Rotational spectrum, structure, and quadrupole coupling of cyclopropylchloromethyldifluorosilane.

Cyclopropylchloromethyldifluorosilane, c-C3H5SiF2CH2Cl, has been synthesized, and its rotational spectrum has been recorded by chirped-pulse Fourier transform microwave spectroscopy. The spectral analysis of several isotopologues indicates the presence of two distinct conformations in the free-jet expansion, which are interconvertible through a rotation of the chloromethyl group. A partial substitution structure is presented for the lower energy conformation and is compared to the equilibrium structure obtained from quantum chemical calculations. Additionally, the presence of the chlorine nucleus leads to the rotational transitions splitting into multiple hyperfine components and χaa, a measure of the electric field gradient along the a axis, is unusually small at merely +0.1393(73) MHz. Various common ab initio and density functional theory methods fail to predict good quadrupole coupling constants (in the principal axis system) that adequately reproduce the observed hyperfine splitting, although diagonalizing the quadrupole coupling tensor from the principal axis system into a nucleus-centered axis system reveals that, overall, these methods calculate reasonably the electric field gradient about the chlorine nucleus. Finally, a total of nine electric dipole forbidden, quadrupole allowed transitions are observed in the rotational spectra of the parent species of the higher energy conformation and the 37Cl isotopologue of the lower energy conformation. These include those of x-type (no change in parity of Ka or Kc), which, to our knowledge, is the first time such transitions have been observed in a chlorine-containing molecule.

Host-derived growth factors drive ERK phosphorylation and MCL1 expression to promote osteosarcoma cell survival during metastatic lung colonization.

PURPOSE: For patients with osteosarcoma, disease-related mortality most often results from lung metastasis-a phenomenon shared with many solid tumors. While established metastatic lesions behave aggressively, very few of the tumor cells that reach the lung will survive. By identifying mechanisms that facilitate survival of disseminated tumor cells, we can develop therapeutic strategies that prevent and treat metastasis. METHODS: We analyzed single cell RNA-sequencing (scRNAseq) data from murine metastasis-bearing lungs to interrogate changes in both host and tumor cells during colonization. We used these data to elucidate pathways that become activated in cells that survive dissemination and identify candidate host-derived signals that drive activation. We validated these findings through live cell reporter systems, immunocytochemistry, and fluorescent immunohistochemistry. We then validated the functional relevance of key candidates using pharmacologic inhibition in models of metastatic osteosarcoma. RESULTS: Expression patterns suggest that the MAPK pathway is significantly elevated in early and established metastases. MAPK activity correlates with expression of anti-apoptotic genes, especially MCL1. Niche cells produce growth factors that increase ERK phosphorylation and MCL1 expression in tumor cells. Both early and established metastases are vulnerable to MCL1 inhibition, but not MEK inhibition in vivo. Combining MCL1 inhibition with chemotherapy both prevented colonization and eliminated established metastases in murine models of osteosarcoma. CONCLUSION: Niche-derived growth factors drive MAPK activity and MCL1 expression in osteosarcoma, promoting metastatic colonization. Although later metastases produce less MCL1, they remain dependent on it. MCL1 is a promising target for clinical trials in both human and canine patients.

A novel auxin-inducible degron system for rapid, cell cycle-specific targeted proteolysis.

The discrimination of protein biological functions in different phases of the cell cycle is limited by the lack of experimental approaches that do not require pre-treatment with compounds affecting the cell cycle progression. Therefore, potential cycle-specific biological functions of a protein of interest could be biased by the effects of cell treatments. The OsTIR1/auxin-inducible degron (AID) system allows "on demand" selective and reversible protein degradation upon exposure to the phytohormone auxin. In the current format, this technology does not allow to study the effect of acute protein depletion selectively in one phase of the cell cycle, as auxin similarly affects all the treated cells irrespectively of their proliferation status. Therefore, the AID system requires coupling with cell synchronization techniques, which can alter the basal biological status of the studied cell population, as with previously available approaches. Here, we introduce a new AID system to Regulate OsTIR1 Levels based on the Cell Cycle Status (ROLECCS system), which induces proteolysis of both exogenously transfected and endogenous gene-edited targets in specific phases of the cell cycle. We validated the ROLECCS technology by down regulating the protein levels of TP53, one of the most studied tumor suppressor genes, with a widely known role in cell cycle progression. By using our novel tool, we observed that TP53 degradation is associated with increased number of micronuclei, and this phenotype is specifically achieved when TP53 is lost in S/G2/M phases of the cell cycle, but not in G1. Therefore, we propose the use of the ROLECCS system as a new improved way of studying the differential roles that target proteins may have in specific phases of the cell cycle.

Electronic transport driven by collective light-matter coupled states in a quantum device.

In the majority of optoelectronic devices, emission and absorption of light are considered as perturbative phenomena. Recently, a regime of highly non-perturbative interaction, ultra-strong light-matter coupling, has attracted considerable attention, as it has led to changes in the fundamental properties of materials such as electrical conductivity, rate of chemical reactions, topological order, and non-linear susceptibility. Here, we explore a quantum infrared detector operating in the ultra-strong light-matter coupling regime driven by collective electronic excitations, where the renormalized polariton states are strongly detuned from the bare electronic transitions. Our experiments are corroborated by microscopic quantum theory that solves the problem of calculating the fermionic transport in the presence of strong collective electronic effects. These findings open a new way of conceiving optoelectronic devices based on the coherent interaction between electrons and photons allowing, for example, the optimization of quantum cascade detectors operating in the regime of strongly non-perturbative coupling with light.

The therapeutic potential of natural killer cells in neuropathic pain.

Novel disease-modifying treatments for neuropathic pain are urgently required. The cellular immune response to nerve injury represents a promising target for therapeutic development. Recently, the role of natural killer (NK) cells in both CNS and PNS disease has been the subject of growing interest. In this opinion article, we set out the case for NK cell-based intervention as a promising avenue for development in the management of neuropathic pain. We explore the potential cellular and molecular targets of NK cells in the PNS by contrasting with their reported functional roles in CNS diseases, and we suggest strategies for using the beneficial functions of NK cells and immune-based therapeutics in the context of neuropathic pain.

Electrically-pumped compact topological bulk lasers driven by band-inverted bound states in the continuum.

One of the most exciting breakthroughs in physics is the concept of topology that was recently introduced to photonics, achieving robust functionalities, as manifested in the recently demonstrated topological lasers. However, so far almost all attention was focused on lasing from topological edge states. Bulk bands that reflect the topological bulk-edge correspondence have been largely missed. Here, we demonstrate an electrically pumped topological bulk quantum cascade laser (QCL) operating in the terahertz (THz) frequency range. In addition to the band-inversion induced in-plane reflection due to topological nontrivial cavity surrounded by a trivial domain, we further illustrate the band edges of such topological bulk lasers are recognized as the bound states in the continuum (BICs) due to their nonradiative characteristics and robust topological polarization charges in the momentum space. Therefore, the lasing modes show both in-plane and out-of-plane tight confinements in a compact laser cavity (lateral size ~3λlaser). Experimentally, we realize a miniaturized THz QCL that shows single-mode lasing with a side-mode suppression ratio (SMSR) around 20 dB. We also observe a cylindrical vector beam for the far-field emission, which is evidence for topological bulk BIC lasers. Our demonstration on miniaturization of single-mode beam-engineered THz lasers is promising for many applications including imaging, sensing, and communications.

Long-term tactile hypersensitivity after nerve crush injury in mice is characterized by the persistence of intact sensory axons.

ABSTRACT: Traumatic peripheral nerve injuries are at high risk of neuropathic pain for which novel effective therapies are urgently needed. Preclinical models of neuropathic pain typically involve irreversible ligation and/or nerve transection (neurotmesis). However, translation of findings to the clinic has so far been unsuccessful, raising questions on injury model validity and clinically relevance. Traumatic nerve injuries seen in the clinic commonly result in axonotmesis (ie, crush), yet the neuropathic phenotype of "painful" nerve crush injuries remains poorly understood. We report the neuropathology and sensory symptoms of a focal nerve crush injury using custom-modified hemostats resulting in either complete ("full") or incomplete ("partial") axonotmesis in adult mice. Assays of thermal and mechanically evoked pain-like behavior were paralleled by transmission electron microscopy, immunohistochemistry, and anatomical tracing of the peripheral nerve. In both crush models, motor function was equally affected early after injury; by contrast, partial crush of the nerve resulted in the early return of pinprick sensitivity, followed by a transient thermal and chronic tactile hypersensitivity of the affected hind paw, which was not observed after a full crush injury. The partially crushed nerve was characterized by the sparing of small-diameter myelinated axons and intraepidermal nerve fibers, fewer dorsal root ganglia expressing the injury marker activating transcription factor 3, and lower serum levels of neurofilament light chain. By day 30, axons showed signs of reduced myelin thickness. In summary, the escape of small-diameter axons from Wallerian degeneration is likely a determinant of chronic pain pathophysiology distinct from the general response to complete nerve injury.

A case of fatal disseminated adenovirus and drug-resistant Pneumocystis pneumonia in a patient who received chemotherapy for mantle cell lymphoma.

Adenovirus (ADV) may cause severe complications in hematopoietic stem cell transplant recipients, but disseminated ADV infections in patients who received chemotherapy alone for hematological malignancies are poorly understood due to the rarity of cases. Concomitant infection with Pneumocystis (PCP) is extremely rare. Despite being diagnostically challenging, a more specific workup needs to be initiated with a low threshold in patients who are exposed to agents with the potential to suppress T cells. We report a fatal case of disseminated ADV and drug-resistant PCP pneumonia in a patient with mantle cell lymphoma who had only received combination chemotherapy. A 75-year-old man who was diagnosed with mantle cell lymphoma 10 months prior was admitted for mild hypoxic respiratory failure. Bendamustine, Rituximab, Cytarabine regimen had resulted in complete remission of his lymphoma, with the last cycle of chemotherapy administered 3 months prior to admission. CT of the chest revealed ground-glass opacities concerning pneumonia. Initial laboratory tests were remarkable for mild leukopenia. The respiratory viral panel was only positive for ADV. He did not respond to empiric antibiotics for community-acquired pneumonia and Trimethoprim / Sulfamethoxazole given later for positive Beta D Glucan (BDG) suggestive of Pneumocystis pneumonia. Then, he developed hemorrhagic cystitis, followed by liver and renal function derangement that prompted checking serum ADV viral load by polymerase chain reaction (PCR). This test took 1 week to return, with a viral load of 50, 000 copies/mL suggesting disseminated ADV infection. Despite initiation of Cidofovir, multi-organ failure continued to progress, and the follow-up viral load had doubled on Day 2. The patient passed away the same day shortly after transition to comfort care. T cell suppression seems to be a risk factor for disseminated ADV disease. Clinicians may need to maintain a low threshold to send serum quantitative ADV PCR when symptoms are not improved by antimicrobial treatment for more conventional infections in patients who received agents that are known to suppress T cells, such as Bendamustine.

Auto-Calibrated Charge-Sensitive Infrared Phototransistor at 9.3 µm.

Charge-sensitive infrared photo-transistors (CSIP) are quantum detectors of mid-infrared radiation (λ=4 µm-14 µm) which have been reported to have outstanding figures of merit and sensitivities that allow single photon detection. The typical absorbing region of a CSIP consists of an AlxGa1-xAs quantum heterostructure, where a GaAs quantum well, where the absorption takes place, is followed by a triangular barrier with a graded x(Al) composition that connects the quantum well to a source-drain channel. Here, we report a CSIP designed to work for a 9.3 µm wavelength where the Al composition is kept constant and the triangular barrier is replaced by tunnel-coupled quantum wells. This design is thus conceptually closer to quantum cascade detectors (QCDs) which are an established technology for detection in the mid-infrared range. While previously reported structures use metal gratings in order to couple infrared radiation in the absorbing quantum well, here, we employ a 45° wedge facet coupling geometry that allows a simplified and reliable estimation of the incident photon flux Φ in the device. Remarkably, these detectors have an "auto-calibrated" nature, which enables the precise assessment of the photon flux Φ solely by measuring the electrical characteristics and from knowledge of the device geometry. We identify an operation regime where CSIP detectors can be directly compared to other unipolar quantum detectors such as quantum well infrared photodetectors (QWIPs) and QCDs and we estimate the corresponding detector figure of merit under cryogenic conditions. The maximum responsivity R = 720 A/W and a photoconductive gain G~2.7 × 104 were measured, and were an order of magnitude larger than those for QCDs and quantum well infrared photodetectors (QWIPs). We also comment on the benefit of nano-antenna concepts to increase the efficiency of CSIP in the photon-counting regime.

Live-Cell Sender-Receiver Co-cultures for Quantitative Measurement of Paracrine Signaling Dynamics, Gene Expression, and Drug Response.

Paracrine signaling is a fundamental process regulating tissue development, repair, and pathogenesis of diseases such as cancer. Herein we describe a method for quantitatively measuring paracrine signaling dynamics, and resultant gene expression changes, in living cells using genetically encoded signaling reporters and fluorescently tagged gene loci. We discuss considerations for selecting paracrine "sender-receiver" cell pairs, appropriate reporters, the use of this system to ask diverse experimental questions and screen drugs blocking intracellular communication, data collection, and the use of computational approaches to model and interpret these experiments.

Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis.

Membranous glomerulonephritis (MGN) is a common cause of nephrotic syndrome in adults, mediated by glomerular antibody deposition to an increasing number of newly recognised antigens. Previous case reports have suggested an association between patients with anti-contactin-1 (CNTN1)-mediated neuropathies and MGN. In an observational study we investigated the pathobiology and extent of this potential cause of MGN by examining the association of antibodies against CNTN1 with the clinical features of a cohort of 468 patients with suspected immune-mediated neuropathies, 295 with idiopathic MGN, and 256 controls. Neuronal and glomerular binding of patient IgG, serum CNTN1 antibody and protein levels, as well as immune-complex deposition were determined. We identified 15 patients with immune-mediated neuropathy and concurrent nephrotic syndrome (biopsy proven MGN in 12/12), and 4 patients with isolated MGN from an idiopathic MGN cohort, all seropositive for IgG4 CNTN1 antibodies. CNTN1-containing immune complexes were found in the renal glomeruli of patients with CNTN1 antibodies, but not in control kidneys. CNTN1 peptides were identified in glomeruli by mass spectroscopy. CNTN1 seropositive patients were largely resistant to first-line neuropathy treatments but achieved a good outcome with escalation therapies. Neurological and renal function improved in parallel with suppressed antibody titres. The reason for isolated MGN without clinical neuropathy is unclear. We show that CNTN1, found in peripheral nerves and kidney glomeruli, is a common target for autoantibody-mediated pathology and may account for between 1 and 2% of idiopathic MGN cases. Greater awareness of this cross-system syndrome should facilitate earlier diagnosis and more timely use of effective treatment.

Photonic Majorana quantum cascade laser with polarization-winding emission.

Topological cavities, whose modes are protected against perturbations, are promising candidates for novel semiconductor laser devices. To date, there have been several demonstrations of topological lasers (TLs) exhibiting robust lasing modes. The possibility of achieving nontrivial beam profiles in TLs has recently been explored in the form of vortex wavefront emissions enabled by a structured optical pump or strong magnetic field, which are inconvenient for device applications. Electrically pumped TLs, by contrast, have attracted attention for their compact footprint and easy on-chip integration with photonic circuits. Here, we experimentally demonstrate an electrically pumped TL based on photonic analogue of a Majorana zero mode (MZM), implemented monolithically on a quantum cascade chip. We show that the MZM emits a cylindrical vector (CV) beam, with a topologically nontrivial polarization profile from a terahertz (THz) semiconductor laser.

Self-Induced Mode-Locking in Electrically Pumped Far-Infrared Random Lasers.

Mode locking, the self-starting synchronous oscillation of electromagnetic modes in a laser cavity, is the primary way to generate ultrashort light pulses. In random lasers, without a cavity, mode-locking, the nonlinear coupling amongst low spatially coherent random modes, can be activated via optical pumping, even without the emission of short pulses. Here, by exploiting the combination of the inherently giant third-order χ(3) nonlinearity of semiconductor heterostructure lasers and the nonlinear properties of graphene, the authors demonstrate mode-locking in surface-emitting electrically pumped random quantum cascade lasers at terahertz frequencies. This is achieved by either lithographically patterning a multilayer graphene film to define a surface random pattern of light scatterers, or by coupling on chip a saturable absorber graphene reflector. Intermode beatnote mapping unveils self-induced phase-coherence between naturally incoherent random modes. Self-mixing intermode spectroscopy reveals phase-locked random modes. This is an important milestone in the physics of disordered systems. It paves the way to the development of a new generation of miniaturized, electrically pumped mode-locked light sources, ideal for broadband spectroscopy, multicolor speckle-free imaging applications, and reservoir quantum computing.

Guillain-Barré Syndrome Following Zika Virus Infection Is Associated With a Diverse Spectrum of Peripheral Nerve Reactive Antibodies.

BACKGROUND AND OBJECTIVES: Recent outbreaks of Zika virus (ZIKV) in South and Central America have highlighted significant neurologic side effects. Concurrence with the inflammatory neuropathy Guillain-Barré syndrome (GBS) is observed in 1:4,000 ZIKV cases. Whether the neurologic symptoms of ZIKV infection are immune mediated is unclear. We used rodent and human live cellular models to screen for anti-peripheral nerve reactive IgG and IgM autoantibodies in the sera of patients with ZIKV with and without GBS. METHODS: In this study, 52 patients with ZIKV-GBS were compared with 134 ZIKV-infected patients without GBS and 91 non-ZIKV controls. Positive sera were taken forward for target identification by immunoprecipitation and mass spectrometry, and candidate antigens were validated by ELISA and cell-based assays. Autoantibody reactions against glycolipid antigens were also screened on an array. RESULTS: Overall, IgG antibody reactivities to rat Schwann cells (SCs) (6.5%) and myelinated cocultures (9.6%) were significantly higher, albeit infrequent, in the ZIKV-GBS group compared with all controls. IgM antibody immunoreactivity to dorsal root ganglia neurones (32.3%) and SCs (19.4%) was more frequently observed in the ZIKV-GBS group compared with other controls, whereas IgM reactivity to cocultures was as common in ZIKV and non-ZIKV sera. Strong axonal-binding ZIKV-GBS serum IgG antibodies from 1 patient were confirmed to react with neurofascin 155 and 186. Serum from a ZIKV-infected patient without GBS displayed strong myelin-binding and putative antilipid antigen reaction characteristics. There was, however, no significant association of ZIKV-GBS with any known antiglycolipid antibodies. DISCUSSION: Autoantibody responses in ZIKV-GBS target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection.

BCL-xL inhibition potentiates cancer therapies by redirecting the outcome of p53 activation from senescence to apoptosis.

Cancer therapies trigger diverse cellular responses, ranging from apoptotic death to acquisition of persistent therapy-refractory states such as senescence. Tipping the balance toward apoptosis could improve treatment outcomes regardless of therapeutic agent or malignancy. We find that inhibition of the mitochondrial protein BCL-xL increases the propensity of cancer cells to die after treatment with a broad array of oncology drugs, including mitotic inhibitors and chemotherapy. Functional precision oncology and omics analyses suggest that BCL-xL inhibition redirects the outcome of p53 transcriptional response from senescence to apoptosis, which likely occurs via caspase-dependent down-modulation of p21 and downstream cytostatic proteins. Consequently, addition of a BCL-2/xL inhibitor strongly improves melanoma response to the senescence-inducing drug targeting mitotic kinase Aurora kinase A (AURKA) in mice and patient-derived organoids. This study shows a crosstalk between the mitochondrial apoptotic pathway and cell cycle regulation that can be targeted to augment therapeutic efficacy in cancers with wild-type p53.

Detection of Strong Light-Matter Interaction in a Single Nanocavity with a Thermal Transducer.

The concept of strong light-matter coupling has been demonstrated in semiconductor structures, and it is poised to revolutionize the design and implementation of components, including solid state lasers and detectors. We demonstrate an original nanospectroscopy technique that permits the study of the light-matter interaction in single subwavelength-sized nanocavities where far-field spectroscopy is not possible using conventional techniques. We inserted a thin (∼150 nm) polymer layer with negligible absorption in the mid-infrared range (5 µm < λ < 12 µm) inside a metal-insulator-metal resonant cavity, where a photonic mode and the intersubband transition of a semiconductor quantum well are strongly coupled. The intersubband transition peaks at λ = 8.3 µm, and the nanocavity is overall 270 nm thick. Acting as a nonperturbative transducer, the polymer layer introduces only a limited alteration of the optical response while allowing to reveal the optical power absorbed inside the concealed cavity. Spectroscopy of the cavity losses is enabled by the polymer thermal expansion due to heat dissipation in the active part of the cavity, and performed using atomic force microscopy (AFM). This innovative approach allows the typical anticrossing characteristic of the polaritonic dispersion to be identified in the cavity loss spectra at the single nanoresonator level. Results also suggest that near-field coupling of the external drive field to the top metal patch mediated by a metal-coated AFM probe tip is possible, and it enables the near-field mapping of the cavity mode symmetry including in the presence of a strong light-matter interaction.

Measurement of Procalcitonin as an Indicator of Severity in Patients With Chronic Obstructive Pulmonary Disease Admitted With Respiratory Illness.

Introduction Exacerbations of chronic obstructive pulmonary disease (COPD) are a frequent reason for hospital admission and a major cause of morbidity and mortality. A useful biomarker or indicator of disease severity at the time of presentation could help guide treatment and identify those with poor prognosis who need early aggressive intervention. We hypothesized that patients who present to the hospital with COPD exacerbations who are found to have elevated procalcitonin (PCT) levels will have worse outcomes such as longer admissions, increased intensive care unit (ICU) utilization, and more frequent readmissions than those with normal levels, regardless of presence or absence of infiltrate on initial chest X-ray (CXR). Methods We conducted a retrospective chart review of patients admitted to our facility with a respiratory complaint and a diagnosis of COPD to examine the relation between PCT and disease severity. A total of 156 unique encounters were reviewed, with 87 included in the final data set. Data was collected on baseline medical conditions as well as clinical status at the time of presentation. Primary endpoints included the need for overnight ICU admission, hospital length of stay greater than seven days, and repeat visit within 30 days of discharge. Secondary endpoints included the need for intubation at the time of admission, in-hospital mortality or discharge to hospice, and ICU length of stay. Results Patients with elevated PCT levels (>0.25ng/mL) had a significantly increased likelihood of a need for ICU admission (odds ratio 3.18) and hospital length of stay greater than seven days (odds ratio 3.38). There was no statistically significant difference in the Emergency Department readmission rate or any of the secondary outcomes. Conclusions Our data suggests that PCT may be a useful early biomarker for patients with COPD presenting with an acute respiratory illness.

Interactions of Si+(2PJ) and Ge+ (2PJ) with rare gas atoms (He-Rn): interaction potentials, spectroscopy, and ion transport coefficients.

Accurate interatomic potentials were calculated for the interaction of a singly-charged silicon cation, Si+, with a single rare gas atom, RG (RG = Kr-Rn), as well as a singly-charged germanium cation, Ge+, with a single rare gas atom, RG (RG = He-Rn). The RCCSD(T) method and basis sets of quadruple-ζ and quintuple-ζ quality were employed; each interaction energy is counterpoise corrected and extrapolated to the basis set limit. The lowest electronic term (2P) of each cation was considered, and the interatomic potentials calculated for the diatomic terms that arise from these: 2Π and 2Σ+. Additionally, the interatomic potentials for the respective spin-orbit levels were calculated, and the effect on the spectroscopic parameters was examined. Variations in several spectroscopic parameters with the increasing atomic number of RG were examined. The presence of incipient chemical interaction was also examined via Birge-Sponer-like plots and various population analyses across the series. In the cases of heavier RG, these were consistent with a small amount of electron transfer from the heavier RG atom to the cation, rationalizing the spin-orbit splittings. This was also supported by the observed larger-than-expected spin-orbit splittings for the Si+-RG complexes. Finally, each set of RCCSD(T) potentials including spin-orbit coupling was employed to calculate transport coefficients for the cation moving through a bath of the RG. The calculated ion mobilities showed significant differences for the two atomic spin-orbit states, arising from subtle changes in the interaction potentials.

In Vitro Visualization of Cell-to-Cell Interactions Between Natural Killer Cells and Sensory Neurons.

Cell-to-cell interactions between the immune and nervous systems are increasingly recognized for their importance in health and disease. Assessment of cellular neuro-immune interactions can be aided by co-culture of two (or more) cells in an in vitro model system that preserves the morphology of neuronal cells. Here we describe methods to investigate the cytotoxic effector functions of natural killer cells on sensory neurons isolated from syngeneic embryonic and adult mice. We present methods for the morphological analysis of axon fragmentation (pruning) and dynamic cell function via live confocal calcium imaging. These techniques can easily be adapted to study interactions between other combinations of immune cell subsets and neuronal populations.

Venous air embolism in CT coronary angiography.

INTRODUCTION: Venous air embolization (VAE) from IV lines is a risk with IV contrast administration. The incidence of VAE ranges from 7% to 23%. While life-threatening VAE is rare, there is the potential risk of serious cerebrovascular events from paradoxical systemic air embolization (SAE) in patients with congenital intracardiac shunts. CT coronary angiogram (CTCA) hypothetically carries a higher risk of VAE as it requires dual injections as compared to single bolus dose contrast used in CT chest (CTC). The aim of this study was to assess the risk of VAE using CTCA as compared to conventional CTC. The incidence of cardiac shunts and their association with paradoxical SAE were also investigated. METHODS: A retrospective study was conducted at a tertiary hospital. Adult patients undergoing CTCA and CTC over a 6-month period in 2017 were included. Images were reviewed on PACS for the presence of VAE. Electronic medical records were interrogated for evidence of neurological sequelae or requiring neurological imaging (CTB/MRIB) within 1 month of the initial imaging. RESULTS: 508 patients were included, 408 underwent CTCA and 100 underwent CTC. The VAE incidence in CTCA was 24% (94 patients) and 10% in the CTC (10 patients). This was statistically significant. Among the CTCA group, 36% (108 patients) had an intracardiac shunt. No statistically significant difference in VAE incidence was identified in CTCA patients with shunts vs without shunts. There was no incidence of SAE in both groups. CONCLUSION: VAE is more common with CTCA than conventional CTC. There were no cases of paradoxical SAE found.