HMGB1 promotes CXCL12-dependent egress of murine B cells from Peyer's patches in homeostasis

High mobility group box-1 protein (HMGB1) is an alarmin that, once released, promotes inflammatory responses, alone and as a complex with the chemokine CXCL12. Here, we report that the HMGB1–CXCL12 complex plays an essential role also in homeostasis by controlling the migration of B lymphocytes. We show that extracellular HMGB1 is critical for the CXCL12-dependent egress of B cells from the Peyer's patches (PP). This promigratory function of the complex was restricted to the PPs, since HMGB1 was not required for B-cell migratory processes in other locations. Accordingly, we detected higher constitutive levels of the HMGB1–CXCL12 complex in PPs than in other lymphoid organs. HMGB1–CXCL12 in vivo inhibition was associated with a reduced basal IgA production in the gut. Collectively, our results demonstrate a role for the HMGB1–CXCL12 complex in orchestrating B-cell trafficking in homeostasis, and provide a novel target to control lymphocyte migration in mucosal immunity.     

ALPK1 Gene Mutations Drive Autoinflammation with Ectodermal Dysplasia and Progressive Vision Loss

Journal of Clinical Immunology -     

Late-Onset Progressive Multifocal Leukoencephalopathy (PML) and Lymphoma in a 65-Year-Old Patient with XIAP Deficiency

Journal of Clinical Immunology -     

Chemoradiation-induced changes in systemic inflammatory markers and their prognostic significance in oesophageal squamous cell carcinoma

Objective:Chemoradiation (CRT) may induce a change in systemic inflammatory state which could affect clinical outcomes in oesophageal cancer. We aimed to evaluate the changes and prognostic significance of systemic inflammatory markers following definitive CRT in oesophageal squamous cell carcinoma.Methods:A total of 53 patients treated with concurrent CRT were included in this retrospective analysis. We compared neutrophils, lymphocytes, platelets, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) before and after CRT using Wilcoxon signed-rank test. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariable and multivariable survival analysis were performed using Cox regression analysis. Clinical univariable survival prognostic factors with p < 0.1 were included in a multivariable cox regression analysis for backward stepwise model selection.Results:Both NLR (median ∆+2.8 [IQR −0.11, 8.62], p < 001) and PLR (median ∆+227 [81.3–523.5], p < 0.001) increased significantly after CRT. Higher levels of pre-CRT, post-CRT and change (∆) in NLR and PLR were associated with inferior OS and PFS. Post-CRT NLR (HR 1.04, 95% CI 1.02–1.07, p < 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.005), cT-stage (HR 3.83, 95% CI 1.39–10.60, p = 0.01) and RT dose (HR 0.41, 95% CI 0.21–0.81, p = 0.01) were independent prognostic factors for OS in multivariable analysis. Change in NLR (HR 1.04, 95% CI 1.01–1.06, p = 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.002), cT-stage (HR 3.98, 95% CI 1.55–10.25, p = 0.004) and RT dose (HR 0.41, 95% CI 0.21–0.80, p = 0.009) were independent prognostic factors for PFS.Conclusion:Both NLR and PLR increased following definitive CRT. Post-CRT NLR and ∆NLR were associated with adverse survival in oesophageal SCC.Advances in knowledge:We showed that CRT increased PLR and NLR, possibly reflecting a systemic inflammatory state which were associated with poor clinical outcomes in oesophageal SCC.     

Osteochondroma of the mandibular condyle: Indications for different surgical methods: A case series of 7 patients

The aim of this study was to evaluate and discuss the long-term outcomes of patients with condylar osteochondroma managed through 3 different surgical techniques.Seven patients with condylar osteochondroma treated in the author's department from May 2012 to January 2019 were included in this retrospective study. Clinical evaluations (visual analogue scale for TMJ pain, jaw function, symmetry, and quality of life), maximum interincisal opening (MIO) and radiological findings were collected pre- and postoperatively. Other parameters assessed included tumour size and location; complications and follow-up. Radical condylectomy with immediate total joint alloplastic reconstruction was performed in 4 patients, local excision in 2 patients and low condylectomy with concomitant orthognathic surgery in 1 patient. During an average follow-up period of 40,8 months no clinical or radiographic signs of recurrence were found. Average MIO increased from 25,5mm to 39,5mm at the longest follow up, and all clinical evaluations were greatly improved.In conclusion, the described surgical techniques appear valuable in the treatment of condylar osteochondroma. Local excision is indicated in tumor involving less than half the surface of the condylar head; radical condylectomy with immediate alloplastic total joint reconstruction is indicated in gigantic lesion compromising the anatomical components and function of the joint. Orthognathic surgery procedures should be combined with tumor resection when correction of associated dentofacial deformities is indicated.     

Expectancies, Socioeconomic Status, and Self-Rated Health: Use of the Simplified TOMCATS Questionnaire

Background

Coping has traditionally been measured with inventories containing many items meant to identify specific coping strategies. An alternative is to develop a shorter inventory that focusses on coping expectancies which may determine the extent to which an individual attempts to cope actively.

Purpose

This paper explores the usefulness and validity of a simplified seven-item questionnaire (Theoretically Originated Measure of the Cognitive Activation Theory of Stress, TOMCATS) for response outcome expectancies defined either as positive (“coping”), negative (“hopelessness”), or none (“helplessness”). The definitions are based on the Cognitive Activation Theory of Stress (CATS; Ursin and Eriksen, Psychoneuroendocrinology, 29(5):567–92, 2004). The questionnaire was tested in two different samples. First, the questionnaire was compared with a traditional test of coping and then tested for validity in relation to socioeconomic differences in self-reported health.

Methods

The first study was a comparison of the brief TOMCATS with a short version of the Utrecht Coping List (UCL; Eriksen et al., Scand J Psychol, 38(3):175–82, 1997). Both questionnaires were tested in a population of 1,704 Norwegian municipality workers. The second study was a cross-sectional analysis of TOMCATS, subjective and objective socioeconomic status, and health in a representative sample of the Swedish working population in 2003–2005 (N?=?11,441).

Results

In the first study, the coping item in the TOMCATS questionnaire showed an expected significant positive correlation with the UCL factors of instrumental mastery-oriented coping and negative correlations with passive and depressive scores. There were also the expected correlations for the helplessness and hopelessness scores, but there was no clear distinction between helplessness and hopelessness in the way they correlated with the UCL. In the second study, the coping item in TOMCATS and the three-item helplessness scores showed clear and monotonous gradients over a subjective socioeconomic status (SES) ladder. Positive response outcome expectancy (“coping”) was related to high subjective SES and no expectancy (“helplessness”) to low subjective SES. In a model including age and sex, TOMCATS scores explained more variance (r ²?=?0.16) in self-reported health than both subjective (r ²?=?0.08) and objective SES (r ²?=?0.02).

Conclusion

The brief TOMCATS questionnaire showed acceptable and significant correlations with a traditional coping questionnaire and is sensitive enough to register systematic differences in response outcome expectancies across the socioeconomic ladder. The results furthermore confirm that psychological and learning factors contribute to the socioeconomic gradient in health.     

Development of a Smoking Abstinence Self-efficacy Questionnaire

Background

Self-efficacy beliefs are an important determinant of (changes in) health behaviors. In the area of smoking cessation, there is a need for a short, feasible, and validated questionnaire measuring self-efficacy beliefs regarding smoking cessation.

Purpose

The purpose of this study is to investigate the psychometric properties of a six-item questionnaire to assess smoking cessation self-efficacy.

Methods

We used longitudinal data from a smoking cessation study. A total of 513 smokers completed the Smoking Abstinence Self-efficacy Questionnaire (SASEQ) and questionnaires assessing depressive symptoms and motivation to quit smoking. After that, they set a quit date and attempted to stop smoking. One year after the quit date, smoking status of participants was assessed by self report. The psychometric properties of the SASEQ were studied and we investigated whether SASEQ scores predicted successful smoking cessation.

Results

Factor analysis yielded one factor, with an Eigenvalue of 3.83, explaining 64% of variance. All factor loadings were ≥0.73. We found a Cronbach’s alpha of 0.89 for the SASEQ, low correlations for the SASEQ with depressive symptoms, and motivation to quit, indicating that self-efficacy is measured independently of these concepts. Furthermore, high baseline SASEQ scores significantly predicted smoking abstinence at 52 weeks after the quit date (OR?=?1.85; 95% CI?=?1.20~2.84).

Conclusions

The SASEQ appeared to be a short, reliable, and valid questionnaire to assess self-efficacy beliefs regarding smoking abstinence. In the present study, this instrument also had good predictive validity. The short SASEQ can easily be used in busy clinical practice to guide smoking cessation interventions.     

Effects of a Cognitive–Behaviorally Based Physical Activity Treatment for 4- and 5-Year-Old Children Attending US Preschools

Background

Inadequate volumes of physical activity may be associated with the increases in inappropriately high weight in children of 5 years of age and younger. Preschools have typically lacked sufficient time in daily physical activity.

Purpose

A preschool-administered physical activity treatment based on social cognitive and self-efficacy theory (Start For Life) was tested for its association with increased physical activity and reduced body mass index (BMI).

Methods

Data from accelerometer and BMI assessments over a 9-month preschool year (18 treatment and 8 control classes of 17 to 20 children each; mean age?=?4.4 years) were used to contrast the behaviorally based treatment of 30 min per day with a usual care condition of the same duration. The sample was primarily African-American. Preschool teachers administered all processes.

Results

The Start For Life treatment was associated with a significantly greater percentage of the preschool day in moderate-to-vigorous and vigorous physical activity (approximately 30 min per week more), with sedentary time unaffected. The treatment was also associated with a significant reduction in BMI, with effect sizes greatest in overweight and obese children.

Conclusions

Although results were positive in contrast to usual care and other related interventions, the specific sample requires that the Start For Life treatment undergo sufficient replication to increase confidence in generalizability of the findings to others. Although reduction in sedentary time may require a different strategy, the practical application of the present treatment suggests possibilities for addressing overweight through increasing moderate-to-vigorous physical activity in preschool settings.     

Updated model of group A Streptococcus M proteins based on a comprehensive worldwide study

Group A Streptococcus (GAS) M protein is an important virulence factor and potential vaccine antigen, and constitutes the basis for strain typing (emm-typing). Although >200 emm-types are characterized, structural data were obtained from only a limited number of emm-types. We aim to evaluate the sequence diversity of near-full-length M proteins from worldwide sources and analyse their structure, sequence conservation and classification. GAS isolates recovered from throughout the world during the last two decades underwent emm-typing and complete emm gene sequencing. Predicted amino acid sequence analyses, secondary structure predictions and vaccine epitope mapping were performed using MUSCLE and Geneious software. A total of 1086 isolates from 31 countries were analysed, representing 175 emm-types. emm-type is predictive of the whole protein structure, independent of geographical origin or clinical association. Findings of an emm-type paired with multiple, highly divergent central regions were not observed. M protein sequence length, the presence or absence of sequence repeats and predicted secondary structure were assessed in the context of the latest vaccine developments. Based on these global data, the M6 protein model is updated to a three representative M protein (M5, M80 and M77) model, to aid in epidemiological analysis, vaccine development and M protein-related pathogenesis studies.