Dynamic regulation of T follicular regulatory cell responses by interleukin 2 during influenza infection.

Interleukin 2 (IL-2) promotes Foxp3+ regulatory T (Treg) cell responses, but inhibits T follicular helper (TFH) cell development. However, it is not clear how IL-2 affects T follicular regulatory (TFR) cells, a cell type with properties of both Treg and TFH cells. Using an influenza infection model, we found that high IL-2 concentrations at the peak of the infection prevented TFR cell development by a Blimp-1-dependent mechanism. However, once the immune response resolved, some Treg cells downregulated CD25, upregulated Bcl-6 and differentiated into TFR cells, which then migrated into the B cell follicles to prevent the expansion of self-reactive B cell clones. Thus, unlike its effects on conventional Treg cells, IL-2 inhibits TFR cell responses.

Persistence and origin of the lunar core dynamo.

The lifetime of the ancient lunar core dynamo has implications for its power source and the mechanism of field generation. Here, we report analyses of two 3.56-Gy-old mare basalts demonstrating that they were magnetized in a stable and surprisingly intense dynamo magnetic field of at least ~13 µT. These data extend the known lifetime of the lunar dynamo by ~160 My and indicate that the field was likely continuously active until well after the final large basin-forming impact. This likely excludes impact-driven changes in rotation rate as the source of the dynamo at this time in lunar history. Rather, our results require a persistent power source like precession of the lunar mantle or a compositional convection dynamo.

Immunotherapy of chronic hepatitis C virus infection with antibodies against programmed cell death-1 (PD-1).

Hepatitis C virus (HCV) persistence is facilitated by exhaustion of CD8+ T cells that express the inhibitory receptor programmed cell death 1 (PD-1). Blockade of PD-1 signaling improves in vitro proliferation of HCV-specific T lymphocytes, but whether antiviral function can be restored in infected individuals is unknown. To address this question, chimpanzees with persistent HCV infection were treated with anti-PD-1 antibodies. A significant reduction in HCV viremia was observed in one of three treated animals without apparent hepatocellular injury. Viremia rebounded in the responder animal when antibody treatment was discontinued. Control of HCV replication was associated with restoration of intrahepatic CD4+ and CD8+ T-cell immunity against multiple HCV proteins. The responder animal had a history of broader T-cell immunity to multiple HCV proteins than the two chimpanzees that did not respond to PD-1 therapy. The results suggest that successful PD-1 blockade likely requires a critical threshold of preexisting virus-specific T cells in liver and warrants consideration of therapeutic vaccination strategies in combination with PD-1 blockade to broaden narrow responses. Anti-PD-1 immunotherapy may also facilitate control of other persistent viruses, notably the hepatitis B virus where options for long-term control of virus replication are limited.

Feasibility of an ambulance-based stroke trial, and safety of glyceryl trinitrate in ultra-acute stroke: the rapid intervention with glyceryl trinitrate in Hypertensive Stroke Trial (RIGHT, ISRCTN66434824).

BACKGROUND AND PURPOSE: The practicalities of doing ambulance-based trials where paramedics perform all aspects of a clinical trial involving patients with ultra-acute stroke have not been assessed. METHODS: We performed a randomized controlled trial with screening, consent, randomization, and treatment performed by paramedics prior to hospitalization. Patients with probable ultra-acute stroke (<4 hours) and systolic blood pressure (SBP) >140 mm Hg were randomized to transdermal glyceryl trinitrate (GTN; 5 mg/24 hours) or none (blinding under gauze dressing) for 7 days with the first dose given by paramedics. The primary outcome was SBP at 2 hours. RESULTS: Of a planned 80 patients, 41 (25 GTN, 16 no GTN) were enrolled >22 months with median age [interquartile range] 79 [16] years; men 22 (54%); SBP 168 [46]; final diagnosis: stroke 33 (80%) and transient ischemic attack 3 (7%). Time to randomization was 55 [75] minutes. After treatment with GTN versus no GTN, SBP at 2 hours was 153 [31] versus 174 [27] mm Hg, respectively, with difference -18 [30] mm Hg (P=0.030). GTN improved functional outcome with a shift in the modified Rankin Scale by 1 [3] point (P=0.040). The rates of death, 4 (16%) versus 6 (38%; P=0.15), and serious adverse events, 14 (56%) versus 10 (63%; P=0.75), did not differ between GTN and no GTN. CONCLUSIONS: Paramedics can successfully enroll patients with ultra-acute stroke into an ambulance-based trial. GTN reduces SBP at 2 hours and seems to be safe in ultra-acute stroke. A larger trial is needed to assess whether GTN improves functional outcome. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com/ISRCTN66434824/66434824. Unique identifier: 66434824.

The Effect of LED Light Spectra on the Growth, Yield and Nutritional Value of Red and Green Lettuce (Lactuca sativa).

Controlled Environment Agriculture (CEA) is a method of increasing crop productivity per unit area of cultivated land by extending crop production into the vertical dimension and enabling year-round production. Light emitting diodes (LED) are frequently used as the source of light energy in CEA systems and light is commonly the limiting factor for production under CEA conditions. In the current study, the impact of different spectra was compared with the use of white LED light. The various spectra were white; white supplemented with ultraviolet b for a week before harvest; three combinations of red/blue lights (red 660 nm with blue 450 nm at 1:1 ratio; red 660 nm with blue 435 nm 1:1 ratio; red 660 nm with blue at mix of 450 nm and 435 nm 1:1 ratio); and red/blue supplemented with green and far red (B/R/G/FR, ratio: 1:1:0.07:0.64). The growth, yield, physiological and chemical profiles of two varieties of lettuce, Carmoli (red) and Locarno (green), responded differently to the various light treatments. However, white (control) appeared to perform the best overall. The B/R/G/FR promoted the growth and yield parameters in both varieties of lettuce but also increased the level of stem elongation (bolting), which impacted the quality of grown plants. There was no clear relationship between the various physiological parameters measured and final marketable yield in either variety. Various chemical traits, including vitamin C content, total phenol content, soluble sugar and total soluble solid contents responded differently to the light treatments, where each targeted chemical was promoted by a specific light spectrum. This highlights the importance of designing the light spectra in accordance with the intended outcomes. The current study has value in the field of commercial vertical farming of lettuce under CEA conditions.

Phylogenetic and Expression Studies of Small GTP-Binding Proteins in Solanum lycopersicum Super Strain B.

This investigation involved a comparative analysis of the small GTPase superfamily in S. lycopersicum super strain B compared to their analogues in leguminous and other non-leguminous species. The small GTPases superfamily members were recognized by tBLASTn searches. The sequences of amino acid were aligned using Clustal Omega and the analysis of phylogeny was performed with the MEGA7 package. Protein alignments were applied for all studied species. Three-dimensional models of RABA2, ROP9, and ROP10 from Solanum lycopersicum "Super strain B" were performed. The levels of mRNA of the Rab, Arf, Rop, and Ran subfamilies were detected in aerial tissues vs. roots. Significant divergences were found in the number of members and groups comprising each subfamily of the small GTPases and Glycine max had the highest count. High expression of Rab and Arf proteins was shown in the roots of legumes whilst in non-legume plants, the highest values were recorded in aerial tissues. S. lycopersicum super strain B had the highest expression of Rab and Arf proteins in its aerial tissues, which may indicate that diazotroph strains have supreme activities in the aerial tissues of strain B and act as associated N-fixing bacteria. The phylogenies of the small GTPase superfamily of the studied plants did not reveal asymmetric evolution of the Ra, Arf, Rop, and Ran subfamilies. Multiple sequence alignments derived from each of the Rab, Arf, and Rop proteins of S. lycopersicum super strain B showed a low frequency of substitutions in their domains. GTPases superfamily members have definite functions during infection, delivery, and maintenance of N2-fixing diazotroph but show some alterations in their function among S. lycopersicum super strain B, and other species.

The Impact of LED Lighting Spectra in a Plant Factory on the Growth, Physiological Traits and Essential Oil Content of Lemon Balm (Melissa officinalis).

With the recent development of LED lighting systems for plant cultivation, the use of vertical farming under controlled conditions is attracting increased attention. This study investigated the impact of a number of LED light spectra (red, blue, green and white) on the growth, development and essential oil content of lemon balm (Melissa officinalis), a herb and pharmaceutical plant species used across the world. White light and red-rich light spectra gave the best outputs in terms of impact on the growth and yield. For blue-rich spectra, the development and yield was lower despite having a significant impact on the photosynthesis activity, including Fv/Fm and NDVI values. For the blue-rich spectra, a peak wavelength of 450 mn was better than that of 435 nm. The results have practical value in terms of increased yield and the reduction of electricity consumption under controlled environmental conditions for the commercial production of lemon balm.

Foliar microstructure and histochemical analysis of the lavender tree (Heteropyxis natalensis Harv.).

Heteropyxis natalensis Harv. is a native South African tree used in traditional medicine among Venda and Zulu communities. In this study, micromorphological investigations using light and scanning electron microscopy identified long, tapered non-glandular trichomes on the abaxial and adaxial surfaces of the leaves. The total number of trichomes appeared to be greater on emergent leaves and decreased as leaves matured. In addition, schizolysigenous secretory cavities and druse crystals were found within the leaves. Swollen subdermal secretory cavities were also distributed in the midrib of the leaves. Transmission electron microscopy confirmed the presence of nuclei, plastids, mitochondria, vesicles, rough endoplasmic reticulum cisternae and Golgi bodies in the secretory epithelia of these cavities. Various histochemical tests revealed the presence of alkaloids, phenolics, lipids, proteins, essential oils, resin acids and trace amounts of unesterified pectins and polysaccharides in the leaves. This study provides new findings and contributes to the existing research regarding H. natalensis with respect to the micromorphology, ultrastructure and histochemical composition of this species.

Selection-driven immune escape is not a significant factor in the failure of CD4 T cell responses in persistent hepatitis C virus infection.

UNLABELLED: Immune escape driven by selection pressure from virus-specific CD8 T cells has been demonstrated in both chimpanzees and humans infected with the hepatitis C virus (HCV). Although escape mutations have also been characterized in major histocompatibility complex (MHC) class II-restricted HCV epitopes, it is unknown whether selection-driven immune escape by CD4 T cell epitopes is a significant factor in the failure of these responses or contributes to persistent infection. To address this issue, evolution of MHC class I- and class II-restricted HCV epitopes was compared in four chimpanzees persistently infected with the virus for more than 10 years. We identified an amino acid change in a CD4 epitope of the HCV NS3 protein in one of the chimpanzees 3 years after infection. This mutation resulted in diminished activation, cytokine production (interferon-gamma and interleukin-2), and proliferation by an epitope-specific CD4 T cell line. We expanded our analysis to determine if mutations were common in multiple CD4 versus CD8 T cell epitopes in the four chronically infected animals. Whereas we observed mutations in over 75% of CD8 T cell epitopes analyzed in this study, only 18% of CD4 T cell epitopes analyzed showed amino acid changes. The frequency of changes in class II epitopes was not different from flanking regions, so CD4 T cells rarely exert selection pressure against the HCV genome. CONCLUSION: Apparent mutational escape can occur in MHC class II-restricted epitopes, but this is uncommon when compared with class I-restricted epitopes in the same individual. This indicates that other mechanisms for silencing CD4 T cells are dominant in persistent HCV infections.

The Impact of Light Spectrum and Intensity on the Growth, Physiology, and Antioxidant Activity of Lettuce (Lactuca sativa L.).

This study focused on the physiology, growth and antioxidant activity response of hydroponically grown lettuce (Lactuca sativa L.) under sole-source LED lighting of differing spectra. Lighting spectra were provided by differing combinations of LEDs of three different peak wavelengths, (Blue 435, Blue 450, and Red 663 nm) with ratios of B450/R663: 1.25 ± 0.1, B450/R663: 1.25 ± 0.1, and B450/R663 1:1 at two light intensities of photosynthetically active radiation (PAR) (270 µmol m-2 s-1 and 60 µmol m-2 s-1). A further experiment was conducted, in which Blue and Red LEDs were supplemented with Green (Blue 450, Red 663, and Green 520 nm) with ratios of B435/R663: 1.25 ± 0.1, B450/R663/G520: 1/0.73/0.26, and B450/R663: 1.25 ± 0.1. LED light intensities under the different spectra were adjusted to deliver the same level of PAR (270 ± 20 µmol m-2 s-1). Results from the first experiment showed that increased fraction of blue 435 nm in combination with red light at 663 nm at high irradiance enhanced the physiology of lettuce (i.e., significantly increased assimilation rate, stomatal conductance and transpiration rate) and increased the yield while having no significant effect on antioxidant activity. At the lower irradiance, the B435/R663 significantly increased antioxidant activity compared to other spectra. Results from the second experiment showed no significant effect of the spectra of LEDs on the physiology and yield of lettuce, but antioxidant activity was very significantly induced by B450/R663 at the ratio of 1.25 ± 0.1. However, the amount was still less than that obtained by B435/R663 1.25 ± 0.1 from the first experiment. This study indicates that LED light with a spectrum of B435/R663 at a ratio of 1.25 ± 0.1 significantly improves lettuce yield and antioxidant activity.

X-ray bi-prism interferometry-A design study of proposed novel hardware.

PURPOSE: Advances in X-ray phase-contrast imaging can obtain excellent soft-tissue contrast of phase-shift, attenuation, and small-angle scatter. Here, we present fringe patterns for different design parameters of X-ray bi-prism interferometry imaging systems. Our aim is to develop bi-prism interferometry imaging systems with excellent polychromatic performance that produce high-contrast fringes with spatially incoherent X-ray illumination. We also introduce a novel X-ray tube design that uses temporal multiplexing to provide simultaneous virtual "electronic phase stepping" that replace "mechanical phase stepping" popular with grating-based interferometry setups. METHODS: In our investigation, we develop expressions for the irradiance distribution pattern of a bi-prism interferometer composed of multiple point sources and multiple bi-prisms. These expressions are used to plot fringe patterns for X-ray design parameters, including size of point source, number of point sources, and point source separation, and bi-prism design parameters including material, angle, number of bi-prisms, period, and bi-prism array to X-ray source and detector distances. RESULTS: Results show that the fringe patterns for a bi-prism interferometry system are not longitudinally periodic as with grating interferometers that produce a Talbot-Lau carpet. It is also shown that at 59 keV X-rays the bi-prism material should be something comparable to nickel to obtain reasonable fringe visibility. CONCLUSION: The irradiance distribution pattern demonstrates that bi-prism interferometry may provide comparable or improved fringe visibility to that of gratings. Special care is given to present our findings within the context of previous advancements. A single-shot image acquisition approach using a temporal multiplexed, high-power X-ray source provides virtual electronic phase stepping without focal spot sweeping. This provides multiple images, each at the same exposure and the same projection view, from different fringe locations that allow one to derive the attenuation, phase, and dark-field images of the sample without mechanical phase stepping of a grating.

Tomography of dark-field scatter including single-exposure Moiré fringe analysis with X-ray biprism interferometry-A simulation study.

PURPOSE: In this work, we present tomographic simulations of a new hardware concept for X-ray phase-contrast interferometry wherein the phase gratings are replaced with an array of Fresnel biprisms, and Moiré fringe analysis is used instead of "phase stepping" popular with grating-based setups. METHODS: Projections of a phantom consisting of four layers of parallel carbon microfibers is simulated using wave optics representation of X-ray electromagnetic waves. Simulated projections of a phantom with preferential scatter perpendicular to the direction of the fibers are performed to analyze the extraction of small-angle scatter from dark-field projections for the following: (1) biprism interferometry using Moiré fringe analysis; (2) grating interferometry using phase stepping with eight grating steps; and (3) grating interferometry using Moiré fringe analysis. Dark-field projections are modeled as projections of voxel intensities represented by a fixed finite vector basis set of scattering directions. An iterative MLEM algorithm is used to reconstruct, from simulated projection data, the coefficients of a fixed set of seven basis vectors at each voxel representing the small-angle scatter distribution. RESULTS: Results of reconstructed vector coefficients are shown comparing the three simulated imaging configurations. The single-exposure Moiré fringe analysis shows not only an increase in noise because of one-eighth the number of projection samples but also is obtained with less dose and faster acquisition times. Furthermore, replacing grating interferometry with biprism interferometry provides better contrast-to-noise. CONCLUSION: The simulations demonstrate the feasibility of the reconstruction of dark-field data acquired with a biprism interferometry system. With the potential of higher fringe visibility, biprism interferometry with Moiré fringe analysis might provide equal or better image quality to that of phase stepping methods with less imaging time and lower dose.

Restricted clonal expression of IL-2 by naive T cells reflects differential dynamic interactions with dendritic cells.

Limited frequencies of T cells express IL-2 in primary antigenic responses, despite activation marker expression and proliferation by most clonal members. To define the basis for restricted IL-2 expression, a videomicroscopic system and IL-2 reporter transgenic model were used to characterize dendritic cell (DC)-T cell interactions. T cells destined to produce IL-2 required prolonged interactions with DCs, whereas most T cells established only transient interactions with DCs and were activated, but did not express IL-2. Extended conjugation of T cells with DCs was not always sufficient to initiate IL-2 expression. Thus, there is intrinsic variability in clonal T cell populations that restricts IL-2 commitment, and prolonged engagement with mature DCs is necessary, but not sufficient, for IL-2 gene transcription.

Coexistence of Primary and Secondary Delusional Parasitosis.

OBJECTIVE: Delusional parasitosis (DP) is a difficult-to-treat condition. It is prevalent in all cultures, societies, and countries. Previous case reports of DP have been published; however, the patient presented in this report is unique because of the co-occurrence of both primary and secondary types of DP. We aim to explore the two subtypes of DP. CONCLUSIONS: We discuss DP from a nosological perspective and also highlight the various theories at play in the pathogenesis of primary and secondary DP. The different subtypes of DP should be taken into consideration as they also have a bearing on the management.

A Pilot Study to Examine the Effect of an Educational Poster on the Knowledge and Practices of Lateral Elbow Radiograph Repositioning in Radiographers.

AIM: This pilot study aimed to evaluate the knowledge and practices of South Australian radiographers regarding lateral elbow repositioning and to determine whether an educational poster could improve repositioning knowledge. METHOD: The study was undertaken in four stages. Stage one involved the development of a survey to explore radiographer knowledge and practices surrounding lateral elbow repositioning. Stage two involved the development of an educational poster. Stage three was a pilot validity study. Three participants (n = 3) were involved in testing the validity and test-retest reliability of the survey and the poster. Stage four was the interventional study which involved the distribution of surveys to two radiography departments in South Australia on two occasions, before and after the distribution of the poster. Six complete data sets were analysed. RESULTS: The pilot validity study ensured the test-retest reliability of the survey was strong (P = .629). It was determined that an educational poster made no significant difference to the knowledge of lateral elbow radiograph repositioning among radiographers (P = .253). It was indicated that this result was not due to familiarity with the presurvey questions (P = .171). Thematic analysis of the open discussion questions found that most participants found the poster helpful but did not consider repositioning to be difficult. The introduction of the poster did not increase image repeat rate and the poster was used moderately over the study length. CONCLUSION: As this study was unable to determine whether a poster could improve the knowledge and practices of lateral elbow repositioning among radiographers, further research is needed.

Variable patterns of programmed death-1 expression on fully functional memory T cells after spontaneous resolution of hepatitis C virus infection.

The inhibitory receptor programmed death-1 (PD-1) is present on CD8(+) T cells in chronic hepatitis C virus (HCV), but expression patterns in spontaneously resolving infections are incompletely characterized. Here we report that PD-1 was usually absent on memory CD8(+) T cells from chimpanzees with resolved infections, but sustained low-level expression was sometimes observed in the absence of apparent virus replication. PD-1-positive memory T cells expanded and displayed antiviral activity upon reinfection with HCV, indicating conserved function. This animal model should facilitate studies of whether PD-1 differentially influences effector and memory T-cell function in resolved versus persistent human infections.

Inhibition of IL-2 responsiveness by IL-6 is required for the generation of GC-TFH cells.

Sustained T cell receptor (TCR) stimulation is required for maintaining germinal center T follicular helper (GC-TFH) cells. Paradoxically, TCR activation induces interleukin-2 receptor (IL-2R) expression and IL-2 production, thereby initiating a feedback loop of IL-2 signaling that normally inhibits TFH cells. It is unclear how GC-TFH cells can receive prolonged TCR signaling without succumbing to the detrimental effects of IL-2. Using an influenza infection model, we show here that GC-TFH cells secreted large amounts of IL-2 but responded poorly to it. To maintain their IL-2 hyporesponsiveness, GC-TFH cells required intrinsic IL-6 signaling. Mechanistically, we found that IL-6 inhibited up-regulation of IL-2Rß (CD122) by preventing association of STAT5 with the Il2rb locus, thus allowing GC-TFH cells to receive sustained TCR signaling and produce IL-2 without initiating a TCR/IL-2 inhibitory feedback loop. Collectively, our results identify a regulatory mechanism that controls the generation of GC-TFH cells.

Testing the robustness of management decisions to uncertainty: Everglades restoration scenarios.

To effectively manage large natural reserves, resource managers must prepare for future contingencies while balancing the often conflicting priorities of different stakeholders. To deal with these issues, managers routinely employ models to project the response of ecosystems to different scenarios that represent alternative management plans or environmental forecasts. Scenario analysis is often used to rank such alternatives to aid the decision making process. However, model projections are subject to uncertainty in assumptions about model structure, parameter values, environmental inputs, and subcomponent interactions. We introduce an approach for testing the robustness of model-based management decisions to the uncertainty inherent in complex ecological models and their inputs. We use relative assessment to quantify the relative impacts of uncertainty on scenario ranking. To illustrate our approach we consider uncertainty in parameter values and uncertainty in input data, with specific examples drawn from the Florida Everglades restoration project. Our examples focus on two alternative 30-year hydrologic management plans that were ranked according to their overall impacts on wildlife habitat potential. We tested the assumption that varying the parameter settings and inputs of habitat index models does not change the rank order of the hydrologic plans. We compared the average projected index of habitat potential for four endemic species and two wading-bird guilds to rank the plans, accounting for variations in parameter settings and water level inputs associated with hypothetical future climates. Indices of habitat potential were based on projections from spatially explicit models that are closely tied to hydrology. For the American alligator, the rank order of the hydrologic plans was unaffected by substantial variation in model parameters. By contrast, simulated major shifts in water levels led to reversals in the ranks of the hydrologic plans in 24.1-30.6% of the projections for the wading bird guilds and several individual species. By exposing the differential effects of uncertainty, relative assessment can help resource managers assess the robustness of scenario choice in model-based policy decisions.

The value of the erect abdominal radiograph for the diagnosis of mechanical bowel obstruction and paralytic ileus in adults presenting with acute abdominal pain.

INTRODUCTION: There is discord on the value of the erect abdominal radiograph for diagnosing acute abdominal pathologies. The erect radiograph can be uncomfortable for patients in pain and increases patient radiation dose. AIM: To determine if including the erect abdominal radiograph in plain abdominal radiography (PAR) improved diagnostic accuracy for identifying mechanical bowel obstruction and/or paralytic ileus in adults presenting with acute abdominal pain. METHODS: PAR of 40 consecutive adults presenting with suspected bowel obstruction or paralytic ileus was retrospectively sampled and independently reviewed by two emergency department (ED) consultants and two radiology consultants for bowel obstruction and paralytic ileus across two sessions. In session 1, the assessors assessed the supine abdominal radiographs (PAR 1) and clinical details in a randomised order, and session 2, at least 6 weeks later, they assessed the supine and erect radiographs (PAR 2) and clinical details of the randomly re-ordered cases. Computed tomography was the reference standard. Pair-wise comparisons of receiver operating characteristic curves were calculated to assess for significant differences in participants' diagnostic accuracy using MedCalc 16.4.3. RESULTS: Average sensitivity, specificity and area under the receiver operating characteristic curves (AUROC) were 69.7%, 61.0% and 0.642 for PAR 1, respectively, and 80.0%, 53.4% and 0.632 for PAR 2 respectively. For AUROC there were no significant differences (P > 0.05) between PAR 1 and PAR 2. Intra-rater and inter-rater agreement improved in PAR 2. CONCLUSION: There was no statistically significant improvement in diagnostic accuracy when including the erect radiograph in PAR for the acute abdomen.

Postoperative Pain Management with Oral Methylprednisolone in Symptomatic Patients with a Pulpal Diagnosis of Necrosis: A Prospective Randomized, Double-blind Study.

INTRODUCTION: The purpose of this prospective randomized, double-blind, placebo-controlled study was to evaluate postoperative pain by using an oral dose regimen of methylprednisolone in symptomatic patients with pulpal necrosis and symptomatic apical periodontitis, a periapical radiolucency, and experiencing preoperative moderate to severe pain. METHODS: One hundred twenty-five adult symptomatic patients presenting for emergency endodontic treatment with a pulpal diagnosis of necrosis and symptomatic apical periodontitis, a periapical radiolucency, and experiencing moderate to severe pain participated. All patients received complete endodontic debridement and were randomly divided into 2 groups. In a double-blind manner, the groups received either an oral regimen of methylprednisolone (96 mg immediately after treatment followed by 48 mg each day for 5 consecutive days) or a lactose placebo. All patients received 600 mg ibuprofen and an opioid-containing escape medication to take if needed. Patients completed a 7-day diary to record pain and number of analgesic medications taken each day. RESULTS: Moderate to severe pain was experienced by 40%-50% of the patients on day 1 and 31% of the patients on day 2, with the pain ratings decreasing during the next 7 days. There were no statistically significant differences in pain ratings between the methylprednisolone and placebo groups. CONCLUSIONS: When compared with a placebo, the current regimen of oral methylprednisolone did not significantly reduce postoperative pain after complete debridement of symptomatic patients presenting for emergency endodontic treatment with a pulpal diagnosis of necrosis and symptomatic apical periodontitis, periapical radiolucency, and experiencing moderate to severe pain.