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Efficacious stem cell-based therapies for traumatic brain injury (TBI) depend on successful delivery, migration, and engraftment of stem cells to induce neuroprotection. L-myc expressing human neural stem cells (LMNSC008) demonstrate an inherent tropism to injury sites after intranasal (IN) administration. We hypothesize that IN delivered LMNSC008 cells migrate to primary and secondary injury sites and modulate biomarkers associated with neuroprotection and tissue regeneration. To test this hypothesis, immunocompetent adult female rats received either controlled cortical impact injury or sham surgery. LMNSC008 cells or a vehicle were administered IN on postoperative days 7, 9, 11, 13, 15, and 17. The distribution and migration of eGFP-expressing LMNSC008 cells were quantified over 1 mm-thick optically cleared (CLARITY) coronal brain sections from TBI and SHAM controls. NSC migration was observed along white matter tracts projecting toward the hippocampus and regions of TBI. ELISA and Nanostring assays revealed a shift in tissue gene expression in LMNSC008 treated rats relative to controls. LMNSC008 treatment reduced expression of genes and pathways involved in inflammatory response, microglial function, and various cytokines and receptors. Our proof-of-concept studies, although preliminary, support the rationale of using intranasal delivery of LMNSC008 cells for functional studies in preclinical models of TBI and provide support for potential translatability in TBI patients.

As the success of stem cell-based therapies is contingent on efficient cell delivery to damaged areas, neural stem cells (NSCs) have promising therapeutic potential because they inherently migrate to sites of central nervous system (CNS) damage. To explore the possibility of NSC-based therapy after traumatic brain injury (TBI), isoflurane-anesthetized adult male rats received a controlled cortical impact (CCI) of moderate severity (2.8 mm deformation at 4 m/s) or sham injury (i.e., no cortical impact). Beginning 1-week post-injury, the rats were immunosuppressed and 1 × 106 human NSCs (LM-NS008.GFP.fLuc) or vehicle (VEH) (2% human serum albumen) were administered intranasally (IN) on post-operative days 7, 9, 11, 13, 15, and 17. To evaluate the spatial distributions of the LM-NSC008 cells, half of the rats were euthanized on day 25, one day after completion of the cognitive task, and the other half were euthanized on day 46. 1 mm thick brain sections were optically cleared (CLARITY), and volumes were imaged by confocal microscopy. In addition, LM-NSC008 cell migration to the TBI site by immunohistochemistry for human-specific Nestin was observed at day 39. Acquisition of spatial learning was assessed in a well-established Morris water maze task on six successive days beginning on post-injury day 18. IN administration of LM-NSC008 cells after TBI (TBI + NSC) significantly facilitated spatial learning relative to TBI + VEH rats (p < 0.05) and had no effect on sham + NSC rats. Overall, these data indicate that IN-administered LM-NSC008 cells migrate to sites of TBI damage and that their presence correlates with cognitive improvement. Future studies will expand on these preliminary findings by evaluating other LM-NSC008 cell dosing paradigms and evaluating mechanisms by which LM-NSC008 cells contribute to cognitive recovery.

Human myxovirus resistance 2 (MX2) can restrict HIV-1 and herpesviruses at a post-entry step through a process requiring an interaction between MX2 and the viral capsids. The involvement of other host cell factors, however, remains poorly understood. Here, we mapped the proximity interactome of MX2, revealing strong enrichment of phenylalanine-glycine (FG)-rich proteins related to the nuclear pore complex as well as proteins that are part of cytoplasmic ribonucleoprotein granules. MX2 interacted with these proteins to form multiprotein cytoplasmic biomolecular condensates that were essential for its anti-HIV-1 and anti-herpes simplex virus 1 (HSV-1) activity. MX2 condensate formation required the disordered N-terminal region and MX2 dimerization. Incoming HIV-1 and HSV-1 capsids associated with MX2 at these dynamic cytoplasmic biomolecular condensates, preventing nuclear entry of their viral genomes. Thus, MX2 forms cytoplasmic condensates that likely act as nuclear pore decoys, trapping capsids and inducing premature viral genome release to interfere with nuclear targeting of HIV-1 and HSV-1. [Display omitted] • Interferon-induced antiviral protein MX2 forms cytoplasmic condensates with FG Nups • MX2's N-terminal domain and dimerization are required for condensate formation • Restriction of HIV-1 and HSV-1 by MX2 requires condensate formation • MX2 condensates trap HIV-1 capsids and cause premature release of HSV-1 genomes MX2 restricts HIV-1 and herpes simplex virus 1 (HSV-1) through a poorly understood mechanism. Moschonas et al. reveal that MX2 assembles FG nucleoporins into cytoplasmic biomolecular condensates that interact with incoming capsids to trap them or induce premature viral genome release. MX2's N-terminal domain controls condensate formation, which is essential for HIV-1 and HSV-1 restriction. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) commonly co‐exists with systolic heart failure (SHF) and its presence is associated with a worse prognosis. Despite this, a rhythm control approach using antiarrhythmic drugs (AADs) to reduce AF burden has demonstrated no prognostic benefit. Catheter ablation (AFA) is more effective than AADs at reducing AF burden. We performed a meta‐analysis to evaluate the impact of AFA on outcomes in SHF. Electronic databases were systematically searched. We included only randomized controlled trials that examined the impact of AFA on clinical outcomes in patients with SHF (LVEF <50%). We included studies with any ablation strategy that incorporated pulmonary vein isolation and any control group. Seven studies (n = 858) were included with a mean follow‐up of 6‐38 months. In comparison to controls, AFA was associated with significant reductions in all‐cause mortality (relative risk [RR] 0.52, P = 0.0009) and unplanned or heart failure hospitalization (RR 0.58, P < 0.00001). Compared to controls, AFA was also associated with significant improvements in LVEF (mean difference 6.30%, P < 0.00001), Minnesota Living with Heart Failure Questionnaire score (mean difference 9.58, P = 0.0003), 6‐minute walk distance (mean difference 31.78 m, P = 0.003) and VO2 max (mean difference 3.17, P = 0.003). However, major procedure‐related complications occurred in 2.4%‐15% of ablation patients. In patients with AF and SHF, catheter ablation has significant benefits. Further work is needed to establish the role of ablation in the routine treatment of SHF patients with AF. We performed a meta‐analysis evaluating the impact of catheter ablation in patients with atrial fibrillation and systolic heart failure. A total of 858 patients were included across seven studies. Compared to controls, ablation was associated with lower all‐cause mortality and hospitalizations, higher LVEF, and improved symptoms and physiologic parameters. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate urinary continence four weeks following Retzius-sparing robot-assisted radical prostatectomy. Patients and methods: Forty patients with T2–T3 prostate cancer underwent Retzius-sparing-robot-assisted radical prostatectomy and their results were compared with those from the 40 patients having robot-assisted radical prostatectomy done by the same surgeon immediately prior to the adoption of Retzius-sparing-robot-assisted radical prostatectomy. Results: Patients in the two groups had similar age, body mass index, prostate specific antigen, biopsy Gleason sum, clinical stage, d’Amico risk profile, blood loss, prostate weight and post-operative hospital stay. Median operating time (200 (interquartile range=155–266) vs 223 (interquartile range=100–238) min; p=0.05) and catheterisation (8 (interquartile range=8–8) vs 14 (interquartile range=14–14) days; p<0.0001) were shorter in the Retzius-sparing group, many of whom had suprapubic catheters inserted. The overall complication rate was lower in Retzius-sparing patients (2.5% vs 8.0%; p=0.36). Positive surgical margin rates were similar for Retzius-sparing and non-Retzius-sparing patients and decreased with greater experience with the Retzius-sparing technique: 16.7% vs 7.7% for pT2 (p=0.65) and 31.8% vs 14.3% for pT3 (p=0.44). Initial prostate specific antigen was <0.1 ng/ml in 97.5% and 100%, respectively (p=1.00). At four weeks post-operation 0, 1 and 2 pads/day were needed in the Retzius-sparing group in 90.0%, 7.5% and 2.5% of patients, compared to 37.5% (p<0.0001), 32.5% (p=0.01) and 30% (p=0.002) of men having conventional surgery. Conclusion: Retzius-sparing-robot-assisted radical prostatectomy is faster than the anterior approach to the prostate, allows a shorter catheterisation time and produces dramatically better continence results at four weeks with 90% of patients being pad-free and 97.5% of patients needing 0–1 pads/day. [ABSTRACT FROM AUTHOR]