Comparison of Fabrication Methods for Fiber‐Optic Ultrasound Transmitters Using Candle‐Soot Nanoparticles

Candle-soot nanoparticles (CSNPs) have shown great promise for fabricating optical ultrasound (OpUS) transmitters. They have a facile, inexpensive synthesis whilst their unique, porous structure enables a fast heat diffusion rate which aids high-frequency ultrasound generation necessary for high-resolution clinical imaging. These composites have demonstrated high ultrasound generation performance showing clinically relevant detail, when applied as macroscale OpUS transmitters comprising both concave and planar surfaces, however, less research has been invested into the translation of this material's technology to fabricate fiber-optic transmitters for image guidance of minimally invasive interventions. Here, are reported two fabrication methods of nanocomposites composed of CSNPs embedded within polydimethylsiloxane (PDMS) deposited onto fiber-optic end-faces using two different optimized fabrication methods: “All-in-One” and “Direct Deposition.” Both types of nanocomposite exhibit a smooth, black domed structure with a maximum dome thickness of 50 µm, broadband optical absorption (>98% between 500 and 1400 nm) and both nanocomposites generated high peak-to-peak ultrasound pressures (>3 MPa) and wide bandwidths (>29 MHz). Further, high-resolution (<40 µm axial resolution) B-mode ultrasound imaging of ex vivo lamb brain tissue demonstrating how CSNP-PDMS OpUS transmitters can allow for high fidelity minimally invasive imaging of biological tissues is demonstrated

MatrixDB, the extracellular matrix interaction database

MatrixDB (http://matrixdb.ibcp.fr) is a freely available database focused on interactions established by extracellular proteins and polysaccharides. Only few databases report protein–polysaccharide interactions and, to the best of our knowledge, there is no other database of extracellular interactions. MatrixDB takes into account the multimeric nature of several extracellular protein families for the curation of interactions, and reports interactions with individual polypeptide chains or with multimers, considered as permanent complexes, when appropriate. MatrixDB is a member of the International Molecular Exchange consortium (IMEx) and has adopted the PSI-MI standards for the curation and the exchange of interaction data. MatrixDB stores experimental data from our laboratory, data from literature curation, data imported from IMEx databases, and data from the Human Protein Reference Database. MatrixDB is focused on mammalian interactions, but aims to integrate interaction datasets of model organisms when available. MatrixDB provides direct links to databases recapitulating mutations in genes encoding extracellular proteins, to UniGene and to the Human Protein Atlas that shows expression and localization of proteins in a large variety of normal human tissues and cells. MatrixDB allows researchers to perform customized queries and to build tissue- and disease-specific interaction networks that can be visualized and analyzed with Cytoscape or Medusa

CuInS2 Quantum Dot and Polydimethylsiloxane Nanocomposites for All-Optical Ultrasound and Photoacoustic Imaging

Dual-modality imaging employing complementary modalities, such as all-optical ultrasound and photoacoustic imaging, is emerging as a well-suited technique for guiding minimally invasive surgical procedures. Quantum dots are a promising material for use in these dual-modality imaging devices as they can provide wavelength-selective optical absorption. The first quantum dot nanocomposite engineered for co-registered laser-generated ultrasound and photoacoustic imaging is presented. The nanocomposites developed, comprising CuInS2 quantum dots and medical-grade polydimethylsiloxane (CIS-PDMS), are applied onto the distal ends of miniature optical fibers. The films exhibit wavelength-selective optical properties, with high optical absorption (> 90%) at 532 nm for ultrasound generation, and low optical absorption (< 5%) at near-infrared wavelengths greater than 700 nm. Under pulsed laser irradiation, the CIS-PDMS films generate ultrasound with pressures exceeding 3.5 MPa, with a corresponding bandwidth of 18 MHz. An ultrasound transducer is fabricated by pairing the coated optical fiber with a Fabry–Pérot (FP) fiber optic sensor. The wavelength-selective nature of the film is exploited to enable co-registered all-optical ultrasound and photoacoustic imaging of an ink-filled tube phantom. This work demonstrates the potential for quantum dots as wavelength-selective absorbers for all-optical ultrasound generation

Limited Trafficking of a Neurotropic Virus Through Inefficient Retrograde Axonal Transport and the Type I Interferon Response

Poliovirus is an enteric virus that rarely invades the human central nervous system (CNS). To identify barriers limiting poliovirus spread from the periphery to CNS, we monitored trafficking of 10 marked viruses. After oral inoculation of susceptible mice, poliovirus was present in peripheral neurons, including vagus and sciatic nerves. To model viral trafficking in peripheral neurons, we intramuscularly injected mice with poliovirus, which follows a muscle–sciatic nerve–spinal cord–brain route. Only 20% of the poliovirus population successfully moved from muscle to brain, and three barriers limiting viral trafficking were identified. First, using light-sensitive viruses, we found limited viral replication in peripheral neurons. Second, retrograde axonal transport of poliovirus in peripheral neurons was inefficient; however, the efficiency was increased upon muscle damage, which also increased the transport efficiency of a non-viral neural tracer, wheat germ agglutinin. Third, using susceptible interferon (IFN) α/β receptor knockout mice, we demonstrated that the IFN response limited viral movement from the periphery to the brain. Surprisingly, the retrograde axonal transport barrier was equivalent in strength to the IFN barrier. Illustrating the importance of barriers created by the IFN response and inefficient axonal transport, IFN α/β receptor knockout mice with muscle damage permitted 80% of the viral population to access the brain, and succumbed to disease three times faster than mice with intact barriers. These results suggest that multiple separate barriers limit poliovirus trafficking from peripheral neurons to the CNS, possibly explaining the rare incidence of paralytic poliomyelitis. This study identifies inefficient axonal transport as a substantial barrier to poliovirus trafficking in peripheral neurons, which may limit CNS access for other viruses

Laminin database: a tool to retrieve high-throughput and curated data for studies on laminins

The Laminin(LM)-database, hosted at http://www.lm.lncc.br, is the first database focusing a non-collagenous extracellular matrix protein family, the LMs. Part of the knowledge available in this website is automatically retrieved, whereas a significant amount of information is curated and annotated, thus placing LM-database beyond a simple repository of data. In its home page, an overview of the rationale for the database is seen and readers can access a tutorial to facilitate navigation in the website, which in turn is presented with tabs subdivided into LMs, receptors, extracellular binding and other related proteins. Each tab opens into a given LM or LM-related molecule, where the reader finds a series of further tabs for ‘protein’, ‘gene structure’, ‘gene expression’ and ‘tissue distribution’ and ‘therapy’. Data are separated as a function of species, comprising Homo sapiens, Mus musculus and Rattus novergicus. Furthermore, there is specific tab displaying the LM nomenclatures. In another tab, a direct link to PubMed, which can be then consulted in a specific way, in terms of the biological functions of each molecule, knockout animals and genetic diseases, immune response and lymphomas/leukemias. LM-database will hopefully be a relevant tool for retrieving information concerning LMs in health and disease, particularly regarding the hemopoietic system

SBDS Expression and Localization at the Mitotic Spindle in Human Myeloid Progenitors

BACKGROUND: Shwachman-Diamond Syndrome (SDS) is a hereditary disease caused by mutations in the SBDS gene. SDS is clinically characterized by pancreatic insufficiency, skeletal abnormalities and bone marrow dysfunction. The hematologic abnormalities include neutropenia, neutrophil chemotaxis defects, and an increased risk of developing Acute Myeloid Leukemia (AML). Although several studies have suggested that SBDS as a protein plays a role in ribosome processing/maturation, its impact on human neutrophil development and function remains to be clarified. METHODOLOGY/PRINCIPAL FINDINGS: We observed that SBDS RNA and protein are expressed in the human myeloid leukemia PLB-985 cell line and in human hematopoietic progenitor cells by quantitative RT-PCR and Western blot analysis. SBDS expression is downregulated during neutrophil differentiation. Additionally, we observed that the differentiation and proliferation capacity of SDS-patient bone marrow hematopoietic progenitor cells in a liquid differentiation system was reduced as compared to control cultures. Immunofluorescence analysis showed that SBDS co-localizes with the mitotic spindle and in vitro binding studies reveal a direct interaction of SBDS with microtubules. In interphase cells a perinuclear enrichment of SBDS protein which co-localized with the microtubule organizing center (MTOC) was observed. Also, we observed that transiently expressed SDS patient-derived SBDS-K62 or SBDS-C84 mutant proteins could co-localize with the MTOC and mitotic spindle. CONCLUSIONS/SIGNIFICANCE: SBDS co-localizes with the mitotic spindle, suggesting a role for SBDS in the cell division process, which corresponds to the decreased proliferation capacity of SDS-patient bone marrow CD34(+) hematopoietic progenitor cells in our culture system and also to the neutropenia in SDS patients. A role in chromosome missegregation has not been clarified, since similar spatial and time-dependent localization is observed when patient-derived SBDS mutant proteins are studied. Thus, the increased risk of myeloid malignancy in SDS remains unexplained

Bilateral infraorbital nerve blocks decrease postoperative pain but do not reduce time to discharge following outpatient nasal surgery

While infraorbital nerve blocks have demonstrated analgesic benefits for pediatric nasal and facial plastic surgery, no studies to date have explored the effect of this regional anesthetic technique on adult postoperative recovery. We designed this study to test the hypothesis that infraorbital nerve blocks combined with a standardized general anesthetic decrease the duration of recovery following outpatient nasal surgery. At a tertiary care university hospital, healthy adult subjects scheduled for outpatient nasal surgery were randomly assigned to receive bilateral infraorbital injections with either 0.5% bupivacaine (Group IOB) or normal saline (Group NS) using an intraoral technique immediately following induction of general anesthesia. All subjects underwent a standardized general anesthetic regimen and were transported to the recovery room following tracheal extubation. The primary outcome was the duration of recovery (minutes) from recovery room admission until actual discharge to home. Secondary outcomes included average and worst pain scores, nausea and vomiting, and supplemental opioid requirements. Forty patients were enrolled. A statistically significant difference in mean [SD] recovery room duration was not observed between Groups IOB and NS (131 [61] min vs 133 [58] min, respectively; P = 0.77). Subjects in Group IOB did experience a reduction in average pain on a 0–100 mm scale (mean [95% confidence interval]) compared to Group NS (−11 [−21 to 0], P = 0.047), but no other comparison of secondary outcomes was statistically significant. When added to a standardized general anesthetic, bilateral IOB do not decrease actual time to discharge following outpatient nasal surgery despite a beneficial effect on postoperative pain

Effect of Functional Capacity Evaluation information on the judgment of physicians about physical work ability in the context of disability claims

Purpose To test whether Functional Capacity Evaluation (FCE) information lead insurance physicians (IPs) to change their judgment about the physical work ability of claimants with musculoskeletal disorders (MSDs). Methods Twenty-seven IPs scored twice the physical work ability of two claimants for 12 specified activities, using a visual analogue scale. One claimant performed an FCE, the other served as a control. Outcome measure was the difference between experimental and control group in number of shifts in the physical work ability for the total of 12 specified activities. Results The IPs changed their judgment about the work ability 141 times when using FCE information compared to 102 times when not using this information (P-value = 0.001), both in the direction of more and less ability. Conclusions The IPs change their judgment of the physical work ability of claimants with MSDs in the context of disability claim procedures more often when FCE information is provide