T helper 2 (Th2) cells are pivotal in the development of allergy. Allergen exposure primes IL-4⁺ Th2 cells in lymph node, but production of effector cytokines including IL-5 and IL-13 is thought to ...require additional signals from antigen and the environment. Here we report that a substantial proportion of naive CD4⁺ T cells in spleen and lymph node express receptors for the epithelium-derived inflammatory cytokine thymic stromal lymphopoietin (TSLP). Culture of naive CD4⁺ T cells in anti-(a)CD3, aCD28, and TSLP-supplemented Th2 conditions enabled the development of a unique population of IL-13-single positive (IL-13-SP) CD4⁺ T cells; TSLP and Th2 conditions were both required for their development. Sorting experiments revealed that IL-13-SP Th2 cells originated from IL-4-negative precursors and coexpressed transcripts for the Th2 cytokines IL-5 and IL-9. In vivo, high TSLP levels acted directly on CD4⁺ T cells to induce the development of IL-13-SP and IL-4⁺IL-13⁺ double-positive populations in lymph node. These cells were phenotypically similar to Th2 effector cells and were CXCR5lowPD1low and expressed low levels of Bcl6 and Il21 transcripts and high levels of Gata3, Il3, and Il5. Our findings suggest a role of TSLP in directly promoting Th2 cell effector function and support the notion of TSLP as a key driver of Th2 inflammation.
The dendritic cell signals required for the in vivo priming of IL-4-producing T cells are unknown. We used RNA sequencing to characterize DCs from skin LN of mice exposed to two different Th2 ...stimuli: the helminth parasite Nippostrongylus brasiliensis (Nb) and the contact sensitizer dibutyl phthalate (DBP)-FITC. Both Nb and DBP-FITC induced extensive transcriptional changes that involved multiple DC subsets. Surprisingly, these transcriptional changes were highly distinct in the two models, with only a small number of genes being similarly regulated in both conditions. Pathway analysis of expressed genes identified no shared pathways between Nb and DBP-FITC, but revealed a type-I IFN (IFN-I) signature unique to DCs from Nb-primed mice. Blocking the IFN-I receptor at the time of Nb treatment had little effect on DC migration and antigen transport to the LN, but inhibited the up-regulation of IFN-I-induced markers on DCs and effectively blunted Th2 development. In contrast, the response to DBP-FITC was not affected by IFN-I receptor blockade, a finding consistent with the known dependence of this response on the innate cytokine TSLP. Thus, the priming of Th2 responses is associated with distinct transcriptional signatures in DCs in vivo, reflecting the diverse environments in which Th2 immune responses are initiated.
The induction of Th2 responses is thought to be multifactorial, and emerge from specific pathways distinct from those associated with antagonistic antibacterial or antiviral Th1 responses. Here, we ...show that the recognition of non-viable
(Nb) in the skin induces a strong recruitment of monocytes and neutrophils and the release of neutrophil extracellular traps (NETs). Nb also activates toll-like receptor 4 (TLR4) signaling with expression of
transcripts in the skin and the development of an IFN type I signature on helminth antigen-bearing dendritic cells in draining lymph nodes. Co-injection of Nb together with about 10,000 Gram-negative bacteria amplified this TLR4-dependent but NET-independent IFN type I response and enhanced the development of Th2 responses. Thus, a limited activation of antibacterial signaling pathways is able to boost antihelminthic responses, suggesting a role for bacterial sensing in the optimal induction of Th2 immunity.
To determine whether prevention of hyposalivation after curative radiotherapy (RT) to the head and neck improves patients’ quality of life (QOL).
Patients were to receive at least 50 Gy to 50% of the ...volume of the major salivary glands, provide unstimulated and stimulated saliva samples, and complete the University of Washington head-and-neck QOL tool before RT and 3 and 6 months after RT. Patients were randomized to receive pilocarpine 5 mg or placebo q.i.d.
A total of 249 patients was randomized between March 1998 and January 2000. Of these, 214 were eligible for QOL analysis. Patients were evenly distributed between arms by race, gender, tobacco use, tumor site, T stage (50% T2-T3), and salivary function. A Karnofsky performance status of 90% was more common in the pilocarpine arm. Twenty percent of the patients on the pilocarpine arm and 29% of the patients on the placebo arm were taking nutritional supplements. The placebo arm patients had greater mouth pain and chewing difficulties. Compliance for the QOL tool at 3 and 6 months was 65% and 50%, respectively. Despite statistically significant (
p = 0.047 and
p = 0.049, respectively) preservation of salivary function in the pilocarpine arm, patients on the pilocarpine arm reported difficulties with swallowing (75%), activity (80%), hyposalivation (64%), and taste (81%). No difference was noted between arms at 3 months in mucositis scores, with both arms demonstrating increased requirement for oral nutrients.
Objective prevention of hyposalivation did not affect patients’ assessment of salivary function or QOL because of the greater impact mucositis plays in QOL after RT.
One hundred and ninety-five series of granulocyte transfusions in 144 patients were evaluated with respect to possible severe pulmonary toxicity from concomitant administration of granulocytes and ...amphotericin B. Dyspnea as a side effect of granulocyte transfusion was equally common among patients receiving amphotericin B and those in a matched control group not receiving amphotericin B. Granulocyte transfusions and amphotericin B were given simultaneously in 35 transfusion series, involving 32 patients. Respiratory deterioration, defined as the appearance of new pulmonary infiltrates on chest x-ray, occurred in 11 of these 35 episodes. Patients developing respiratory deterioration were similar to those not developing respiratory deterioration in age, diagnosis, disease status, duration of concomitant therapy, and outcome, but more often had positive fungal cultures as an indication for treatment (91% versus 58%; p = 0.1). In 8 patients, the episodes of respiratory deterioration were readily explained by congestive heart failure, by simultaneous bacteremia or fungemia, or by fungal pneumonia discovered at autopsy. One patient had a leukoagglutinin reaction (responsive to steroids) and the other 2 had unexplained, but reversible respiratory deterioration. We conclude that concomitant administration of granulocyte transfusions and amphotericin B is not associated with unexpected or rapidly fatal pulmonary toxicity and when appropriate, can be safely accomplished.
Objective
Ethnicity and migrant status result in disparities with cancer burden and survival, with communication difficulties cited as the main barrier to access. Our research team tested a ...communication intervention package comprising consultation audio‐recordings (ARs) and question prompt lists (QPLs) for low English‐speaking (LES) patients with cancer. This study explored LES patient experiences, preferences, and recommendations regarding the communication package.
Methods
Participants completed a questionnaire and qualitative interview regarding ARs and QPLs. Eligibility criteria comprised aged ≥18 years old; a consultation with an oncologist between June 1, 2015 and April 1, 2016; an Arabic, Cantonese, Greek, or Mandarin professional interpreter booked for that consultation; and randomised to receive the communication intervention.
Results
Eighteen patients completed the qualitative interview and 17 completed the questionnaire. Fifteen reported listening to the AR at least once. Participants reported that QPLs and ARs provide support and assistance with remembering and understanding medical information. Both resources were seen as having applicability beyond the oncology setting in regards to improving health service delivery and continuity of care. However, patients felt that individual tailoring of the resources should be considered. Patients also found it useful to share ARs with family.
Conclusions
The LES participants in this study considered the ARs and QPLs useful for most, but not all contexts. Recommendations regarding delivery and use highlight that these resources should be tailored and patient‐driven. Further, patients foresaw a range of additional uses for consultation ARs within the broader healthcare context.
Dehorning is common in the cattle industry, and there is a need for research evaluating pain mitigation techniques. The objective of this study was to determine the effects of oral meloxicam, a ...non-steroidal anti-inflammatory, on cattle behavior post-dehorning by monitoring the percent of time spent standing, walking, and lying in specific locations within the pen using accelerometers and a remote triangulation device. Twelve calves approximately ten weeks of age were randomized into 2 treatment groups (meloxicam or control) in a complete block design by body weight. Six calves were orally administered 0.5 mg/kg meloxicam at the time of dehorning and six calves served as negative controls. All calves were dehorned using thermocautery and behavior of each calf was continuously monitored for 7 days after dehorning using accelerometers and a remote triangulation device. Accelerometers monitored lying behavior and the remote triangulation device was used to monitor each calf's movement within the pen.
Analysis of behavioral data revealed significant interactions between treatment (meloxicam vs. control) and the number of days post dehorning. Calves that received meloxicam spent more time at the grain bunk on trial days 2 and 6 post-dehorning; spent more time lying down on days 1, 2, 3, and 4; and less time at the hay feeder on days 0 and 1 compared to the control group. Meloxicam calves tended to walk more at the beginning and end of the trial compared to the control group. By day 5, the meloxicam and control group exhibited similar behaviors.
The noted behavioral changes provide evidence of differences associated with meloxicam administration. More studies need to be performed to evaluate the relationship of behavior monitoring and post-operative pain. To our knowledge this is the first published report demonstrating behavioral changes following dehorning using a remote triangulation device in conjunction with accelerometers.
A computer program for the recording of data and calculation of results from leukapheresis and plateletpheresis procedures is described. It provides a printout of cell yields and other results for ...each procedure, as well as an updated list of donors and phereses. The data are kept on tape, accessible for periodic statistical analysis. While primarily set up for use with Haemonetics (intermittent-flow centrifugation) equipment, the program is adaptable for other systems.
Dehorning is a common practice involving calves on dairy operations in the United States. However, less than 20% of producers report using analgesics or anesthetics during dehorning. Administration ...of a systemic analgesic drug at the time of dehorning may be attractive to dairy producers since cornual nerve blocks require 10 - 15 min to take effect and only provide pain relief for a few hours. The primary objectives of this trial were to (1) describe the compartmental pharmacokinetics of meloxicam in calves after IV administration at 0.5 mg/kg and (2) to determine the effect of meloxicam (n = 6) or placebo (n = 6) treatment on serum cortisol response, plasma substance P (SP) concentrations, heart rate (HR), activity and weight gain in calves after scoop dehorning and thermocautery without local anesthesia.
Plasma meloxicam concentrations were detectable for 50 h post-administration and fit a 2-compartment model with a rapid distribution phase (mean T(1/2α) = 0.22 ± 0.087 h) and a slower elimination phase (mean T(1/2β) = 21.86 ± 3.03 h). Dehorning caused a significant increase in serum cortisol concentrations and HR (P < 0.05). HR was significantly lower in the meloxicam-treated calves compared with placebo-treated calves at 8 h (P = 0.039) and 10 h (P = 0.044) after dehorning. Mean plasma SP concentrations were lower in meloxicam treated calves (71.36 ± 20.84 pg/mL) compared with control calves (114.70 ± 20.84 pg/mL) (P = 0.038). Furthermore, the change in plasma SP from baseline was inversely proportional to corresponding plasma meloxicam concentrations (P = 0.008). The effect of dehorning on lying behavior was less significant in meloxicam-treated calves (p = 0.40) compared to the placebo-treated calves (P < 0.01). Calves receiving meloxicam prior to dehorning gained on average 1.05 ± 0.13 kg bodyweight/day over 10 days post-dehorning compared with 0.40 ± 0.25 kg bodyweight/day in the placebo-treated calves (p = 0.042).
To our knowledge, this is the first published report examining the effects of meloxicam without local anesthesia on SP, activity and performance of calves post-dehorning. These findings suggest that administration of meloxicam alone immediately prior to dehorning does not mitigate signs of acute distress but may have long term physiological, behavior and performance effects.
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