Social media, extremism, and radicalization.

Fears that YouTube recommendations radicalize users are overblown, but social media still host and profit from dubious and extremist content.

Bigger Is Not Always Better: Effects of Electrocautery Setting on Tissue Injury in a Porcine Model.

Introduction Electrosurgery for dissection and hemostasis remains one of the foundational tools for the field of surgery as a whole. Monopolar cautery remains the most utilized modality for achieving the aforementioned goals. Given the prolonged history and pre-modern development of "Bovie" cautery, there remains a paucity of data regarding appropriate settings and intensity for various tissue types, procedures, or locales. As a result, utilized settings depend on precedent and personal preference. We aimed to determine the amount of secondary soft tissue injury by volume and depth beyond the electrocautery pen tip in the skin and subcutaneous tissue as well as skeletal muscle.  Methods Porcine samples were used for experimental testing using two testing types: 1) skin and subcutaneous tissue and 2) Skeletal muscle. Sample sizes were standardized at 1 cm3 cubes. For skin samples, tissue injury was created with either a scalpel or electrocautery pen on cut setting, and tested at intensities from 10 to 150 in increments of 10. Skeletal muscle samples were similarly tested using the electrocautery pen only in either a cut or coagulation setting. Samples were tested at incremental intensities from 10 to 120 for both settings. Electrocautery was tested for a period of five seconds with a continuous current. All samples were placed in formalin and underwent histologic staining with hematoxylin and eosin staining to be assessed for the extent of tissue injury in terms of depth, radius, and volume. The measurements were recorded in millimeters. Results For skin incision, there was a positive and significant correlation with respect to the radius (R=.73, p=0.006). When considering intensity with an interval of 10-70 there was a positive and significant correlation with respect to the radius, depth, and volume. The cold knife incision had no notable soft tissue injury beyond the depth of the incision. Regarding skeletal muscle, again, a significant and positive correlation between increasing monopolar settings was noted for both the coagulation and cut functions (R=.84, p=.0005; R=0.84, p=0.0006). A positive correlation was found between increasing cut intensity and volume of soft tissue injury (R=0.73, p=.008); this was not reflected in the coagulation setting. When limited to an intensity range of 10-60, a significant relationship was noted for depth, radius and volume (R=.95, p= <0.001; R=0.98, p= <.001; R=.92, p=.001). Conclusion In all samples, apart from the cold knife skin incision, additional soft tissue injury beyond the tip of the electrocautery pen was noted. Given our findings, recommendations include using the lowest setting required for the purposes of the given surgical case as well as minimizing electrocautery use for skin incisions given its association with a larger volume of tissue injury in comparison with a scalpel. Additionally, electrocautery should be used with care in, and around neurovascular structures as soft tissue injury did occur several millimeters beyond the tip of the electrocautery pen. Further study is needed to see if these patterns are similar in living animals as well as human tissue and whether they bear any clinical impact on surgical wound healing or other surgical complications.

5 ns electric pulses induce Ca2+-dependent exocytotic release of catecholamine from adrenal chromaffin cells.

Previously we reported that adrenal chromaffin cells exposed to a 5 ns, 5 MV/m pulse release the catecholamines norepinephrine (NE) and epinephrine (EPI) in a Ca2+-dependent manner. Here we determined that NE and EPI release increased with pulse number (one versus five and ten pulses at 1 Hz), established that release occurs by exocytosis, and characterized the exocytotic response in real-time. Evidence of an exocytotic mechanism was the appearance of dopamine-ß-hydroxylase on the plasma membrane, and the demonstration by total internal reflection fluorescence microscopy studies that a train of five or ten pulses at 1 Hz triggered the release of the fluorescent dye acridine orange from secretory granules. Release events were Ca2+-dependent, longer-lived relative to those evoked by nicotinic receptor stimulation, and occurred with a delay of several seconds despite an immediate rise in Ca2+. In complementary studies, cells labeled with the plasma membrane fluorescent dye FM 1-43 and exposed to a train of ten pulses at 1 Hz underwent Ca2+-dependent increases in FM 1-43 fluorescence indicative of granule fusion with the plasma membrane due to exocytosis. These results demonstrate the effectiveness of ultrashort electric pulses for stimulating catecholamine release, signifying their promise as a novel electrostimulation modality for neurosecretion.

Fundamental principles of rehabilitation and musculoskeletal tissue healing.

OBJECTIVE: To review fundamental principles of tissue healing and physical rehabilitation as they apply to dogs recovering from cranial cruciate ligament (CCL) surgery. STUDY DESIGN: Invited Review. SAMPLE POPULATION: None. METHODS: A multidisciplinary group of specialists in small animal surgery, rehabilitation/sports medicine, and human physical and occupational therapy reviewed the currently available evidence for rehabilitation post-CCL surgery. Because current evidence is limited, this group proposes guidelines for rehabilitation after CCL surgery based on the fundamental principles of tissue healing and physical therapy. RESULTS: This Review proposes four fundamental principles of small animal physical rehabilitation based on the foundations of tissue healing and patient-centric and goal-oriented therapy. Postoperative rehabilitation programs should be designed such that patient progress is based on individual assessment according to the degree of tissue healing, strength, and achievement of functional goals. Therapists must fully understand phases of tissue healing, reassess the patient frequently, and use clinical reasoning skills to progress treatment appropriately for the individual patient. CONCLUSION: Until more robust evidence is available to guide treatment protocols, fundamental principles of rehabilitation should ideally be adhered to when providing rehabilitation, including after CCL surgery. CLINICAL SIGNIFICANCE: While this Review specifically addresses post-CCL surgery rehabilitation, these fundamental principles should be applied broadly to animals enrolled in rehabilitation programs.

Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants.

Respiratory syncytial virus (RSV) infection remains a significant global health burden disproportionately affecting infants and leading to long-term lung disease. Interleukin (IL)-17A has been shown to be involved in regulating viral and allergic lung inflammatory responses, which has led to a more recent interest in its role in RSV infection. Using a neonatal mouse model of RSV, we demonstrate that neonates fail to develop IL-17A responses compared with adult mice; the main immediate IL-17A contributor in adults were γδ T cells. Antibody neutralization of IL-17A in adult mice caused increased lung inflammation and airway mucus from RSV, whereas exogenous IL-17A administration to RSV-infected neonates caused decreased inflammation but no change in airway mucus. We also observed a lack of pro-inflammatory cytokine production (IL-1ß, IL-6) from infected neonates. Using human cord blood mononuclear cells (CBMCs) and adult peripheral blood mononuclear cells (PBMCs), we compared inflammasome activation by direct retinoic acid-inducible gene I agonism; CBMCs failed to induce pro-inflammatory cytokines or IL-17A(+) γδ T cells compared with PBMCs. Our results indicate that RSV disease severity is in part mediated by a lack of inflammasome activation and IL-17A production in neonates.

Design and Potential of Non-Integrating Lentiviral Vectors.

Lentiviral vectors have demonstrated promising results in clinical trials that target cells of the hematopoietic system. For these applications, they are the vectors of choice since they provide stable integration into cells that will undergo extensive expansion in vivo. Unfortunately, integration can have unintended consequences including dysregulated cell growth. Therefore, lentiviral vectors that do not integrate are predicted to have a safer profile compared to integrating vectors and should be considered for applications where transient expression is required or for sustained episomal expression such as in quiescent cells. In this review, the system for generating lentiviral vectors will be described and used to illustrate how alterations in the viral integrase or vector Long Terminal Repeats have been used to generate vectors that lack the ability to integrate. In addition to their safety advantages, these non-integrating lentiviral vectors can be used when persistent expression would have adverse consequences. Vectors are currently in development for use in vaccinations, cancer therapy, site-directed gene insertions, gene disruption strategies, and cell reprogramming. Preclinical work will be described that illustrates the potential of this unique vector system in human gene therapy.

The Wikipedia Gender Gap Revisited: Characterizing Survey Response Bias with Propensity Score Estimation.

Opt-in surveys are the most widespread method used to study participation in online communities, but produce biased results in the absence of adjustments for non-response. A 2008 survey conducted by the Wikimedia Foundation and United Nations University at Maastricht is the source of a frequently cited statistic that less than 13% of Wikipedia contributors are female. However, the same study suggested that only 39.9% of Wikipedia readers in the US were female - a finding contradicted by a representative survey of American adults by the Pew Research Center conducted less than two months later. Combining these two datasets through an application and extension of a propensity score estimation technique used to model survey non-response bias, we construct revised estimates, contingent on explicit assumptions, for several of the Wikimedia Foundation and United Nations University at Maastricht claims about Wikipedia editors. We estimate that the proportion of female US adult editors was 27.5% higher than the original study reported (22.7%, versus 17.8%), and that the total proportion of female editors was 26.8% higher (16.1%, versus 12.7%).

Using Pulmozyme DNase treatment in lentiviral vector production.

In the production of lentiviral vector for clinical studies the purity of the final product is of vital importance. To remove plasmid and producer cell line DNA, investigators have incubated the vector product with Benzonase, a bacterially derived DNase. As an alternative we investigated the use of Pulmozyme, a U.S. Food and Drug Administration-approved human DNase for the treatment of cystic fibrosis, by comparing the efficiency of DNA removal from lentiviral vector preparations. A green fluorescent protein-expressing lentiviral vector was prepared by transient calcium phosphate transfection of HEK 293T cells and DNA removal was compared when treating vector after harvest or immediately after transfection. The effectiveness of DNase treatment was measured by quantitative PCR using primers for vesicular stomatitis virus glycoprotein G viral envelope plasmid. When treating the final product, 1-hr incubations (37°C) with Pulmozyme at 20 U/ml reduced plasmid DNA to undetectable levels. Longer incubations (up to 4 hr) did not improve DNA removal at lower concentrations and the effectiveness was equivalent to or better than Benzonase at 50 U/ml. Attempting to use Pulmozyme immediately after transfection, but before final medium change, as a means to decrease Pulmozyme concentration in the final product provided a 2-log reduction in DNA but was inferior to treatment at the end of production. Pulmozyme, at concentrations up to 100 U/ml, had no measurable effect on infectious titer of the final vector product. The use of Pulmozyme is likely to increase the cost of DNase treatment when preparing vector product and should be considered when generating clinical-grade vector products.