Efficacy and moderators of cognitive therapy versus behavioural activation for adults with depression: study protocol of a systematic review and meta-analysis of individual participant data

This is the final version. Available on open access from Cambridge University Press via the DOI in this record. Data availability is not applicable to this article as no new data were created or analysed for this study protocol paperBACKGROUND: Cognitive therapy and behavioural activation are both widely applied and effective psychotherapies for depression, but it is unclear which works best for whom. Individual participant data (IPD) meta-analysis allows for examining moderators at the participant level and can provide more precise effect estimates than conventional meta-analysis, which is based on study-level data. AIMS: This article describes the protocol for a systematic review and IPD meta-analysis that aims to compare the efficacy of cognitive therapy and behavioural activation for adults with depression, and to explore moderators of treatment effect. (PROSPERO: CRD42022341602). METHOD: Systematic literature searches will be conducted in PubMed, PsycINFO, EMBASE and the Cochrane Library, to identify randomised clinical trials comparing cognitive therapy and behavioural activation for adult acute-phase depression. Investigators of these trials will be invited to share their participant-level data. One-stage IPD meta-analyses will be conducted with mixed-effects models to assess treatment effects and to examine various available demographic, clinical and psychological participant characteristics as potential moderators. The primary outcome measure will be depressive symptom level at treatment completion. Secondary outcomes will include post-treatment anxiety, interpersonal functioning and quality of life, as well as follow-up outcomes. CONCLUSIONS: To the best of our knowledge, this will be the first IPD meta-analysis concerning cognitive therapy versus behavioural activation for adult depression. This study has the potential to enhance our knowledge of depression treatment by using state-of-the-art statistical techniques to compare the efficacy of two widely used psychotherapies, and by shedding more light on which of these treatments might work best for whom.Medical Research Council (MRC)Netherlands Organization of Scientific ResearchNational Institutes of HealthNational Center for Advancing Translational Sciences and Clinical and Translational Science

SecA, a remarkable nanomachine

Biological cells harbor a variety of molecular machines that carry out mechanical work at the nanoscale. One of these nanomachines is the bacterial motor protein SecA which translocates secretory proteins through the protein-conducting membrane channel SecYEG. SecA converts chemically stored energy in the form of ATP into a mechanical force to drive polypeptide transport through SecYEG and across the cytoplasmic membrane. In order to accommodate a translocating polypeptide chain and to release transmembrane segments of membrane proteins into the lipid bilayer, SecYEG needs to open its central channel and the lateral gate. Recent crystal structures provide a detailed insight into the rearrangements required for channel opening. Here, we review our current understanding of the mode of operation of the SecA motor protein in concert with the dynamic SecYEG channel. We conclude with a new model for SecA-mediated protein translocation that unifies previous conflicting data

Identification of Surprisingly Diverse Type IV Pili, across a Broad Range of Gram-Positive Bacteria

In Gram-negative bacteria, type IV pili (TFP) have long been known to play important roles in such diverse biological phenomena as surface adhesion, motility, and DNA transfer, with significant consequences for pathogenicity. More recently it became apparent that Gram-positive bacteria also express type IV pili; however, little is known about the diversity and abundance of these structures in Gram-positives. Computational tools for automated identification of type IV pilins are not currently available.To assess TFP diversity in Gram-positive bacteria and facilitate pilin identification, we compiled a comprehensive list of putative Gram-positive pilins encoded by operons containing highly conserved pilus biosynthetic genes (pilB, pilC). A surprisingly large number of species were found to contain multiple TFP operons (pil, com and/or tad). The N-terminal sequences of predicted pilins were exploited to develop PilFind, a rule-based algorithm for genome-wide identification of otherwise poorly conserved type IV pilins in any species, regardless of their association with TFP biosynthetic operons (http://signalfind.org). Using PilFind to scan 53 Gram-positive genomes (encoding >187,000 proteins), we identified 286 candidate pilins, including 214 in operons containing TFP biosynthetic genes (TBG+ operons). Although trained on Gram-positive pilins, PilFind identified 55 of 58 manually curated Gram-negative pilins in TBG+ operons, as well as 53 additional pilin candidates in operons lacking biosynthetic genes in ten species (>38,000 proteins), including 27 of 29 experimentally verified pilins. False positive rates appear to be low, as PilFind predicted only four pilin candidates in eleven bacterial species (>13,000 proteins) lacking TFP biosynthetic genes.We have shown that Gram-positive bacteria contain a highly diverse set of type IV pili. PilFind can be an invaluable tool to study bacterial cellular processes known to involve type IV pilus-like structures. Its use in combination with other currently available computational tools should improve the accuracy of predicting the subcellular localization of bacterial proteins

The Genome Characteristics and Predicted Function of Methyl-Group Oxidation Pathway in the Obligate Aceticlastic Methanogens, Methanosaeta spp

In this work, we report the complete genome sequence of an obligate aceticlastic methanogen, Methanosaeta harundinacea 6Ac. Genome comparison indicated that the three cultured Methanosaeta spp., M. thermophila, M. concilii and M. harundinacea 6Ac, each carry an entire suite of genes encoding the proteins involved in the methyl-group oxidation pathway, a pathway whose function is not well documented in the obligately aceticlastic methanogens. Phylogenetic analysis showed that the methyl-group oxidation-involving proteins, Fwd, Mtd, Mch, and Mer from Methanosaeta strains cluster with the methylotrophic methanogens, and were not closely related to those from the hydrogenotrophic methanogens. Quantitative PCR detected the expression of all genes for this pathway, albeit ten times lower than the genes for aceticlastic methanogenesis in strain 6Ac. Western blots also revealed the expression of fwd and mch, genes involved in methyl-group oxidation. Moreover, 13C-labeling experiments suggested that the Methanosaeta strains might use the pathway as a methyl oxidation shunt during the aceticlastic metabolism. Because the mch mutants of Methanosarcina barkeri or M. acetivorans failed to grow on acetate, we suggest that Methanosaeta may use methyl-group oxidation pathway to generate reducing equivalents, possibly for biomass synthesis. An fpo operon, which encodes an electron transport complex for the reduction of CoM-CoB heterodisulfide, was found in the three genomes of the Methanosaeta strains. However, an incomplete protein complex lacking the FpoF subunit was predicted, as the gene for this protein was absent. Thus, F420H2 was predicted not to serve as the electron donor. In addition, two gene clusters encoding the two types of heterodisulfide reductase (Hdr), hdrABC, and hdrED, respectively, were found in the three Methanosaeta genomes. Quantitative PCR determined that the expression of hdrED was about ten times higher than hdrABC, suggesting that hdrED plays a major role in aceticlastic methanogenesis

Trends in the incidence of adenocarcinoma of the oesophagus and cardia in the Netherlands 1989–2003

Over the 15-year period 1989–2003, the incidence of oesophagus–cardia adenocarcinoma in the Netherlands rose annually by 2.6% for males and 1.2% for females. This was the net outcome of annual increases in the incidence of adenocarcinoma of the oesophagus (ACO) of 7.2% for males and 3.5% for females and annual declines in the incidence of adenocarcinoma of the gastric cardia (AGC) of more than 1% for both genders. Nonlinear cohort patterns were found in females with ACO and for both genders in AGC; a nonlinear period pattern was observed only in males with AGC. These differing epidemiological patterns for ACO and AGC do not support a common aetiology. Proposed underlying factors for the rise in ACO incidence appear to have little effect on AGC incidence. This and the secular decline in smoking among males may have led to the decline in AGC incidence

Changing climate—changing pathogens: Toxoplasma gondii in North-Western Europe

In this review, we describe the effects of global climate change for one specific pathogen: the parasite Toxoplasma gondii. It is postulated that an increase of T. gondii prevalence in humans can occur in some regions of North-Western Europe as a result of changing environmental conditions. Such a change can be predicted by using Global Climate Change models. We have elaborated such a prediction for one scenario (SRES A1) by using one specific model (CCSR/NRIES) as an example. Next to environmental factors, also anthropogenic factors may contribute to increased prevalence of T. gondii in this region. In order to counter the potential severe consequences of a potential increase resulting from the combination of climatic and anthropogenic factors, there is an urgent need for the development of a human vaccine. Until a vaccine that offers complete protection is developed, the emphasis should be on treatment optimization and prevention

A Behavioral Change Perspective of Maroon Soil Fertility Management in Traditional Shifting Cultivation in Suriname

In Suriname, the Maroons have practiced shifting cultivation for generations, but now the increasing influence of modern society is causing a trend of decreasing fallow periods with potentially adverse effects for the vulnerable tropical soils. Adoption of appropriate soil fertility management (SFM) practices is currently slow. Combining methods from cultural ecology and environmental psychology, this study identifies two groups with divergent behavioral intentions which we term semi-permanent cultivators and shifting cultivators. Semi-permanent cultivators intend to practice more permanent agriculture and experiment individually with plot-level SFM. Shifting cultivators rely on traditional knowledge that is not adequate for their reduced fallow periods, but perceive constraints that prevent them practicing more permanent agriculture. Semi-permanent cultivators act as a strong reference group setting a subjective norm, yet feel no need to exchange knowledge with shifting cultivators who are in danger of feeling marginalized. Drawing on a political ecology perspective, we conclude that cultural ecological knowledge declined due to negative perceptions of external actors setting a strong subjective norm. Semi-permanent cultivators who wish to enter the market economy are most likely to adopt SFM. We conclude that any future SFM intervention must be based on an in-depth understanding of each group’s behavior, in order to avoid exacerbating processes of marginalization