- Risk Prediction Tools Available for Germline BRCA1/2 Mutations Underperform in Prostate Cancer Patients. [Journal Article]
- EUEur Urol Oncol 2019 Jul 12
- Early identification of germline BRCA1/2 mutations may be relevant for the management of patients with prostate cancer (PC) and to prevent future breast and ovarian cancers in their relatives. Severa…
Early identification of germline BRCA1/2 mutations may be relevant for the management of patients with prostate cancer (PC) and to prevent future breast and ovarian cancers in their relatives. Several prediction tools have been developed to estimate the likelihood of a germline BRCA1/2 mutation and are widely used to optimize screening in breast and ovarian cancer patients. We aimed to elucidate the proportion of PC patients with known BRCA1/2 mutations who would have qualified for testing using two risk calculation models (BRCAPRO and the Manchester scoring system [MSS]). We analyzed 106 families with known BRCA1/BRCA2 mutations, including 23 with PC cases. Only 30% and 48% of PC patients who were known BRCA1/BRCA2 mutations carriers would have qualified for testing using BRCAPRO and MSS, respectively. A median of two breast and/or ovarian cancer cases per family had occurred between the first PC identified in a carrier and the cancer case leading to germline testing. PATIENT SUMMARY: We tested two models developed to predict the probability of inherited BRCA1/BRCA2 mutations and found that these tools underperform in men with prostate cancer and should not be used to optimize testing in this population.
- Olivary hypertrophy improved by steroid treatment: Two case reports with unique presentations. [Journal Article]
- JNJ Neuroimmunol 2019 Jul 05; 334:577003
- Olivary hypertrophy (OH) is the secondary degeneration of the inferior olivary nucleus (ION). It is observed one month after the onset of a primary lesion within the dento-rubro-olivary pathway and i…
Olivary hypertrophy (OH) is the secondary degeneration of the inferior olivary nucleus (ION). It is observed one month after the onset of a primary lesion within the dento-rubro-olivary pathway and is usually associated with oculopalatal tremors. Here, we report two unique cases with rare autoimmune diseases leading to OH development with progressive cerebellar ataxia, both of which improved with steroid treatment. The first patient was a 59-year-old man with slowly progressive dysarthria and ataxic gait without palatal tremor. Anti-N-methyl-d-aspartate (NMDA) receptor antibody was positive in the CSF, supporting a diagnosis of anti-NMDA receptor encephalitis. The second patient was a 56-year-old man who developed dysarthria, ataxia, gait disturbance, and palatal tremor. He was diagnosed with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), based on presence of a punctate contrast-enhancing lesion in the middle cerebellar peduncle, pons, and cerebellum on magnetic resonance imaging (MRI). Brain MRI in both patients demonstrated high signal intensity regions in the bilateral IONs. Semi-quantitative volume analysis of MRI revealed significant reduction in ION volume after steroid treatment and accordingly cerebellar ataxia was improved in both cases. Clinical and radiological features of the two cases were unique, indicating potential novel etiologies in the pathophysiology of OH associated with cerebellar ataxia.
- Axial GaAs/Ga(As,Bi) nanowire heterostructures. [Journal Article]
- NNanotechnology 2019 Jul 15
- Bi-containing III-V semiconductors constitute an exciting class of metastable compounds with wide-ranging potential optoelectronic and electronic applications. However, the growth of III-V-Bi alloys …
Bi-containing III-V semiconductors constitute an exciting class of metastable compounds with wide-ranging potential optoelectronic and electronic applications. However, the growth of III-V-Bi alloys requires group-III-rich growth conditions, which pose severe challenges for planar growth. In this work, we exploit the naturally-Ga-rich environment present inside the metallic droplet of a self-catalyzed GaAs nanowire to synthesize metastable GaAs/GaAs<sub>1-x</sub>Bi<sub>x</sub> axial nanowire heterostructures with high Bi contents. The axial GaAs<sub>1-x</sub>Bi<sub>x</sub> segments are realized with molecular beam epitaxy by first enriching only the vapor-liquid-solid (VLS) Ga droplets with Bi, followed by exposing the resulting Ga-Bi droplets to As<sub>2</sub> at temperatures ranging from 270 to 380<sup>○</sup>C to precipitate GaAs<sub>1-x</sub>Bi<sub>x</sub> only under the nanowire droplets. Microstructural and elemental characterization reveals the presence of single crystal zincblende GaAs<sub>1-x</sub>Bi<sub>x</sub> axial nanowire segments with Bi contents up to (10±2)%. This work illustrates how the unique local growth environment present during the VLS nanowire growth can be exploited to synthesize heterostructures with metastable compounds.
- Comparative evaluation of a biotrickling filter and a tubular photobioreactor for the continuous abatement of toluene. [Journal Article]
- JHJ Hazard Mater 2019 Jul 02; 380:120860
- The negative effects of volatile organic compounds (VOCs) on humans' health and the environment have boosted the enforcement of regulations, resulting in the need of effective and environmentally fri…
The negative effects of volatile organic compounds (VOCs) on humans' health and the environment have boosted the enforcement of regulations, resulting in the need of effective and environmentally friendly off-gas treatment technologies. In this work, the synergism between microalgae and bacteria was investigated as a sustainable platform to enhance the biological degradation of toluene, herein selected as a model VOC. An innovative algal-bacterial tubular photobioreactor (TPBR) was systematically compared with a conventional biotrickling filter (BTF). The BTF supported average removal efficiencies close to those obtained in the TPBR (86 ± 9% and 88 ± 4%, respectively) at the highest inlet load (∼23 g m3 h-1) and lowest gas residence time (0.75 min). However, the BTF was more sensitive towards the accumulation of secondary metabolites. In this regard, photosynthetic O2 supplementation (resulting in dissolved oxygen concentrations of ∼7.3 mg O2 L-1) and CO2 consumption by microalgae (which reduced the impact of acidification) enhanced toluene abatement performance and process stability.
- Degenerative inferior olivary nucleus and medullary tegmentum produced the characteristic magnetic resonance imaging signs in Alexander disease: A case report. [Letter]
- JNJ Neurol Sci 2019 Jul 02; 403:159-161
- Microfluidic protein isolation and sample preparation for high-resolution cryo-EM. [Journal Article]
- PNProc Natl Acad Sci U S A 2019 Jul 10
- High-resolution structural information is essential to understand protein function. Protein-structure determination needs a considerable amount of protein, which can be challenging to produce, often …
High-resolution structural information is essential to understand protein function. Protein-structure determination needs a considerable amount of protein, which can be challenging to produce, often involving harsh and lengthy procedures. In contrast, the several thousand to a few million protein particles required for structure determination by cryogenic electron microscopy (cryo-EM) can be provided by miniaturized systems. Here, we present a microfluidic method for the rapid isolation of a target protein and its direct preparation for cryo-EM. Less than 1 μL of cell lysate is required as starting material to solve the atomic structure of the untagged, endogenous human 20S proteasome. Our work paves the way for high-throughput structure determination of proteins from minimal amounts of cell lysate and opens more opportunities for the isolation of sensitive, endogenous protein complexes.
- Implementing alcohol use disorder pharmacotherapy in primary care settings: a qualitative analysis of provider-identified barriers and impact on implementation outcomes. [Journal Article]
- ASAddict Sci Clin Pract 2019 Jul 10; 14(1):24
- CONCLUSIONS: CFIR constructs were useful for identifying pre-implementation barriers that informed refinements to the implementation intervention. The number and type of pre-implementation barriers identified did not demonstrate a clear relationship to the degree to which sites were able to improve AUD pharmacotherapy prescribing rate. Site-level implementation process factors such as leadership support and provider turn-over likely also interacted with pre-implementation barriers to drive implementation outcomes.
- Ag Nanoparticles/α-Ag2WO4 Composite Formed by Electron Beam and Femtosecond Irradiation as Potent Antifungal and Antitumor Agents. [Journal Article]
- SRSci Rep 2019 Jul 09; 9(1):9927
- The ability to manipulate the structure and function of promising systems via external stimuli is emerging with the development of reconfigurable and programmable multifunctional materials. Increasin…
The ability to manipulate the structure and function of promising systems via external stimuli is emerging with the development of reconfigurable and programmable multifunctional materials. Increasing antifungal and antitumor activity requires novel, effective treatments to be diligently sought. In this work, the synthesis, characterization, and in vitro biological screening of pure α-Ag2WO4, irradiated with electrons and with non-focused and focused femtosecond laser beams are reported. We demonstrate, for the first time, that Ag nanoparticles/α-Ag2WO4 composite displays potent antifungal and antitumor activity. This composite had an extreme low inhibition concentration against Candida albicans, cause the modulation of α-Ag2WO4 perform the fungicidal activity more efficient. For tumor activity, it was found that the composite showed a high selectivity against the cancer cells (MB49), thus depleting the populations of cancer cells by necrosis and apoptosis, without the healthy cells (BALB/3T3) being affected.
- Insights into the G-rich VEGF-binding aptamer V7t1: when two G-quadruplexes are better than one! [Journal Article]
- NANucleic Acids Res 2019 Jul 05
- The G-quadruplex-forming VEGF-binding aptamer V7t1 was previously found to be highly polymorphic in a K+-containing solution and, to restrict its conformational preferences to a unique, well-defined …
The G-quadruplex-forming VEGF-binding aptamer V7t1 was previously found to be highly polymorphic in a K+-containing solution and, to restrict its conformational preferences to a unique, well-defined form, modified nucleotides (LNA and/or UNA) were inserted in its sequence. We here report an in-depth biophysical characterization of V7t1 in a Na+-rich medium, mimicking the extracellular environment in which VEGF targeting should occur, carried out combining several techniques to analyse the conformational behaviour of the aptamer and its binding to the protein. Our results demonstrate that, in the presence of high Na+ concentrations, V7t1 behaves in a very different way if subjected or not to annealing procedures, as evidenced by native gel electrophoresis, size exclusion chromatography and dynamic light scattering analysis. Indeed, not-annealed V7t1 forms both monomeric and dimeric G-quadruplexes, while the annealed oligonucleotide is a monomeric species. Remarkably, only the dimeric aptamer efficiently binds VEGF, showing higher affinity for the protein compared to the monomeric species. These findings provide new precious information for the development of improved V7t1 analogues, allowing more efficient binding to the cancer-related protein and the design of effective biosensors or theranostic devices based on VEGF targeting.
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- Advancements towards the implementation of clinical phase-contrast breast computed tomography at Elettra. [Journal Article]
- JSJ Synchrotron Radiat 2019 Jul 01; 26(Pt 4):1343-1353
- Breast computed tomography (BCT) is an emerging application of X-ray tomography in radiological practice. A few clinical prototypes are under evaluation in hospitals and new systems are under develop…
Breast computed tomography (BCT) is an emerging application of X-ray tomography in radiological practice. A few clinical prototypes are under evaluation in hospitals and new systems are under development aiming at improving spatial and contrast resolution and reducing delivered dose. At the same time, synchrotron-radiation phase-contrast mammography has been demonstrated to offer substantial advantages when compared with conventional mammography. At Elettra, the Italian synchrotron radiation facility, a clinical program of phase-contrast BCT based on the free-space propagation approach is under development. In this paper, full-volume breast samples imaged with a beam energy of 32 keV delivering a mean glandular dose of 5 mGy are presented. The whole acquisition setup mimics a clinical study in order to evaluate its feasibility in terms of acquisition time and image quality. Acquisitions are performed using a high-resolution CdTe photon-counting detector and the projection data are processed via a phase-retrieval algorithm. Tomographic reconstructions are compared with conventional mammographic images acquired prior to surgery and with histologic examinations. Results indicate that BCT with monochromatic beam and free-space propagation phase-contrast imaging provide relevant three-dimensional insights of breast morphology at clinically acceptable doses and scan times.