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Our recent work highlights unique requirements for the induction of Th17 cells at the oral/gingival mucosal barrier. Unlike other barrier sites, such as the skin and gastrointestinal tract, we found that Th17 cells can develop at the gingiva independently of commensal microbiota colonization. Instead, we identified that damage, which occurs physiologically due to mastication, promotes induction of Th17 cells and tones homeostatic immunity at the gingiva. [ABSTRACT FROM AUTHOR]

Systemic immune responses caused by chronic hypercholesterolaemia contribute to atherosclerosis initiation, progression and complications 1 . However, individuals often change their dietary habits over time 2 , and the effects of an alternating high-fat diet (HFD) on atherosclerosis remain unclear. Here, to address this relevant issue, we developed a protocol using atherosclerosis-prone mice to compare an alternating versus continuous HFD while maintaining similar overall exposure periods. We found that an alternating HFD accelerated atherosclerosis in Ldlr -/- and Apoe -/- mice compared with a continuous HFD. This pro-atherogenic effect of the alternating HFD was also observed in Apoe -/- Rag2 -/- mice lacking T, B and natural killer T cells, ruling out the role of the adaptive immune system in the observed phenotype. Discontinuing the HFD in the alternating HFD group downregulated RUNX1 3 , promoting inflammatory signalling in bone marrow myeloid progenitors. After re-exposure to an HFD, these cells produced IL-1β, leading to emergency myelopoiesis and increased neutrophil levels in blood. Neutrophils infiltrated plaques and released neutrophil extracellular traps, exacerbating atherosclerosis. Specific depletion of neutrophils or inhibition of IL-1β pathways abolished emergency myelopoiesis and reversed the pro-atherogenic effects of the alternating HFD. This study highlights the role of IL-1β-dependent neutrophil progenitor reprogramming in accelerated atherosclerosis induced by alternating HFD., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Andean highland soils contain significant quantities of soil organic carbon (SOC); however, more efforts still need to be made to understand the processes behind the accumulation and persistence of SOC and its fractions. This study modeled SOC variables-SOC, refractory SOC (RSOC), and the 13 C isotope composition of SOC (δ 13 C SOC )-using machine learning (ML) algorithms in the Central Andean Highlands of Peru, where grasslands and wetlands ("bofedales") dominate the landscape surrounded by Junin National Reserve. A total of 198 soil samples (0.3 m depth) were collected to assess SOC variables. Four ML algorithms-random forest (RF), support vector machine (SVM), artificial neural networks (ANNs), and eXtreme gradient boosting (XGB)-were used to model SOC variables using remote sensing data, land-use and land-cover (LULC, nine categories), climate topography, and sampled physical-chemical soil variables. RF was the best algorithm for SOC and δ 13 C SOC prediction, whereas ANN was the best to model RSOC. "Bofedales" showed 2-3 times greater SOC (11.2 ± 1.60%) and RSOC (1.10 ± 0.23%) and more depleted δ 13 C SOC (- 27.0 ± 0.44 ‰) than other LULC, which reflects high C persistent, turnover rates, and plant productivity. This highlights the importance of "bofedales" as SOC reservoirs. LULC and vegetation indices close to the near-infrared bands were the most critical environmental predictors to model C variables SOC and δ 13 C SOC . In contrast, climatic indices were more important environmental predictors for RSOC. This study's outcomes suggest the potential of ML methods, with a particular emphasis on RF, for mapping SOC and its fractions in the Andean highlands., Supplementary Information: The online version contains supplementary material available at 10.1007/s10021-024-00928-7., (© The Author(s) 2024.)

In high-risk myeloid malignancy, relapse is reduced using cord blood transplant (CBT) but remains the principal cause of treatment failure. We previously described T-cell expansion in CBT recipients receiving granulocyte transfusions. We now report the safety and tolerability of such transfusions, T-cell expansion data, immunophenotype, cytokine profiles and clinical response in children with post-transplant relapsed acute leukaemia who received T-replete, HLA-mismatched CBT and pooled granulocytes within a phase I/II trial (ClinicalTrials.Gov NCT05425043). All patients received the transfusion schedule without significant clinical toxicity. Nine of ten patients treated had detectable measurable residual disease (MRD) pre-transplant. Nine patients achieved haematological remission, and eight became MRD negative. There were five deaths: transplant complications (n = 2), disease (n = 3), including two late relapses. Five patients are alive and in remission with 12.7 months median follow up. Significant T-cell expansion occurred in nine patients with a greater median lymphocyte count than a historical cohort between days 7-13 (median 1.73 × 10 9 /L vs. 0.1 × 10 9 /L; p < 0.0001). Expanded T-cells were predominantly CD8 + and effector memory or TEMRA phenotype. They exhibited markers of activation and cytotoxicity with interferon-gamma production. All patients developed grade 1-3 cytokine release syndrome (CRS) with elevated serum IL-6 and interferon-gamma., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Understanding how conservation agricultural management improves soil nitrogen (N) stability in the face of climate change can help increase agroecosystem productivity and mitigate runoff, leaching and downstream water quality issues. We conducted a 2-year field study in a 36-year-old rain-fed cotton production system to evaluate the impacts of changing climatic factors (temperature and precipitation) on soil N under conservation management, including moderate inorganic N fertilizer application (0 and 67 kg N ha -1 ), winter cover crops (fallow; winter wheat, Triticum aestivum L.; hairy vetch, Vicia villosa Roth), and reduced tillage (no-till; disk tillage). Structural equation modeling (SEM) was used to quantify and compare the effects of conservation management and climatic factors on soil N concentrations. Fertilizer and vetch cover crops increased soil total N concentration by 16% and 18%, respectively, and also increased microbial N transformation rate by 41% and 168%. In addition, vetch cover crops also increased soil labile N concentrations by 57%, 21%, and 79%, i.e., extractable organic N, ammonium, and nitrate, respectively. The highest soil δ 15 N value (6.4 ± 0.3‰) was observed under the 67 kg N ha -1 fertilizer-wheat-disk tillage treatment, and the lowest value (4.8 ± 0.3‰) under the zero-fertilizer-wheat-no-till treatment, indicating fertilizer and tillage might accelerate microbial N transformation. The SEM showed positive effects of temperature and precipitation on labile N concentrations, suggesting destabilization of soil N and the potential for soil N loss under increased temperature and intensified precipitation. Fertilizer and vetch use might mitigate some of the effects of temperature by accelerating microbial N transformations, with vetch having a larger effect than fertilizer (0.35 vs. 0.15, Table 1). No-till can reduce some of the effects of precipitation on soil labile N by maintaining soil structure. Our study suggests that fertilizer, vetch cover crop, and no-till might help improve function and resilience of agroecosystems in relation to soil N cycling. Soil N stabilization in cropping systems can be enhanced by adjusting agricultural management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Marijuana is the most widely used illicit substance during pregnancy. Technology-delivered brief interventions and text messaging have shown promise in general and pregnant samples but have not yet been applied to marijuana use in pregnancy., Objective: The objective of the study was to evaluate, among pregnant women and prenatal care providers, the acceptability of an electronic brief intervention and text messaging plan for marijuana use in pregnancy., Methods: Participants included patients (n=10) and medical staff (n=12) from an urban prenatal clinic. Patient-participants were recruited directly during a prenatal care visit. Those who were eligible reviewed the interventions individually and provided quantitative and qualitative feedback regarding software acceptability and helpfulness during a one-on-one interview with research staff. Provider-participants took part in focus groups in which the intervention materials were reviewed and discussed. Qualitative and focus group feedback was transcribed, coded manually, and classified by category and theme., Results: Patient-participants provided high ratings for satisfaction, with mean ratings for respectfulness, interest, ease of use, and helpfulness ranging between 4.4 and 4.7 on a 5-point Likert scale. Of the 10 participants, 5 reported that they preferred working with the program versus their doctor, and 9 of 10 said the intervention made them more likely to reduce their marijuana use. Provider-participants received the program favorably, stating the information presented was both relevant and important for their patient population., Conclusions: The findings support the acceptability of electronic brief intervention and text messaging for marijuana use during pregnancy. This, combined with their ease of use and low barrier to initiation, suggests that further evaluation in a randomized trial is appropriate., (©Justin Gray, Jessica R Beatty, Dace S Svikis, Karoline S Puder, Ken Resnicow, Janine Konkel, Shetoya Rice, Lucy McGoron, Steven J Ondersma. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 08.11.2017.)

Leukocyte adhesion deficiency type I (LAD-I), a disease syndrome associated with frequent microbial infections, is caused by mutations on the CD18 subunit of β₂ integrins. LAD-I is invariably associated with severe periodontal bone loss, which historically has been attributed to the lack of neutrophil surveillance of the periodontal infection. We provide an alternative mechanism by showing that the cytokine interleukin-17 (IL-17) plays a major role in the oral pathology of LAD-I. Defective neutrophil recruitment in LAD-I patients or in LFA-1 (CD11a/CD18)-deficient mice--which exhibit the LAD-I periodontal phenotype--was associated with excessive production of predominantly T cell-derived IL-17 in the periodontal tissue, although innate lymphoid cells also contributed to pathological IL-17 elevation in the LFA-1-deficient mice. Local treatment with antibodies to IL-17 or IL-23 in LFA-1-deficient mice not only blocked inflammatory periodontal bone loss but also caused a reduction in the total bacterial burden, suggesting that the IL-17-driven pathogenesis of LAD-I periodontitis leads to dysbiosis. Therefore, our findings support an IL-17-targeted therapy for periodontitis in LAD-I patients.

Background: Web-based programs for health promotion, disease prevention, and disease management often experience high rates of attrition. There are 3 questions which are particularly relevant to this issue. First, does engagement with program content predict long-term outcomes? Second, which users are most likely to drop out or disengage from the program? Third, do particular intervention strategies enhance engagement?, Objective: To determine: (1) whether engagement (defined by the number of Web sections opened) in a Web-based smoking cessation intervention predicts 6-month abstinence, (2) whether particular sociodemographic and psychographic groups are more likely to have lower engagement, and (3) whether particular components of a Web-based smoking cessation program influence engagement., Methods: A randomized trial of 1866 smokers was used to examine the efficacy of 5 different treatment components of a Web-based smoking cessation intervention. The components were: high- versus low-personalized message source, high- versus low-tailored outcome expectation, efficacy expectation, and success story messages. Moreover, the timing of exposure to these sections was manipulated, with participants randomized to either a single unified Web program with all sections available at once, or sequential exposure to each section over a 5-week period of time. Participants from 2 large health plans enrolled to receive the online behavioral smoking cessation program and a free course of nicotine replacement therapy (patch). The program included: an introduction section, a section focusing on outcome expectations, 2 sections focusing on efficacy expectations, and a section with a narrative success story (5 sections altogether, each with multiple screens). Most of the analyses were conducted with a stratification of the 2 exposure types. Measures included: sociodemographic and psychosocial characteristics, Web sections opened, perceived message relevance, and smoking cessation 6-months following quit date., Results: The total number of Web sections opened was related to subsequent smoking cessation. Participants who were younger, were male, or had less formal education were more likely to disengage from the Web-based cessation program, particularly when the program sections were delivered sequentially over time. More personalized source and high-depth tailored self-efficacy components were related to a greater number of Web sections opened. A path analysis model suggested that the impact of high-depth message tailoring on engagement in the sequentially delivered Web program was mediated by perceived message relevance., Conclusions: Results of this study suggest that one of the mechanisms underlying the impact of Web-based smoking cessation interventions is engagement with the program. The source of the message, the degree of message tailoring, and the timing of exposure appear to influence Web-based program engagement.

Background: Tailored health communications to date have been based on a rather narrow set of theoretical constructs., Purpose: This study was designed to test whether tailoring a print-based fruit and vegetable (F & V) intervention on relatively novel constructs from self-determination theory (SDT) and motivational interviewing (MI) increases intervention impact, perceived relevance, and program satisfaction. The study also aimed to explore possible user characteristics that may moderate intervention response., Methods: African American adults were recruited from two integrated health care delivery systems, one based in the Detroit Metro area and the other in the Atlanta Metro area, and then randomized to receive three tailored newsletters over 3 months. One set of newsletters was tailored only on demographic and social cognitive variables (control condition), whereas the other (experimental condition) was tailored on SDT and MI principles and strategies. The primary focus of the newsletters and the primary outcome for the study was fruit and vegetable intake assessed with two brief self-report measures. Preference for autonomy support was assessed at baseline with a single item: "In general, when it comes to my health I would rather an expert just tell me what I should do". Most between-group differences were examined using change scores., Results: A total of 512 (31%) eligible participants, of 1,650 invited, were enrolled, of which 423 provided complete 3-month follow-up data. Considering the entire sample, there were no significant between-group differences in daily F & V intake at 3 month follow-up. Both groups showed similar increases of around one serving per day of F & V on the short form and half a serving per day on the long form. There were, however, significant interactions of intervention group with preference for autonomy-supportive communication as well as with age. Specifically, individuals in the experimental intervention who, at baseline, preferred an autonomy-supportive style of communication increased their F & V intake by 1.07 servings compared to 0.43 servings among controls. Among younger controls, there was a larger change in F & V intake, 0.59 servings, than their experimental group counterparts, 0.29 servings. Conversely, older experimental group participants showed a larger change in F & V, 1.09 servings, than older controls, 0.48., Conclusion: Our study confirms the importance of assessing individual differences as potential moderators of tailored health interventions. For those who prefer an autonomy-supportive style of communication, tailoring on values and other motivational constructs can enhance message impact and perceived relevance.

The purpose of this study is to assess the impact of real refractive indices, using different itraconazole suspensions, on the associated particle size distributions. Instrumental particle size measurement remains the practical option for determining the particle size distribution of a suspension. In this study, the suspension particle size distribution was measured by static light scattering, which requires knowledge of both the real and imaginary components of the complete refractive index. The real refractive indices of micronized itraconazole raw material, as well as vacuum-dried itraconazole suspension samples obtained from different formulations, polymorphs, manufacturing methods and particle size distributions, were determined using the Becke line method. Identical samples were analyzed by two contract laboratories in order to assess consistency. For the static light scattering equipment used in this study, the complete relative refractive index (RRI = n(particte) / n(dispersant) - ik) input required for software calculation is denoted by a refractive index kernel (RRI input) comprising a relative real component and an imaginary component. The reported real refractive indices for the itraconazole raw material as well as vacuum dried itraconazole suspension samples were different, ranging from 1.608 to 1.65 (selected kernel range of 120A010I to 124A010I). The imaginary component of itraconazole suspension was determined in a previous study to be 010I. The average real refractive index was calculated to be 1.62 (122A010I). The particle size distributions obtained using 120A010I and 124A010I were in good agreement with one generated using 122A010I. Therefore, itraconazole suspensions that were produced using different manufacturing methods/formulations or exhibited different particle size distributions/polymorphic forms may use 122A010I in determining particle size distribution. The particle size distributions determined using RRI input outside the range of 120A010I to 124A010I may not be reliable. However, it is recommended that similar investigations be conducted for other drug suspensions on a case-by-case basis.

A high performance liquid chromatography (HPLC) method for Poloxamer 188 using size-exclusion chromatography (SEC) was developed and two different detection mechanisms, evaporative light scattering (ELSD) and electrospray ionization mass spectrometry (ESI-MS), were compared for their quantification capabilities in itraconazole formulation. Both detection techniques coupled with SEC separation were highly effective for the determination of Poloxamer 188, which is difficult to analyze by other common HPLC methods. As expected, ESI-MS detection provided sensitivity and selectivity superior to ELSD. But since the analyte is an excipient in the formulation, high sensitivity was not required and ELSD's simplicity and ruggedness made it more appropriate for routine analysis of this formulation.