Quantification of Dendritic Cells and Osteoclasts in the Bone Marrow of Patients with Monoclonal Gammopathy

The purpose of this study was to find histological clues for reliable differentiation between monoclonal gammopathy of undetermined significance (MGUS) and myeloma when clinical parameters are controversial. Differential appearance of dendritic cells and osteoclasts, two cell types developing from the monocytic lineage upon distinct cytokine activation profile, might be a useful approach. Bone and bone-marrow biopsies performed in 105 patients were studied using histomorphometry after identification of osteoclasts (by histochemical identification of tartrate resistant acid phosphatase) and dendritic cells (by immunohistochemical detection of the S-100 protein). Patients were classified by the World Health Organization criteria but histopathological criteria were more adapted to identify MGUS (53 cases), myeloma (46), B-cell lymphoma (six) since six myeloma were not correctly classified. Histomorphometry was compared to 15 control cases. The number of marrow dendritic cell was significantly increased with B-cell lymphoma >MGUS >myeloma > controls. Dendritic cell were often mixed with lymphoma cells. Myeloma had increased bone resorption with a high osteoclast number and moderate increase in dendritic cells. B-cell lymphomas had a considerable increase in dendritic cell but presented mononucleated osteoclasts. These findings can help in the classification of MGUS in the early stages of the disease and could help to propose preventive treatments.     

Idiopathic ventricular fibrillation associated with long-coupled Purkinje ectopy

Introduction

Idiopathic ventricular fibrillation (IVF) is mainly associated with and triggered by short-coupled (R-on-T) ventricular ectopics. However, little is known about the risk of VF associated with long-coupled premature ventricular complexes (LCPVCs).

Objective

To examine the prevalence and characteristics of IVF patients presenting with LCPVCs.

Methods

Consecutive patients with IVF and PVCs from five arrhythmia referral centers were reviewed. We included patients presenting LCPVCs, defined as PVCs falling after the end of the T wave, with a normal QTc interval. We evaluated demographics, medical history, and clinical circumstances associated with PVCs and VF episodes. The origin of PVCs was determined by invasive mapping.

Results

Seventy-nine patients with IVF were reviewed. Among them, 12 (15.2%) met the inclusion criteria (8 women, age 36 ± 14 years). Eleven patients had documented LCPVCs initiating repetitive PVCs or sustained VF, whereas 1 had only documented isolated PVCs. In 10 of 12 patients, PVCs were recorded showing both long and short coupling intervals of 418 ± 46 and 304 ± 33 ms, respectively. Mapping showed that PVCs originated from the left Purkinje in 10 patients, from the right Purkinje in 1 patient, and both in 1 patient. Compared to other patients from the initial cohort, IVF with LCPVCs was associated with a left-sided origin of PVCs (92% in long-coupled IVF vs. 46% of left Purkinje PVCs in short-coupled IVF, p = .004).

Conclusion

Long-coupled fascicular PVCs, traditionally recognized as benign, can be associated with IVF in a subset of patients. They can induce IVF by themselves or in association with short-coupled PVCs.     

Intraspecific evolution of the intercellular signaling network underlying a robust developmental system

Many biological systems produce an invariant output when faced with stochastic or environmental variation. This robustness of system output to variation affecting the underlying process may allow for “cryptic” genetic evolution within the system without change in output. We studied variation of cell fate patterning of Caenorhabditis elegans vulva precursors, a developmental system that relies on a simple intercellular signaling network and yields an invariant output of cell fates and lineages among C. elegans wild isolates. We first investigated the system’s genetic variation in C. elegans by means of genetic tools and cell ablation to break down its buffering mechanisms. We uncovered distinct architectures of quantitative variation along the Ras signaling cascade, including compensatory variation, and differences in cell sensitivity to induction along the anteroposterior axis. In the unperturbed system, we further found variation between isolates in spatio-temporal dynamics of Ras pathway activity, which can explain the phenotypic differences revealed upon perturbation. Finally, the variation mostly affects the signaling pathways in a tissue-specific manner. We thus demonstrate and characterize microevolution of a developmental signaling network. In addition, our results suggest that the vulva genetic screens would have yielded a different mutation spectrum, especially for Wnt pathway mutations, had they been performed in another C. elegans genetic background.     

Does age worsen sleep‐dependent memory consolidation?

Slow wave sleep (SWS) is known to favour episodic memory consolidation. Given that ageing is associated with a reduction in SWS and episodic memory impairment, our aim was to investigate whether memory continues to benefit from sleep in older adults. Episodic memory consolidation was tested in 20 young (22.1 ± 1.7 years) and 20 older volunteers (68.9 ± 5.3 years) who performed a visuospatial two‐dimensional object‐location task. Retention capacities were evaluated after 12 h of wakefulness or 12 h of sleep. Performances before and after the interval allowed us to calculate a forgetting rate. Sleep architecture was measured by polysomnography (older adults = 410 min; young adults: 467 min). Our results showed that the beneficial effect of sleep on memory consolidation was reduced in older adults compared to young adults. In older adults, sleep did not enhance memory consolidation significantly compared to wakefulness. Sleep prevented young adults from forgetting (?0.10% ± 2.1), while the forgetting rate in older adults was still important after a period of sleep (16.60% ± 4.2; P = 0.05). The sleep architecture of older adults was characterized by a decrease in sleep efficiency (?12%; P < 0.05), in total cycle time (?137 min; P < 0.05), in percentage of total cycle time (?21%; P < 0.05) and in rapid eye movement time (?41 min; P < 0.05) compared to young adults. However, no difference in slow wave sleep was observed (?1%; not significant) and no correlation was found with performance. Age‐related changes in sleep parameters may have a negative impact on memory consolidation in older adults.     

Fever,malaria and primary repetition rates amongst school children in Mali: Combining demographic and health surveys (DHS) with spatial malariological measures

This study estimates the relative importance to child school performance (indicated by primary repetition) of fever, malaria and some social determinants at the cluster level. It uses individual, household and cluster surveys from the Demographic and Health Surveys conducted in Mali in 2001 and 2006 (MDHS). It also provides a discussion about the use of fever as an indicator of malaria in large cross-sectional surveys by comparing the 2001 and 2006 MDHS, which were realised during two different transmission seasons (dry and rainy seasons). Geographic Information System and DHS Global Positioning System datasets were used to extract age-specific malariological measures from reliable maps of the prevalence and transmission intensity of malaria. We show that fever is not a reliable proxy for malaria at the cluster level, and we recommend the use of spatial measures of malaria prevalence for future research. Cross-sectional regression analysis on data aggregated to the group-level suggests that a higher prevalence of malaria in a community is linked to higher primary repetition rates, but confirmatory studies are needed.     

Photic-induced sensitization: eye-specific neural plasticity and effect of behavioral state

We reported previously that exposure to repetitive visual stimulation in ordinary adult rats results in acquisition of an enduring increase in magnitude and change in character of visual cortical responses. This sensitization is consistent with experience-dependent neuroplastic changes, but could also reflect alterations in response with behavioral state during testing. The aim of this study was to distinguish the contributions of behavioral state and neural plasticity in this photic-induced sensitization. We used repetitive light-emitting diode flashes delivered monocularly and recorded electrocorticographically in the albino rat in which retino-geniculo-cortical projections are predominantly crossed. This enabled comparison of visual responses of sensitized visual circuitry associated with one eye to responses from effectively unsensitized circuitry associated with the second eye at similar time points in an animal, thus providing an internal control for behavioral state. Following sensitization, monocular stimulation of one eye produced the characteristic high amplitude driven spike-wave response in corresponding contralateral visual cortex, but not ipsilateral cortex. Expression of the sensitized driven response was optimal in the quiet awake state and suppressed during active exploration, drowsiness, or anesthesia. When the animal was in the quiet awake state, producing sensitized responses to stimulation of the first eye, no such response was observed on alternate trials upon stimulation of the second eye. Only after extended exposure of the second eye did the high amplitude driven spike-wave response in contralateral visual cortex develop. The data further suggest some degree of sensitization of ipsilateral pathways may accompany monocular stimulation and that effects of monocular sensitization could include suppression in pathways related to the unstimulated eye. Thus, while behavioral state influences expression of the sensitized driven visual response, the eye-specific nature of the effect provides strong evidence that response enhancement reflects neuroplasticity in visual pathways and not a more general change in behavioral state during testing.     

Malaria and primary education in Mali: A longitudinal study in the village of Donéguébougou

This article assesses the role of malaria and certain social determinants on primary education, especially on educational achievement in Donéguébougou, a small village in a malaria-endemic area near Bamako, Mali. Field data was collected by the authors between November 2007 and June 2008 on 227 schoolchildren living in Donéguébougou. Various malaria indicators and econometric models were used to explain the variation in cognitive abilities, teachers’ evaluation scores, school progression and absences. Malaria is the primary cause of school absences. Fixed-effects estimates showed that asymptomatic malaria and the presence of falciparum malaria parasites had a direct correlation with educational achievement and cognitive performance. The evidence suggests that the correlation is causal.