Is an enhanced behaviour change intervention cost-effective compared with physiotherapy for patients with chronic low back pain? : Results from a multicentre trial in Israel

Objective To assess the cost-effectiveness of an enhanced transtheoretical model of behaviour change in conjunction with physiotherapy compared with standard care (physiotherapy) in patients with chronic lower back pain (CLBP). Design Cost-utility and cost-effectiveness analyses alongside a multicentre controlled trial from a healthcare perspective with a 1-year time horizon. Setting The trial was conducted in eight centres within the Sharon district in Israel. Participants 220 participants aged between 25 and 55 years who suffered from CLBP for a minimum of 3 months were recruited. Interventions The intervention used a model of behaviour change that sought to increase the adherence and implementation of physical activity in conjunction with physiotherapy. The control arm received standard care in the form of physiotherapy. Primary and secondary measures The primary outcome was the incremental cost per quality-adjusted life year (QALY) of the intervention arm compared with standard care. The secondary outcome was the incremental cost per Roland-Morris Disability Questionnaire point. Results The cost per QALY point estimate was 10 645 New Israeli shekels (NIS) (£1737.11). There was an 88% chance the intervention was cost-effective at NIS50 000 per QALY threshold. Excluding training costs, the intervention dominated the control arm, resulting in fewer physiotherapy and physician visits while improving outcomes. Conclusions The enhanced transtheoretical model intervention appears to be a very cost-effective intervention leading to improved outcomes for low cost. Given limitations within this study, there is justification for examining the intervention within a larger, long-term randomised controlled trial

A synthetic biology approach for evaluating the functional contribution of designer cellulosome components to deconstruction of cellulosic substrates

BACKGROUND: Select cellulolytic bacteria produce multi-enzymatic cellulosome complexes that bind to the plant cell wall and catalyze its efficient degradation. The multi-modular interconnecting cellulosomal subunits comprise dockerin-containing enzymes that bind cohesively to cohesin-containing scaffoldins. The organization of the modules into functional polypeptides is achieved by intermodular linkers of different lengths and composition, which provide flexibility to the complex and determine its overall architecture. RESULTS: Using a synthetic biology approach, we systematically investigated the spatial organization of the scaffoldin subunit and its effect on cellulose hydrolysis by designing a combinatorial library of recombinant trivalent designer scaffoldins, which contain a carbohydrate-binding module (CBM) and 3 divergent cohesin modules. The positions of the individual modules were shuffled into 24 different arrangements of chimaeric scaffoldins. This basic set was further extended into three sub-sets for each arrangement with intermodular linkers ranging from zero (no linkers), 5 (short linkers) and native linkers of 27–35 amino acids (long linkers). Of the 72 possible scaffoldins, 56 were successfully cloned and 45 of them expressed, representing 14 full sets of chimaeric scaffoldins. The resultant 42-component scaffoldin library was used to assemble designer cellulosomes, comprising three model C. thermocellum cellulases. Activities were examined using Avicel as a pure microcrystalline cellulose substrate and pretreated cellulose-enriched wheat straw as a model substrate derived from a native source. All scaffoldin combinations yielded active trivalent designer cellulosome assemblies on both substrates that exceeded the levels of the free enzyme systems. A preferred modular arrangement for the trivalent designer scaffoldin was not observed for the three enzymes used in this study, indicating that they could be integrated at any position in the designer cellulosome without significant effect on cellulose-degrading activity. Designer cellulosomes assembled with the long-linker scaffoldins achieved higher levels of activity, compared to those assembled with short-and no-linker scaffoldins. CONCLUSIONS: The results demonstrate the robustness of the cellulosome system. Long intermodular scaffoldin linkers are preferable, thus leading to enhanced degradation of cellulosic substrates, presumably due to the increased flexibility and spatial positioning of the attached enzymes in the complex. These findings provide a general basis for improved designer cellulosome systems as a platform for bioethanol production

Estimating Cell Depth from Somatic Mutations

The depth of a cell of a multicellular organism is the number of cell divisions it underwent since the zygote, and knowing this basic cell property would help address fundamental problems in several areas of biology. At present, the depths of the vast majority of human and mouse cell types are unknown. Here, we show a method for estimating the depth of a cell by analyzing somatic mutations in its microsatellites, and provide to our knowledge for the first time reliable depth estimates for several cells types in mice. According to our estimates, the average depth of oocytes is 29, consistent with previous estimates. The average depth of B cells ranges from 34 to 79, linearly related to the mouse age, suggesting a rate of one cell division per day. In contrast, various types of adult stem cells underwent on average fewer cell divisions, supporting the notion that adult stem cells are relatively quiescent. Our method for depth estimation opens a window for revealing tissue turnover rates in animals, including humans, which has important implications for our knowledge of the body under physiological and pathological conditions

Processing DNA molecules as text

Polymerase Chain Reaction (PCR) is the DNA-equivalent of Gutenberg’s movable type printing, both allowing large-scale replication of a piece of text. De novo DNA synthesis is the DNA-equivalent of mechanical typesetting, both ease the setting of text for replication. What is the DNA-equivalent of the word processor? Biology labs engage daily in DNA processing—the creation of variations and combinations of existing DNA—using a plethora of manual labor-intensive methods such as site-directed mutagenesis, error-prone PCR, assembly PCR, overlap extension PCR, cleavage and ligation, homologous recombination, and others. So far no universal method for DNA processing has been proposed and, consequently, no engineering discipline that could eliminate this manual labor has emerged. Here we present a novel operation on DNA molecules, called Y, which joins two DNA fragments into one, and show that it provides a foundation for DNA processing as it can implement all basic text processing operations on DNA molecules including insert, delete, replace, cut and paste and copy and paste. In addition, complicated DNA processing tasks such as the creation of libraries of DNA variants, chimeras and extensions can be accomplished with DNA processing plans consisting of multiple Y operations, which can be executed automatically under computer control. The resulting DNA processing system, which incorporates our earlier work on recursive DNA composition and error correction, is the first demonstration of a unified approach to DNA synthesis, editing, and library construction

Health promotion programs in prison: attendance and role in promoting physical activity and subjective health status

IntroductionMaintaining an inmate’s health can serve as a challenge due to unhealthy background, risky behavior, and long imprisonment. This study aimed to analyze the prevalence of participation in health promotion activities among Israeli inmates and its association with their physical activity levels and subjective health status.MethodsA cross-sectional study was designed to examine 522 inmates (429 males, 93 females). The data were collected by trained face-to-face interviewers and self-report questionnaires.ResultsMost of the participants (82.37%) did not meet the recommended physical activity level. Half of the participants reported that their physical activity levels decreased since they were in prison compared with 29.50% who reported that their physical activity levels increased. Physical activity and subjective health status were significantly higher among younger male inmates. Furthermore, participation in health-promoting activities was associated with higher levels of physical activity and subjective health status.DiscussionHealth promotion activities may play an important role in addressing the challenges of maintaining inmate health. Implications of the findings are further discussed

Embryonic Pig Pancreatic Tissue Transplantation for the Treatment of Diabetes

BACKGROUND: Transplantation of embryonic pig pancreatic tissue as a source of insulin has been suggested for the cure of diabetes. However, previous limited clinical trials failed in their attempts to treat diabetic patients by transplantation of advanced gestational age porcine embryonic pancreas. In the present study we examined growth potential, functionality, and immunogenicity of pig embryonic pancreatic tissue harvested at different gestational ages. METHODS AND FINDINGS: Implantation of embryonic pig pancreatic tissues of different gestational ages in SCID mice reveals that embryonic day 42 (E42) pig pancreas can enable a massive growth of pig islets for prolonged periods and restore normoglycemia in diabetic mice. Furthermore, both direct and indirect T cell rejection responses to the xenogeneic tissue demonstrated that E42 tissue, in comparison to E56 or later embryonic tissues, exhibits markedly reduced immunogenicity. Finally, fully immunocompetent diabetic mice grafted with the E42 pig pancreatic tissue and treated with an immunosuppression protocol comprising CTLA4-Ig and anti–CD40 ligand (anti-CD40L) attained normal blood glucose levels, eliminating the need for insulin. CONCLUSIONS: These results emphasize the importance of selecting embryonic tissue of the correct gestational age for optimal growth and function and for reduced immunogenicity, and provide a proof of principle for the therapeutic potential of E42 embryonic pig pancreatic tissue transplantation in diabetes

Noncoding deletions reveal a gene that is critical for intestinal function.

Large-scale genome sequencing is poised to provide a substantial increase in the rate of discovery of disease-associated mutations, but the functional interpretation of such mutations remains challenging. Here we show that deletions of a sequence on human chromosome 16 that we term the intestine-critical region (ICR) cause intractable congenital diarrhoea in infants1,2. Reporter assays in transgenic mice show that the ICR contains a regulatory sequence that activates transcription during the development of the gastrointestinal system. Targeted deletion of the ICR in mice caused symptoms that recapitulated the human condition. Transcriptome analysis revealed that an unannotated open reading frame (Percc1) flanks the regulatory sequence, and the expression of this gene was lost in the developing gut of mice that lacked the ICR. Percc1-knockout mice displayed phenotypes similar to those observed upon ICR deletion in mice and patients, whereas an ICR-driven Percc1 transgene was sufficient to rescue the phenotypes found in mice that lacked the ICR. Together, our results identify a gene that is critical for intestinal function and underscore the need for targeted in vivo studies to interpret the growing number of clinical genetic findings that do not affect known protein-coding genes

Reconstruction of Cell Lineage Trees in Mice

The cell lineage tree of a multicellular organism represents its history of cell divisions from the very first cell, the zygote. A new method for high-resolution reconstruction of parts of such cell lineage trees was recently developed based on phylogenetic analysis of somatic mutations accumulated during normal development of an organism. In this study we apply this method in mice to reconstruct the lineage trees of distinct cell types. We address for the first time basic questions in developmental biology of higher organisms, namely what is the correlation between the lineage relation among cells and their (1) function, (2) physical proximity and (3) anatomical proximity. We analyzed B-cells, kidney-, mesenchymal- and hematopoietic-stem cells, as well as satellite cells, which are adult skeletal muscle stem cells isolated from their niche on the muscle fibers (myofibers) from various skeletal muscles. Our results demonstrate that all analyzed cell types are intermingled in the lineage tree, indicating that none of these cell types are single exclusive clones. We also show a significant correlation between the physical proximity of satellite cells within muscles and their lineage. Furthermore, we show that satellite cells obtained from a single myofiber are significantly clustered in the lineage tree, reflecting their common developmental origin. Lineage analysis based on somatic mutations enables performing high resolution reconstruction of lineage trees in mice and humans, which can provide fundamental insights to many aspects of their development and tissue maintenance

Outcomes in distressed patients with chronic low back pain: Subgroup analysis of a clinical trial

STUDY DESIGN: Subgroup analysis of a controlled clinical trial. BACKGROUND: Current evidence suggests that people with chronic low back pain who are distressed may require different interventions than do those who are not distressed. Recently, the enhanced transtheoretical model intervention (ETMI) reported significant improvements in disability and pain and increased physical activity in patients with chronic low back pain compared to physical therapy as usual. OBJECTIVES: To compare outcomes between ETMI and physical therapy interventions for participants with and without self-reported distress. METHODS: We tested the interaction between intervention (ETMI versus physical therapy) and distress status (using the Medical Outcomes Study 12-Item Short-Form Health Survey cut point), and performed between-group comparisons on 3 separate outcomes (disability, pain, and physical activity) at 3 and 12 months. RESULTS: In the ETMI group, 57 of 108 participants were considered distressed, versus 62 of 106 participants in the physical therapy group. The interaction between intervention and distress at 12 months was significant. Participants improved with both interventions, but the magnitude of change in distressed participants who received ETMI was larger than that in distressed participants who received physical therapy (mean ± SD difference from baseline in disability of 6.1 ± 6.1 in the ETMI group, compared with 3.4 ± 6.7 in the physical therapy group). CONCLUSION: The enhanced transtheoretical model intervention was significantly more effective than physical therapy in participants with distress

Increasing recreational physical activity in patients with chronic low back pain: A pragmatic controlled clinical trial

Background: Clinical guidelines recommend physical activity for the treatment of chronic low back pain. But engaging patients in physical activity has proven difficult. Known obstacles to physical activity include low self-efficacy and fear avoidance.Objectives: This study tested the effectiveness of an enhanced transtheoretical model intervention (ETMI) aimed at increasing recreational physical activity in patients with chronic low back pain, in comparison to usual physical therapy.MethodsPatients (n = 220) referred to physical therapy for chronic low back pain were allocated to ETMI or to a control group. The ETMI was delivered by physical therapists and based on behavior-change principles, combined with increased reassurance, therapeutic alliance, and exposure to reduce fear avoidance. The primary outcome was back pain-related disability (Roland-Morris Disability Questionnaire). Secondary outcomes included pain intensity, mental and physical health, and levels of physical activity.Results: Intention-to-treat analysis in 189 patients at 12 months indicated that patients in the ETMI group had significantly lower disability compared to usual physical therapy. The difference in mean change from baseline between the interventions was 2.7 points (95% confidence interval: 0.9, 4.5) on the Roland-Morris Disability Questionnaire. At 12 months, worst pain, physical activity, and physical health were all significantly better in patients receiving ETMI. The average number of sessions was 3.5 for the ETMI group and 5.1 for controls.Conclusion: Targeting obstacles to physical activity with an intervention that includes components to address self-efficacy and fear avoidance appears to be more effective than usual physical therapy care in reducing long-term disability. Further research is needed to explore the mechanisms that impact outcomes in this intervention package