Learning to love the null

Children’s behaviour and mental health has the power to surprise us, readers and authors of the Journal of Child Psychology and Psychiatry and laymen alike, if not for the endless variation among people, then for the ever-changing context in which they develop. The hypothetico-deductive method in combination with null-hypothesis significance testing has turned surprise into scientific knowledge. Null effects may in themselves also be surprising and informative, but appear less well represented in the literature. This editorial highlights emerging methodological practices for studying null effects in the most informative way.     

MPGES-1-derived PGE2 suppresses CD80 expression on tumor-associated phagocytes to inhibit anti-tumor immune responses in breast cancer

Prostaglandin E₂ (PGE₂) favors multiple aspects of tumor development and immune evasion. Therefore, microsomal prostaglandin E synthase (mPGES-1/-2), is a potential target for cancer therapy. We explored whether inhibiting mPGES-1 in human and mouse models of breast cancer affects tumor-associated immunity. A new model of breast tumor spheroid killing by human PBMCs was developed. In this model, tumor killing required CD80 expression by tumor-associated phagocytes to trigger cytotoxic T cell activation. Pharmacological mPGES-1 inhibition increased CD80 expression, whereas addition of PGE₂, a prostaglandin E2 receptor 2 (EP2) agonist, or activation of signaling downstream of EP2 reduced CD80 expression. Genetic ablation of mPGES-1 resulted in markedly reduced tumor growth in PyMT mice. Macrophages of mPGES-1^−/− PyMT mice indeed expressed elevated levels of CD80 compared to their wildtype counterparts. CD80 expression in tumor-spheroid infiltrating mPGES-1^−/− macrophages translated into antigen-specific cytotoxic T cell activation. In conclusion, mPGES-1 inhibition elevates CD80 expression by tumor-associated phagocytes to restrict tumor growth. We propose that mPGES-1 inhibition in combination with immune cell activation might be part of a therapeutic strategy to overcome the immunosuppressive tumor microenvironment.     

An integrative approach for the identification of prognostic and predictive biomarkers in rectal cancer

Introduction

Colorectal cancer is the third most common cancer in the world, a small fraction of which is represented by locally advanced rectal cancer (LARC). If not medically contraindicated, preoperative chemoradiotherapy, represent the standard of care for LARC patients. Unfortunately, patients shows a wide range of response rates in which approximately 20% has a complete pathological response, whereas in 20 to 40% the response is poor or absent.

Results

The following specific gene signature, able to discriminate responders'' patients from non-responders, were founded: AKR1C3, CXCL11, CXCL10, IDO1, CXCL9, MMP12 and HLA-DRA. These genes are mainly involved in immune system pathways and interact with drugs traditionally used in the adjuvant treatment of rectal cancer.

Discussion

The present study suggests that new ideas for therapy could be found not only limited to studying genes differentially expressed between the two groups of patients but deepening the mechanisms, associated to response, in which they are involved.

Methods

Gene expression studies performed by: Agostini et al., Rimkus et al. and Kim et al. have been merged through a meta-analysis of the raw data. Gene expression data-sets have been processed using A-MADMAN. Common differentially expressed gene (DEG) were identified through SAM analysis. To further characterize the identified DEG we deeply investigated its biological role using an integrative computational biology approach.     

Interaction of child disability and stressful life events in predicting maternal psychological health. Results of an area-based study of very preterm infants at two years corrected age

This study aimed at exploring the relationship between severe neuromotor and/or sensory disability in very preterm infants assessed at 2 years corrected age and their mothers’ psychological health. Data on 581 Italian singletons born at 22–31 weeks of gestation in five Italian regions and their mothers were analyzed. Maternal psychological distress was measured through the General Health Questionnaire short version (GHQ-12). The prevalence of any maternal distress (GHQ scores ≥ 2) and of clinical distress (scores ≥ 5) were 31.3% and 8.1% respectively. At multivariable analysis, we found a statistically significant association between child's disability and mothers’ GHQ scoring ≥5 (OR 3.45, 95% CI 1.07–11.15). Also lower maternal education appeared to increase the likelihood of psychological distress (OR 1.38, 95% CI 1.14–1.66). The impact of child disability was weaker in women who had experienced additional stressful life events since delivery, pointing to the existence of a “ceiling” effect. Maternal psychological assessment and support should be included in follow-up programs targeting very preterm infants.     

The processing of compounds in bilingual aphasia: A multiple‐case study

Background: While converging evidence has led to the view that people with aphasia exploit compositional procedures when producing compound words, the issue of what compound‐internal characteristics are at play during these procedures is still under debate. It has been argued that constituent position and/or morphosyntactic prominence, i.e., being the head constituent of a compound, may influence the manner in which compounds are accessed. However, findings obtained from patient performances are thus far inconclusive, because positional and headedness effects are frequently confounded in a language.

Aims: In order to disentangle position‐in‐the‐string and headedness effects in compound production in aphasia, the main objective of this study is to investigate the performance of bilingual patients speaking languages in which these effects can be teased apart. Our secondary goal is to probe the roles of grammatical category (adjectives vs nouns) and of between‐language phonological similarity, as both these factors have been demonstrated to influence compound processing.

Methods & Procedures: Three English–French bilingual persons with aphasia participated in the study. Three experimental tasks, reading, repetition, and translation of isolated compound words, were administrated in each language. We contrasted French and English compounds that differ in the position of the head constituent: left for French and right for English.

Outcomes & Results: Two participants showed a similar pattern—a significantly reduced number of errors for the head (or first) constituent as compared to the non‐head (or second) constituent in French and an equivalent number of errors for both constituents in English—pointing to the cumulative effects of headedness and first‐position‐in‐the‐string in French, and to the mutual cancelling out of these effects in English. The third participant exhibited a non‐head constituent advantage in both languages, indicating that semantic modification of the head constituent by the non‐head constituent plays a prominent role in her accessing procedures. For all three participants phonological similarity influenced production, while grammatical category did not.

Conclusions: Our results reveal that headedness and position interact in the processing of compounds. They also demonstrate that compound constituents are processed asymmetrically across and within languages, thus confirming that people with aphasia are sensitive to compound‐internal structure. Moreover, they show that patients rely on varying structural information when accessing compounds.     

Automation and validation of a fast method for the assessment of in vivo oxidative stress levels.

BACKGROUND: The d-ROMs test for the evaluation of serum hydroperoxides (HP) is simple, reliable, and cheap. Furthermore, it can easily be adapted to automated analyzers. Changing from the manual to an automated procedure allows the simultaneous processing of a large number of samples in a greatly reduced time, avoiding manual handling of samples and reagents and reducing variability sources. METHODS: This study was performed to adjust the manual procedure to a routine automated method in the clinical laboratory. We carried out the d-ROMs test in sera from 90 subjects of both sexes (34 men and 56 women) with age ranging from 20 to 80 years (mean 51+/-14 years). All subjects were free from acute or chronic inflammatory disease, immunological disease and history or evidence of malignancy. Subjects were not on vitamin and/or antioxidant therapies. RESULTS: The detection limit of the assay was 40 AU. Linearity was observed up to 475 AU. The recovery ranged between 97% and 105%. Within- and between-run imprecision was <5%. The mean HP value was 304+/-8 AU, with no significant difference between men (291+/-10 AU) and women (311+/-11 AU). A significant positive correlation was observed between age and HP in the whole population (r=0.4, p=0.0002). CONCLUSIONS: The automated test for the estimation of serum hydroperoxides represents a reliable and feasible procedure for increasing efficiency and reducing costs compared to the manual method, and is particularly suitable for evaluating oxidative stress in a variety of clinical conditions.