IL-33-induced neutrophilic inflammation and NETosis underlie rhinovirus-triggered exacerbations of asthma.

Rhinovirus-induced neutrophil extracellular traps (NETs) contribute to acute asthma exacerbations; however, the molecular factors that trigger NETosis in this context remain ill-defined. Here, we sought to implicate a role for IL-33, an epithelial cell-derived alarmin rapidly released in response to infection. In mice with chronic experimental asthma (CEA), but not naïve controls, rhinovirus inoculation induced an early (1 day post infection; dpi) inflammatory response dominated by neutrophils, neutrophil-associated cytokines (IL-1α, IL-1ß, CXCL1), and NETosis, followed by a later, type-2 inflammatory phase (3-7 dpi), characterised by eosinophils, elevated IL-4 levels, and goblet cell hyperplasia. Notably, both phases were ablated by HpARI (Heligmosomoides polygyrus Alarmin Release Inhibitor), which blocks IL-33 release and signalling. Instillation of exogenous IL-33 recapitulated the rhinovirus-induced early phase, including the increased presence of NETs in the airway mucosa, in a PAD4-dependent manner. Ex vivo IL-33-stimulated neutrophils from mice with CEA, but not naïve mice, underwent NETosis and produced greater amounts of IL-1α/ß, IL-4, and IL-5. In nasal samples from rhinovirus-infected people with asthma, but not healthy controls, IL-33 levels correlated with neutrophil elastase and dsDNA. Our findings suggest that IL-33 blockade ameliorates the severity of an asthma exacerbation by attenuating neutrophil recruitment and the downstream generation of NETs.

Maternal diet modulates the infant microbiome and intestinal Flt3L necessary for dendritic cell development and immunity to respiratory infection.

Poor maternal diet during pregnancy is a risk factor for severe lower respiratory infections (sLRIs) in the offspring, but the underlying mechanisms remain elusive. Here, we demonstrate that in mice a maternal low-fiber diet (LFD) led to enhanced LRI severity in infants because of delayed plasmacytoid dendritic cell (pDC) recruitment and perturbation of regulatory T cell expansion in the lungs. LFD altered the composition of the maternal milk microbiome and assembling infant gut microbiome. These microbial changes reduced the secretion of the DC growth factor Flt3L by neonatal intestinal epithelial cells and impaired downstream pDC hematopoiesis. Therapy with a propionate-producing bacteria isolated from the milk of high-fiber diet-fed mothers, or supplementation with propionate, conferred protection against sLRI by restoring gut Flt3L expression and pDC hematopoiesis. Our findings identify a microbiome-dependent Flt3L axis in the gut that promotes pDC hematopoiesis in early life and confers disease resistance against sLRIs.

Posterior Lateral Meniscal Root Tears Increase Strain on the Reconstructed Anterior Cruciate Ligament: A Cadaveric Study.

PURPOSE: To quantify the amount of strain across an anterior cruciate ligament reconstruction (ACLR) before and after a lateral meniscus (LM) posterior root complex tear and determine whether a meniscal root repair effectively protects the ACLR against excessive strain. METHODS: Fresh-frozen cadaveric knees were tested with an 88-N anterior drawer force and an internal and external torque of 5-Nm applied at 0°, 15°, 30°, 60°, and 90° of flexion. A simulated pivot shift was also applied at 0, 15, and 30° of flexion. Rotation and translation of the tibia, and strain across the ACL graft were recorded. Testing was repeated for the following four conditions: ACL-intact, ACLR with intact LM, ACLR with LM posterior root complex tear, and ACLR with root repair. RESULTS: The kinematic data from 12 fresh frozen cadaveric knees underwent analysis. Only 11 specimens had usable strain data. Sectioning the meniscofemoral ligaments and the LM posterior root increased rotational and translational laxity at 30° of knee flexion. ACLR graft strain significantly increased when an anterior load and internal torque were applied. Repair of the LM posterior root reduced strain when the knee was internally rotated but was unable to normalize strain when an anterior force was applied. CONCLUSIONS: This cadaveric biomechanical study suggests injury to the LM posterior root complex increases rotational and anterior laxity of the knee and places increased strain across reconstructed ACL grafts. Subsequent root repair did not result in a statistically significant reduction in strain. CLINICAL RELEVANCE: This study provides quantitative data on the implications of a LM posterior root injury in the setting of an ACL reconstruction to help guide clinical decision-making.

Insect reproductive behaviors are important mediators of carrion nutrient release into soil.

Current declines in terrestrial insect biomass and abundance have raised global concern for the fate of insects and the ecosystem services they provide. However, the ecological and economic contributions of many insects have yet to be quantified. Carrion-specializing invertebrates are important mediators of carrion decomposition; however, the role of their reproductive activities in facilitating this nutrient pulse into ecosystems is poorly understood. Here, we investigate whether insects that sequester carrion belowground for reproduction alter soil biotic and abiotic properties in North American temperate forests. We conducted a field experiment that measured soil conditions in control, surface carrion alone, and beetle-utilized carrion treatments. Our data demonstrate that Nicrophorus beetle reproduction and development results in changes in soil characteristics which are consistent with those observed in surface carrion decomposition alone. Carrion addition treatments increase soil labile C, DON and DOC, while soil pH and microbial C:N ratios decrease. This study demonstrates that the decomposition of carrion drives soil changes but suggests that the behaviors of insect scavengers play an important role in the release of carrion nutrients directly into the soil by sequestering carrion resources in the ecosystem where they were deposited.

Spatiotemporal niche partitioning in a specious silphid community (Coleoptera: Silphidae Nicrophorus).

Resource niche partitioning mediates the coexistence of similar species by reducing the chance of competitive encounters. For co-occurring species that share an ephemeral resource, contrasting activity in space and time may facilitate their persistence. Burying beetles (Silphidae: Nicrophorus) depend entirely on small vertebrate carcasses to reproduce. Given the unpredictability of this resource, and its value to congeners and other scavenger species, burying beetles likely endure intense competition to secure a carcass. Here, contrasting spatial and temporal niche patterns are explored as resource allocation strategies among five sympatric species of burying beetles (N. americanus, N. marginatus, N. pustulatus, N. orbicollis, and N. tomentosus). Specifically, the space-use and daily activity patterns are measured, at a fine scale, across species pairs to extrapolate contrasting niche-use patterns within a nicrophorine-rich grassland community in North-Central Oklahoma, USA. The results of this study reveal an important interplay between space-use and daily temporal activity in mediating the scramble competition associated with carrion resources. Where spatial or temporal overlap between burying beetle species is high, direct competition is mediated along an alternative niche dimension. For instance, N. americanus and N. orbicollis, a species dyad thought to be in direct competition, do overlap temporally but were found to have segregated space-use patterns. Our findings provide key insights into the competitive interactions within a necrophilous community and further inform our broader understanding of the spatial and temporal resource dimensions that drive the ecological niche.

Hamstring Injuries in Major League Baseball Pitchers: Implications in Graft Selection for Ulnar Collateral Ligament Reconstruction.

BACKGROUND: Hamstring tendons are commonly harvested as autograft for ulnar collateral ligament reconstruction. There is no consensus in the literature whether the hamstring tendon should be harvested from the ipsilateral (drive) leg or contralateral (landing) leg of baseball pitchers undergoing ulnar collateral ligament reconstruction. Hamstring injuries commonly occur in baseball players, but there are no reports on their incidence specifically among Major League Baseball (MLB) pitchers, nor are there reports on whether they occur more commonly in the drive leg or the landing leg. HYPOTHESIS: Hamstring injuries occur more commonly in the landing legs of MLB pitchers. STUDY DESIGN: Descriptive epidemiology study. METHODS: MLB pitchers who sustained hamstring injuries requiring time spent on the disabled list were identified from publicly available sources over 10 seasons. Demographics of the pitchers and injury and return-to-sport data were collected. Hamstring injuries to the drive leg were compared with injuries to the landing leg. RESULTS: Sixty-five pitchers had 78 disabled list stints due to hamstring injuries over 10 seasons. The landing leg was injured in 67.9% of cases, and the most common mechanism of injury was pitching. There were no significant differences in demographics between pitchers who sustained drive leg and landing leg injuries. There was no significant difference in mechanism of injury or time to return to sport between pitchers who sustained drive leg and landing leg injuries. CONCLUSION: The landing leg is more commonly injured than the drive leg among MLB pitchers who sustain hamstring injuries. There is no difference in time to return to sport between pitchers who sustain drive leg and landing leg injuries. More research is required to determine whether there is a difference in performance or future injury between hamstring tendons harvested from the drive leg and the landing leg for ulnar collateral ligament reconstruction among pitchers.

Cost-benefit analysis of routine pathology examination in primary shoulder arthroplasty.

BACKGROUND: The annual number of shoulder arthroplasty procedures is continuing to increase. Specimens from shoulder arthroplasty cases are routinely sent for pathologic examination. This study sought to evaluate the clinical utility and associated costs of routine pathologic examination of tissue removed during primary shoulder arthroplasty cases and to determine cost-effectiveness of this practice. METHODS: This is a retrospective review of primary shoulder arthroplasty cases. Patients whose humeral head was sent for routine pathologic examination were included. Cases were determined to have concordant, discrepant, or discordant diagnoses based on preoperative/postoperative diagnosis and pathology diagnosis. Costs were estimated in 2015 U.S. dollars, and cost-effectiveness was determined by the cost per discrepant diagnosis and cost per discordant diagnosis. RESULTS: We identified 714 cases of primary shoulder arthroplasty in 646 patients who met inclusion criteria. The prevalence of concordant diagnoses was 94.1%, the prevalence of discrepant diagnoses was 5.9%, and no cases had discordant diagnoses. There were 172 cases that had biceps tendon specimens sent for pathology examination, and none led to a change in patient care. Total estimated costs were $77,309.34 in 2015 U.S. dollars. Cost per discrepant diagnosis for humeral head specimens was $1424.09, and cost per discordant diagnosis is at least $59,811.78. DISCUSSION/CONCLUSION: Primary shoulder arthroplasty has a high rate of concordant diagnosis. Discrepant diagnoses were 5.9% in our study, and there were no discordant diagnoses. This study showed limited clinical utility in routinely sending specimens from primary shoulder arthroplasty cases for pathology examination, and calculation using a traditional life-year value of $50,000 showed that the standard for cost-effectiveness is not met.

Porous titanium bases for osteochondral tissue engineering.

Tissue engineering of osteochondral grafts may offer a cell-based alternative to native allografts, which are in short supply. Previous studies promote the fabrication of grafts consisting of a viable cell-seeded hydrogel integrated atop a porous, bone-like metal. Advantages of the manufacturing process have led to the evaluation of porous titanium as the bone-like base material. Here, porous titanium was shown to support the growth of cartilage to produce native levels of Young's modulus, using a clinically relevant cell source. Mechanical and biochemical properties were similar or higher for the osteochondral constructs compared to chondral-only controls. Further investigation into the mechanical influence of the base on the composite material suggests that underlying pores may decrease interstitial fluid pressurization and applied strains, which may be overcome by alterations to the base structure. Future studies aim to optimize titanium-based tissue engineered osteochondral constructs to best match the structural architecture and strength of native grafts. STATEMENT OF SIGNIFICANCE: The studies described in this manuscript follow up on previous studies from our lab pertaining to the fabrication of osteochondral grafts that consist of a bone-like porous metal and a chondrocyte-seeded hydrogel. Here, tissue engineered osteochondral grafts were cultured to native stiffness using adult chondrocytes, a clinically relevant cell source, and a porous titanium base, a material currently used in clinical implants. This porous titanium is manufactured via selective laser melting, offering the advantages of precise control over shape, pore size, and orientation. Additionally, this manuscript describes the mechanical influence of the porous base, which may have applicability to porous bases derived from other materials.

Public perception regarding anterior cruciate ligament reconstruction.

BACKGROUND: Relatively little information exists regarding the public's perception of anterior cruciate ligament (ACL) injuries and their treatment. The objective of this study was to test the hypothesis that the public's understanding of ACL surgery may be incorrect with regard to various aspects of this procedure and to identify issues to emphasize in patient education. METHODS: This study utilized a forty-three-question survey designed to measure an individual's knowledge base and perception of ACL reconstruction with regard to the anatomy, function, indications, operative technique, risks, recovery time, and overall benefits of the procedure. Eligible individuals were between fifteen and sixty years of age. Study participants were recruited from an academic orthopaedic sports medicine clinic, a collegiate athletic training room, and various public venues. RESULTS: A total of 210 individuals (106 men and 104 women) with a mean age of thirty were surveyed. Educational level of the respondents varied widely. Twenty-seven percent of the respondents were employed in a health-care setting. Sixty-five percent of the respondents rated their ACL knowledge level as "little" or "none." Participants' self-perception of ACL knowledge was highly correlated with their survey scores on questions with a specific correct answer (p < 0.001). Almost one-third thought that surgical treatment involved repair of the torn ligament rather than reconstruction. Over half (56%) of the respondents preferred an autograft for ligament reconstruction, compared with 4% who preferred an allograft. The ability to return to sports after ACL surgery was the most important concern, followed by the risk of developing osteoarthritis. CONCLUSIONS: There is wide variability in the lay public's knowledge level of ACL injuries; a substantial number of misguided perceptions were identified. Return to sports and risk for future osteoarthritis following ACL surgery appear to be the most important factors to the lay public. Focusing educational efforts on areas of knowledge deficits may be particularly important for patients of physicians who treat ACL injuries.

Magnetic resonance imaging as a predictor of return to play following syndesmosis (high) ankle sprains in professional football players.

BACKGROUND: Syndesmosis ankle sprains cause greater disability and longer duration of recovery than lateral ankle sprains. OBJECTIVE: To describe the severity of syndesmosis sprains using several accepted magnetic resonance imaging (MRI) criteria and to assess the interrater reliability of diagnosing syndesmosis injury using these same criteria in professional American football players. HYPOTHESIS: There is a high degree of interrater reliability of MRI findings in American football players with syndesmosis ankle sprains. These radiographic findings will correlate with time lost to injury, indicating severity of the sprain. STUDY DESIGN: Uncontrolled retrospective review. METHODS: Player demographics and time lost to play were recorded among professional football players who had sustained a syndesmosis ankle sprain and underwent standardized ankle MRI. Each image was independently read by 3 blinded musculoskeletal radiologists. RESULTS: Seventeen players met study criteria. There was almost perfect agreement among the radiologists for diagnosing injury to the syndesmotic membrane; substantial agreement for diagnosing injury to the posterior inferior tibiofibular ligament (PITFL) and in determining the proximal extent of syndesmotic edema/injury; but only fair agreement for diagnosing injury to the anterior inferior tibiofibular ligament and in determining the width of syndesmotic separation. There was a significant correlation between the width of syndesmotic separation and time lost, but no significant correlation between individual syndesmotic ligament injury or proximal extent of syndesmotic edema/injury and time lost. CONCLUSION: While ankle MRI can identify syndesmotic disruption with a high degree of interobserver agreement, no association was demonstrated between the extent of injury on MRI and the time to return to play following a high ankle sprain. CLINICAL RELEVANCE: In athletes with suspected high ankle sprains, MRI may help confirm diagnosis or suggest alternative diagnoses when the syndesmotic supporting structures are intact. However, the severity of ligamentous and syndesmotic disruption on MRI cannot help predict recovery times.

Inhibition of microorganisms on a carrion breeding resource: the antimicrobial peptide activity of burying beetle (Coleoptera: Silphidae) oral and anal secretions.

Competition between scavengers and microorganisms for the nutrients within carrion is well documented. As a significant contributor to food web energetics, carrion serves not only as a food source for scavengers, but also as a reproductive resource for many insects. One example are the burying beetles of the Nicrophorus genus (Coleoptera: Silphidae) whose reproduction is dependent on locating and successfully sequestering vertebrate carrion. Throughout the cooperative preparation of carrion and feeding of the larval offspring, parental beetles coat the carrion with oral and anal secretions known to attenuate the growth of molds and bacteria in the laboratory. We test the hypotheses that Nicrophorus secretions attenuate the growth of naturally occurring microorganisms likely to be found colonizing the carrion resource, and that the active antimicrobial components of the secretions are small antimicrobial peptides (AMPs) similar to those produced by other insects.

Hearing and spatial behavior in Gryllotalpa major Saussure (Orthoptera: Gryllotalpidae).

The prairie mole cricket (Gryllotalpa major Saussure) is a rare orthopteran insect of the tallgrass prairie ecosystem of the south central USA. Populations are known to currently occupy fragmented prairie sites in Oklahoma, Arkansas, Kansas and Missouri, including The Nature Conservancy's Tallgrass Prairie Preserve in north central Oklahoma. Prairie mole cricket populations were surveyed at this site and at another site in Craig County, OK during the spring of 2005 and 2006, using the male cricket's acoustic call to locate advertising aggregations of males. Five males from one large aggregation were removed in a study to describe (1) the hearing thresholds across the call's range of frequencies, (2) the distances over which the higher harmonic components of the male's calls are potentially detectable, (3) the species' sensitivity to ultrasound and (4) the spatio-auditory dynamics of the prairie mole cricket lek. Results indicate that G. major has a bimodal pattern of frequency tuning, with hearing sensitivities greatest at the 2 kHz carrier frequency (41 dB SPL) and declining through the call's frequency range (84 dB at 10 kHz). A second sensitivity peak is evident in the ultrasound range at 25 kHz (62 dB SPL). Spatial analysis of G. major lek sites indicates that approximately 73% of males within the lek are spaced in such a way as to allow acoustic interaction at the species' carrier frequency, while any information in higher harmonic overtones in the call appears to be available only to nearest neighbors.

Antipsychotic-induced alterations in CB1 receptor-mediated G-protein signaling and in vivo pharmacology in rats.

Dysregulation of the endocannabinoid and dopamine systems has been implicated in schizophrenia. The purpose of this study was to examine the effects of sub-chronic treatment with two antipsychotics on CB1 receptor-mediated in vitro and in vivo effects. Adult and adolescent male and female rats were injected twice daily with haloperidol (0.3 mg/kg), clozapine (10 mg/kg), or saline for 10 days. Subsequently, CB1 receptor number and function were assessed by [3H]SR141716 and WIN55,212-2-stimulated [35S]GTPgammaS binding, respectively. The effects of sub-chronic antipsychotic treatment on the in vivo actions of Delta9-tetrahydrocannabinol (Delta9-THC) were also evaluated. In adult female rats, antipsychotic treatment attenuated maximal stimulation of CB1 receptor-mediated G-protein activity in the striatum (clozapine) and prefrontal cortex (both antipsychotics), but not in the ventral midbrain. Associated changes in CB1 receptor number were not observed, suggesting that this attenuation was not due to downregulation. In vivo, sub-chronic treatment with clozapine, but not haloperidol, attenuated Delta9-THC-induced suppression of activity in adult females, whereas neither drug altered hypothermia or catalepsy. In contrast, antipsychotic treatment did not change CB1 receptor-mediated G-protein activation in any brain region in adult male rats and in adolescents of either sex. In vivo, haloperidol, but not clozapine, enhanced Delta9-THC-mediated suppression of activity and hypothermia in adult male rats whereas neither antipsychotic affected Delta9-THC-induced in vivo effects in adolescent rats. These findings suggest that modulation of the endocannabinoid system might contribute in a sex- and age-selective manner to differences in motor side effects of clozapine versus haloperidol.