Characteristics of effective psychological treatments of depression: A metaregression analysis.

Although many meta-analyses have shown that psychological therapies are effective in the treatment of depression, no comprehensive metaregression analysis has been conducted to examine which characteristics of the intervention, target population, and study design are related to the effects. The authors conducted such a metaregression analysis with 83 studies (135 comparisons) in which a psychological treatment was compared with a control condition. The mean effect size of all comparisons was 0.69 (95% confidence interval = 0.60-0.79). In multivariate analyses, several variables were significant: Studies using problem-solving interventions and those aimed at women with postpartum depression or specific populations had higher effect sizes, whereas studies with students as therapists, those in which participants were recruited from clinical populations and through systematic screening, and those using care-as-usual or placebo control groups had lower effect sizes

CXCR3 Antagonism of SDF-1(5-67) Restores Trabecular Function and Prevents Retinal Neurodegeneration in a Rat Model of Ocular Hypertension

Glaucoma, the most common cause of irreversible blindness, is a neuropathy commonly initiated by pathological ocular hypertension due to unknown mechanisms of trabecular meshwork degeneration. Current antiglaucoma therapy does not target the causal trabecular pathology, which may explain why treatment failure is often observed. Here we show that the chemokine CXCL12, its truncated form SDF-1(5-67), and the receptors CXCR4 and CXCR3 are expressed in human glaucomatous trabecular tissue and a human trabecular cell line. SDF-1(5-67) is produced under the control of matrix metallo-proteinases, TNF-α, and TGF-β2, factors known to be involved in glaucoma. CXCL12 protects in vitro trabecular cells from apoptotic death via CXCR4 whereas SDF-1(5-67) induces apoptosis through CXCR3 and caspase activation. Ocular administration of SDF-1(5-67) in the rat increases intraocular pressure. In contrast, administration of a selective CXCR3 antagonist in a rat model of ocular hypertension decreases intraocular pressure, prevents retinal neurodegeneration, and preserves visual function. The protective effect of CXCR3 antagonism is related to restoration of the trabecular function. These data demonstrate that proteolytic cleavage of CXCL12 is involved in trabecular pathophysiology, and that local administration of a selective CXCR3 antagonist may be a beneficial therapeutic strategy for treating ocular hypertension and subsequent retinal degeneration

Age-related changes of the human ciliary muscle. A quantitative morphometric study

The age-related changes of the ciliary muscle of human eyes (33-87 years) were studied on histological meridional sections. Eighty-five melanoma eyes and 10 eyes of normal donors were investigated. The total area and the length of the muscle, the area of the three main portions and the distance of the inner apex of the muscle to the scleral spur were determined and correlated with age. Total area and length of the muscle show a continuous and significant decrease with age. The area of the longitudinal and reticular portion continuously decreases, whereas the area of the circular portion significantly increases with age. The decrease in area is more pronounced in the longitudinal portion than in the reticular portion of the muscle, which shows an age-related increase in connective tissue. In addition, the distance of the inner apex of the muscle to the scleral spur shortens continuously. Thus, with increasing age the ciliary muscle adopts an anterior-inward position. A similar form is seen in young eyes after ciliary muscle contraction only. There might be a functional relationship between the observed age-changes in the ciliary muscle system and the phenomenon of the so-called 'lens paradox' (steepening of the anterior and posterior curvatures of the disaccommodated lens with age)

Age-related changes of the ciliary muscle in comparison with changes induced by treatment with prostaglandin F2 alpha. An ultrastructural study in rhesus and cynomolgus monkeys

The relationship between individual ciliary muscle cells and the surrounding connective tissue was studied in the eyes of three normal, young (3-4 years) cynomolgus monkeys (Macaca fascicularis), three aged (34-36 years) rhesus monkeys (Macaca mulatta) and seven young (3-7 years) cynomolgus monkeys topically treated with prostaglandin F2 alpha (PGF2 alpha) for 4-8 days. In normal eyes, collagen fibrils and microfibrils are in places in continuity with the muscle cells' basal lamina, which is connected to the cell membrane by fine fibrillous material. In old eyes, the basal lamina is markedly thickened, masking the connection of fibrils with the muscle cells' membrane. A distinctive finding in several muscle cells of old eyes are electronlucent clefts, 60-80 nm wide, between basal lamina and cell membrane, which are not transversed by fibrils or fibrillous material. The cell membrane of these muscle cells shows large folds filled with disarranged myofilaments. Additionally, these cells contain inclusion bodies consisting of concentrically arranged double membranes. Following treatment with PGF2 alpha, similar changes are seen in young animals, too. Here, the muscle cells have lost their connection to the extracellular fibrils due to a PGF2 alpha-induced lysis of extracellular material. Lack of attachment between basal lamina and altered muscle cells in aged eyes might indicate an involvement of the extracellular matrix in age-related changes of the individual ciliary muscle cells

Posterior attachment of ciliary muscle in young, accommodating old, presbyopic monkeys

The authors studied the posterior attachment of the ciliary muscle in seven young (3-10 yr) and five old (26-34 yr) rhesus monkeys by light microscopy and electron microscopy. Posterior attachment of the muscle bundles consisted of elastic tendons, exclusively. The elastic tendons were continuous with the elastic lamina of Bruch's membrane and were also connected by smaller elastic fibers to an elastic meshwork that surrounds the pars plana vessels. In some areas, the tendons formed focal contacts with the endothelial cells. The authors found that in old eyes, the tendons and the elastic fibers of the posterior ciliary body showed pronounced structural changes. The tendons appeared thickened, showed increased amounts of associated microfibrils, and were surrounded by dense layers of thick collagen fibrils. An increased amount of collagen fibrils was also seen between the elastic layer of Bruch's membrane and the pigmented epithelium. A mechanical link between those collagen fibrils and the elastic fibers is suggested by the presence of osmiophilic points of contact. The age-related increase in elastic fibrillar material could cause decreased compliance of the posterior insertion of ciliary muscle and could be an essential factor for presbyopia in rhesus monkeys

Contractile cells in the human scleral spur

The scleral spur in 37 human (age 17-87 years) and six cynomolgus monkey eyes (2-4 years) was investigated. Serial meridional and tangential sections were studied with ultrastructural and immunocytochemical methods. The bundles of the ciliary muscle do not enter the scleral spur, but their tendons, which consist of elastic fibres join the elastic fibres in the scleral spur. Within the scleral spur a population of circularly oriented and spindle-shaped cells is found. In contrast to the ciliary muscle cells, the scleral spur cells form no bundles, but are loosely aggregated. They have long cytoplasmic processes and are connected to each other by adherens-type and gap junctions. They stain intensely for alpha-smooth muscle actin, myosin and vimentin. In contrast to the ciliary muscle cells, they do not stain for desmin. Ultrastructurally, the scleral spur cells contain abundant thin (actin) filaments, but do not otherwise show the typical ultrastructural features of ciliary muscle cells. The scleral spur cells do not express a complete basal lamina. They form individual tendinous connections with the elastic fibres in the scleral spur, which are continuous with the elastic fibres of the trabecular meshwork. The scleral spur cells are in close contact with nerve terminals containing small agranular (30-60 nm) and large granular (65-110 nm) vesicles but also with terminals containing small granular (30-60 nm) vesicles which are regarded as typical for adrenergic terminals. We conclude that the scleral spur cells are contractile myofibroblasts. Their contraction might influence the rate of the aqueous outflow

Ozone profile retrieval from limb scatter measurements in the Hartley bands: further retrieval details and profile comparisons

Abstract. SCIAMACHY limb scatter radiance measurements at selected wavelengths in the HARTLEY bands have been used to retrieve ozone profiles in the upper stratosphere and lower mesosphere. Comparisons with profiles measured by a ground based radiometer in Norway, MIPAS on board ENVISAT, HALOE on UARS and MLS on AURA indicate an agreement within 15 % between 40 and 55 km and show that the retrieval provides reliable ozone profiles at these altitudes. Above 55 km, an increasing overestimation is observed. Beside the profile comparisons, further retrieval features of the current retrieval (version 1.26) are described.