Moral appraisals guide intuitive legal determinations.

OBJECTIVES: We sought to understand how basic competencies in moral reasoning influence the application of private, institutional, and legal rules. HYPOTHESES: We predicted that moral appraisals, implicating both outcome-based and mental state reasoning, would shape participants' interpretation of rules and statutes-and asked whether these effects arise differentially under intuitive and reflective reasoning conditions. METHOD: In six vignette-based experiments (total N = 2,473; 293 university law students [67% women; age bracket mode: 18-22 years] and 2,180 online workers [60% women; mean age = 31.9 years]), participants considered a wide range of written rules and laws and determined whether a protagonist had violated the rule in question. We manipulated morally relevant aspects of each incident-including the valence of the rule's purpose (Study 1) and of the outcomes that ensued (Studies 2 and 3), as well as the protagonist's accompanying mental state (Studies 5 and 6). In two studies, we simultaneously varied whether participants decided under time pressure or following a forced delay (Studies 4 and 6). RESULTS: Moral appraisals of the rule's purpose, the agent's extraneous blameworthiness, and the agent's epistemic state impacted legal determinations and helped to explain participants' departure from rules' literal interpretation. Counter-literal verdicts were stronger under time pressure and were weakened by the opportunity to reflect. CONCLUSIONS: Under intuitive reasoning conditions, legal determinations draw on core competencies in moral cognition, such as outcome-based and mental state reasoning. In turn, cognitive reflection dampens these effects on statutory interpretation, allowing text to play a more influential role. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Expression of the B cell differentiation factor BAFF and chemokine CXCL13 in a murine model of Respiratory Syncytial Virus infection.

Innate immune responses are known to influence the subsequent development of adaptive immunity. We have previously shown that RSV infection of human airway epithelial cells results in production of the B cell growth factor, BAFF. To better understand how the airway responds to RSV infection by production of this and other factors to support or enhance local B cell responses to infection, we analysed the lung expression of BAFF and B cell homeostatic chemokines CXCL12, CXCL13, CCL19 and CCL21 in a murine model of RSV infection. Following infection with A2 strain RSV, the highest RSV N gene expression was observed at day 4 after challenge with virus. In contrast, two peaks of elevated BAFF expression at days 2 and 7 were observed. CXCL13 was significantly elevated at days 1, 2 and 7. CXCL12, CCL19 and CCL21 were expressed within lung tissue from control and RSV challenged animals but no significant difference in expression was found. Immunofluorescence showed BAFF to be present throughout the tissue however CXCL13 expression was localized to cell rich areas probably constituting lymphoid aggregates. Our results define the kinetics of B cell chemoattractant and growth factor expression during RSV infection and indicate an important role for these cytokines in the airway response to RSV infection.

Reverse oblique end screws in nonlocking plates decrease construct strength in synthetic osteoporotic bone medium.

Fracture stability can be challenging for osteoporotic individuals. The end screw of nonlocked plates is subjected to the greatest loading and is typically the site of construct failure. To enhance fixation, the end screw can be angled away from the fracture. The current study biomechanically evaluated screws angled the other direction: toward the fracture using 3.5-mm dynamic compression plates in an osteoporotic bone model. Three different plate lengths (6-, 8-, 12-hole) were tested in three-point bending with an oblique, perpendicular, or reverse oblique end screw. The peak load for loss of screw fixation for the reverse oblique end screw constructs was significantly less than the other screw orientations for all plate lengths. The 12-hole peak load, energy, and displacement magnitudes for all three screw orientations were significantly greater than all 6- and 8-hole constructs. The use of a reverse oblique end screw is inferior to both perpendicular and oblique end screws.

Increased numbers and functional activity of CD56⁺ T cells in healthy cytomegalovirus positive subjects.

Human T cells expressing CD56 are capable of tumour cell lysis following activation with interleukin-2 but their role in viral immunity has been less well studied. Proportions of CD56(+) T cells were found to be highly significantly increased in cytomegalovirus-seropositive (CMV(+) ) compared with seronegative (CMV(-) ) healthy subjects (9.1 ± 1.5% versus 3.7 ± 1.0%; P < 0.0001). Proportions of CD56(+) T cells expressing CD28, CD62L, CD127, CD161 and CCR7 were significantly lower in CMV(+) than CMV(-) subjects but those expressing CD4, CD8, CD45RO, CD57, CD58, CD94 and NKG2C were significantly increased (P < 0.05), some having the phenotype of T effector memory cells. Levels of pro-inflammatory cytokines and CD107a were significantly higher in CD56(+) T cells from CMV(+) than CMV(-) subjects following stimulation with CMV antigens. This also resulted in higher levels of proliferation in CD56(+) T cells from CMV(+) than CMV(-) subjects. Using Class I HLA pentamers, it was found that CD56(+) T cells from CMV(+) subjects contained similar proportions of antigen-specific CD8(+) T cells to CD56(-) T cells in donors of several different HLA types. These differences may reflect the expansion and enhanced functional activity of CMV-specific CD56(+) memory T cells. In view of the link between CD56 expression and T-cell cytotoxic function, this strongly implicates CD56(+) T cells as being an important component of the cytotoxic T-cell response to CMV in healthy carriers.

Differential immunogenicity and allergenicity of native and recombinant human lactoferrins: role of glycosylation.

Human native milk lactoferrin (LF) and recombinant forms of lactoferrin (rLF) are available with identical aa sequences, but different glycosylation patterns. Native lactoferrin (NLF) possesses the intrinsic ability to stimulate vigorous IgG and IgE antibody responses in BALB/c mice, whereas recombinant forms (Aspergillus or rice) are 40-fold less immunogenic and 200-fold less allergenic. Such differences are independent of endotoxin or iron content and the glycans do not contribute to epitope formation. A complex glycoprofile is observed for NLF, including sialic acid, fucose, mannose, and Lewis (Le)(x) structures, whereas both rLF species display a simpler glycoprofile rich in mannose. Although Le(x) type sugars play a Th2-type adjuvant role, endogenous expression of Le(x) on NLF did not completely account for the more vigorous IgE responses it provoked. Furthermore, coadminstration of rLF downregulated IgE and upregulated IgG2a antibody responses provoked by NLF, but was without effect on responses to unrelated peanut and chicken egg allergens. These results suggest glycans on rLF impact the induction phase to selectively inhibit IgE responses and that differential glycosylation patterns may impact on antigen uptake, processing and/or presentation, and the balance between Th1 and Th2 responses.

Chemokine binding protein M3 of murine gammaherpesvirus 68 modulates the host response to infection in a natural host.

Murine γ-herpesvirus 68 (MHV-68) infection of Mus musculus-derived strains of mice is an attractive model of γ-herpesvirus infection. Surprisingly, however, ablation of expression of MHV-68 M3, a secreted protein with broad chemokine-binding properties in vitro, has no discernable effect during experimental infection via the respiratory tract. Here we demonstrate that M3 indeed contributes significantly to MHV-68 infection, but only in the context of a natural host, the wood mouse (Apodemus sylvaticus). Specifically, M3 was essential for two features unique to the wood mouse: virus-dependent inducible bronchus-associated lymphoid tissue (iBALT) in the lung and highly organized secondary follicles in the spleen, both predominant sites of latency in these organs. Consequently, lack of M3 resulted in substantially reduced latency in the spleen and lung. In the absence of M3, splenic germinal centers appeared as previously described for MHV-68-infected laboratory strains of mice, further evidence that M3 is not fully functional in the established model host. Finally, analyses of M3's influence on chemokine and cytokine levels within the lungs of infected wood mice were consistent with the known chemokine-binding profile of M3, and revealed additional influences that provide further insight into its role in MHV-68 biology.

The effects of IL-17 upon human natural killer cells.

These experiments were designed to investigate the effects of IL-17 upon the phenotype and function of human Natural Killer (NK) cells. Peripheral blood mononuclear cells from healthy subjects were cultured in the presence or absence of different combinations of IL-17s and changes in relative numbers and cell surface phenotype of NK cells and CD56+CD3+ cells measured by flow cytometry. Real time PCR was used to measure changes in expression of the cytotoxicity-related genes perforin A and granzymes A and B and IL-17 receptors. A chromium release assay was used to measure cytotoxic function against K562 tumour cells. IL-17D, IL-17A, IL-17F or the combination of both of the latter had little effect upon NK cell surface expression of Killer Immunoglobulin-like Receptors, although IL-17A modestly increased NK cell numbers. Slight but not significant increases in expression of perforin and granzymes were induced by IL-17A and/or IL-17F. Both IL-17A and D significantly increased cytotoxic function of NK cells at some E:T ratios. Similarly, numbers of NK cells induced to express CD107a after interaction with K562 cells were increased, but not significantly, by all combinations of IL-17s tested. IL-17RC was not found at the NK cell surface but was expressed at the message level and the protein detected intracellularly. NK cells are known to produce IL-17 but here we report that there is little response to this cytokine although some isoforms may moderately enhance cytotoxic function. There may therefore be some enhancement of NK cell function resulting from Th17 cell activation.

Association between the expression of toll-like receptors, cytokines, and homeostatic chemokines in SARS-CoV-2 infection and COVID-19 severity.

The recent identification of the involvement of the immune system response in the severity and mortality of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection highlights the importance of cytokines and chemokines as important factors in the clinical outcomes of COVID-19. However, the impact and roles of the BAFF/APRIL cytokine system, homeostatic chemokines (CXCL12, CXCL13, CCL19, and CCL21), as well as Toll-like receptor (TLR)-3/4 in COVID-19, have not been investigated. We sought to assess the expression levels and roles of TLR3/4, BAFF, APRIL, IFN-ß, homeostatic chemokines (CXCL12, CXCL13, CCL19, and CCL21), SARS-CoV-2 IgG and IgM antibodies in patients with critical (ICU) and non-ICU (mild) COVID-19 and their association with mortality and disease severity. Significant high levels of TLR-4 mRNA, IFN-ß, APRIL, CXCL13, and IgM and IgG antibodies were observed in ICU patients with severe COVID-19 compared to non-ICU COVID-19 patients and healthy controls. On the other hand, BAFF and CCL21 expression were significantly upregulated in non-ICU patients with COVID-19 compared with that in critical COVID-19 patients. The two groups did not differ in TLR-3, CXCL12, and CCL19 levels. Our findings show high expression levels of some inflammatory chemokines in ICU patients with COVID-19. These findings highlight the potential utility of chemokine antagonists as an immune-based treatment for the severe form of COVID-19. We also believe that selective targeting of TLR/spike protein interactions might lead to the development of a new COVID-19 therapy.

A health economic analysis of clinical islet transplantation.

Islet cell transplantation is in clinical development for type 1 diabetes. There are no data on the cost in relationship to its benefits. We performed a cost-effectiveness analysis and made a comparison with standard insulin therapy, using Markov modeling and Monte Carlo simulations. The patient population was adults aged 20 yr suffering from hypoglycemia unawareness. Data were estimates from literature and clinical trials: costs were based on the situation in the United States. For insulin therapy, cumulative cost per patient during a 20-yr follow-up was $663,000, and cumulative effectiveness was 9.3 quality-adjusted life years (QALY), the average cost-effectiveness ratio being $71,000 per QALY. Islet transplantation had a cumulative cost of $519,000, a cumulative effectiveness of 10.9 QALY, and an average cost-effectiveness ratio of $47,800. During the first 10 yr, costs for transplantation were higher, but cumulative effectiveness was higher from the start onwards. In sensitivity analyses, the need for one instead of two transplants during the first year did not affect the conclusions, and islet transplantation remained cost-saving up to an initial cost of the procedure of $240,000. This exploratory evaluation shows that islet cell transplantation is more effective than standard insulin treatment, and becomes cost-saving at about 9-10 yr after transplantation.

Respiratory syncytial virus binds and undergoes transcription in neutrophils from the blood and airways of infants with severe bronchiolitis.

BACKGROUND: Neutrophils are the predominant cell in the lung inflammatory infiltrate of infants with respiratory syncytial virus (RSV) bronchiolitis. Although it has previously been shown that neutrophils from both blood and bronchoalveolar lavage (BAL) are activated, little is understood about their role in response to RSV infection. This study investigated whether RSV proteins and mRNA are present in neutrophils from blood and BAL of infected infants. METHODS: We obtained blood and BAL samples from 20 infants with severe RSV bronchiolitis and 8 healthy control infants. Neutrophil RSV F, G, and N proteins, RSV N genomic RNA, and messenger RNA (mRNA) were quantified. RESULTS: RSV proteins were found in BAL and blood neutrophils in infants with RSV disease but not in neutrophils from healthy infants. BAL and blood neutrophils from infants with RSV disease, but not those from healthy infants, expressed RSV N genomic RNA, indicating uptake of whole virus; 17 of 20 BAL and 8 of 9 blood neutrophils from patients expressed RSV N mRNA. CONCLUSIONS: This work shows, for the first time, the presence of RSV proteins and mRNA transcripts within BAL and blood neutrophils from infants with severe RSV bronchiolitis.

Plasma levels of BAFF and APRIL are elevated in patients with asthma in Saudi Arabia.

B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) are members of the tumor necrosis factor superfamily of cytokines and can induce B cell activation, differentiation, and antibody production via interaction with their receptors, including transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI), B-cell maturation antigen (BCMA), and B-cell activating factor receptor (BAFF-R). Herein, we assessed the plasma protein levels of BAFF and APRIL in patients with asthma to determine whether their expression is correlated with total IgE production and examined the surface expression of BAFF/APRIL receptors on B cells. Blood samples were collected from 47 patients with controlled asthma symptoms and 20 healthy normal controls, and plasma levels of APRIL, BAFF, and total IgE protein were quantified by corresponding ELISA assays. Furthermore, lymphocytes were isolated and B cells were analyzed for the presence of BAFF-R, BCMA, and TACI receptors using flow cytometry. Our results showed that IgE, BAFF, and APRIL plasma levels were markedly increased in patients with asthma compared with healthy controls. Moreover, expression of BAFF-R and BCMA, but not that of TACI, was significantly increased in patients with asthma compared with healthy controls. Overall, the findings suggest BAFF and APRIL as key mediators of asthma, and determination of their plasma levels may be useful in monitoring asthma symptoms and treatment response.

A health-economic analysis of porcine islet xenotransplantation.

BACKGROUND: Islet cell transplantation is a promising treatment for type 1 diabetes. To overcome the shortage of deceased human pancreas donors, porcine islet cell xenotransplantation is being developed as an alternative to allotransplantation. The objective of this study was to perform a cost-effectiveness analysis of porcine islet transplantation in comparison with standard insulin therapy. The patient population for this study was young adults, ages 20 to 40, for whom standard medical care is inadequate in controlling blood glucose levels (hypoglycemia unawareness). Since trial data were lacking, estimates used extrapolations from data found in the literature and ongoing trials in clinical allotransplantation. Cost estimates were based on the data available in the USA. METHODS: Markov modeling and Monte Carlo simulations using software specifically developed for health-economic evaluations were used. Outcomes data for ongoing clinical islet allotransplantation from the University of Minnesota were used, along with probabilities of complications from the Diabetes Control and Complications Trial. Quality-adjusted life years (QALYs) were the effectiveness measure. The upper limit of being cost-effective is $100,000 per QALY. Cost data from the literature were used and adjusted to 2007 US dollars using the medical care portion of the Consumer Price Index. RESULTS: In both Markov modeling and Monte Carlo simulations, porcine islet xenotransplantation was both more effective and less costly over the course of the 20-yr model. For standard insulin therapy, cumulative cost per patient was $661,000, while cumulative effectiveness was 9.4 QALYs, for a cost of $71,100 per QALY. Transplantation had a cumulative cost of $659 000 per patient, a cumulative effectiveness of 10.9 QALYs, and a cost per QALY of $60,700. Islet transplantation became cost-effective at 4 yr after transplantation, and was more cost-effective than standard insulin treatment at 14 yr. These findings are related to relative high costs in the transplantation arm of the evaluation during the first years while those in the insulin arm became higher later in follow-up. Throughout the follow-up period, effectiveness of transplantation was higher than that of insulin treatment. In sensitivity analysis, duplication or triplication of one-time initial costs such as costs of donor animal, islet manufacturing and transplantation had no effect on long-term outcome in terms of cost-saving or cost-effectiveness, but the outcome of transplantation in terms of diabetes complications in cases with partial graft function could affect cost-saving and cost-effectiveness conclusions. CONCLUSION: Despite limitations in the model and lack of trial data, and under the assumption that islet transplantation outcomes for young adult type 1 diabetes patients are not dependent on the source of islet cells, this health-economic evaluation suggests that porcine islet cell xenotransplantation may prove to be a cost-effective and possibly cost-saving procedure for type 1 diabetes compared to standard management.

Absence of spermatozoal CD46 protein expression and associated rapid acrosome reaction rate in striped field mice (Apodemus agrarius).

BACKGROUND: In rodents, the cell surface complement regulatory protein CD46 is expressed solely on the spermatozoal acrosome membrane. Ablation of the CD46 gene is associated with a faster acrosome reaction. Sperm from Apodemus flavicollis (yellow-necked field mice), A. microps (pygmy field mice) and A. sylvaticus (European wood mice) fail to express CD46 protein and exhibit a more rapid acrosome reaction rate than Mus (house mice) or BALB/c mice. A. agrarius (striped field mice) belong to a different Apodemus subgenus and have pronounced promiscuity and large relative testis size. The aim of this study was to determine whether A. agrarius sperm fail to express CD46 protein and, if so, whether A. agrarius have a faster acrosome reaction than Mus. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was used to assess whether A. agrarius transcribe testicular CD46 mRNA. RT-PCR was supplemented with 3'- and 5'-rapid amplification of cDNA ends to determine the complete nucleotide sequence of A. agrarius CD46. Fluorescence microscopy was used to assess whether CD46 protein is expressed by A. agrarius sperm. The acrosome status of A. agrarius sperm was calculated over time by immunocytochemistry using peanut agglutinin lectin. RESULTS: We demonstrate that A. agrarius mice transcribe two unique alternatively spliced testicular CD46 mRNA transcripts, both lacking exon 7, which differ from those described previously in other Apodemus species. The larger A. agrarius CD46 transcript has an insert between exons 10 and 11 which, if translated, would result in a novel cytoplasmic tail. In addition, A. agrarius CD46 transcripts have an extended AU-rich 3'-untranslated region (UTR) and a truncated 5'-UTR, resulting in failure to express spermatozoal CD46 protein. We show that A. agrarius has a significantly faster spontaneous acrosome reaction rate than A. sylvaticus and Mus. CONCLUSION: Absence of CD46 protein expression is associated with acrosomal instability in rodents. A. agrarius mice express novel CD46 transcripts, resulting in the trade of spermatozoal CD46 protein expression for a rapid acrosome reaction rate, in common with other species of field mice. This provides a strategy to increase competitive sperm advantage for individuals, leading to faster fertilisation in this highly promiscuous genus.

Cytokine profiling of chemical allergens in mice: measurement of message versus protein.

Chemical respiratory allergy is an important occupational health problem, but there are currently available no validated methods for hazard identification. There has been interest for some time in the application of cytokine profiling for the characterization of chemical allergens. We have now examined whether these cytokine expression patterns are regulated at the level of mRNA and/or protein production. Mice (BALB/c strain) were exposed topically to the contact allergen 2,4-dinitrochlorobenzene (DNCB), or to the respiratory allergen trimellitic anhydride (TMA). Thirteen days after the initiation of exposure, a single cell suspension of draining (auricular) lymph node cells (LNC) was prepared. Cells were cultured for 24-120h and supernatants analyzed for cytokine protein by cytokine bead array. In parallel experiments total RNA was prepared from freshly isolated or cultured cells and cytokine gene expression was analyzed by ribonuclease protection assay (RPA) or by real time reverse transcription-polymerase chain reaction (RT-PCR). DNCB-activated LNC secreted high levels of the type 1 cytokines interferon (IFN)-gamma and IL-12 compared with TMA-stimulated LNC. The converse type 2 pattern was observed following treatment with TMA. Freshly isolated LNC from TMA-treated mice displayed a selective type 2 cytokine mRNA profile as measured by RPA. In contrast, RNA isolated from DNCB-activated LNC displayed a more mixed cytokine phenotype with relatively low levels of transcripts for both type 1 and type 2 cell products. When cytokine gene expression was measured by the more sensitive real time RT-PCR technique, more vigorous expression of IL-4 was recorded for TMA-activated LNC compared with DNCB-activated LNC but there was no evidence for elevated IFN-gamma transcripts for the latter treatment. The observation that IFN-gamma mRNA expression is not increased in DNCB-activated LNC despite robust secretion of this cytokine indicates that production is controlled mainly at the level of translation of previously transcribed mRNA or of protein secretion. Furthermore, the preferential cytokine profile recorded following TMA exposure was more clearly contrasting when measured at the level of protein secretion rather than at the level of mRNA expression. Experience to date suggests that the measurement of induced cytokine profiles shows promise for the hazard identification and characterization of chemical respiratory allergens, and that the end point best suited for this purpose is cytokine secretion rather than mRNA expression.

Effect of ivacaftor on mucociliary clearance and clinical outcomes in cystic fibrosis patients with G551D-CFTR.

BACKGROUND: The ability to restore cystic fibrosis transmembrane regulator (CFTR) function with effective small molecule modulators in patients with cystic fibrosis provides an opportunity to study relationships between CFTR ion channel function, organ level physiology, and clinical outcomes. METHODS: We performed a multisite, prospective, observational study of ivacaftor, prescribed in patients with the G551D-CFTR mutation. Measurements of lung mucociliary clearance (MCC) were performed before and after treatment initiation (1 and 3 months), in parallel with clinical outcome measures. RESULTS: Marked acceleration in whole lung, central lung, and peripheral lung MCC was observed 1 month after beginning ivacaftor and was sustained at 3 months. Improvements in MCC correlated with improvements in forced expiratory volume in the first second (FEV1) but not sweat chloride or symptom scores. CONCLUSIONS: Restoration of CFTR activity with ivacaftor led to significant improvements in MCC. This physiologic assessment provides a means to characterize future CFTR modulator therapies and may help to predict improvements in lung function. TRIAL REGISTRATION: ClinicialTrials.gov, NCT01521338. FUNDING: CFF Therapeutics (GOAL11K1).

Impact of human metapneumovirus and respiratory syncytial virus co-infection in severe bronchiolitis.

We have previously shown high rates of co-infection with Respiratory Syncytial Virus (RSV) and human Metapneumovirus (hMPV) in infants with severe bronchiolitis at our institution in 2000-2002, and that co-infection was associated with increased disease severity. In this study, we have attempted to identify differences in intubated infants with severe RSV infection with and without hMPV co-infection. Here we show that RSV+/hMPV+ were clinically symptomatic for longer than RSV+/hMPV- infants, but that no differences in airway total cell concentration, differential cell count or cytokine/chemokine concentrations were detectable.

Acute Disassembly and Dissociation of a Dual-Mobility Next-Generation Prosthesis.

The use of bipolar components in hip surgery was introduced more than 40 years ago with the rationale of a dual-mobility hip implant. This design used a small femoral head that would decrease the rate of wear because of the smaller surface area but would still provide implant stability because of the larger outer shell that articulated with the acetabulum, decreasing dislocation rates. In April 2011, the E1 Active Articulation Hip System (Biomet, Warsaw, Indiana) was introduced to the orthopedic market. It is considered to be part of the next generation of bipolar designs, with similar designs available from competing companies, such as Stryker (Mahwah, New Jersey). These designs merge the concept of an articulating outer shell with an all-polyethylene spacer with the primary articulation of a ceramic head and an outer polyethylene shell spacer. This case report describes disassembly and dissociation at the site of the primary articulation of a bipolar system that occurred between the ceramic femoral head and the outer all-polyethylene articulating shell in a patient who had revision total hip arthroplasty because of metallosis. The patient had a stable nonpainful metal-on-metal arthroplasty at first, immediately after the initial procedure. Although previous intraprosthetic dislocations (also called retentive failures) have occurred, this case has several unique features. [Orthopedics.2016; 39(5):e980-e983.].

Interleukin 9 production in the lungs of infants with severe respiratory syncytial virus bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis is the most prevalent acute wheezing disorder in infants and is associated with recurrent wheeze and asthma in childhood. Interleukin 9, a type 2 cytokine has been proposed as a key cytokine in susceptibility to asthma. We aimed to investigate whether interleukin 9 was produced in the lungs of infants with severe RSV disease and if found, from which cells it originated. METHODS: We did 150 non-bronchoscopic bronchoalveolar lavages during the course of ventilation in 24 term infants and 21 preterm infants ventilated for RSV bronchiolitis. We also did 10 bronchoalveolar lavages on the day of intubation in 10 control infants ventilated for non-respiratory causes. We measured pulmonary interleukin 9 mRNA and protein in samples from all groups. We used immunostaining to identify the cells that produce interleukin 9. FINDINGS: Interleukin 9 mRNA expression, which persisted over the course of ventilation, was noted in all infants with bronchiolitis. Three of the control group also showed interleukin 9 mRNA expression. Median interleukin 9 protein concentration on day 1 (1.9 microg/L [range 0.1-36.2]) was significantly greater in term infants with bronchiolitis than either preterm infants (0.4 microg/L [0.1-2.9]; p<0.05) or the control group (0.7 microg/L [0.4-2.5]; p<0.05). There was a trend for interleukin 9 protein concentrations in term, but not preterm infants to decrease over time. Immunostained cell smears showed that most interleukin 9 expression in bronchoalveolar lavage was by neutrophils. INTERPRETATION: In term infants with RSV bronchiolitis, we noted large amounts of interleukin 9 mRNA and interleukin 9 protein. Neutrophils seem to be the main source of this type 2 cytokine. Interleukin 9 production by neutrophils may contribute to the pathogenesis of RSV disease. These findings may be relevant to other disease processes in the lung where neutrophils are the predominant inflammatory cell type.

Reducing Fracture Risk Adjacent to a Plate With an Angulated Locked End Screw.

OBJECTIVES: Locking screws often are used in the treatment of osteoporotic fractures. Studies show that locking screws can increase bone stresses at the plate end, which increases the possibility of peri-implant fracture. This study evaluates whether the technique used to insert the end screw is related to the fracture tolerance adjacent to the plate. METHODS: Twelve groups of plate constructs were evaluated using a fibular diaphyseal surrogate with mechanical properties similar to osteoporotic bone. All inboard screws were nonlocked with only the end screw fixation differing among groups. The end screws were inserted either perpendicularly to the plate or at an angle of 30 degrees for 6- and 12-hole plates. For both orientations, the end screws were inserted nonlocked, locked, or by a locked overdrilling technique, resulting in 6 groups per plate length. The perpendicular nonlocked screws represented a control group. The constructs were tested to failure in 4-point bending to determine peak load, failure energy, and stiffness. RESULTS: All constructs failed by peri-implant fracture along a plane through the 2 cortical holes of the end screw. Compared with the control group, an angulated locked screw at the plate end significantly increased the peak bending moment and energy required to produce a fracture for both plate lengths (6-hole, P = 0.008, P < 0.001; 12-hole, P = 0.006, P < 0.001). CONCLUSIONS: The use of an angulated locked end screw may enhance the resistance of osteoporotic bone to peri-implant fractures caused by bending forces.

Chemical allergy: considerations for the practical application of cytokine profiling.

Chemical respiratory allergy is an important occupational health problem, but there are currently available no validated methods for hazard identification. This is due in part to the fact that the relevant cellular and molecular mechanisms of sensitization of the respiratory tract have been unclear, with particular controversy regarding the role of IgE. There is now increasing evidence that respiratory sensitization is associated with the preferential activation of type 2 T lymphocytes and the expression of type 2 cytokines interleukin (IL)-4, IL-5, IL-10, and IL-13. Type 2 cell products favor immediate type hypersensitivity reactions, serving as growth and differentiation factors for mast cells and eosinophils, the cellular effectors of the clinical manifestations of the allergic responses, and promoting IgE antibody production. There has been considerable interest in the application of cytokine profiling for the characterization of chemical allergens, with cytokine phenotypes analyzed in freshly isolated tissue, or following culture in the presence or absence of mitogen at the level of protein secretion or mRNA expression. Experience to date suggests that the measurement of induced cytokine secretion profiles shows promise for the hazard identification and characterization of chemical respiratory allergens. The purpose of this brief review article is to consider the approaches available and to highlight key procedural issues.