Different but Equal: Outcomes of Prolonged Postanesthesia Care Unit Stay After Trauma Laparotomy.

INTRODUCTION: Hospital overcrowding is common and can lead to delays in intensive care unit (ICU) admission, resulting in increased morbidity and mortality in medical and surgical patients. Data on delayed ICU admission are limited in the postsurgical trauma cohort. Damage control laparotomy with temporary abdominal closure (DCL-TAC) for severely injured patients is often followed by an aggressive early resuscitation phase, usually occurring in the ICU. We hypothesized that patients who underwent DCL-TAC with initial postanesthesia care unit (PACU) stay would have worse outcomes than those directly admitted to ICU. METHODS: A retrospective chart review identified all trauma patients who underwent DCL-TAC at a level 1 trauma center over a 5 y period. Demographics, injuries, and resuscitation markers at 12 and 24 h were collected. Patients were stratified by location after index laparotomy (PACU versus ICU) and compared. Outcomes included composite morbidity and mortality. Multivariable logistic regression was performed. RESULTS: Of the 561 patients undergoing DCL-TAC, 134 (24%) patients required PACU stay due to ICU bed shortage, and 427 (76%) patients were admitted directly to ICU. There was no difference in demographics, injury severity score, time to resuscitation, complications, or mortality between PACU and ICU groups. Only 46% of patients were resuscitated at 24 h; 76% underwent eventual primary fascial closure. Under-resuscitation at 24 h (adjusted odds ratio [AOR] 0.55; 95% confidence interval [CI] 0.31-0.95, P = 0.03), increased age (AOR 1.04; 95% CI 1.02-10.55, P < 0.0001), and increased injury severity score (AOR 1.04; 95% CI 1.02-1.07, P < 0.0001) were associated with mortality on multivariable logistic regression. The median time in PACU was 3 h. CONCLUSIONS: PACU hold is not associated with worse outcomes in patients undergoing DCL-TAC. While ICU was designed for the resuscitation of critically ill patients, PACU is an appropriate alternative when an ICU bed is unavailable.

Management of Extraperitoneal Bladder Injuries in Patients With Pelvic Fractures.

BACKGROUND: The management of extraperitoneal bladder injuries (EBIs) when present with concomitant pelvic fractures is controversial. Current evidence is divided between supporting non-operative management with catheter drainage compared to operative management of bladder injury. The purpose of this study was to evaluate current management of EBI in the setting of pelvic fractures at our institution. We hypothesize there is no difference between operative and non-operative groups. METHODS: Retrospective review of patients with concomitant bladder injuries and pelvic fractures at a level 1 trauma center from 2017 to 2022 was performed. Demographics, injury characteristics, management strategies, and complications were collected. Patients were stratified by management (cystorrhaphy vs non-operative) and compared. RESULTS: Of 90 patients with bladder injuries and pelvic fractures, 50 patients (56%) presented with EBI, 26 patients (29%) presented with only intraperitoneal injuries, and 14 patients (16%) presented with a combined injury. Of patients with EBI, 18 (36%) underwent cystorrhaphy and 32 (64%) underwent non-operative management. There was no difference in demographics, orthopedic pelvic operative intervention, length of stay, or mortality between groups. Patients in the operative cohort had more bladder leaks [7 (39%) vs 4 (13%), P = .0406], compared to those in the non-operative cohort. Composite complications [7 (39%) vs 7 (22%), P = .1984] were similar between groups. CONCLUSIONS: Patients with EBI and pelvic fractures who underwent cystorrhaphy had more bladder leaks on follow-up imaging, although there was no difference in composite complications, when compared to those who underwent non-operative management.

Anti-predator defences are linked with high levels of genetic differentiation in frogs.

Predator-prey interactions have been suggested as drivers of diversity in different lineages, and the presence of anti-predator defences in some clades is linked to higher rates of diversification. Warning signals are some of the most widespread defences in the animal world, and there is evidence of higher diversification rates in aposematic lineages. The mechanisms behind such species richness, however, are still unclear. Here, we test whether lineages that use aposematism as anti-predator defence exhibit higher levels of genetic differentiation between populations, leading to increased opportunities for divergence. We collated from the literature more than 3000 pairwise genetic differentiation values across more than 700 populations from over 60 amphibian species. We find evidence that over short geographical distances, populations of species of aposematic lineages exhibit greater genetic divergence relative to species that are not aposematic. Our results support a scenario where the use of warning signals could restrict gene flow, and suggest that anti-predator defences could impact divergence between populations and potentially have effects at a macro-evolutionary scale.

The Influence of an Online Platform (Hernia U) in Surgical Education and Patient Management.

Introduction: Hernia U was created with the objective to expand the educational landscape of abdominal wall surgery. It is an online platform where surgeons can register with no cost and subscribe for different courses. The aim of this study is to evaluate the impact of the platform on patient management and surgical education. Methods: A questionnaire regarding the influence of Hernia U in surgical education and patient management was emailed to professionals who had previously participated in any course of the Hernia U. Variables were shown with absolute and relative frequencies. Pearson's χ2 and Fisher's exact test were performed to analyze relationships between variables as appropriate. Results: Nine hundred three participants responded to the questionnaire. Seven hundred fifty-two (83.3%) were men; 248 (27.4%) participants were older than 50 years old; 240 (26.6%) were between 41 and 50 years old. Two hundred seventy-four (30.4%) participants had been in practice for more than 20 years, 242 (26.8%) between 11 and 20 years, and 161(17.8%) between 5 and 10 years. When analyzing the impact of time spent on the platform, spending over an hour per week was significantly associated with self-reported change in practice patterns compared to spending less than an hour per week (p < 0.0003). More experienced surgeons (10 or more years of practice) were less likely to change their practice patterns when compared to less experienced surgeons. Conclusion: Hernia U has allowed surgeons to change their daily practice and to boost their education. Surgeons spending more than one hour weekly in the platform are more likely to adopt changes.

Do surgical emergencies stay at home? Observations from the first United States Coronavirus epicenter.

BACKGROUND: During the coronavirus disease 2019 pandemic, New York instituted a statewide stay-at-home mandate to lower viral transmission. While public health guidelines advised continued provision of timely care for patients, disruption of safety-net health care and public fear have been proposed to be related to indirect deaths because of delays in presentation. We hypothesized that admissions for emergency general surgery (EGS) diagnoses would decrease during the pandemic and that mortality for these patients would increase. METHODS: A multicenter observational study comparing EGS admissions from January to May 2020 to 2018 and 2019 across 11 NYC hospitals in the largest public health care system in the United States was performed. Emergency general surgery diagnoses were defined using International Classification Diseases, Tenth Revision, codes and grouped into seven common diagnosis categories: appendicitis, cholecystitis, small/large bowel, peptic ulcer disease, groin hernia, ventral hernia, and necrotizing soft tissue infection. Baseline demographics were compared including age, race/ethnicity, and payor status. Outcomes included coronavirus disease (COVID) status and mortality. RESULTS: A total of 1,376 patients were admitted for EGS diagnoses from January to May 2020, a decrease compared with both 2018 (1,789) and 2019 (1,668) (p < 0.0001). This drop was most notable after the stay-at-home mandate (March 22, 2020; week 12). From March to May 2020, 3.3%, 19.2%, and 6.0% of EGS admissions were incidentally COVID positive, respectively. Mortality increased in March to May 2020 compared with 2019 (2.2% vs. 0.7%); this difference was statistically significant between April 2020 and April 2019 (4.1% vs. 0.9%, p = 0.045). CONCLUSION: Supporting our hypothesis, the coronavirus disease 2019 pandemic and subsequent stay-at-home mandate resulted in decreased EGS admissions between March and May 2020 compared with prior years. During this time, there was also a statistically significant increase in mortality, which peaked at the height of COVID infection rates in our population. LEVEL OF EVIDENCE: Epidemiological, level IV.

Endoscopic onlay repair for ventral hernia and rectus abdominis diastasis repair: Why so many different names for the same procedure? A qualitative systematic review.

BACKGROUND: A subcutaneous endoscopic onlay repair for ventral hernia with an anterior plication of diastasis recti (DR) has been published under different names in different countries. The aim of this systematic review is to assess the safety and feasibility of different named techniques with the same surgical concept. METHODS: The PRISMA guidelines were followed during all stages of this systematic review. The MINORS score system was used to perform qualitative assessment of all studies included in this review. Recommendations were then summarized for the following pre-defined key items: protocol, research question, search strategy, study eligibility, data extraction, study designs, risk of bias, publication bias, heterogeneity, and statistical analysis. RESULTS: The systematic literature search found 2548 articles, 317 of which were duplicates and excluded from analysis. The titles and abstracts from the remaining 2231 articles were assessed. After careful evaluation, 2125 articles were determined to be unrelated to our study and subsequently excluded. The full text of the remaining 106 articles was thoroughly assessed. Case reports, editorials, letters to the editor, and general reviews were then excluded. A total of 13 articles were ultimately included for this review, describing a similar subcutaneous endoscopic approach for repair of concomitant ventral hernias and rectus diastasis defined under nine different named techniques on 716 patients. The number of patients in those studies varied from 10 to 201. The mean operative time varied from 68.5 to 195 min. The most common complication was seroma, followed by pain requiring intervention, hematoma, and surgical site infection. CONCLUSIONS: There are a few technique variations described in different studies, but with no significant differences in outcomes. We, therefore, propose to unify these procedures under one term, ENDoscopic Onlay Repair (ENDOR). This technique has shown to be effective and safe, with seroma being the most common complication.

Maternal reproductive output and F1 hybrid fitness may influence contact zone dynamics.

The outcome of secondary contact between divergent lineages or species may be influenced by both the reproductive traits of parental species and the fitness of offspring; however, their relative contributions have rarely been evaluated, particularly in longer-lived vertebrate species. We performed pure and reciprocal laboratory crosses between Ctenophorus decresii (tawny dragon) and C. modestus (swift dragon) to examine how parental reproductive traits and ecologically relevant offspring fitness traits may explain contact zone dynamics in the wild. The two species meet in a contact zone of post-F1 hybrids with asymmetric backcrossing and predominantly C. modestus mtDNA haplotypes. We found no evidence for reduced parental fecundity or offspring fitness for F1 hybrid crosses. However, maternal reproductive strategy differed between species, irrespective of the species of their mate. Ctenophorus modestus females had higher fecundity and produced more and larger clutches with lower embryonic mortality. Parental species also influenced sex ratios and offspring traits, with C. modestus ♀ × C. decresii ♂ hybrids exhibiting higher trait values for more fitness measures (growth rate, sprint speed, bite force) than offspring from all other pairings. Together, these patterns are consistent with the prevalence of C. modestus mtDNA in the contact zone, and asymmetric backcrossing likely reflects fitness effects that manifest in the F2 generation. Our results highlight how parental species can influence multiple offspring traits in different ways, which together may combine to influence offspring fitness and shape contact zone dynamics.

Convergence and divergence in lizard colour polymorphisms.

Colour polymorphic species are model systems for examining the evolutionary processes that generate and maintain discrete phenotypic variation in natural populations. Lizards have repeatedly evolved strikingly similar polymorphic sexual signals in distantly related lineages, providing an opportunity to examine convergence and divergence in colour polymorphism, correlated traits and associated evolutionary processes. Herein, we synthesise the extensive literature on lizard colour polymorphisms in both sexes, including recent advances in understanding of the underlying biochemical, cellular and genetic mechanisms, and correlated behavioural, physiological and life-history traits. Male throat, head or ventral colour morphs generally consist of red/orange, yellow and white/blue morphs, and sometimes mixed morphs with combinations of two colours. Despite these convergent phenotypes, there is marked divergence in correlated behavioural, physiological and life-history traits. We discuss the need for coherence in morph classification, particularly in relation to 'mixed' morphs. We highlight future research directions such as the genetic basis of convergent phenotypes and the role of environmental variation in the maintenance of polymorphism. Research in this very active field promises to continue to provide novel insights with broad significance to evolutionary biologists.

SubCutaneous OnLay endoscopic Approach (SCOLA) mesh repair for small midline ventral hernias with diastasis recti: An initial US experience.

BACKGROUND: Patients presenting for evaluation of umbilical and epigastric hernias are often found to have diastasis recti (DR). As isolated hernia repair in these patients may be associated with higher rates of recurrence, prior international publications have described a prefascial mesh repair in combination with anterior plication of DR. We present our initial United States (US) experience with a SubCutaneous OnLay endoscopic Approach (SCOLA) to address these concurrent pathologies in a single hybrid procedure. METHODS: Between July 2018 and December 2019, a prospective cohort of 16 patients underwent the SCOLA procedure. Subcutaneous dissection was carried out from the suprapubic region superiorly to the xiphoid process and laterally to the linea semilunaris. Hernia contents were reduced and defects were incorporated into anterior DR plication, which was performed with running barbed suture. Onlay mesh was placed to cover the entire dissected space, and subcutaneous drains were placed. Three separate attendings performed cases with one supervising attending for standard technique. RESULTS: Of 16 patients, 14 (87.5%) were female. The mean age was 45.7 (11.9) years; mean BMI was 29.0 (3.6) kg/m2. The mean hernia defect size was 1.9 (0.7) cm. Mean operative time was 146 (46.3) minutes; two (15%) cases were performed robotically. The mean follow-up time was approximately two months (63 days). Three (18.8%) patients developed seroma, one (6.3%) patient developed an infected seroma, and two (12.5%) patients developed hernia recurrence. CONCLUSIONS: SCOLA technique is shown to be a safe and effective approach for patients presenting with small midline ventral hernias and concomitant DR. Our preliminary US data demonstrates higher rates of post-operative complication in patients with higher BMI, which suggests that patient selection and pre-operative counseling is essential to achieve better technical outcomes in our patient population.

Divergent male and female mate preferences do not explain incipient speciation between lizard lineages.

Diversification in sexual signals is often taken as evidence for the importance of sexual selection in speciation. However, in order for sexual selection to generate reproductive isolation between populations, both signals and mate preferences must diverge together. Furthermore, assortative mating may result from multiple behavioral mechanisms, including female mate preferences, male mate preferences, and male-male competition; yet their relative contributions are rarely evaluated. Here, we explored the role of mate preferences and male competitive ability as potential barriers to gene flow between 2 divergent lineages of the tawny dragon lizard, Ctenophorus decresii, which differ in male throat coloration. We found stronger behavioral barriers to pairings between southern lineage males and northern lineage females than between northern males and southern females, indicating incomplete and asymmetric behavioral isolating barriers. These results were driven by both male and female mate preferences rather than lineage differences in male competitive ability. Intrasexual selection is therefore unlikely to drive the outcome of secondary contact in C. decresii, despite its widely acknowledged importance in lizards. Our results are consistent with the emerging view that although both male and female mate preferences can diverge alongside sexual signals, speciation is rarely driven by divergent sexual selection alone.

Conserved visual sensitivities across divergent lizard lineages that differ in an ultraviolet sexual signal.

The sensory drive hypothesis predicts the correlated evolution of signaling traits and sensory perception in differing environments. For visual signals, adaptive divergence in both color signals and visual sensitivities between populations may contribute to reproductive isolation and promote speciation, but this has rarely been tested or shown in terrestrial species. We tested whether opsin protein expression differs between divergent lineages of the tawny dragon (Ctenophorus decresii) that differ in the presence/absence of an ultraviolet sexual signal. We measured the expression of four retinal cone opsin genes (SWS1, SWS2, RH2, and LWS) using droplet digital PCR. We show that gene expression between lineages does not differ significantly, including the UV wavelength sensitive SWS1. We discuss these results in the context of mounting evidence that visual sensitivities are highly conserved in terrestrial systems. Multiple competing requirements may constrain divergence of visual sensitivities in response to sexual signals. Instead, signal contrast could be increased via alternative mechanisms, such as background selection. Our results contribute to a growing understanding of the roles of visual ecology, phylogeny, and behavior on visual system evolution in reptiles.

Simulating the Mechanics of Lens Accommodation via a Manual Lens Stretcher.

The goal of this protocol is to mimic the biomechanics of physiological accommodation in a cost-efficient, practical manner. Accommodation is achieved through the contraction of the ciliary body and relaxation of zonule fibers, which results in the thickening of the lens necessary for near vision. Here, we present a novel, simple method in which accommodation is replicated by tensing the zonules connected to the lens capsule via a manual lens stretcher (MLS). This method monitors the radial stretching achieved by a lens when subjected to a consistent force and allows for a comparison of accommodating lenses, which can be stretched, to non-accommodating lenses, which cannot be stretched. Importantly, the stretcher couples to the zonules directly, and not to the sclera of the eye, thus only requiring the lens, zonules, and ciliary body rather than the entire globe sample. This difference can significantly decrease the cost of acquiring donor cadaver lenses by about 62% compared to acquiring an entire globe.

Obesity and anthropometry in spina bifida: What is the best measure.

OBJECTIVE: Diagnosis of obesity using traditional body mass index (BMI) using length may not be a reliable indicator of body composition in spina bifida (SB). We examine traditional and surrogate measures of adiposity in adults with SB, correlated with activity, metabolic disease, attitudes towards exercise and quality of life. DESIGN: Adult subjects with SB underwent obesity classification using BMI by length and arm span, abdominal girth and percent trunk fat (TF) on dual energy X-ray absorptiometry (DXA). Quality of life measures, activity level and metabolic laboratory values were also reviewed. RESULTS: Among eighteen subjects (6 male, 12 female), median age was 26.5 (range 19-37) years, with level of lesion 16.7% ≤L2, 61.1% L3-4, and 22.2% ≥L5, respectively. Median weight was 71.8 (IQR 62.4, 85.8) kg, similar between sexes (P = 0.66). With median length of 152.0 (IQR 141.8, 163.3) cm, median conventional BMI was 29.4 m/kg2, with 7 (43.8%) subjects with BMI >30. Median BMI by arm span was 30.2 m/kg2, abdominal girth of 105.5 cm, and TF 45.7%. More subjects were classified as obese using alternate measures, with 9 (56.3%) by arm span, 14 (82.4%) by abdominal girth and 15 (83.3%) by TF (P = 0.008). Reclassification of obesity from conventional BMI was significant when using TF (P = 0.03). No difference in quality of life measures, activity level and metabolic abnormalities was demonstrated between obese and non-obese subjects. CONCLUSIONS: Conventional determination of obesity using BMI by length is an insensitive marker in adults with SB. Adults with SB are more often classified as obese using TF by DXA.

Risk Factors and Timing of Early Stricture Recurrence After Urethroplasty.

OBJECTIVE: To compare recurrence after urethroplasty, identifying associated risk factors for early recurrence. MATERIALS AND METHODS: Among 262 urethroplasties (2001-2010) with ≥6 months of follow-up, we identified 65 patients (24.8%) with recurrence (defined by obstruction in the area of repair on cystoscopy). RESULTS: Median stricture length was 4.5 cm (range 1-24 cm). Median follow-up was 85.2 (6.7-160.1) months, with median time to recurrence of 8.0 (0.5-88.0) months. Substitution urethroplasty was the most frequent repair (70.8%), followed by excision and primary anastomosis (23.1%). When graft was used, buccal was most common (66.0%), followed by abdominal wall skin (AWS) (24.5%). Twenty-one percent of recurrences presented within 3 months, 40.0% by 6 months, 55.4% by 1 year, whereas 9.2% recurred more than 5 years later. Recurrences ≤6 months were significantly longer strictures (median 5.5 cm vs 4.0 cm, P = .009). Strictures ≤4 cm, ≤3 cm, and ≤2 cm recurred at a median of 10.6, 18.2, and 30.3 months, respectively (P = .08). Most lichen sclerosis (LS)-related recurrences occurred within 6 months (62%). Patients recurring within 6 months were older, had history of LS, or more likely had AWS. Forty percent suffered from multiple recurrences at a median of 12 months and were associated with longer stricture, prior instrumentation, substitution urethroplasty, AWS, and LS. CONCLUSION: Half of recurrences following urethroplasty present within one year, with most declaring within 6 months. Early recurrence is associated with older age, LS, AWS and longer strictures. The duration and intensity of surveillance protocols following urethroplasty should be individualized in order to account for these characteristics.

Quality of life related to urinary continence in adult spina bifida patients.

INTRODUCTION: To analyze the correlations of bladder management technique, ambulatory status and urologic reconstruction on quality of life (QOL) as affected by urinary symptoms in adult spina bifida (SB) patients. MATERIAL AND METHODS: Sixty-six adult SB patients completed the RAND 36-Item Health Survey (mSF-36) and Incontinence Quality of Life (I-QOL). Demographic information, history of urinary reconstruction, and bladder management techniques were reviewed and analyzed with respect to survey scores. RESULTS: Mean age of patients was 32.3 (SD ±7.2) years and 44 patients (66.7%) were female. Forty-five patients (68.2%) were mainly ambulatory, 21 (31.8%) use a wheelchair and 10 (15.2%) had urologic reconstruction, while 56 (83.3%) did not. Twelve patients (18.2%) void, 42 (63.6%) perform clean intermittent catheterization (CIC), 4 (6.1%) use an indwelling catheter, 3 (4.5%) have an ileal conduit (IC) and 5 (7.6%) mainly use diapers. Mean mSF-36 General Health score was 56.5 (SD ±22.9) and mean I-QOL Sum score was 50.9 (SD ±21.7), where lower scores reflect lower QOL. mSF-36 and I-QOL scores did not significantly correlate with bladder management technique, ambulatory status or urologic reconstruction. A correlation was noted between I-QOL scales and most mSF-36 scales (all p <0.02). CONCLUSIONS: In our cohort study of adult SB patients, bladder management technique and urologic reconstruction did not correlate with urinary (I-QOL) or general health (mSF-36) domains, although I-QOL and mSF-36 scores correlated closely, suggesting urinary continence is significantly related to general QOL. However, we are unable to identify a single factor that improves either urinary or general QOL.

Predicting Patients with Inadequate 24- or 48-Hour Urine Collections at Time of Metabolic Stone Evaluation.

PURPOSE: We aimed to understand the characteristics of patients who are less likely to submit adequate urine collections at metabolic stone evaluation. METHODS: Inadequate urine collection was defined using two definitions: (1) Reference ranges for 24-hour creatinine/kilogram (Cr/24) and (2) discrepancy in total 24-hour urine Cr between 24-hour urine collections. There were 1502 patients with ≥1 kidney stone between 1998 and 2014 who performed a 24- or 48-hour urine collection at Northwestern Memorial Hospital and who were identified retrospectively. Multivariate analysis was performed to analyze predictor variables for adequate urine collection. RESULTS: A total of 2852 urine collections were analyzed. Mean age for males was 54.4 years (range 17-86), and for females was 50.2 years (range 8-90). One patient in the study was younger than 17 years old. (1) Analysis based on the Cr 24/kg definition: There were 50.7% of patients who supplied an inadequate sample. Females were nearly 50% less likely to supply an adequate sample compared with men, P<0.001. Diabetes (odds ratio [OR] 1.42 [1.04-1.94], P=0.026) and vitamin D supplementation (OR 0.64 [0.43-0.95], P=0.028) predicted receiving an adequate/inadequate sample, respectively. (2) Analysis based on differences between total urinary Cr: The model was stratified based on percentage differences between samples up to 50%. At 10%, 20%, 30%, 40%, and 50% differences, inadequate collections were achieved in 82.8%, 66.9%, 51.7%, 38.5%, and 26.4% of patients, respectively. Statistical significance was observed based on differences of ≥40%, and this was defined as the threshold for an inadequate sample. Female sex (OR 0.73 [0.54-0.98], P=0.037) predicted supplying inadequate samples. Adequate collections were more likely to be received on a Sunday (OR 1.6 [1.03-2.58], P=0.038) and by sedentary workers (OR 2.3 [1.12-4.72], P=0.023). CONCLUSION: Urine collections from patients during metabolic evaluation for nephrolithiasis may be considered inadequate based on two commonly used clinical definitions. This may have therapeutic or economic ramifications and the propensity for females to supply inadequate samples should be investigated further.

STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA.

Multidimensional cancer genome analysis and validation has defined Quaking (QKI), a member of the signal transduction and activation of RNA (STAR) family of RNA-binding proteins, as a novel glioblastoma multiforme (GBM) tumor suppressor. Here, we establish that p53 directly regulates QKI gene expression, and QKI protein associates with and leads to the stabilization of miR-20a; miR-20a, in turn, regulates TGFßR2 and the TGFß signaling network. This pathway circuitry is substantiated by in silico epistasis analysis of its components in the human GBM TCGA (The Cancer Genome Atlas Project) collection and by their gain- and loss-of-function interactions in in vitro and in vivo complementation studies. This p53-QKI-miR-20a-TGFß pathway expands our understanding of the p53 tumor suppression network in cancer and reveals a novel tumor suppression mechanism involving regulation of specific cancer-relevant microRNAs.

Counterregulation between the FcepsilonRI pathway and antiviral responses in human plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) play essential roles in directing immune responses. These cells may be particularly important in determining the nature of immune responses to viral infections in patients with allergic asthma as well those with other atopic diseases. The purposes of this study were 1) to compare the functional capacity of pDCs in patients with one type of allergic disorder, allergic asthma, and controls; 2) to determine whether IgE cross-linking affects antiviral responses of influenza-exposed pDCs; and 3) to determine whether evidence of counterregulation of FcepsilonRIalpha and IFN-alpha pathways exists in these cells. pDC function was assessed in a subset of asthma patients and in controls by measuring IFN-alpha production after exposure of purified pDCs to influenza viruses. FcepsilonRIalpha expression on pDCs was determined by flow cytometry in blood samples from patients with allergic asthma and controls. pDCs from patients with asthma secreted significantly less IFN-alpha upon exposure to influenza A (572 versus 2815; p = 0.03), and secretion was inversely correlated with serum IgE levels. Moreover, IgE cross-linking prior to viral challenge resulted in 1) abrogation of the influenza-induced pDC IFN-alpha response; 2) diminished influenza and gardiquimod-induced TLR-7 upregulation in pDCs; and 3) interruption of influenza-induced upregulation of pDC maturation/costimulatory molecules. In addition, exposure to influenza and gardiquimod resulted in upregulation of TLR-7, with concomitant downregulation of FcepsilonRIalpha expression in pDCs. These data suggest that counterregulation of FcepsilonRI and TLR-7 pathways exists in pDCs, and that IgE cross-linking impairs pDC antiviral responses.

Suppression of phagocytic and bactericidal functions of rat alveolar macrophages by the organic component of diesel exhaust particles.

Exposure to diesel exhaust particles (DEP) was shown to increase the susceptibility of the lung to bacterial infection in rats. In this study, the effects of DEP on alveolar macrophage (AM) phagocytic and bactericidal functions and cytokine secretion by AM and lymphocytes in response to Listeria monocytogenes infection were investigated in vitro and the roles of different DEP components in these processes were compared. Exposure to DEP or the organic extracts of DEP (eDEP) significantly decreased the phagocytosis and killing of L. monocytogenes by AM obtained from normal rats. Washed DEP (wDEP) also decreased AM phagocytosis and bacterial killing to a lesser extent, whereas carbon black (CB) reduced AM phagocytosis but had no significant effect on AM bactericidal activity. DEP or eDEP concentration-dependently suppressed L. monocytogenes-induced secretion of tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-12 by AM and of IL-2 and interferon-gamma by lymphocytes obtained from L. monocytogenes-infected rats, but augmented the AM secretion of IL-10. wDEP or CB, however, exerted little or no effect on these L. monocytogenes-induced cytokines. These results provide direct evidence that DEP, through the actions of organic components, suppresses AM phagocytic and bactericidal functions in vitro. Inhibition of AM phagocytic function and alterations of AM and lymphocyte cytokine secretion by DEP and DEP organic compounds may be implicated in the diminished AM bactericidal activity and the lymphatic arm of the host immune system, thus resulting in an suppressed pulmonary clearance of L. monocytogenes and an increased susceptibility of the lung to bacterial infection.