Lysozyme: an endogenous antimicrobial protein with potent activity against extracellular, but not intracellular Mycobacterium tuberculosis.

Endogenous antimicrobial peptides (AMPs) play a key role in the host defense against pathogens. AMPs attack pathogens preferentially at the site of entry to prevent invasive infection. Mycobacterium tuberculosis (Mtb) enters its host via the airways. AMPs released into the airways are therefore likely candidates to contribute to the clearance of Mtb immediately after infection. Since lysozyme is detectable in airway secretions, we evaluated its antimicrobial activity against Mtb. We demonstrate that lysozyme inhibits the growth of extracellular Mtb, including isoniazid-resistant strains. Lysozyme also inhibited the growth of non-tuberculous mycobacteria. Even though lysozyme entered Mtb-infected human macrophages and co-localized with the pathogen we did not observe antimicrobial activity. This observation was unlikely related to the large size of lysozyme (14.74 kDa) because a smaller lysozyme-derived peptide also co-localized with Mtb without affecting the viability. To evaluate whether the activity of lysozyme against extracellular Mtb could be relevant in vivo, we incubated Mtb with fractions of human serum and screened for antimicrobial activity. After several rounds of sub-fractionation, we identified a highly active fraction-component as lysozyme by mass spectrometry. In summary, our results identify lysozyme as an antimycobacterial protein that is detectable as an active compound in human serum. Our results demonstrate that the activity of AMPs against extracellular bacilli does not predict efficacy against intracellular pathogens despite co-localization within the macrophage. Ongoing experiments are designed to unravel peptide modifications that occur in the intracellular space and interfere with the deleterious activity of lysozyme in the extracellular environment.

Do Sheriff-Coroners Underreport Officer-Involved Homicides?

Introduction: In the United States, each state sets its own standards for its death investigation system. These may require independent medical examiners and coroners or allow for the sheriff to assume the role of coroner. Motivated by the well-established fact that counts of officer-involved homicides in official data sets grossly undercount the number of these incidents, we examine the possibility that different death investigation systems may lead to different death classification outcomes. Methods: To examine the potential differences in officer-involved homicide underreporting by presence of sheriff-coroner and violent death type (gunshot, intentional use of force, pursuit, or other vehicle accident), we compare ratios of incidents from both the Federal Bureau of Investigation's Supplementary Homicide Reports and the restricted Multiple-Cause of Death files from the National Vital Statistics System to the Fatal Encounters data across coroner contexts in California between 2000 and 2018; we quantify differences descriptively and examine bivariate tests of means. Results: We find significantly greater underreporting of officer-involved deaths in sheriff-coroner counties in both official data sets for all incidents compared with non-sheriff-coroner counties, independently of the period considered. These underreporting differences in the National Vital Statistics System are robust to restricting to gunshot and intentional use of force deaths, the type of incident expected to be less prone to misclassification in that data set. Conclusions: Officer-involved death underreporting in sheriff-coroner counties necessitates further scrutiny. Disparities in officer-involved death reporting suggest political pressure may play a role in classifying deaths.

Assessing Data Completeness, Quality, and Representativeness of Justifiable Homicides in the FBI's Supplementary Homicide Reports: A Research Note.

Introduction: The most widely used data set for studying police homicides-the Supplementary Homicide Reports (SHR) kept by the Federal Bureau of Investigation-is collected from a voluntary sample. Materials and Methods: Using a journalist-curated database of police-related deaths, we find the SHR police homicide data to be substantially incomplete. This is due to both non-reporting and substantial under-reporting by agencies. Further, our inquiry discloses a pattern of error in identifying "victims" and "offenders" in the data, and finds that investigating agencies are often incorrectly listed as the responsible agency, which seriously jeopardizes police department-level analyses. Finally, there is evidence of sample bias such that the SHR data system is not representative of all police departments, nor is it representative of large police departments. Conclusions: We conclude that the SHR data is of dubious value for assessing correlates of police homicides in the United States, as all analyses using it will reflect these widespread biases and significant undercounts. Analysis of SHR data for these purposes should cease.

Endovascular catheter manometry reliability: a benchtop validation study.

OBJECTIVE: Catheter manometry is used frequently in neuroendovascular surgery for assessing cerebrovascular pathology. The accuracy of pressure data with different catheter setups requires further validation. METHODS: In a silicone human vascular model with a pulsatile pump, pressure measurements were taken through multiple arrangements of 2 guide catheters and 6 microcatheters. The systolic pressure, diastolic pressure, mean pressure, pulse pressure, and area under the curve of the waveform were recorded through catheters with controls at arterial blood pressure ranges. Linear regression modeling was performed, correlating transduction area and relative pulse pressure. Thresholds for acceptable accuracy were ≥ 90%. RESULTS: Mean pressure demonstrated < 4% variation between all 24 catheter setups and respective controls. A strong linear correlation (r2 = 0.843, p < 0.0005) between microcatheter transduction area and relative pulse pressure with a threshold of 0.50 mm2 was seen (i.e., 0.031-inch inner diameter [ID]). For guide catheters with indwelling microcatheters, there was also a strong linear correlation (r2 = 0.840, p < 0.0005) of transduction area to pulse pressure. The guide catheters with obstructing microcatheters required a transduction area over fourfold higher compared with unobstructed microcatheters (2.21 mm2 vs 0.50 mm2). CONCLUSIONS: Mean pressure measurements are accurate through microcatheters as small as 0.013-inch ID. Pulse pressure and waveform morphology may require a microcatheter ≥ 0.031-inch ID to achieve 90% accuracy, although the 0.027-inch ID microcatheter reached 85% accuracy. A 0.070-inch guide catheter with a microcatheter ≤ 0.042-inch outer diameter (e.g., Marksman 0.027-inch ID or smaller) allows accurate transduction of pulse pressure. Further validation of these benchtop findings is necessary before application in a clinical setting.

"Using Crowd-Sourced Data to Explore Police-Related-Deaths in the United States (2000-2017): The Case of Fatal Encounters".

Objectives: We evaluated the Fatal Encounters (FE) database as an open-source surveillance system for tracking police-related deaths (PRDs). Methods: We compared the coverage of FE data to several known government sources of police-related deaths and police homicide data. We also replicated incident selection from a recent review of the National Violent Death Reporting System. Results: FE collected data on n = 23,578 PRDs from 2000-2017. A pilot study and ongoing data integration suggest greater coverage than extant data sets. Advantages of the FE data include circumstance of death specificity, incident geo-locations, identification of involved police-agencies, and near immediate availability of data. Disadvantages include a high rate of missingness for decedent race/ethnicity, potentially higher rates of missing incidents in older data, and the exclusion of more comprehensive police use-of-force and nonlethal use-of-force data-a critique applicable to all extant data sets. Conclusions: FE is the largest collection of PRDs in the United States and remains as the most likely source for historical trend comparisons and police-department level analyses of the causes of PRDs.

Injuries associated with police use of force.

BACKGROUND: Use of force [UOF] by police can result in serious injuries and fatalities. The risk of significant injuries associated with different force modalities is poorly defined. We sought to determine the incidence of police UOF and compare the likelihood of significant injury with different force modalities. METHODS: A prospective multicenter observational study of all UOF incidents was conducted via mandatory UOF investigations at three mid-sized police agencies over a two year period. Expert physicians reviewed police and medical records to determine injury severity using a priori injury severity stratification criteria. RESULTS: There were 893 UOF incidents, representing a UOF rate of 0.086% of 1,041,737 calls for service (1 in 1167) and 0.78% of 114,064 criminal arrests(1 in 128). Suspects were primarily young (mean age, 31 years; range, 12-86 years) males (89%). The 1,399 force utilizations included unarmed physical force (n = 710, 51%), CEWs (504, 30%), chemical (88, 6.3%), canines (47, 3.4%), impact weapons (9, 0.6%), kinetic impact munitions (8, 0.6%), firearms (6, 0.4%), and other (27, 1.9%). Among 914 suspects, 898 (98%) sustained no or mild injury after police UOF. Significant (moderate or severe) injuries occurred in 16 (1.8%) subjects. Logistic regression analysis shows these are most associated with firearm and canine use. There was one fatality (0.1%) due to gunshots. No significant injuries occurred among 504 CEW uses (0%; 95% confidence interval, 0.0-0.9%). Of the 355 suspects transported to a medical facility, 78 (22%) were hospitalized. The majority of hospitalizations were unrelated to UOF (n = 59, 76%), whereas a minority (n = 19, 24%) were due to injuries related to police UOF. CONCLUSION: Police UOF is rare. When force is used officers most commonly rely on unarmed physical force and CEWs. Significant injuries are rare. Transport for medical evaluation is a poor surrogate for significant injury due to UOF. LEVEL OF EVIDENCE: Epidemiological, level II.