Brief cognitive behavioral therapy compared to general practitioners care for depression in primary care: a randomized trial

Background

Previous studies of acupuncture show favourable results for both subjective and objective outcomes of dry eye. However, firm conclusions could not be drawn from these studies because the quality of the trials was too low to establish concrete evidence. Therefore, this study was designed both to avoid the flaws of the existing trials and to assess the effectiveness, cost-effectiveness and qualitative characteristics of acupuncture treatment for dry eye.

Methods/design

One hundred fifty participants with dry eye will be recruited into three independent hospitals from different areas: Korea Institute of Oriental Medicine, DongGuk University Ilsan Oriental Hospital and Dongshin University Gwangju Oriental Hospital. The number of participants required was calculated from the data of a previous, relevant study. These patients will be randomly allocated into acupuncture treatment or artificial tear groups. Either 17 acupuncture points (bilateral BL2, GB14, TE 23, Ex1, ST1, GB20, LI4, LI11 and single GV23) will be used 3 times a week or disposable artificial tear drops (Refresh Plus^®, ALLERGAN) will be provided for use at least once a day for 4 weeks. The ocular surface disease index (OSDI), tear film break-up time (TFBUT), Schirmer I test, visual analogue scale (VAS) for self-assessment of ocular discomfort, general assessment (by both acupuncture practitioners and participants) and quality of life (QOL) through the Measure Yourself Medical Outcome Profile-2 (MYMOP-2) will be assessed for approximately 3-months for each study participant. In addition, qualitative study and cost-effectiveness of acupuncture treatment will be conducted.

Trial registration

ClinicalTrials.gov (Identifier: NCT01105221).     

Reassessment of hydrogen tolerance in <Emphasis Type="Italic">Caldicellulosiruptor saccharolyticus</Emphasis>

Background

Caldicellulosiruptor saccharolyticus has the ability to produce hydrogen (H₂) at high yields from a wide spectrum of carbon sources, and has therefore gained industrial interest. For a cost-effective biohydrogen process, the ability of an organism to tolerate high partial pressures of H₂ (P_H2) is a critical aspect to eliminate the need for continuous stripping of the produced H₂ from the bioreactor.

Results

Herein, we demonstrate that, under given conditions, growth and H₂ production in C. saccharolyticus can be sustained at P_H2 up to 67 kPa in a chemostat. At this P_H2, 38% and 16% of the pyruvate flux was redirected to lactate and ethanol, respectively, to maintain a relatively low cytosolic NADH/NAD ratio (0.12 mol/mol). To investigate the effect of the redox ratio on the glycolytic flux, a kinetic model describing the activity of the key glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was developed. Indeed, at NADH/NAD ratios of 0.12 mol/mol (K i of NADH = 0.03 ± 0.01 mM) GAPDH activity was inhibited by only 50% allowing still a high glycolytic flux (3.2 ± 0.4 mM/h). Even at high NADH/NAD ratios up to 1 mol/mol the enzyme was not completely inhibited. During batch cultivations, hydrogen tolerance of C. saccharolyticus was dependent on the growth phase of the organism as well as the carbon and energy source used. The obtained results were analyzed, based on thermodynamic and enzyme kinetic considerations, to gain insight in the mechanism underlying the unique ability of C. saccharolyticus to grow and produce H₂ under relatively high P_H2.

Conclusion

C. saccharolyticus is able to grow and produce hydrogen at high P_H2, hence eliminating the need of gas sparging in its cultures. Under this condition, it has a unique ability to fine tune its metabolism by maintaining the glycolytic flux through regulating GAPDH activity and redistribution of pyruvate flux. Concerning the later, xylose-rich feedstock should be preferred over the sucrose-rich one for better H₂ yield.

     

Celecoxib: considerations regarding its potential disease-modifying properties in osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive loss of articular cartilage, subchondral bone sclerosis, osteophyte formation, and synovial inflammation, causing substantial physical disability, impaired quality of life, and significant health care utilization. Traditionally, non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase (COX)-2 inhibitors, have been used to treat pain and inflammation in OA. Besides its anti-inflammatory properties, evidence is accumulating that celecoxib, one of the selective COX-2 inhibitors, has additional disease-modifying effects. Celecoxib was shown to affect all structures involved in OA pathogenesis: cartilage, bone, and synovium. As well as COX-2 inhibition, evidence indicates that celecoxib also modulates COX-2-independent signal transduction pathways. These findings raise the question of whether celecoxib, and potentially other coxibs, is more than just an anti-inflammatory and analgesic drug. Can celecoxib be considered a disease-modifying osteoarthritic drug? In this review, these direct effects of celecoxib on cartilage, bone, and synoviocytes in OA treatment are discussed.     

Can anti-cyclic citrullinated peptide antibody-negative RA be subdivided into clinical subphenotypes?

Introduction  

Studies investigating genetic risk factors for susceptibility to rheumatoid arthritis (RA) studied anti-citrullinated peptide antibody (CCP)-positive RA more frequently than anti-CCP-negative RA. One of the reasons for this is the perception that anti-CCP-negative RA may include patients that fulfilled criteria for RA but belong to a wide range of diagnoses. We aimed to evaluate the validity of this notion and explored whether clinical subphenotypes can be discerned within anti-CCP-negative RA.     

Streamlining genomes: toward the generation of simplified and stabilized microbial systems

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Highlights? Top-down and bottom-up approaches to genome streamlining. ? Computational support for constructing and refactoring streamlined genomes. ? From genome engineering to metabolic reprogramming. ? Perspectives in applied genome engineering.     

PHLDA2 is an imprinted gene in cattle

Genomic imprinting is an epigenetic non-Mendelian phenomenon found predominantly in placental mammals. Imprinted genes display differential expression in the offspring depending on whether the gene is maternally or paternally inherited. Currently, some 100 imprinted genes have been reported in mammals, and while some of these genes are imprinted across most mammalian species, others have been shown to be imprinted in only a few species. The PHLDA2 gene that codes for a pleckstrin homology-like domain, family A (member 2), protein has to date been shown to be a maternally expressed imprinted gene in humans, mice and pigs. Genes subject to imprinting can have major effects on mammalian growth, development and disease. For instance, disruption of imprinted genes can lead to aberrant growth syndromes in cloned domestic mammals, and it has been demonstrated that PHLDA2 mRNA expression levels are aberrant in the placenta of somatic clones of cattle. In this study, we demonstrate that PHLDA2 is expressed across a range of cattle foetal tissues and stages and provide the first evidence that PHLDA2 is a monoallelically expressed imprinted gene in cattle foetal tissues, and also in the bovine placenta.     

In vitro glucocorticoid sensitivity is associated with clinical glucocorticoid therapy outcome in rheumatoid arthritis

Introduction

Genetic and disease-related factors give rise to a wide spectrum of glucocorticoid (GC) sensitivity in rheumatoid arthritis (RA). In clinical practice, GC treatment is not adapted to these differences in GC sensitivity. In vitro assessment of GC sensitivity before the start of therapy could allow more individualized GC therapy. The aim of the study was to investigate the association between in vitro and in vivo GC sensitivity in RA.

Methods

Thirty-eight early and 37 established RA patients were prospectively studied. In vitro GC sensitivity was assessed with dexamethasone-induced effects on interleukin-2 (IL-2) and glucocorticoid-induced leucine zipper (GILZ) messenger RNA expression in peripheral blood mononuclear cells (PBMCs). A whole-cell dexamethasone-binding assay was used to measure number and affinity (1/K_D) of glucocorticoid receptors (GRs).In vivo GC sensitivity was determined by measuring the disease activity score (DAS) and health assessment questionnaire disability index (HAQ-DI) score before and after 2 weeks of standardized GC treatment.

Results

GR number was positively correlated with improvement in DAS. IL-2-EC₅₀ and GILZ-EC₅₀ values both had weak near-significant correlations with clinical improvement in DAS in intramuscularly treated patients only. HAQ responders had lower GILZ-EC₅₀ values and higher GR number and K_D.

Conclusions

Baseline cellular in vitro glucocorticoid sensitivity is modestly associated with in vivo improvement in DAS and HAQ-DI score after GC bridging therapy in RA. Further studies are needed to evaluate whether in vitro GC sensitivity may support the development of tailor-made GC therapy in RA.     

Induction of long-term B-cell depletion in refractory rheumatoid arthritis patients preferentially affects autoreactive more than protective humoral immunity

Introduction

B-cell depletion has become a common treatment strategy in anti-TNF-refractory rheumatoid arthritis (RA). Although the exact mechanism of how B-cell depletion leads to clinical amelioration in RA remains to be elucidated, repetitive treatment with B-cell-depleting agents leading to long-term B-cell depletion has been reported to be beneficial. The latter has led to the hypothesis that the beneficial effects of B-cell depletion might act through their influence on pathogenic autoreactive plasma cells.

Methods

In this study, we investigated the effects of a fixed retreatment regimen with anti-CD20 mAbs on the humoral (auto)immune system in a cohort of therapy-refractory RA patients.

Results

Fixed retreatment led to long-term B-cell depletion in peripheral blood, bone marrow and, to a lesser extent, synovium. Also, pathologic autoantibody secretion (that is, anticitrullinated peptide antibodies (ACPAs)) was more profoundly affected by long-term depletion than by physiological protective antibody secretion (that is, against measles, mumps and rubella). This was further illustrated by a significantly shorter estimated life span of ACPA-IgG secretion compared to total IgG secretion as well as protective antibody secretion.

Conclusion

By studying plasma cell function during an extensive 2-year period of B-cell depletion, autoantibody secretion was significantly shorter-lived than physiologically protective antibody secretion. This suggests that the longevity of autoreactive plasma cells is different from protective long-lived plasma cells and might indicate a therapeutic window for therapies that target plasma cells.