Activity-Induced Remodeling of Olfactory Bulb Microcircuits Revealed by Monosynaptic Tracing

The continued addition of new neurons to mature olfactory circuits represents a remarkable mode of cellular and structural brain plasticity. However, the anatomical configuration of newly established circuits, the types and numbers of neurons that form new synaptic connections, and the effect of sensory experience on synaptic connectivity in the olfactory bulb remain poorly understood. Using in vivo electroporation and monosynaptic tracing, we show that postnatal-born granule cells form synaptic connections with centrifugal inputs and mitral/tufted cells in the mouse olfactory bulb. In addition, newly born granule cells receive extensive input from local inhibitory short axon cells, a poorly understood cell population. The connectivity of short axon cells shows clustered organization, and their synaptic input onto newborn granule cells dramatically and selectively expands with odor stimulation. Our findings suggest that sensory experience promotes the synaptic integration of new neurons into cell type-specific olfactory circuits

Host Cell Factors in HIV Replication: Meta-Analysis of Genome-Wide Studies

We have analyzed host cell genes linked to HIV replication that were identified in nine genome-wide studies, including three independent siRNA screens. Overlaps among the siRNA screens were very modest (<7% for any pairwise combination), and similarly, only modest overlaps were seen in pairwise comparisons with other types of genome-wide studies. Combining all genes from the genome-wide studies together with genes reported in the literature to affect HIV yields 2,410 protein-coding genes, or fully 9.5% of all human genes (though of course some of these are false positive calls). Here we report an “encyclopedia” of all overlaps between studies (available at http://www.hostpathogen.org), which yielded a more extensively corroborated set of host factors assisting HIV replication. We used these genes to calculate refined networks that specify cellular subsystems recruited by HIV to assist in replication, and present additional analysis specifying host cell genes that are attractive as potential therapeutic targets

A comparison of Selective Aortic Arch Perfusion and Resuscitative Endovascular Balloon Occlusion of the Aorta for the management of hemorrhage-induced traumatic cardiac arrest: A translational model in large swine

<div><p>Background</p><p>Survival rates remain low after hemorrhage-induced traumatic cardiac arrest (TCA). Noncompressible torso hemorrhage (NCTH) is a major cause of potentially survivable trauma death. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) at the thoracic aorta (Zone 1) can limit subdiaphragmatic blood loss and allow for IV fluid resuscitation when intrinsic cardiac activity is still present. Selective Aortic Arch Perfusion (SAAP) combines thoracic aortic balloon hemorrhage control with intra-aortic oxygenated perfusion to achieve return of spontaneous circulation (ROSC) when cardiac arrest has occurred.</p><p>Methods and findings</p><p>Male Yorkshire Landrace cross swine (80.0 ± 6.0 kg) underwent anesthesia, instrumentation for monitoring, and splenectomy. TCA was induced by laparoscopic liver lobe resection combined with arterial catheter blood withdrawal to achieve a sustained systolic blood pressure <10 mmHg, cardiac arrest. After 3 min of arrest, swine were allocated to one of three interventions: (1) REBOA plus 4 units of IV fresh whole blood (FWB), (2) SAAP with oxygenated lactated Ringer’s (LR), 1,600 mL/2 min, or (3) SAAP with oxygenated FWB 1,600 mL/2 min. Primary endpoint was survival to the end of 60 min of resuscitation, a simulated prehospital phase. Thirty animals were allocated to 3 groups (10 per group)—5 protocol exclusions resulted in a total of 35 animals being used. Baseline measurements and time to cardiac arrest were not different amongst groups. ROSC was achieved in 0/10 (0%, 95% CI 0.00–30.9) REBOA, 6/10 (60%, 95% CI 26.2–87.8) SAAP-LR and 10/10 (100%, 95% CI 69.2–100.0) SAAP-FWB animals, <i>p</i> < 0.001. Survival to end of simulated 60-minute prehospital resuscitation was 0/10 (0%, 95% CI 0.00–30.9) for REBOA, 1/10 (10%, 95% CI 0.25–44.5) for SAAP-LR and 9/10 (90%, 95% CI 55.5–99.7) for SAAP-FWB, <i>p</i> < 0.001. Total FWB infusion volume was similar for REBOA (2,452 ± 0 mL) and SAAP-FWB (2,250 ± 594 mL). This study was undertaken in laboratory conditions, and as such may have practical limitations when applied clinically. Cardiac arrest in this study was defined by intra-aortic pressure monitoring that is not feasible in clinical practice, and as such limits the generalizability of findings. Clinical trials are needed to determine if the beneficial effects of SAAP-FWB observed in this laboratory study will translate into improved survival in clinical practice.</p><p>Conclusions</p><p>SAAP conferred a superior short-term survival over REBOA in this large animal model of hemorrhage-induced traumatic cardiac arrest with NCTH. SAAP using an oxygen-carrying perfusate was more effective in this study than non-oxygen carrying solutions in TCA. SAAP can effect ROSC from hemorrhage-induced electrocardiographic asystole in large swine.</p></div

Animal baseline and injury characteristics.

<p>Animal baseline and injury characteristics.</p

Secondary outcomes.

<p>Mean SBP, left carotid artery flow, ETCO₂, and proximal NIRS throughout the protocol. ETCO₂, end-tidal carbon dioxide; NIRS, near-infrared spectroscopy; SBP, systolic blood pressure.</p

Protocol timeline.

<p>SAAP (inflation of an aortic occlusion balloon, and a 2-min intra-aortic oxygenated infusion of either LR solution, or FWB), REBOA (inflation of an aortic occlusion balloon, and a 5-min IV infusion of FWB). FWB, fresh whole blood; IV, intravenous; LR, lactated Ringer’s; REBOA, Resuscitative Emergency Balloon Occlusion of the Aorta; SAAP, Selective Aortic Arch Perfusion.</p

SAAP catheter (photograph by EGB Barnard).

<p>To determine the efficacy of SAAP in resuscitating NCTH-induced TCA compared to REBOA, we modified an existing large swine translational model of NCTH. [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1002349#pmed.1002349.ref016" target="_blank">16</a>] We hypothesized that in this translational model of NCTH-induced TCA, SAAP would significantly increase ROSC and 60-min survival (a surrogate for prehospital survival) as compared to REBOA, and that SAAP efficacy requires oxygen carrying capacity in the resuscitation fluid infused. NCTH, noncompressible torso hemorrhage; REBOA, Resuscitative Endovascular Balloon Occlusion of the Aorta; ROSC, return of spontaneous circulation; SAAP, Selective Aortic Arch Perfusion; TCA, traumatic cardiac arrest.</p

SAAP circuit.

<p>SAAP, Selective Aortic Arch Perfusion.</p

SAAP-FWB group survivors (<i>n</i> = 9) comparison of baseline and end-of-protocol physiology.

<p>SAAP-FWB group survivors (<i>n</i> = 9) comparison of baseline and end-of-protocol physiology.</p

Primary outcome.

<p>Prehospital (60-min) survival of REBOA group (<i>n</i> = 10), compared to SAAP-LR group (<i>n</i> = 10), and SAAP-FWB group (<i>n</i> = 10). REBOA, Resuscitative Endovascular Balloon Occlusion of the Aorta; SAAP-FWB, Selective Aortic Arch perfusion with 1,600 ml of intra-aortic oxygenated fresh whole blood; SAAP-LR, Selective Aortic Arch Perfusion with 1,600 ml of intra-aortic oxygenated lactated Ringer’s solution.</p