The αβ T Cell Receptor Clustering Upon Superantigen/MHC Recognition

Antigen recognition by T cells is the key event for the antigen specific immune responses to be triggered. This recognition is initiated by the binding of the T cell receptor (TCR) to antigen peptide/major histocompatibility complex (MHC) on the surface of the antigen presenting cells. TCR on most of the T cells is a heterodimer composed of α and β chains which are associated with CD3 γδε as well as ζ chains, the signal transmission molecules. The dynamics of this TCR complex upon antigen/MHC recognition, however, has not been well understood. In this paper the authors analyse the configuration of TCR complex on T cells from a TCR β chain gene transgenic mouse (TGM) strain. Unlike many other TGM strains reported, a considerable proportion of T cells from this TGM expresses both transgene-encoded (Vβ3) and endogenous TCR β chains on their surface. By immunoprecipitation and immunoblotting analysis of T cells stimulated with a superantigen, staphylococcal enterotoxin B (SEB), the authors found that Vβ3 was coprecipitated with Vβ8, demonstrating the clustering of TCR αβ upon superantigen/MHC recognition.     

Ecological-Level Associations Between Highly Processed Food Intakes and Plasma Phospholipid Elaidic Acid Concentrations: Results From a Cross-Sectional Study Within the European Prospective Investigation Into Cancer and Nutrition (EPIC)

Elaidic acid is the main unnatural trans fatty acid isomer occurring during partial hydrogenation of vegetable oils used as ingredients for the formulation of processed foods. The main objective is to assess associations between processed food intakes and plasma phospholipid elaidic acid concentrations within the European Prospective Investigation into Cancer and Nutrition study. A cross-sectional study was used to determine fatty acid profiles in 3,003 subjects from 16 centers. Single 24-h dietary recalls (24-HDR) were collected using a standardized computerized interview program. Food intakes were computed according to their degree of processing (moderately/nonprocessed foods, processed staple foods, highly processed foods). Adjusted ecological and individual correlations were calculated between processed food intakes and plasma elaidic acid levels. At the population level, mean intakes of highly processed foods were strongly correlated with mean levels of plasma elaidic acid in men (P = 0.0016) and in women (P = 0.0012). At the individual level, these associations remained but at a much lower level in men (r = 0.08, P = 0.006) and in women (r = 0.09, P = 0.0001). The use of an averaged 24-HDR measure of highly processed food intakes is adequate for predicting mean levels of plasma elaidic acid among European populations.     

Prevalent diabetes and risk of total,colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium

Background We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity.Methods We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis.Results A total of 667,916 individuals were included with an overall median (P25–P75) age at recruitment of 62.3 (57–67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86–1.04; I² = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08–1.26; I² = 0%) and a similar HR in women (1.13; 95% CI: 0.82–1.56; I² = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77–0.85; I² = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89–1.03; I² = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity.Conclusions Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.Subject terms: Risk factors, Cancer epidemiology     

Olanzapine in the treatment of depression with psychotic features: A prospective open-label study

Objective. Depression with psychotic features is a severe subtype of major depression associated with the presence of delusions, hallucinations and specific neurobiological features. Despite clinical consensus and guideline recommendations, data comparing the efficacy of combining antipsychotics with antidepressants compared to antidepressants alone remain inconclusive. The aim of the study was to investigate effectiveness and tolerability of the atypical antipsychotic olanzapine in acute depression with psychotic features. Methods. Seventeen inpatients with major depressive disorder with psychosis (MDDp) were treated with a combination of an antidepressant and olanzapine for 6 weeks in a prospective open-label study. Depressive and psychotic symptoms, extrapyramidal and general side effects were assessed every 2 weeks. Sixteen patients were eligible for final analysis. Results. The Brief Psychiatric Rating Scale (BPRS) showed a 30% symptom reduction after week 2, a 45% symptom reduction after week 4 and no considerable improvement thereafter. Depressive symptoms (Bech–Rafaelsen Melancholia Scale, BRMS) receded by 37% after week 2 and 50% after week 4. No extrapyramidal side effects occurred. Conclusion. Olanzapine is effective and tolerable in combination with an antidepressant in an MDDp inpatient sample. The results concur with data supporting good efficacy in negative and depressive symptoms of patients with schizophrenic and schizoaffective diseases.     

Association of scientific and nonscientific factors to citation rates of articles of renowned orthopedic journals

Purpose

The physician often relies on the prestige of a journal to identify the most relevant articles to be read in his field. This investigation studied associations of scientific and nonscientific criteria with the citation frequency of articles in two top-ranked international orthopedic journals.

Methods

The 100 most (mean, 88 citations/5 years for cases) and 100 least (mean, two citations/5 years for controls) cited articles published between 2000 and 2004 in the Journal of Bone and Joint Surgery and the Bone & Joint Journal (formerly known as JBJS (Br)), two of the most distributed general orthopedic journals, were identified. The association of scientific and nonscientific factors on their citation rate was quantified.

Results

Randomized controlled trials, as well as multicenter studies with large sample sizes, were significantly more frequent in the high citation rate group. The unadjusted odds of a highly cited article to be supported by industry were 2.8 (95 % confidence interval 1.5, 5.6; p?<?0.05) if compared with a lowly cited article.

Conclusion

Beside scientific factors, nonscientific factors such as industrial support seem associated to the citation rate of published articles. This, together with publication bias, questions whether scientific facts reach the readers in a balanced fashion. Level of Evidence 3     

No influence of brain-derived neurotrophic factor (BDNF) polymorphisms on treatment response in a naturalistic sample of patients with major depression

The role of the brain-derived neurotrophic factor (BDNF) in the pathophysiology of major depressive disorder (MDD) remains to be elucidated. Recent post hoc analyses indicated a potential association of three polymorphisms in the BDNF gene with worse treatment outcome in patients with the subtype of melancholic depression. We aimed at replicating these findings in a German naturalistic multicenter follow-up. Three polymorphisms in the BDNF gene (rs7103411, rs6265 (Val66Met) and rs7124442) were genotyped in 324 patients with MDD and 470 healthy controls. We applied univariate tests and logistic regression models stratifying for depression subtype and gender. The three polymorphisms were not associated with MDD as diagnosis. Further, no associations were found in univariate tests. With logistic regression, we only found a tendency towards an association of the rs6265 (Val66Met) polymorphism with overall response to treatment (response rates: GG (val/val) < GA (val/met) < AA (met/met); p = 0.0129) and some gender differences for the rs6265 (Val66Met) and rs7103411 polymorphisms. Treatment outcome stratified for subtypes of depression did not differ significantly between the investigated polymorphisms or using haplotype analyses. However, results showed a tendency towards significance. At this stage, we cannot support an influence of these three polymorphisms. Further studies in larger patient samples to increase sample sizes of subgroups are warranted.     

Fatal Mycoplasma pneumoniae pneumonia in a previously healthy 18-year-old girl

A case of fatal Mycoplasma pneumoniae pneumonia in a previously healthy 18-year-old girl is reported. On hospital day 9, the antibody titer to M. pneumoniae was 1:512 in the complement fixation test and 1:5120 in the microparticle agglutination assay. After five weeks in the intensive care unit, the patient died from necrotizing hemorrhagic pneumonia with multi-organ failure. No significant superinfections occurred during ICU treatment. Corticosteroids (hospital day 8 onward) did not influence the course of the disease. It is noteworthy that, as in some previously reported cases, the clinical state deteriorated during presumably adequate antibiotic treatment (2 days before admission onward), and despite documented eradication of the pathogen from the respiratory tract (PCR from bronchoalveolar fluid on hospital day 22 was negative). However, the illness had lasted for several days before admission to the hospital, therefore the potentially beneficial effect of antibiotic treatment at an early stage of the disease cannot be assessed. Clearly, in default of other treatment options, correct diagnosis and early treatment of mycoplasma community-acquired pneumonia seems mandatory. This is the third case of fatal mycoplasma pneumonia reported from Austria in recent years, making this topic worthy of further scientific attention.     

Real-time assessment of anteroposterior stability of spinal segments

Purpose

While anteroposterior instability of spinal segments is regarded as an important biomechanical aspect in the clinical evaluation of lumbar pathologies, the reliability of the available diagnostic tools is limited and an intraoperative method to quantify stability is lacking. The aim of this study was to develop and validate an instrument to measure the anteroposterior stability of a spinal segments in real-time.

Methods

Torsi of five fresh-frozen human cadavers were used for this study. After pedicle screw insertion, a specifically modified reposition tool composed with load and linear sensors was used to measure the segmental anteroposterior motion caused by 100 N anterior and posterior force during 5 loading cycles on either side of the instrumentation by two different operators. The spinal segments were then resected from the torsi and anteroposterior loading with ± 100 N was repeated in an advanced biomechanical spine testing setup as a reference measurement. The Inter-correlation coefficient (ICC) was used for validation of the “intraoperative” device.

Results

Inter-operator repeatability of the measurements showed an ICC of 0.93 (p < 0.0001) and the bilateral (left–right) comparison had an ICC of 0.73 (p < 0.0001). The ICC resulting from the comparison to the reference measurement was 0.82 (p < 0.0001) without offset correction, and 0.9 (p < 0.0001) with offset correction. The ICC converged at this value already after two of the five performed loading cycles.

Conclusion

An accurate and reliable measurement tool is developed and validated for real-time quantification of anteroposterior stability of spinal segments and serves as a basis for future intraoperative use.