Nature of the thymocytes associated with dendritic cells and macrophages in thymic rosettes

Thymic rosettes, structures consisting of 3-30 thymic lymphoid cells attached to a central macrophage or dendritic cell, were released from mouse thymus tissue by collagenase digestion. They were shown to be preexistent structures within the thymus, but to be subject to extensive exchange with free thymocytes under certain conditions. An isolation procedure was developed, using a new technique of zonal unit-gravity elutriation, which minimized exchange and produced a completely pure sample of the larger rosettes. The rosette-associated thymocytes were analyzed by two- and three-color immunofluorescent staining and flow cytometry. The dominant cell type was a small, CD4+CD8+, cortical-type thymocyte. However, all of the established thymus subpopulations defined by CD4 and CD8, including CD4-CD8+ and CD4+CD8- mature thymocytes and CD4-CD8- early thymocytes, were also present in rosettes. Very few of the cells present were of an intermediate or transitional phenotype. Rosette-associated thymocytes were somewhat enriched in large dividing thymocytes, in CD4-CD8- thymocytes, and in mature thymocytes expressing the T-cell antigen receptor-CD3 complex. Their most striking characteristic was a marked depletion in small thymocytes lacking surface H-2K expression, a major population among free thymocytes. The physiological role of the rosette structure is discussed, and it is suggested that the heterogeneity of the associated thymocytes in part reflects the existence of different types of rosettes in different areas of the thymus.     

Thaimycins,new anthelmintic and antiprotozoal antibiotics produced by Streptomyces michiganensis var. amylolyticus var. nova

Summary A new microorganism, isolated in our laboratories and identified as Streptomyces michiganensis var. amylolyticus var. nova is described.Thaimycins can be obtained by submerged fermentation of this microorganism on a suitable culture medium.Three new related compounds, thaimycins A, B and C have been obtained and characterized by their physical and chemical properties.Data on the antiprotozoal and anthelmintic activities in vitro as well as in vivo are reported.     

Aging and sex influence the permeability of the blood-brain barrier in the rat

The aim of the present study was to investigate the existence of aging- and sex-related alterations in the permeability of the blood-brain barrier (BBB) in the rat, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer [14C]-alpha-aminoisobutyric acid. We observed that: a) the permeability of the BBB significantly increased within the frontal and temporo-parietal cortex, hypothalamus and cerebellum in 28-30 week old rats, in comparison with younger animals; b) in several brain areas of female intact rats higher Ki values (even though not significantly different) were calculated at oestrus than at proestrus; c) in 1-week ovariectomized rats there was a marked increase of Ki values at the level of the frontal, temporo-parietal and occipital cortex, cerebellum and brain-stem. One can speculate that aging- and sex-related alterations in the permeability of the BBB reflect respectively changes in brain neurochemical system activity and in plasma steroid hormone levels.     

Modelling the potential spread of Hyalomma marginatum ticks in Europe by migratory birds

This study modelled the probability of introduction of Hyalomma marginatum into Europe by predicting the potential migratory routes of 28 bird species and the probability to carry immatures of the tick. Flyways were modelled as a spatio-temporal feature, at weekly intervals, using satellite-derived data of temperature and vegetal phenology, together with cost surfaces derived from speed and direction of the wind (years 2002–2018). The expected period of activity of tick immatures defined the probability of ticks being carried by birds along the modelled flyways. The probability of moulting of the engorged nymphs was modelled as a linear relationship of the daily sum of temperatures after tick introduction by birds. Positive probabilities of tick introduction extend the known northern range of permanent populations to central and western France, and large portions of central Europe. The flight of birds into an area and thence the risk of introduction of H. marginatum is very heterogeneous, with sites receiving “waves” of different bird species at diverse times of the year. Therefore, there is not a clear period of time for introduction, as it depends on the modelled behaviour of the bird species. The probability of introduction into Baltic and Nordic countries is small. We hypothesise that conditions of a warmer climate might support permanent populations of H. marginatum if a high number of immatures is introduced. Active surveys in risky territories, where the tick is not yet established, are advisable for rapid intervention.     

Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial

Introduction

Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.

Methods

Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO₂, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise).

Results

The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO₂ (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study.

Conclusion

A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients.

Trial registration

NCT01515163.     

A Bayesian multi-risks survival (MRS) model in the presence of double censorings

Semi-competing risks data include the time to a nonterminating event and the time to a terminating event, while competing risks data include the time to more than one terminating event. Our work is motivated by a prostate cancer study, which has one nonterminating event and two terminating events with both semi-competing risks and competing risks present as well as two censoring times. In this paper, we propose a new multi-risks survival (MRS) model for this type of data. In addition, the proposed MRS model can accommodate noninformative right-censoring times for nonterminating and terminating events. Properties of the proposed MRS model are examined in detail. Theoretical and empirical results show that the estimates of the cumulative incidence function for a nonterminating event may be biased if the information on a terminating event is ignored. A Markov chain Monte Carlo sampling algorithm is also developed. Our methodology is further assessed using simulations and also an analysis of the real data from a prostate cancer study. As a result, a prostate-specific antigen velocity greater than 2.0 ng/mL per year and higher biopsy Gleason scores are positively associated with a shorter time to death due to prostate cancer.     

Automated Entire Thrombus Density Measurements for Robust and Comprehensive Thrombus Characterization in Patients with Acute Ischemic Stroke

Background and Purpose

In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements.

Materials and Method

In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described using medians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between the median of entire thrombus measurements and commonly applied manual measurements using 3 regions of interest were determined using linear regression.

Results

Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density.

Conclusions

Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, discrimination of low and high density thrombi is improved with the automated method.