Randomised controlled non-inferiority trial with 3-year follow-up of internet-delivered versus face-to-face group cognitive behavioural therapy for depression

Background

Guided internet-delivered cognitive behaviour therapy (ICBT) has been found to be effective in the treatment of mild to moderate depression, but there have been no direct comparisons with the more established group-based CBT with a long-term follow-up.

Method

Participants with mild to moderate depression were recruited from the general population and randomized to either guided ICBT (n=33) or to live group treatment (n=36). Measures were completed before and after the intervention to assess depression, anxiety, and quality of life. Follow-ups were conducted at one-year and three-year after the treatment had ended.

Results

Data were analysed on an intention-to-treat basis using linear mixed-effects regression analysis. Results on the self-rated version of the Montgomery–Åsberg Depression Scale showed significant improvements in both groups across time indicating non-inferiority of guided ICBT, and there was even a tendency for the guided ICBT group to be superior to group-based CBT at three year follow-up. Within-group effect sizes for the ICBT condition at post-treatment showed a Cohen′s d=1.46, with a similar large effect at 3-year follow-up, d=1.78. For the group CBT the corresponding within-group effects were d=0.99 and d=1.34, respectively.

Limitations

The study was small with two active treatments and there was no placebo or credible control condition.

Conclusions

Guided ICBT is at least as effective as group-based CBT and long-term effects can be sustained up to 3 years after treatment.     

Caspase-6 activity predicts lower episodic memory ability in aged individuals

Caspase-6 (Casp6), a cysteinyl protease that induces axonal degeneration, is activated early in Alzheimer Disease (AD) brains. To determine whether Casp6 activation is responsible for early cognitive impairment, we investigated the abundance of Casp6 activity, paired helical filament–1 (PHF-1) phosphorylated Tau and amyloid beta peptide (Aβ) pathology by immunohistochemistry in the hippocampal formation of aged non–cognitively impaired (NCI) individuals. Casp6 activity was restricted to the entorhinal cortex (ERC) and CA1 regions of the hippocampus. Pathology scores were then correlated with cognitive scores obtained within 1 year of death. Regression analyses revealed that ERC and CA1 Casp6 activity were the main contributor to lower episodic memory performance, whereas ERC PHF-1 pathology predicted lower semantic and working memory performance. Aβ did not correlate with any of the cognitive tests. Because Casp6 activity and PHF-1 pathology are intimately associated with AD pathology and memory decline is an early event in AD, we conclude that Casp6 activity and PHF-1 immunoreactivity in ERC identifies aged individuals at risk for developing AD.     

For many but not for all: how the conformational flexibility of the peptide/MHCII complex shapes epitope selection

The adaptive immune response starts when CD4+ T cells recognize peptide antigens presented by class II molecules of the Major Histocompatibility Complex (MHCII). Two outstanding features of MHCII molecules are their polymorphism and the ability of each allele to bind a large panoply of peptides. The ability of each MHCII molecule to interact with a limited, though broad, range of amino acid sequences, or “permissive specificity” of binding, is the result of structural flexibility. This flexibility has been identified through biochemical and biophysical studies, and molecular dynamic simulations have modeled the conformational rearrangements that the peptide and the MHCII undergo during interaction. Moreover, there is evidence that the structural flexibility of the peptide/MHCII complex correlates with the activity of the “peptide-editing” molecule DM. In light of the impact that these recent findings have on our ability to predict MHCII epitopes, a review of the structural and thermodynamic determinants of peptide binding to MHCII is proposed.     

Network remodeling of intramural coronary resistance arteries in the aged rat: A statistical analysis of geometry

AimsTo identify the geometrical alterations in the age-remodeled rat coronary artery network and to develop a useful technique to analyze network properties in the rat heart.Methods and resultsWe analyzed the networks of the left anterior descendent coronary arteries on in situ perfused hearts of young (3 months) and old (18 months) male rats. All segments and branching over >80 μm diameter were analyzed using 50 μm long cylindrical ring units of the networks. Arterial widening and paucity, increased tortuosity were typical features in the old network. In addition, axis angles deviated more from the mother branches in the old, whereas the diameters of daughter branches fit the Murray law in both groups. The detected changes in the old network resulted in a longer blood flow route for the same direct distance.ConclusionWe developed a useful method to investigate arterial network property changes in the rat heart. Ageing resulted in longer, more tortuous flow route in the LAD network that might be hemodynamically disadvantageous.     

Lithium-associated hyperparathyroidism and hypercalcaemia: A case-control cross-sectional study

Background

Lithium is recommended as a first-line treatment for Bipolar Disorder (BD). Thyroid and renal alterations are well known lithium side-effects, while effects on parathyroids are less studied. The aim of this case-control cross-sectional study is to compare parathyroid hormone (PTH) and calcium levels in lithium-exposed bipolar patients and in subjects who had never been exposed to lithium.

Methods

112 BD patients were enrolled, 58 on lithium since at least 1 month (mean exposure 60.8±74.8 months) and 54 in the control group. Blood exams included complete blood count, PTH, total and ionized calcium, TSH, T3 and T4, creatinine, urea, sodium and potassium, and lithium serum levels. The Student's t-test and the Pearson's Chi-square test were used for bivariate analyses. A linear regression model was used to analyze the relationship between the duration of exposure to lithium and PTH and calcium levels.

Results

PTH and ionized calcium levels were significantly higher in lithium-exposed patients; the proportions of subjects with hyperparathyroidism (8.6%) and hypercalcaemia (24.1%) were significantly greater in lithium-exposed patients. The linear regression analyses showed a significant effect of exposure to lithium in months on ionized calcium levels but not on PTH levels.

Limitations

Given the cross-sectional design of the study we could not identify the exact time of occurrence of hyperparathyroidism.

Conclusions

Our results indicate that lithium-associated stimulation of parathyroid function is more common than assumed to date. Among parameters to be evaluated prior to lithium implementation and during long-term lithium maintenance, calcium (and eventually PTH) should be added.     

VEGF Production by Osteoarthritic Chondrocytes Cultured in Micromass and Stimulated by IL-17 and TNF-α

We compared the secretion of vascular endothelial growth factor (VEGF) by chondrocytes isolated from cartilage of patients with osteoarthritis (OA) and maintained in monolayer or in three-dimensional culture. Chondrocytes, immediately after isolation, or after one passage in monolayer culture (subculture), were seeded in monolayer or pelleted in micromasses. Cells cultured differently were immunoassayed for the secretion of VEGF in basal conditions or after stimulation with IL-17, TNF-α or B IL-17+TNF-α. Chondrocytes cultured in micromasses secreted lower levels of VEGF in comparison with those in monolayer culture. In micromass cultures TNF-α was more stimulating than IL-17 and their combined effect was additional. On the basis of alkaline phosphatase/cathespin B activities, primary cultures in micromass, characterized by low VEGF secretion, represented the best condition for maximal cell differentiation. Our results suggest that the culture of chondrocytes in micromasses represents a good condition to study the physiology of these cells to a maximum degree when micromasses are obtained with freshly isolated chondrocytes.