Efficient conversion of hemicellulose sugars from spent sulfite liquor into optically pure L-lactic acid by Enterococcus mundtii.

Spent sulfite liquor (SSL), a waste stream from wood pulp production, has great potential as carbon source for future industrial fermentations. In the present study, SSL was separated into a hemicellulose derived sugar syrup (HDSS) and a lignosulfonic fraction by simulated moving bed chromatography. The recovery of SSL sugars in the HDSS was 89% and the fermentation inhibitors furfural, 5-hydroxymethylfurfural and acetic acid were removed by 98.7%, 60.5% and 75.5%, respectively. The obtained sugars have been converted to L-lactic acid, a building block for bioplastics, by fermentation with the lactic acid bacterium Enterococcus mundtii DSM4838. Batch fermentations on HDSS produced up to 56.3 g/L L-lactic acid. Simultaneous conversion of pentose and hexose sugars during fed-batch fermentation of wildtype E. mundtii led to 87.9 g/L optically pure (>99%) L-lactic acid, with maximum productivities of 3.25 g/L.h and yields approaching 1.00 g/g during feeding phase from HDSS as carbon source.

Pre-birth origins of allergy and asthma.

Allergy is a chronic disease that can develop as early as infancy, suggesting that early life factors are important in its aetiology. Variable associations between size at birth, a crude marker of the fetal environment, and allergy have been reported in humans and require comprehensive review. Associations between birth weight and allergy are however confounded in humans, and we and others have therefore begun exploring the effects of early life events on allergy in experimental models. In particular, we are using ovine models to investigate whether and how a restricted environment before birth protects against allergy, whether methyl donor availability contributes to allergic protection in IUGR, and why maternal asthma during pregnancy is associated with increased risks of allergic disease in children. We found that experimental intrauterine growth restriction (IUGR) in sheep reduced cutaneous responses to antigens in progeny, despite normal or elevated IgE responses. Furthermore, maternal methyl donor supplementation in late pregnancy partially reversed effects of experimental IUGR, consistent with the proposal that epigenetic pathways underlie some but not all effects of IUGR on allergic susceptibility. Ovine experimental allergic asthma with exacerbations reduces relative fetal size in late gestation, with some changes in immune populations in fetal thymus suggestive of increased activation. Maternal allergic asthma in mice also predisposes progeny to allergy development. In conclusion, these findings in experimental models provide direct evidence that a perturbed environment before birth alters immune system development and postnatal function, and provide opportunities to investigate underlying mechanisms and develop and evaluate interventions.

Airway remodelling and inflammation in sheep lungs after chronic airway challenge with house dust mite.

BACKGROUND: Remodelling of airway walls is a significant morbidity factor in patients suffering from chronic asthma. The relationship between airway remodelling and the inflammatory response is not well defined. Sheep have been used extensively to model airway disease in humans and represent a suitable model to examine airway remodelling. OBJECTIVE: The aim of the present study was to develop a model for airway remodelling in sheep after repeated challenge with a relevant human allergen to assess the relationship of airway remodelling with inflammation. METHODS: Repeated challenges of house dust mite (HDM) extract or saline (control) were administered to local lung segments of sheep for a period of 6 months. After the last challenge, lung tissues from both challenged and unchallenged lung compartments of the same sheep were compared using morphometric image analysis and (immuno) histological studies. RESULTS: All HDM-challenged sheep developed significant bronchoalveolar lavage eosinophilia during challenge. At the end of the challenge period, significant increases in airway collagen and airway smooth muscle content were found in a proportion (3/7) of the HDM-challenged sheep. Hyperplasia of goblet cells and epithelial cells were observed in small bronchi and bronchioles exposed to allergen. Irrespective of airway remodelling changes, all HDM-challenged, but no saline-challenged sheep, displayed significant increases in mast cells in alveolar septa and airway walls of challenged lungs compared with untreated lung compartments of the same sheep. Significant increases were also observed in CD5 and gamma delta T cell subpopulations in all allergen-exposed lung parenchyma. CONCLUSION: A proportion of atopic sheep develop typical airway remodelling changes after chronic allergen challenge, which is not directly related to the level of allergic inflammation.

Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite.

BACKGROUND: Previous sheep models of asthma are based on sheep sensitized to nematode (Ascaris) allergens and these have been used to evaluate the physiological and pharmacological effects of potential anti-asthma agents. The immunological mechanisms associated with the allergic response in sheep lungs has not been examined in detail. OBJECTIVE: To develop an experimental sheep model of allergic lung inflammation based on a relevant major human allergen, house dust mite, and to define the immunological features of the allergic response in this model. METHODS: Sheep immunized subcutaneously with solubilized house dust mite extract were given a single bronchial challenge with house dust mite. Bronchoalveolar lavage (BAL) and peripheral blood leucocytes were collected before and after challenge for flow cytometry, and tissue samples were taken post-mortem (48 h post-challenge) for histology and immunohistochemical analyses. RESULTS: Immunizations with 50 microg house dust mite induced an allergen-specific IgE response in 50 to 60% of sheep (allergic sheep), with higher antigen doses increasing specific IgG1 but not IgE. Lung challenge of allergic sheep with house dust mite led to the initial recruitment of neutrophils (at 6 h post-challenge) followed by eosinophils and activated lymphocytes into the lung tissue and BAL, similar to the late-phase allergic response seen in human asthma. Eosinophil recruitment peaked at 48 h post-challenge, representing 10 to 33% of BAL leucocytes in allergen-challenged allergic sheep compared to 0 to 3% in allergen-challenged control (naïve) sheep. Lymphocytes recovered from the lung after allergen challenge were enriched for CD4+ T cells and were more activated than lymphocytes in blood. There was significant down-regulation of CD62L (L-selectin) and CD49d (VLA-4) expression after allergen challenge on BAL eosinophils and lymphocytes compared to blood. In addition, VCAM-1 (ligand for VLA-4) was up-regulated on blood vessels of allergen-challenged lungs. Eosinophils, CD4+ T cells and CD45R+ B cells were the most prominent leucocytes found in lung tissue 48 h after allergen challenge. CONCLUSION: This study demonstrates, for the first time, the ability of house dust mite to induce allergic responses in sheep lungs. This novel sheep model of allergic lung inflammation using relevant human allergens, exhibits similarities to human asthmatic disease and will be a useful tool for studies of the immunological and physiological mechanisms of allergic asthma.

Cellular kinetics of an allergic-type response in a sheep mammary gland model of inflammation.

BACKGROUND: Tissue recruitment of eosinophils and activated lymphocytes is a characteristic feature of allergic reactions. However, little is known about the involvement of specific adhesion molecules in the traffic of leucocytes during the allergic response. OBJECTIVE: To use a sheep mammary infusion model to characterize the kinetics of cell recruitment and expression of cellular adhesion molecules and activation markers on eosinophils and lymphocytes involved in an allergic-type response. METHODS: Mature non-lactating ewes were primed and challenged by direct infusion of the mammary glands with nematode larvae. Using a non-invasive method of saline infusion and 'milking' of the glands, large numbers of inflammatory cells were repeatedly sampled over 10 to 96 h following their migration into the mammary gland lumen, and analyzed by 2-colour flow cytometry. RESULTS: Leucocyte recruitment into the mammary lumen was characterized by two separate phases involving an acute neutrophilic response at 10 h post-challenge, followed by a dramatic reduction in neutrophils and appearance of eosinophils and activated lymphocytes. From 48 h post-challenge, eosinophils were predominant and represented 40 to 65% of leucocytes in the mammary lavage (MAL). Increases in activated CD4+ T cells and gammadelta+ T cells were also observed at this time-point. The kinetics of expression of cell surface molecules on eosinophils and lymphocytes in blood and MAL were compared during the course of the allergic-type reaction. Adhesion molecule expression on lymphocytes was modulated following allergen challenge and an activation of MAL vs. blood lymphocytes was seen during the later stages of the allergic response. Eosinophil expression of VLA-4 and l-selectin was down-regulated compared with blood at all time-points examined. There were high levels of expression of CD11b and CD44 on eosinophils during the early compared to the late-phase of the allergic reaction. CONCLUSION: These results indicate the existence of two separate mechanisms of eosinophil recruitment during the allergic inflammatory response.

Isolation, characterisation and expression of mRNAs encoding the ovine CC chemokines, monocyte chemoattractant protein (MCP)-1alpha and -2.

CC chemokines are important mediators of immune responses, orchestrating the differential recruitment of various leukocyte populations. Despite the large number of known CC chemokines in other species, no cDNA encoding ovine CC chemokines have been isolated. A homology cloning strategy was utilised to isolate the cDNA of ovine CC chemokines. Full-length monocyte chemoattractant protein (MCP)-1alpha and -2 cDNA have been isolated. The predicted ovine MCP-1alpha amino acid sequence shares 87 and 75% identity with bovine MCP-1alpha and porcine MCP-1, respectively. The predicted ovine MCP-2 amino acid sequence shares 92 and 85% identity with bovine and porcine MCP-2, respectively. Northern blot analysis of MCP-1alpha revealed that it is strongly expressed in cells isolated from mammary lavage fluid (MAL) of ewes given intramammary infusions of Haemonchus contortus. Weak signals were detected in mammary and abomasal tissue. Southern blot analysis of reverse transcriptase-polymerase chain reaction (RT-PCR) products indicates that MCP-1alpha mRNA levels increase in abomasum after challenge with H. contortus. MCP-1alpha mRNA levels were also increased in bronchoalveolar lavage (BAL) cells and lung tissue after house dust mite extract (HDME) challenge. Similarly, MCP-2 mRNA was detected by Northern blot analysis at high levels in MAL cells after H. contortus intramammary infusion, and increased in BAL cells and lung tissue in HDME-challenged sheep. MCP-2 mRNA was not detected by Northern blots in whole mammary or abomasal tissue, but Southern blot analysis of RT-PCR products also indicates that MCP-2 mRNA increases in abomasal tissue after challenge with H. contortus. Hence, two ovine CC chemokine mRNA have been isolated that are up-regulated in response to parasite infection and allergen challenge. Ultimately the isolation of these and other ovine CC chemokines will help elucidate a wide variety of immune responses in sheep.

Comparative T-cell responses during pregnancy in large animals and humans.

PROBLEM: Placentation in different large animal species shows a remarkable diversity in the level of trophoblast invasion into the maternal endometrial tissues. We wish to determine the influence of implantation on T-cell responses during pregnancy. METHOD OF STUDY: Review of the literature and current data. RESULTS: alphabeta-TCR+ T cells are only prominent during early pregnancy in species with relatively non-invasive placentation (pig and horse) but are rapidly downregulated in species with more invasive placentae. gammadelta-TCR+ T cells are prominent in species with moderate trophoblast invasion (ruminants) where they increase dramatically during mid and late pregnancy. gammadelta-TCR+ T cells remain prominent during late gestation in species with highly invasive placentation (humans) and, in addition, a distinct gammadelta T-cell population is present in first trimester decidua where it may play a regulatory role in controlling natural killer cell activity. The gammadelta-TCR+ population present in both ruminants and humans shows large granular morphology and contains antimicrobial proteins, suggesting their function may be to protect the uterine environment from infection during pregnancy and parturition. CONCLUSION: The comparative analysis of T-cell responses during pregnancy in different large animal species supports an increasing role for cells of the innate immune response (NK and gammadelta T cells) and a downregulation of the adaptive immune response with increasingly invasive placentation.

Polysomnographic effects of adjuvant ginkgo biloba therapy in patients with major depression medicated with trimipramine.

Sleep disturbance and cognitive impairment are frequent complaints of depressed patients under standard antidepressant medication. Therefore, additional therapies are required which specifically focus on the improvement of these deficits without exerting major side effects. Ginkgo biloba extract (EGb) has been shown to improve cognitive abilities in elderly subjects and in patients with disorders of the dementia spectrum. Animal studies surmise that EGb may reduce CRH activity, which is substantially related to depressive mood and behavior, predominantly cognition and sleep. An open non-randomized pilot study has been conducted to investigate the effects of ginkgo biloba extract (EGb Li 1370) on cognitive performance and sleep regulation in depressed inpatients. 16 patients were treated with a trimipramine (T)-monotherapy (200 mg) for six weeks. In eight of the 16 patients, an adjunct EGb therapy (240 mg/d) was applied for four weeks after a baseline week, the other eight patients remained on trimipramine monotherapy (200 mg) during the entire study. Polysomnography, cognitive psychomotor performance and psychopathology were assessed at baseline, after short-term and long-term adjunct EGb treatment, and after one week of ginkgo discontinuation (at the respective evaluation times in the eight patients on T-monotherapy). This report focuses on the results of EGb on sleep EEG pattern. EGb significantly improved sleep pattern by an increase of sleep efficiency and a reduction of awakenings. In addition, sleep stage 1 and REM-density were reduced, while stage 2 was increased. Non-REM sleep, predominantly slow wave sleep in the first sleep cycle, was significantly enhanced compared to trimipramine monotherapy. Discontinuation of EGb reversed most of these effects. Based on the animal data, these results suggest that EGb may improve sleep continuity and enhance Non-REM sleep due to a weakening of tonic CRH-activity. The compensation of the deficient Non-REM component in depression by the EGb application may provide a new additional treatment strategy, especially in the treatment of the depressive syndrome with sleep disturbance.

Origin and conservation genetics of the threatened Ute ladies'-tresses, Spiranthes diluvialis (Orchidaceae).

The Ute ladies'-tresses, Spiranthes diluvialis, is listed as a threatened orchid in west-central United States by the Federal government. Information on its origin and patterns of genetic variation is needed to develop effective conservation strategies for this species. DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to evaluate genetic variation and structure of 23 populations of S. diluvialis. In addition, four congeneric species were analyzed to determine possible origins of the putative allotetraploid S. diluvialis. DNA sequencing and PCR-RFLP analysis of the nuclear ribosomal internal transcribed spacer (ITS) and mitochondrial and chloroplast DNA noncoding regions revealed no genetic variation within or among populations of S. diluvialis. DNA sequencing revealed that S. diluvialis has rDNA of both S. magnicamporum and S. romanzoffiana, supporting the proposed origin of the allotetraploid. Parsimony and maximum likelihood analyses of cpDNA and mtDNA sequences revealed that these S. diluvialis organellar sequences were most closely related to those of S. romanzoffiana, providing evidence that the latter species is the maternal parent of S. diluvialis. The lack of genetic diversity is significant for the development of a long-term conservation strategy for S. diluvialis.

The colony-stimulating factors and collagen-induced arthritis: exacerbation of disease by M-CSF and G-CSF and requirement for endogenous M-CSF.

There is increasing evidence that the colony-stimulating factors (CSFs) may play a part in chronic inflammatory autoimmune diseases, such as rheumatoid arthritis (RA). We examined the involvement of macrophage CSF (M-CSF or CSF-1) and granulocyte CSF (G-CSF) in collagen-induced arthritis (CIA), a murine model of RA. Daily injections of M-CSF or G-CSF, 20-24 days postprimary immunization with type II collagen, exacerbated disease symptoms in suboptimally immunized DBA/1 mice. Support for the involvement of endogenous M-CSF in CIA was obtained by studies in which neutralizing monoclonal antibody reduced the severity of established CIA and also by studies showing the resistance of M-CSF-deficient op/op mice to CIA induction. These studies show that M-CSF and G-CSF can be proinflammatory in CIA and provide evidence that macrophage- and granulocyte-lineage cells can exacerbate CIA. Our results also show that M-CSF-dependent cells are essential for CIA development, suggesting M-CSF may be a suitable target for therapeutic intervention in RA.

Leucocyte phenotypes in involuting and fully involuted mammary glandular tissues and secretions of sheep.

Mammary glandular tissues and mammary secretions were obtained from sheep at 2-60 d after weaning to study the leucocyte phenotypes associated with mammary involution. From 2-4 d after weaning, neutrophils were the predominant leucocytes in the alveolar and ductal lumina. Lymphocytes were present in the alveolar and ductal epithelium, interalveolar and periductal areas. Most of the lymphocytes in the alveolar and ductal epithelium (IEL) were CD8+, some were CD45R+ and few were CD4+. In the periductal clusters and in the interalveolar areas most of the lymphocytes were CD4+. There was a significant increase (P < 0.05) in the percentages of CD45R+ granulated IEL from 2 to 7 d after weaning, and this paralleled the increase in the percentages of apoptotic cells in the glandular epithelium. By 7-60 d after weaning, most cells within the alveolar and ductal lumina were macrophages followed by predominantly CD8+ lymphocytes. CD8+ lymphocytes were still predominant in the alveolar and ductal epithelium while CD4+ cells were predominant in the interalveolar areas. Very few gammadelta+ T cells were observed at all the stages examined. The cells in the mammary secretions correlated with those observed in the alveolar and ductal lumina. At the early stages of involution, the neutrophils and macrophages were heavily laden with lipid droplets, casein and cellular debris. The most interesting feature was the presence of cells either with extensive cytoplasmic processes (LCA+MHC class II+) or cytoplasmic veils (LCA+MHC class II+CD1+), probably dendritic cells. It is concluded that the cellular constituents of the mammary gland at the latter part of involution may afford the mammary gland more resistance to infection than the lactating gland and the gland at early stages of involution. The CD45R+IEL may trigger apoptotic cell death in the mammary glandular epithelium during mammary involution.

Effect of zopiclone and temazepam on sleep EEG parameters, psychomotor and memory functions in healthy elderly volunteers.

RATIONALE: The increased prevalence of sleep disturbance in old age is accompanied by a higher prescription rate of hypnotics, predominantly benzodiazepines in the elderly. In young volunteers zopiclone exerts a beneficial effect on sleep continuity without suppression of SWS and REM sleep; psychomotor performance and vigilance seemed to be less impaired than under classical benzoediazepines. OBJECTIVE: The present study investigates the effects of zopiclone on sleep EEG and cognitive performance in comparison to temazepam and placebo in the elderly population. METHODS: Single oral doses of zopiclone (7.5 mg), temazepam (20 mg) and placebo were administered in a randomized double-blind, completely counterbalanced cross-over design to 12 healthy elderly men and women (65.9 +/- 3.6 years, range 60-70 years). On each of the 3 study nights a sleep EEG was registered from 10 p.m. to 6.30 a.m. and cognitive performance tests were applied at 8 p.m., 2 a.m. (when subjects were awake for 30 min), 7 a.m. and 9 a.m. RESULTS: After zopiclone treatment, sleep continuity had significantly improved and sleep stage 4 was increased compared to temazepam and placebo. In addition, both active substances significantly reduced REM density. Neither active compound substantially altered psychomotor and memory performance. CONCLUSIONS: Zopiclone and temazepam can be considered as effective hypnotics in elderly subjects when administered in that dosage. The superiority of zopiclone on sleep architecture may be related to a more specific action of zopiclone at the GABA-A benzodiazepine receptor complex. The suppression of REM density by both compounds and their subtle effects on cognition may reflect a GABAergic mediated reduction of cholinergic neuro-transmission.

Exacerbation of acute inflammatory arthritis by the colony-stimulating factors CSF-1 and granulocyte macrophage (GM)-CSF: evidence of macrophage infiltration and local proliferation.

CSF-1 and GM-CSF have been implicated in the pathogenesis of rheumatoid arthritis. We report the effects of CSF-1 and GM-CSF in the development of an acute methylated bovine serum albumin (mBSA)-induced murine arthritis model. Examination of histopathological features revealed that the systemic administration of CSF-1 or GM-CSF following mBSA administration into the knee resulted in the exacerbation of arthritis. This included synovial hyperplasia and joint inflammation, most evident at 7 and 14 days post-mBSA administration, and the appearance of erosive pannus tissue. The exacerbation by CSF-1 and GM-CSF was not sustained but declined in incidence and severity by 21 days post-mBSA administration, similar to the effects of IL-1beta in this model, reported here and previously. Macrophages expressing Mac-2 and F4/80 were a prominent feature of the pathology observed, particularly the infiltration of Mac-2+ macrophages seen in all mice administered CSF-1, GM-CSF or IL-1beta. Present in inflamed knees was a locally dividing population of cells which included Mac-2+ and F4/80+ macrophages. These studies demonstrate that CSF-1 and GM-CSF can exacerbate and prolong the histopathology of acute inflammatory arthritis and lend support to monocytes/macrophages being a driving influence in the pathogenesis of inflammatory arthritis.

Quality and outcomes management in the primary care practice.

In response to the trend away from thinking of health care as a commodity to one in which quality is a differentiating feature among providers, primary care practices must focus on outcomes management. This article reviews the various clinical and office-based processes that influence practice outcomes. These include patient management, chart management, practice guidelines, clinical pathways, case management, and patient information. The key to a quality program and successful outcomes management is a commitment on the part of physicians to managing these processes so that best outcomes are achievable.

MRL/lpr and MRL+/+ macrophage DNA synthesis in the absence and the presence of colony-stimulating factor-1 and granulocyte-macrophage colony-stimulating factor.

Macrophage accumulation and proliferation as well as altered macrophage properties have been observed in autoimmune MRL mice. To determine whether there might be innate differences in the proliferative responses, we examined the DNA synthesis responses of peritoneal macrophages and macrophages derived in vitro from bone marrow precursors (bone marrow-derived macrophages (BMM)). Murine peritoneal exudate macrophages normally require the addition of macrophage CSF (CSF-1) to enter cell cycle in vitro. In contrast, we have found that many thioglycollate-induced adherent peritoneal macrophages, but not resident peritoneal macrophages, from both MRL/lpr and MRL+/+ mice atypically underwent DNA synthesis even in the absence of added CSF-1. They also responded very well to granulocyte-macrophage CSF. These findings may help to explain the appearance of increased macrophage numbers in MRL lesions. In contrast to a previous report, it was found that MRL/lpr and MRL+/+ BMM did not have an enhanced response to CSF-1 and that modulation of CSF-1 receptor expression was not more rapid in MRL BMM. We also found no evidence for abnormal CSF-1 internalization and degradation or for the lpr mutation to have any enhanced effect on BMM survival in the absence of CSF-1. TNF-alpha lowered the DNA synthesis response to CSF-1 of MRL/lpr BMM rather than enhanced it, as has been reported. Our data suggest that the enhanced accumulation of macrophages in the MRL/lpr kidney cannot be explained by a proposed model of enhanced responsiveness of MRL/lpr BMM to CSF-1, including a contribution by TNF-alpha.

Protection from collagen-induced arthritis in granulocyte-macrophage colony-stimulating factor-deficient mice.

The involvement of granulocyte-macrophage CSF (GM-CSF) in collagen-induced arthritis (CIA) was examined using GM-CSF-deficient mice. Although CIA is generally considered to be restricted to mice of the H-2q or H-2r haplotypes, we examined the role of GM-CSF in the CIA model using GM-CSF-deficient (-/-) and wild-type (+/+) mice on a C57BL/6 (H-2b) background. Mice were immunized by intradermal injection at the base of the tail with chick type II collagen followed by a repeat injection 21 days later. We found, based on both clinical and histologic assessments, that wild-type mice on this background developed severe CIA, while the GM-CSF-deficient mice had virtually no disease. Mice that were heterozygous for the GM-CSF gene (+/-) collectively displayed an intermediate response between those of the GM-CSF(+/+) and GM-CSF(-/-) groups, suggesting a gene dosage effect. GM-CSF(+/+) and GM-CSF(+/-) mice exhibited CIA responses ranging from mild (single digits) to severe swelling of all four paws, while in the few GM-CSF(-/-) mice that developed CIA the disease was confined to single digits. Despite the putative role of GM-CSF in dendritic cell development, GM-CSF-deficient mice exhibited both humoral and cellular (delayed-type hypersensitivity) responses to type II collagen; however, the cellular response was significantly reduced in the GM-CSF-deficient mice compared with the wild-type controls. These findings suggest that GM-CSF is required for CIA development in mice and support the idea that GM-CSF is a key cytokine in inflammatory joint disease.

Microsleep during partial sleep deprivation in depression.

BACKGROUND: Sleep deprivation (SD) exerts a beneficial effect on mood and sleep in about 60% of depressed patients usually followed by a relapse into depression after the recovery night. Short phases of sleepiness, especially naps in the early morning, may be responsible for this phenomenon. METHODS: To evaluate the effect of short, even ultrashort phases of sleep-microsleep (MS) during partial sleep deprivation (PSD) on mood, cognitive psychomotor performance (CPP), and sleep, an electroencephalograph (EEG) was continuously recorded over 60 hours in 12 patients with major depression. Subjective mood was assessed by a visual analogue scale and CPP by a letter cancellation test. RESULTS: The results illustrate that in depressed patients during PSD the amount of MS is increased, predominantly in the early morning, which was subjectively unrecognized and not observed by nursing staff. Patients with a low cumulative amount of MS during PSD improved significantly in mood, CPP, and sleep pattern compared to the patients with a high amount of MS who showed only slight changes. CONCLUSION: Therefore, accumulated MS may influence the SD-induced positive effects in depressed patients.