulated gene 15 (ISG15). Interestingly, VP24 also promotes the cytoplasmic translocation and downmodulation of barrier-to-autointegration factor (BAF), leading to repression of the BAF-regulated CSF1 gene. Finally, we show that EBOV infection also results in the activation of pathways associated with nuclear envelope damage, consistent with our observations in cells expressing VP24. These results reveal novel activities of EBOV VP24 protein, resulting in a cell phenotype similar to that of most laminopathies, with potential impact on EBOV replication