A Randomised Controlled Trial of Neuronavigated Repetitive Transcranial Magnetic Stimulation (rTMS) in Anorexia Nervosa

Background

Anorexia nervosa (AN) is associated with morbid fear of fatness, extreme food restriction and altered self-regulation. Neuroimaging data implicate fronto-striatal circuitry, including the dorsolateral prefrontal cortex (DLPFC).

Methods

In this double-blind parallel group study, we investigated the effects of one session of sham-controlled high-frequency repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC (l-DLPFC) in 60 individuals with AN. A food exposure task was administered before and after the procedure to elicit AN-related symptoms.

Outcomes

The primary outcome measure was ‘core AN symptoms’, a variable which combined several subjective AN-related experiences. The effects of rTMS on other measures of psychopathology (e.g. mood), temporal discounting (TD; intertemporal choice behaviour) and on salivary cortisol concentrations were also investigated. Safety, tolerability and acceptability were assessed.

Results

Fourty-nine participants completed the study. Whilst there were no interaction effects of rTMS on core AN symptoms, there was a trend for group differences (p = 0.056): after controlling for pre-rTMS scores, individuals who received real rTMS had reduced symptoms post-rTMS and at 24-hour follow-up, relative to those who received sham stimulation. Other psychopathology was not altered differentially following real/sham rTMS. In relation to TD, there was an interaction trend (p = 0.060): real versus sham rTMS resulted in reduced rates of TD (more reflective choice behaviour). Salivary cortisol concentrations were unchanged by stimulation. rTMS was safe, well–tolerated and was considered an acceptable intervention.

Conclusions

This study provides modest evidence that rTMS to the l-DLPFC transiently reduces core symptoms of AN and encourages prudent decision making. Importantly, individuals with AN considered rTMS to be a viable treatment option. These findings require replication in multiple-session studies to evaluate therapeutic efficacy.

Trial Registration

www.Controlled-Trials.com ISRCTN22851337     

Effects of products from macrophages, blood mononuclear cells and or retinol on collagenase secretion and collagen synthesis in chondrocyte culture

Collagenase secretion was studied on cultures of rabbit articular chondrocytes. Differentiation of the cells was assessed by characterizing the type of 3H-labelled collagen produced during treatment with (1) conditioned media from rabbit peritoneal macrophages and human blood mononuclear cells, and (2) with retinol, a potent cartilage resorbing agent in tissue culture. Conditioned media stimulated collagenase secretion. Total collagen synthesis was reduced due to a decrease of synthesis of alpha 1 chains; the amount of alpha 2 chains synthesized was unchanged. This is thought to be due to a reduction in type II synthesis. Retinol did not stimulate collagenase secretion. Total collagen synthesis was reduced by retinol. alpha 2 chain synthesis, however, was significantly increased, suggesting a switch of collagen synthesis in favor of type I collagen, and therefore, dedifferentiation. These results demonstrate that dedifferentiation of chondrocytes with respect to collagen synthesis is not necessarily associated with a stimulation of collagenase secretion.     

Homogeneous cell populations from rabbit kidney cortex. Proximal, distal tubule, and renin-active cell isolated by free-flow electrophoresis

A single-cell suspension has been prepared from rabbit kidney cortex by using a Ca-binding medium and gentle mechanical forces. The suspension was subjected to carrier-free electrophoresis, and several cell fractions were obtained. Proximal and distal tubule cell populations could be identified by their morphology. Renin-containing cells were located by means of radioimmunoassay. The morphology of the cells and their vitality (uridine incorporation) are discussed.     

The [FeFe] hydrogenase of Nyctotherus ovalis has a chimeric origin

Background

The hydrogenosomes of the anaerobic ciliate Nyctotherus ovalis show how mitochondria can evolve into hydrogenosomes because they possess a mitochondrial genome and parts of an electron-transport chain on the one hand, and a hydrogenase on the other hand. The hydrogenase permits direct reoxidation of NADH because it consists of a [FeFe] hydrogenase module that is fused to two modules, which are homologous to the 24 kDa and the 51 kDa subunits of a mitochondrial complex I.

Results

The [FeFe] hydrogenase belongs to a clade of hydrogenases that are different from well-known eukaryotic hydrogenases. The 24 kDa and the 51 kDa modules are most closely related to homologous modules that function in bacterial [NiFe] hydrogenases. Paralogous, mitochondrial 24 kDa and 51 kDa modules function in the mitochondrial complex I in N. ovalis. The different hydrogenase modules have been fused to form a polyprotein that is targeted into the hydrogenosome.

Conclusion

The hydrogenase and their associated modules have most likely been acquired by independent lateral gene transfer from different sources. This scenario for a concerted lateral gene transfer is in agreement with the evolution of the hydrogenosome from a genuine ciliate mitochondrion by evolutionary tinkering.     

A tool for analyzing mate pairs in assemblies (TAMPA).

The current generation of genome assembly programs uses distance and orientation relationships of paired end reads of clones (mate pairs) to order and orient contigs. Mate pair data can also be used to evaluate and compare assemblies after the fact. Earlier work employed a simple heuristic to detect assembly problems by scanning across an assembly to locate peak concentrations of unsatisfied mate pairs. TAMPA is a novel, computational geometry-based approach to detecting assembly breakpoints by exploiting constraints that mate pairs impose on each other. The method can be used to improve assemblies and determine which of two assemblies is correct in the case of sequence disagreement. Results from several human genome assemblies are presented.