Novel contrast-enhanced ultrasound imaging in prostate cancer

The purposes of this paper were to present the current status of contrast-enhanced transrectal ultrasound imaging and to discuss the latest achievements and techniques now under preclinical testing. Although grayscale transrectal ultrasound is the standard method for prostate imaging, it lacks accuracy in the detection and localization of prostate cancer. With the introduction of contrast-enhanced ultrasound (CEUS), perfusion imaging of the microvascularization became available. By this, cancer-induced neovascularisation can be visualized with the potential to improve ultrasound imaging for prostate cancer detection and localization significantly. For example, several studies have shown that CEUS-guided biopsies have the same or higher PCa detection rate compared with systematic biopsies with less biopsies needed. This paper describes the current status of CEUS and discusses novel quantification techniques that can improve the accuracy even further. Furthermore, quantification might decrease the user-dependency, opening the door to use in the routine clinical environment. A new generation of targeted microbubbles is now under pre-clinical testing and showed avidly binding to VEGFR-2, a receptor up-regulated in prostate cancer due to angiogenesis. The first publications regarding a targeted microbubble ready for human use will be discussed. Ultrasound-assisted drug delivery gives rise to a whole new set of therapeutic options, also for prostate cancer. A major breakthrough in the future can be expected from the clinical use of targeted microbubbles for drug delivery for prostate cancer diagnosis as well as treatmen

A Missense Mutation in a Highly Conserved Alternate Exon of Dynamin-1 Causes Epilepsy in Fitful Mice

Dynamin-1 (Dnm1) encodes a large multimeric GTPase necessary for activity-dependent membrane recycling in neurons, including synaptic vesicle endocytosis. Mice heterozygous for a novel spontaneous Dnm1 mutation—fitful—experience recurrent seizures, and homozygotes have more debilitating, often lethal seizures in addition to severe ataxia and neurosensory deficits. Fitful is a missense mutation in an exon that defines the DNM1a isoform, leaving intact the alternatively spliced exon that encodes DNM1b. The expression of the corresponding alternate transcripts is developmentally regulated, with DNM1b expression highest during early neuronal development and DNM1a expression increasing postnatally with synaptic maturation. Mutant DNM1a does not efficiently self-assemble into higher order complexes known to be necessary for proper dynamin function, and it also interferes with endocytic recycling in cell culture. In mice, the mutation results in defective synaptic transmission characterized by a slower recovery from depression after trains of stimulation. The DNM1a and DNM1b isoform pair is highly conserved in vertebrate evolution, whereas invertebrates have only one isoform. We speculate that the emergence of more specialized forms of DNM1 may be important in organisms with complex neuronal function

Mechanism of Splicing Regulation of Spinal Muscular Atrophy Genes

Spinal muscular atrophy (SMA) is one of the major genetic disorders associated with infant mortality. More than 90% cases of SMA result from deletions or mutations of Survival Motor Neuron 1 (SMN1) gene. SMN2, a nearly identical copy of SMN1, does not compensate for the loss of SMN1due to predominant skipping of exon 7. However, correction of SMN2 exon 7 splicing has proven to confer therapeutic benefits in SMA patients. The only approved drug for SMA is an antisense oligonucleotide (Spinraza™/Nusinersen), which corrects SMN2 exon 7 splicing by blocking intronic splicing silencer N1 (ISS-N1) located immediately downstream of exon 7. ISS-N1 is a complex regulatory element encompassing overlapping negative motifs and sequestering a cryptic splice site. More than 40 protein factors have been implicated in the regulation of SMN exon 7 splicing. There is evidence to support that multiple exons of SMN are alternatively spliced during oxidative stress, which is associated with a growing number of pathological conditions. Here, we provide the most up to date account of the mechanism of splicing regulation of the SMN genes

Outbreak of H3N2 influenza at a US military base in Djibouti during the H1N1 pandemic of 2009.

PMC3855413BACKGROUND: Influenza pandemics have significant operational impact on deployed military personnel working in areas throughout the world. The US Department of Defense global influenza-like illness (ILI) surveillance network serves an important role in establishing baseline trends and can be leveraged to respond to outbreaks of respiratory illness. OBJECTIVE: We identified and characterized an operationally unique outbreak of H3N2 influenza at Camp Lemonnier, Djibouti occurring simultaneously with the H1N1 pandemic of 2009 [A(H1N1)pdm09]. METHODS: Enhanced surveillance for ILI was conducted at Camp Lemonnier in response to local reports of a possible outbreak during the A(H1N1)pdm09 pandemic. Samples were collected from consenting patients presenting with ILI (utilizing a modified case definition) and who completed a case report form. Samples were cultured and analyzed using standard real-time reverse transcriptase PCR (rt-RT-PCR) methodology and sequenced genetic material was phylogenetically compared to other published strains. RESULTS: rt-RT-PCR and DNA sequencing revealed that 25 (78%) of the 32 clinical samples collected were seasonal H3N2 and only 2 (6%) were A(H1N1)pdm09 influenza. The highest incidence of H3N2 occurred during the month of May and 80% of these were active duty military personnel. Phylogenetic analysis revealed that sequenced H3N2 strains were genetically similar to 2009 strains from the United States of America, Australia, and South east Asia. CONCLUSIONS: This outbreak highlights challenges in the investigation of influenza among deployed military populations and corroborates the public health importance of maintaining surveillance systems for ILI that can be enhanced locally when needed.JH Libraries Open Access Fun

Metal- and Alloy-Based Core-Shell Particles in Nitrate Senary Salt with Low Thermal Hysteresis for Solar Thermal Energy Storage

In this work, the microencapsulated phase change materials, Sn/amorphous-carbon (Sn/a-C), and SnBi/amorphous carbon (SnBi/a-C) microparticles (MPs) were successfully synthesized. The thermal stabilities of Sn/a-C and SnBi/a-C core-shell MPs were verified by cycling tests, and stable latent heats of 56 and 45.7 J/g were obtained for Sn/a-C and SnBi/a-C MPs, respectively. Compared to the high melting point of 231 °C and large thermal hysteresis (TH) of ∼106 °C for the Sn/a-C MPs, the SnBi/a-C MPs exhibited a lower melting point of 125 °C and a smaller TH of 20 °C. The nitrate senary salt with a lower melting point of ∼75 °C than that of the commercial HITEC salt (melting point of ∼142 °C) was also synthesized to enlarge the working temperature range of the working fluid in a solar thermal power plant and to demonstrate the latent heat-enhanced thermal energy storage using the SnBi/a-C MPs. The heat capacity can be enhanced by 200% by doping with 20 wt % Sn/a-C MPs into the HITEC salt, and it can be enhanced by 734% by doping with 20 wt % SnBi/a-C MPs into the senary salt. In addition, the viscosities of the HITEC salt and senary salt doped with the Sn/a-C and SnBi/a-C MPs were not appreciably raised by doping with the MPs. The various approaches accomplished in this work demonstrate (1) enhancing heat capacity of the working fluid by exploiting the latent heats of the embedded MPs; (2) lowering the TH of the MPs by using the alloy metal particles; and (3) extending the working temperature range by synthesizing the senary salt. These approaches could be applied for enhancing energy storage in solar thermal power plants and facilitating waste heat recovery.This research was supported by the Ministry of Science and Technology through grants no 110-2622-E-007 -017, 110-2634-F-007-023-, 110-2112-M-007-032-MY3, 110-2221-E-007-057-MY3 and 110-2119-M-007 -003 -MBK. The authors gratefully acknowledge the use of HRTEM and SPM equipment belonging to the Instrument Center of National Tsing Hua University. Y.-L.C. greatly appreciates the use of the facility at CNMM