Chloride secretion by cultures of pig tracheal gland cells.

Malfunction of airway submucosal glands contributes to the pathology of cystic fibrosis (CF), and cell cultures of CF human airway glands show defects in Cl(-) and water transport. Recently, a transgenic pig model of CF (the CF pig) has been developed. Accordingly, we have developed cell cultures of pig airway gland epithelium for use in investigating alterations in gland function in CF. Our cultures form tight junctions (as evidenced by high transepithelial electrical resistance) and show high levels of active anion secretion (measured as amiloride-insensitive short-circuit current). In agreement with recent results on human airway glands, neurohumoral agents that elevate intracellular Ca(2+) potently stimulated anion secretion, while elevation of cAMP was comparatively ineffective. Our cultures express lactoferrin and lysozyme (serous gland cell markers) and MUC5B (the main mucin of airway glands). They are, therefore, potentially useful in determining if CF-related alterations in anion transport result in altered secretion of serous cell antimicrobial agents or mucus.

In vitro and in vivo methods to study bacterial colonization of hydrogel dermal fillers.

Preclinical in vitro and in vivo methods to study bacterial interactions with dermal fillers and infection pathogenesis are lacking. In this work, first in vitro methods to assess protein biofouling and effective pore size of commercial dermal fillers, including degradable hyaluronic acid (HA)-based fillers and other semi-degradable or permanent fillers (non-HA), were developed. The results were then related to Staphylococcus aureus (S. aureus) adhesion rates in vitro. HA fillers had less protein sorption than non-HA fillers and overall had smaller effective pore sizes. The properties correlated with levels of bacterial adhesion, where the control glass surface had the most rapid increase in bacterial cell adhesion, with a slope of 0.29 cm-2  min-1 , three unique non-HA fillers had intermediate adhesion with slopes of 0.11 and 0.06 cm-2  min-1 , and three unique HA fillers had the least adhesion with slopes of 0.02, 0.02, and 0.01 cm-2  min-1 . S. aureus had greater motility on the HA fillers than on non-HA fillers. Next, a mouse model for dermal filler biofilm and infection was developed. Mice were inoculated with a controlled amount of bioluminescent bacteria (Xen36 S. aureus) and polyacrylamide hydrogels of different stiffness were injected. In vivo bioluminescence was monitored longitudinally for 35 days to ensure that lasting colonization was established. The inoculum was optimized to achieve adequate bioluminescent signal, and bacterial bioburden over time and inter-animal variability in bioburden were determined. These in vitro and in vivo approaches can be used for future studies of antimicrobial interventions for dermal fillers.

Recovery of Pediatric Patients After Firearm Injury: Can Health Systems Do More?

BACKGROUND: Firearm injuries are the second leading cause of death among youth in the United States. Nonfatal firearm injuries far outnumber fatalities, yet data detailing the recovery and post-injury needs of pediatric patients after hospital discharge are limited. This study evaluated health system support of pediatric patients after firearm injury, from acute hospitalization to outpatient follow-up. METHODS: We conducted a retrospective chart review of patients <18 years who presented to an urban level 1 trauma center between 2014 and 2019. Cases were categorized as accidental or intentional (stratified as assault-related or "crossfire" injuries). Outcomes included biopsychosocial assessment (BA) utilization, trauma psychology service consultation, and linkage to outpatient services. RESULTS: Among 115 patients, 94% were victims of community violence. Black (50%) and Latinx (44%) patients were disproportionately affected, as were males aged 15-16 years (71%). Overall mortality was 8%. Biopsychosocial assessment and trauma psychology consultations occurred in 43% and 20% of cases, respectively. Of eligible patients, 71% received referral to post-hospitalization support services. The most commonly identified needs were counseling, gang intervention, and help with the carceral system. CONCLUSION: Health systems should support long-term recovery of pediatric patients after firearm injury, particularly addressing social and structural determinants of health. Inpatient-to-outpatient linkages should be strengthened, and prospective follow-up is needed.

A Comparison of Defense and Plaintiff Expert Witnesses in Orthopaedic Surgery Malpractice Litigation.

BACKGROUND: According to the American Academy of Orthopaedic Surgeons (AAOS) Standards of Professionalism, the responsible testimony of expert witnesses in orthopaedic surgery malpractice lawsuits is important to the public interest. However, these expert witnesses are recruited and compensated without established standards, and their testimony can potentially sway court opinion, with substantial consequences. The objective of this study was to characterize defense and plaintiff expert orthopaedic surgeon witnesses in orthopaedic surgery malpractice litigation. METHODS: Utilizing the WestlawNext legal database, defense and plaintiff expert witnesses involved in orthopaedic surgery malpractice lawsuits from 2013 to 2017 were identified. Each witness's subspecialty, mean years of experience, involvement in academic or private practice, fellowship training, and scholarly impact, as measured by the Hirsch index (h-index), were determined through a query of professional profiles, the Scopus database, and a PubMed search. Statistical comparisons were made for each parameter among defense and plaintiff expert witnesses. RESULTS: Between 2013 and 2017, 306 expert medical witnesses for orthopaedic cases were identified; 174 (56.9%) testified on behalf of the plaintiff, and 132 (43.1%) testified on behalf of the defense. Orthopaedic surgeons who identified themselves as general orthopaedists comprised the largest share of expert witnesses on both the plaintiff (n = 61) and defense (n = 25) sides. The plaintiff witnesses averaged 36 years of experience versus 31 years for the defense witnesses (p < 0.001); 26% of the plaintiff witnesses held an academic position versus 43% of the defense witnesses (p = 0.013). Defense witnesses exhibited a higher proportion of fellowship training in comparison to plaintiff expert witnesses (80.5% versus 64.5%, respectively, p = 0.003). The h-index for the plaintiff group was 6.6 versus 9.1 for the defense group (p = 0.04). Two witnesses testified for both the plaintiff and defense sides. CONCLUSIONS: Defense expert witnesses held higher rates of academic appointments and exhibited greater scholarly impact than their plaintiff counterparts, with both sides averaging >30 years of experience. These data collectively show that there are differences in characteristics between plaintiff and defense witnesses. Additional study is needed to illuminate the etiology of these differences.

Distribution and size of mucous glands in the ferret tracheobronchial tree.

A transgenic ferret model of cystic fibrosis has recently been generated. It is probable that malfunction of airway mucous glands contributes significantly to the airway pathology of this disease. The usefulness of the ferret model may therefore depend in part on how closely the airway glands of ferrets resemble those of humans. Here, we show that in the ferret trachea glands are commonest in its most ventral aspect and disappear about half way up the lateral walls; they are virtually absent from the dorsal membranous portion. Further, the aggregate volume of glands per unit mucosal surface declines progressively by about 60% between the larynx and the carina. The average frequency of glands openings for the ferret trachea as a whole is only about one-fifth that in humans (where gland openings are found at approximately the same frequency throughout the trachea). Glands in the ferret trachea are on average about one-third the size of those in the human. Therefore, the aggregate volume of tracheal glands (per unit mucosal surface area) in the ferret is only about 6% that in humans. As in other mammalian species, airway glands in the ferret disappear at an airway internal diameter of ∼1 mm, corresponding approximately in this species to airway generation 6.

Spatiotemporal processing deficits in female CGG KI mice modeling the fragile X premutation.

The fragile X premutation is a tandem CGG trinucleotide repeat expansion in the fragile X mental retardation 1 (FMR1) gene between 55 and 200 repeats in length. A CGG knock-in (CGG KI) mouse has been developed that models the neuropathology and cognitive deficits reported in fragile X premutation carriers. It has been suggested that carriers of the premutation demonstrate a spatiotemporal hypergranularity, or reduced resolution of spatial and temporal processing. A temporal ordering of spatial locations task was used to evaluate the ability of CGG KI mice to process temporal and spatial information with either high or low levels of spatial interference. The results indicate that CGG KI mice showed difficulty performing a spatial novelty detection task when there were high levels of spatial interference, but were able to perform the novelty detection task when there was low spatial interference. These data suggest that CGG KI mice show reduced spatial and temporal resolution that are modulated by the dosage of the Fmr1 gene mutation, such that when behavioral tasks require mice to overcome high levels of either spatial or temporal interference, the CGG KI mice perform increasingly poorly as the CGG repeat length increases.