Treatment of chronically depressed patients: A multisite randomized controlled trial testing the effectiveness of \u27Cognitive Behavioral Analysis System of Psychotherapy\u27 (CBASP) for chronic depressions versus usual secondary care

Background \u27Cognitive Behavioral Analysis System of Psychotherapy\u27 (CBASP) is a form of psychotherapy specifically developed for patients with chronic depression. In a study in the U.S., remarkable favorable effects of CBASP have been demonstrated. However, no other studies have as yet replicated these findings and CBASP has not been tested outside the United States. This protocol describes a randomized controlled trial on the effectiveness of CBASP in the Netherlands. Methods/Design The purpose of the present paper is to report the study protocol of a multisite randomized controlled trial testing the effectiveness of \u27Cognitive Behavioral Analysis System of Psychotherapy\u27 (CBASP) for chronic depression in the Netherlands. In this study, CBASP in combination with medication, will be tested versus usual secondary care in combination with medication. The aim is to recruit 160 patients from three mental health care organizations. Depressive symptoms will be assessed at baseline, after 8 weeks, 16 weeks, 32 weeks and 52 weeks, using the 28-item Inventory for Depressive Symptomatology (IDS). Effect modification by co morbid anxiety, alcohol consumption, general and social functioning and working alliance will be tested. GEE analyses of covariance, controlling for baseline value and center will be used to estimate the overall treatment effectiveness (difference in IDS score) at post-treatment and follow up. The primary analysis will be by \u27intention to treat\u27 using double sided tests. An economic analysis will compare the two groups in terms of mean costs and cost-effectiveness from a societal perspective. Discussion The study will provide an answer to the question whether the favorable effects of CBASP can be replicated outside the US. Trial Registration The Dutch Cochrane Center, NTR1090

Traffic-related microplastic particles, metals, and organic pollutants in an urban area under reconstruction

In urban environments, particularly areas under reconstruction, metals, organic pollutants (OP), and microplastics (MP), are released in large amounts due to heavy traffic. Road runoff, a major transport route for urban pollutants, contributes significantly to a deteriorated water quality in receiving waters. This study was conducted in Gothenburg, Sweden, and is unique because it simultaneously investigates the occurrence of OP, metals, and MP on roads and in stormwater from an urban area under reconstruction. Correlations between the various pollutants were also explored. The study was carried out by collecting washwater and sweepsand generated from street sweeping, road surface sampling, and flow-proportional stormwater sampling on several occasions. The liquid and solid samples were analyzed for metals, polycyclic aromatic hydrocarbons (PAH), oxy-PAH, aliphatics, aromatics, phthalates, and MP. The occurrence of OP was also analyzed with a non-target screening method of selected samples. Microplastics, i.e. plastic fragments/fibers, paint fragments, tire wear particles (TWP) and bitumen, were analyzed with a method based on density separation with sodium iodide and identification with a stereo microscope, melt-tests, and tactile identification. MP concentrations amounted to 1500 particles/L in stormwater, 51,000 particles/L in washwater, and 2.6 7 106 particles/kg dw in sweepsand. In stormwater, washwater and sweepsand, MP ≥20 μm were found to be dominated by TWP (38%, 83% and 78%, respectively). The results confirm traffic as an important source to MP, OP, and metal emissions. Concentrations exceeding water and sediment quality guidelines for metals (e.g. Cu and Zn), PAH, phthalates, and aliphatic hydrocarbons in the C16–C35 fraction were found in most samples. The results show that the street sweeper collects large amounts of polluted materials and thereby prevents further spread of the pollutants to the receiving stormwater

The role of complement in ocular pathology

Functionally active complement system and complement regulatory proteins are present in the normal human and rodent eye. Complement activation and its regulation by ocular complement regulatory proteins contribute to the pathology of various ocular diseases including keratitis, uveitis and age-related macular degeneration. Furthermore, a strong relationship between age-related macular degeneration and polymorphism in the genes of certain complement components/complement regulatory proteins is now well established. Recombinant forms of the naturally occurring complement regulatory proteins have been exploited in the animal models for treatment of these ocular diseases. It is hoped that in the future recombinant complement regulatory proteins will be used as novel therapeutic agents in the clinic for the treatment of keratitis, uveitis, and age-related macular degeneration

Male reproductive health and environmental xenoestrogens

EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, "Reproduced with permission from Environmental Health Perspectives") and a reference provided for the article from which the material was reproduced.Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.Supported by EU Contract BMH4-CT96-0314

Evaluating the Suitability of Using Rat Models for Preclinical Efficacy and Side Effects with Inhaled Corticosteroids Nanosuspension Formulations

Inhaled corticosteroids (ICS) are often prescribed as first-line therapy for patients with asthma Despite their efficacy and improved safety profile compared with oral corticosteroids, the potential for systemic side effects continues to cause concern. In order to reduce the potential for systemic side effects, the pharmaceutical industry has begun efforts to generate new drugs with pulmonary-targeted topical efficacy. One of the major challenges of this approach is to differentiate both efficacy and side effects (pulmonary vs. systemic) in a preclinical animal model. In this study, fluticasone and ciclesonide were used as tool compounds to explore the possibility of demonstrating both efficacy and side effects in a rat model using pulmonary delivery via intratracheal (IT) instillation with nanosuspension formulations. The inhibition of neutrophil infiltration into bronchoalveolar lavage fluid (BALF) and cytokine (TNFα) production were utilized to assess pulmonary efficacy, while adrenal and thymus involution as well as plasma corticosterone suppression was measured to assess systemic side effects. Based on neutrophil infiltration and cytokine production data, the ED50s for ciclesonide and fluticasone were calculated to be 0.1 and 0.03 mg, respectively. At the ED50, the average adrenal involution was 7.6 ± 5.3% for ciclesonide versus 16.6 ± 5.1% for fluticasone, while the average thymus involution was 41.0 ± 4.3% for ciclesonide versus 59.5 ± 5.8% for fluticasone. However, the differentiation became less significant when the dose was pushed to the EDmax (0.3 mg for ciclesonide, 0.1 mg for fluticasone). Overall, the efficacy and side effect profiles of the two compounds exhibited differentiation at low to mid doses (0.03–0.1 mg ciclesonide, 0.01–0.03 mg fluticasone), while this differentiation diminished at the maximum efficacious dose (0.3 mg ciclesonide, 0.1 mg fluticasone), likely due to overdosing in this model. We conclude that the rat LPS model using IT administration of nanosuspensions of ICS is a useful tool to demonstrate pulmonary-targeted efficacy and to differentiate the side effects. However, it is only suitable at sub-maximum efficacious levels

A Recombinant Vaccine Effectively Induces C5a-Specific Neutralizing Antibodies and Prevents Arthritis

OBJECTIVES: To develop and validate a recombinant vaccine to attenuate inflammation in arthritis by sustained neutralization of the anaphylatoxin C5a. METHODS: We constructed and expressed fusion protein of C5a and maltose binding protein. Efficacy of specific C5a neutralization was tested using the fusion protein as vaccine in three different arthritis mouse models: collagen induced arthritis (CIA), chronic relapsing CIA and collagen antibody induced arthritis (CAIA). Levels of anti-C5a antibodies and anti-collagen type II were measured by ELISA. C5a neutralization assay was done using a rat basophilic leukemia cell-line transfected with the human C5aR. Complement activity was determined using a hemolytic assay and joint morphology was assessed by histology. RESULTS: Vaccination of mice with MBP-C5a led to significant reduction of arthritis incidence and severity but not anti-collagen antibody synthesis. Histology of the MBP-C5a and control (MBP or PBS) vaccinated mice paws confirmed the vaccination effect. Sera from the vaccinated mice developed C5a-specific neutralizing antibodies, however C5 activation and formation of the membrane attack complex by C5b were not significantly altered. CONCLUSIONS: Exploitation of host immune response to generate sustained C5a neutralizing antibodies without significantly compromising C5/C5b activity is a useful strategy for developing an effective vaccine for antibody mediated and C5a dependent inflammatory diseases. Further developing of such a therapeutic vaccine would be more optimal and cost effective to attenuate inflammation without affecting host immunity

Chronic Fluid Flow Is an Environmental Modifier of Renal Epithelial Function

Although solitary or sensory cilia are present in most cells of the body and their existence has been known since the sixties, very little is been known about their functions. One suspected function is fluid flow sensing- physical bending of cilia produces an influx of Ca++, which can then result in a variety of activated signaling pathways. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a progressive disease, typically appearing in the 5th decade of life and is one of the most common monogenetic inherited human diseases, affecting approximately 600,000 people in the United States. Because ADPKD is a slowly progressing disease, I asked how fluid flow may act, via the primary cilium, to alter epithelial physiology during the course of cell turnover. I performed an experiment to determine under what conditions fluid flow can result in a change of function of renal epithelial tissue. A wildtype epithelial cell line derived the cortical collecting duct of a heterozygous offspring of the Immortomouse (Charles River Laboratory) was selected as our model system. Gentle orbital shaking was used to induce physiologically relevant fluid flow, and periodic measurements of the transepithelial Sodium current were performed. At the conclusion of the experiment, mechanosensitive proteins of interest were visualized by immunostaining. I found that fluid flow, in itself, modifies the transepithelial sodium current, cell proliferation, and the actin cytoskeleton. These results significantly impact the understanding of both the mechanosensation function of primary cilia as well as the understanding of ADPKD disease progression

A Dutch guideline for the treatment of scoliosis in neuromuscular disorders

<p>Abstract</p> <p>Background</p> <p>Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is considered the primary treatment option for correcting severe scoliosis in neuromuscular disorders. Surgery in this population requires a multidisciplinary approach, careful planning, dedicated surgical procedures, and specialized after care.</p> <p>Methods</p> <p>The guideline is based on scientific evidence and expert opinions. A multidisciplinary working group representing experts from all relevant specialties performed the research. A literature search was conducted to collect scientific evidence in answer to specific questions posed by the working group. Literature was classified according to the level of evidence.</p> <p>Results</p> <p>For most aspects of the treatment scientific evidence is scarce and only low level cohort studies were found. Nevertheless, a high degree of consensus was reached about the management of patients with scoliosis in neuromuscular disorders. This was translated into a set of recommendations, which are now officially accepted as a general guideline in the Netherlands.</p> <p>Conclusion</p> <p>In order to optimize the treatment for scoliosis in neuromuscular disorders a Dutch guideline has been composed. This evidence-based, multidisciplinary guideline addresses conservative treatment, the preoperative, perioperative, and postoperative care of scoliosis in neuromuscular disorders.</p