Distributed X chromosome inactivation in brain circuitry is associated with X-linked disease penetrance of behavior.

The precise anatomical degree of brain X chromosome inactivation (XCI) that is sufficient to alter X-linked disorders in females is unclear. Here, we quantify whole-brain XCI at single-cell resolution to discover a prevalent activation ratio of maternal to paternal X at 60:40 across all divisions of the adult brain. This modest, non-random XCI influences X-linked disease penetrance: maternal transmission of the fragile X mental retardation 1 (Fmr1)-knockout (KO) allele confers 55% of total brain cells with mutant X-active, which is sufficient for behavioral penetrance, while 40% produced from paternal transmission is tolerated.

Endogenous pathology in tauopathy mice progresses via brain networks.

Neurodegenerative tauopathies are hypothesized to propagate via brain networks. This is uncertain because we have lacked precise network resolution of pathology. We therefore developed whole-brain staining methods with anti-p-tau nanobodies and imaged in 3D PS19 tauopathy mice, which have pan-neuronal expression of full-length human tau containing the P301S mutation.

Synergy in IR-Hybrid CT/C-arm in the setting of critical trauma.

Access to multi-detector computed tomography (MDCT) scanning for interventional procedures can prove to be logistically challenging as resources are often in different areas within the hospital. At some institutions, interventional radiology suites have moved to the operating room, separate from the diagnostic radiology department. At these institutions, complex interventional procedures requiring both fluoroscopy and MDCT may pose logistical challenges, especially as they pertain to timely patient transfers.

Regional, Layer, and Cell-Type-Specific Connectivity of the Mouse Default Mode Network.

The evolutionarily conserved default mode network (DMN) is a distributed set of brain regions coactivated during resting states that is vulnerable to brain disorders. How disease affects the DMN is unknown, but detailed anatomical descriptions could provide clues. Mice offer an opportunity to investigate structural connectivity of the DMN across spatial scales with cell-type resolution.

Comparing Occlusive Balloon Performance Using 3-Dimensional Printed Models of Intracranial Aneurysmal Defects.

Objective: Balloon remodeling microcatheters are essential in assisting endovascular coiling of brain aneurysms, but the performance and pressure requirements of different balloon types when used in aneurysmal defects are currently unknown.

Methods: We used Tinkercad (Autodesk, Montreal, Quebec) to create model vessels with aneurysmal defects and 3-dimensionally printed these designs with polylactic acid using the Ultimaker2 (Ultimaker, Geldermalsen, Netherlands). We constructed a pressurized box capable of reaching physiologic pressures that housed our vessels and then tested compliant remodeling balloons under fluoroscopy from 3 manufacturers: Hyperglide (Medtronic, Minneapolis, Minnesota, USA), Transform (Stryker Neurovascular, Fremont, California, USA), and Scepter C (Microvention, Tustin, California, USA).

Intermediate to Long-Term Clinical Outcomes of Percutaneous Cryoablation for Renal Masses.

Purpose: The purpose of this study was to evaluate the effectiveness and adverse outcomes of percutaneous cryoablation (CA) for treatment of renal masses in a large cohort of patients.

Materials And Methods: This retrospective analysis included 299 CA procedures (297 masses in 277 patients) performed between July 2007 and May 2018 at a single institution. The mean patient age was 66.

Hierarchical organization of cortical and thalamic connectivity.

The mammalian cortex is a laminar structure containing many areas and cell types that are densely interconnected in complex ways, and for which generalizable principles of organization remain mostly unknown. Here we describe a major expansion of the Allen Mouse Brain Connectivity Atlas resource, involving around a thousand new tracer experiments in the cortex and its main satellite structure, the thalamus. We used Cre driver lines (mice expressing Cre recombinase) to comprehensively and selectively label brain-wide connections by layer and class of projection neuron.

Outcomes after Peripancreatic Fluid Drainage in Patients with Simultaneous Pancreas-Kidney Transplantation.

Purpose: To determine the clinical outcomes of patients who underwent image-guided drainage of peripancreatic fluid collections after simultaneous pancreas-kidney (SPK) transplantation.

Materials And Methods: A retrospective review of all patients who underwent peripancreatic fluid collection drainage after SPK, from January 2000 to August 2017, at a single institution was performed. Patient characteristics, surgical technique, medication regimen, microbial analysis, and clinical outcomes were reviewed.

High-resolution data-driven model of the mouse connectome.

Knowledge of mesoscopic brain connectivity is important for understanding inter- and intraregion information processing. Models of structural connectivity are typically constructed and analyzed with the assumption that regions are homogeneous. We instead use the Allen Mouse Brain Connectivity Atlas to construct a model of whole-brain connectivity at the scale of 100 μm voxels.

An Abnormal Tibial Position Is Associated With Alterations in the Meniscal Matrix: A 3-Year Longitudinal Study After Anterior Cruciate Ligament Reconstruction.

Background: An altered tibial position is still present despite anterior cruciate ligament (ACL) reconstruction. It has been demonstrated that an abnormal tibial position after an ACL injury may play a role in subsequent injuries to the meniscus, which can lead to early cartilage degeneration.

Purpose: To determine changes in both the tibial position and the meniscal matrix present before and after ACL reconstruction as well as to evaluate the association between these 2 variables in ACL-injured knees 3 years after reconstruction.

Whole brain imaging reveals distinct spatial patterns of amyloid beta deposition in three mouse models of Alzheimer's disease.

A variety of Alzheimer's disease (AD) mouse models overexpress mutant forms of human amyloid precursor protein (APP), producing high levels of amyloid β (Aβ) and forming plaques. However, the degree to which these models mimic spatiotemporal patterns of Aβ deposition in brains of AD patients is unknown. Here, we mapped the spatial distribution of Aβ plaques across age in three APP-overexpression mouse lines (APP/PS1, Tg2576, and hAPP-J20) using in vivo labeling with methoxy-X04, high throughput whole brain imaging, and an automated informatics pipeline.

Phosphorylation of tau at Y18, but not tau-fyn binding, is required for tau to modulate NMDA receptor-dependent excitotoxicity in primary neuronal culture.

Background: Hyperexcitability of neuronal networks can lead to excessive release of the excitatory neurotransmitter glutamate, which in turn can cause neuronal damage by overactivating NMDA-type glutamate receptors and related signaling pathways. This process (excitotoxicity) has been implicated in the pathogenesis of many neurological conditions, ranging from childhood epilepsies to stroke and neurodegenerative disorders such as Alzheimer's disease (AD). Reducing neuronal levels of the microtubule-associated protein tau counteracts network hyperexcitability of diverse causes, but whether this strategy can also diminish downstream excitotoxicity is less clear.

DNA repair factor BRCA1 depletion occurs in Alzheimer brains and impairs cognitive function in mice.

Maintaining DNA integrity is vital for all cells and organisms. Defective DNA repair may contribute to neurological disorders, including Alzheimer's disease (AD). We found reduced levels of BRCA1, but not of other DNA repair factors, in the brains of AD patients and human amyloid precursor protein (hAPP) transgenic mice.

Increasing the Receptor Tyrosine Kinase EphB2 Prevents Amyloid-β-induced Depletion of Cell Surface Glutamate Receptors by a Mechanism That Requires the PDZ-binding Motif of EphB2 and Neuronal Activity.

Diverse lines of evidence suggest that amyloid-β (Aβ) peptides causally contribute to the pathogenesis of Alzheimer disease (AD), the most frequent neurodegenerative disorder. However, the mechanisms by which Aβ impairs neuronal functions remain to be fully elucidated. Previous studies showed that soluble Aβ oligomers interfere with synaptic functions by depleting NMDA-type glutamate receptors (NMDARs) from the neuronal surface and that overexpression of the receptor tyrosine kinase EphB2 can counteract this process.

Tau reduction prevents Aβ-induced axonal transport deficits by blocking activation of GSK3β.

Axonal transport deficits in Alzheimer's disease (AD) are attributed to amyloid β (Aβ) peptides and pathological forms of the microtubule-associated protein tau. Genetic ablation of tau prevents neuronal overexcitation and axonal transport deficits caused by recombinant Aβ oligomers. Relevance of these findings to naturally secreted Aβ and mechanisms underlying tau's enabling effect are unknown.