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Chronic Course (chronic + course)
Selected AbstractsThe phenomenology of bipolar disorder: what drives the high rate of medical burden and determines long-term prognosis?DEPRESSION AND ANXIETY, Issue 1 2009Isabella Soreca M.D. Abstract Bipolar disorder (BD) has been classically described as one of episodic mood disturbances. New evidence suggests that a chronic course and multisystem involvement is the rule, rather than the exception, and that together with disturbances of circadian rhythms, mood instability, cognitive impairment, a high rate of medical burden is often observed. The current diagnostic approach for BD neither describes the multisystem involvement that the recent literature has highlighted nor points toward potential predictors of long- term outcome. In light of the new evidence that the long-term course of BD is associated with a high prevalence of psychiatric comorbidity and an increased mortality from medical disease, we propose a multidimensional approach that includes several symptom domains, namely affective instability, circadian rhythm dysregulation, and cognitive and executive dysfunction, presenting in various combinations that give shape to each individual presentation, and offers potential indicators of overall long-term prognosis. Depression and Anxiety, 2009. © 2008 Wiley-Liss, Inc. [source] The needs of carers of patients with anorexia and bulimia nervosaEUROPEAN EATING DISORDERS REVIEW, Issue 1 2008Holmer Graap Abstract Objective This study aims to assess the degree of distress and the need for support of carers of patients with anorexia and bulimia nervosa (BN). Methods Thirty-two carers filled out the General Health Questionnaire (GHQ-12) and the Burden Inventory (BI). In addition, they were interviewed with a semi-structured research interview, the Carers' Needs Assessment (CNA), to assess relevant problem areas as well as the needs for helpful interventions. Patients were interviewed with the Eating Disorder Examination (EDE) to assess the severity of the eating disorder. All patients met criteria for anorexia (n,=,16) or BN (n,=,16) according to DSM-IV criteria. Results The mean duration of illness was 5.6 years. The mean age of the carers was 41 years. Most of the carers were mothers or partners. In the CNA we found high numbers of problems as well as high numbers of needed interventions. The most frequently mentioned problem area was ,disappointment caused by the chronic course of the illness, concerns about the patient's future' and the most frequently reported need for support was ,counselling and support by a professional'. In three problem areas carers of persons suffering from anorexia nervosa (AN) reported significantly higher scores than carers of persons suffering from BN. Conclusions Our results suggest that carers themselves have high levels of needs which are usually not addressed in clinical practice. Copyright © 2007 John Wiley & Sons, Ltd and Eating Disorders Association. [source] Night time eating: a review of the literatureEUROPEAN EATING DISORDERS REVIEW, Issue 1 2003Martina de Zwaan Abstract This study reviews the published research on night time eating, including the night eating syndrome (NES) and the nocturnal eating/drinking syndrome (NEDS). Studies were identified by a computerized literature search (PubMed, PsycInfo) and by references from the papers obtained. In addition, published abstracts from recent conferences in the areas of eating disorders and obesity were included. Individual studies were reviewed and their results summarized. Wakeful night time eating appears to be a frequent symptom which is more common among the obese. The data suggest an early age of onset with a chronic course in many patients. There appears to be considerable overlap between NES and NEDS. Treatment studies are sparse. The clinical features of these syndromes, their comorbidities, and their prevalence rates remain a matter of debate. It is unclear if the night eating syndrome presents a distinct entity that is of clinical relevance. The current nosologies may not capture the natural clustering of eating and sleep-related pathology as it occurs in general population samples. Copyright © 2003 John Wiley & Sons, Ltd and Eating Disorders Association. [source] CTL quality and the control of human retroviral infectionsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2009Charles R. M. Bangham Abstract The CTL response plays a central part in deciding the outcome of viral infections. Evidence from host and viral genetics, gene expression microarrays and assays of T-cell phenotype and function indicate that individual differences in the efficiency of the virus-specific CTL response strongly determine the outcome of infection with the human retroviruses HTLV-1 and HIV-1. It is now believed that differences in anti-viral CTL efficiency or "quality" at the single-cell level are critical in determining the efficacy of the host response to viruses. However, it is difficult to identify and quantify the reasons for this apparent individual variation in CTL efficiency, because of the chronic course of infection and the dynamical complexity of the equilibrium that is established between the virus and the host immune response. Specifically, it is unclear whether the observed variations among infected hosts, i.e. in the frequency, phenotype and function or quality of T cells, are the causes or effects , or both , of the variation in the efficiency of virus control. [source] Serotonin norepinephrine reuptake inhibitors (SNRIs) in anxiety disorders: a comprehensive review of their clinical efficacyHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2010Bernardo Dell'Osso Abstract Anxiety disorders are common psychiatric conditions that typically require long-term treatment. This review summarizes current knowledge of the pharmacological treatment of anxiety disorders with serotonin norepinephrine reuptake inhibitors (SNRIs) with specific emphasis on the findings of recent randomized clinical trials and relevant neurobiological investigations. It is now well established that gabaergic, noradrenergic and serotonergic systems play a critical role in the pathophysiology of anxiety disorders, abnormalities in these systems being related to structural and functional alterations in specific brain areas such as the amygdala, prefrontal cortex, locus coeruleus and hippocampus, as repeatedly shown by neuroimaging studies. SNRIs selectively inhibit norepinephrine and serotonin reuptake and have shown to be efficacious and generally well tolerated treatments in patients with anxiety disorders, with some potential clinical advantages over selective serotonin reuptake inhibitors (SSRIs), which are considered by many to represent first-line pharmacological treatments in patients with anxiety disorders. Anxiety disorders are characterized by a typically chronic course, high rates of comorbidity and frequent partial response to standard treatments, and the increasing use of SNRIs reflects currently unmet clinical need, in terms of overall response, remission rates and treatment tolerability. Copyright © 2009 John Wiley & Sons, Ltd. [source] An itchy vesiculobullous eruption in a patient with chronic lymphocytic leukaemiaINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 12 2004B. Cocuroccia Summary Exaggerated reactions to insect bites are characteristic of patients with haemoproliferative disorders, particularly chronic lymphocytic leukaemia (CLL). Skin lesions usually appear after the diagnosis of leukaemia and seem unrelated to laboratory findings, disease course or therapy. Rarely, the eruption may precede the diagnosis of the haematologic malignancy. The patients usually do not recall of insect bites, and the diagnosis may require histological and laboratory investigations to exclude specific lesions or autoimmune bullous diseases. Lesions may run a chronic course and represent a therapeutic challenge. Here, we report an adult patient with CLL who developed itchy recurrent papulovesicular and bullous lesions. Differential diagnosis was made with cutaneous specific lesions of CLL, bullous pemphigoid and pemphigus vulgaris, but laboratory and histological investigations confirmed the diagnosis of an insect bite reaction. The patient was treated with oral H1 anti-histamines and topical corticosteroids under occlusion, with marked improvement after 10 days. [source] Quality of medical care of patients with acne vulgaris in Germany , nationwide survey of pharmacy clientsJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 12 2009Nadine Franzke Summary Background: No empirical "real world" data on the health care of patients with acne vulgaris in Germany currently exist. The objective of this study was to get an informative basis of health care of patients with acne vulgaris in Germany, taking into account both doctor-prescribed medication and self-medication. Patients and Methods: Surveying both medically and self-treated patients, n = 504 patients with acne vulgaris were interviewed in 48 pharmacies nationwide. In addition to socio-demographic data, the duration of illness, localization and therapy as well as patient-relevant outcomes such as patient benefit, psychological strain and markers of compliance were evaluated. The participation and significance of individual treatment providers were also evaluated. Results: A large percentage of the patients found acne vulgaris to be burdensome. Despite the longstanding necessity of treatment and the chronic course of the illness, the treatment of acne vulgaris was deemed a rather satisfactory experience by most of those affected. Dermatologists were most frequently consulted for treatment. A great number of medicinal products were further acquired through self-medication or after consulting with a pharmacist. The medically regulated therapies predominantly complied with the latest guidelines. Conclusions: Acne vulgaris is a burdensome, socio-economically relevant illness, and dermatologists treat most cases in Germany. Surveying across a network of pharmacies offers a unique access to relevant treatment data. Selection effects, particularly by choice of doctors and self-medication, were minimized. [source] GLYCOSIDASE INHIBITORY ACTIVITY AND ANTIOXIDANT PROPERTIES OF A POLYSACCHARIDE FROM THE MUSHROOM INONOTUS OBLIQUUSJOURNAL OF FOOD BIOCHEMISTRY, Issue 2010HAIXIA CHEN ABSTRACT A water-soluble polysaccharide from Inonotus obliquus (IOPS) was isolated from the mushroom Inonotus obliquus (Fr.) Pilat. The chemical compositions, molecular weight and inhibitory activities on glycosidase and antioxidant properties of IOPS were investigated. The results indicated that IOPS was an acid protein-bound polysaccharide, with a molecular weight of 1.7 × 104 Da and the contents of neutral sugar, protein and uronic acids being 42.5, 18.5 and 6.1%, respectively. IOPS exhibited an inhibitory activity against ,-glucosidase with the IC50 value of 93.3 µg/mL, whereas it had no effective inhibition on ,-amylase. Results of antioxidant activity assays revealed that IOPS had inhibitory activity on the concentration-dependent quenching of 1,1-Diphenyl-2-picrylhydrazyl and hydroxyl radicals. Furthermore, IOPS inhibited the formation of thiobarbituric acid-reactive substances in Fe2+/ascorbate-induced lipid peroxidation in rat liver tissue. These results clearly demonstrated that IOPS was one of the main bioactive components of I. obliquus that contributed to hypoglycemic activity and antioxidant activity. PRACTICAL APPLICATIONS Diabetes mellitus is one of the primary threats to human health because of its increasing prevalence, chronic course and disabling complications. Postprandial hyperglycemia plays an important role in the development of type 2 diabetes mellitus and complications associated with the disease. One therapeutic approach to decrease postprandial hyperglycemia is to retard the absorption of glucose through inhibition of carbohydrate-hydrolyzing enzymes in the digestive organs. In this study, a polysaccharide isolated from the mushroom Inonotus obliquus (IOPS) was shown to have notable glycosidase inhibitory effects and antioxidant activities. This research will benefit for the investigation of effective and safe ,-glucosidase inhibitors from natural materials. IOPS could be a good candidate for application in food and medicinal fields. It might be developed for functional food or lead compounds for use in antidiabetes. [source] The role of selected neuropeptides in pathogenesis of atopic dermatitisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2008J Salomon Abstract Background Atopic dermatitis (AD) is an inflammatory skin disease of a chronic course. The role of neuropeptides in pathogenesis of this disorder is probably not crucial; however, there is evidence that these substances influence the development and course of AD. Objective The aim of this study was to evaluate the plasma level of substance P, neuropeptide Y (NPY) and calcitonin gene related peptide (CGRP) in AD patients during exacerbation and remission of the disease. Material and methods Forty-nine patients with AD, aged 17 to 56 years, participated in the study. Among this group, there were 25 males (51%) and 24 females (49%). The disease lasted from 1 to 55 years. The severity of the disease was assessed with SCORAD index. The severity of pruritus was evaluated with Visual Analog Scale and a specially designed questionnaire. Neuropeptides plasma level was detected with radioimmunoassay. Results Substance P plasma level in AD patients during exacerbation and remission was significantly higher than in the control group. There was a negative correlation between substance P plasma level and total IgE level. CGRP plasma level during exacerbation of AD was significantly lower than in healthy controls and increased in the remission. Significantly higher CGRP concentration was observed in patients suffering from severe pruritus; however, both in patients with more and less severe pruritus, CGRP plasma level was lower than in controls. Higher CGRP plasma level was also observed in patients with more severe disease. NPY plasma level in patients with AD was significantly increased both during exacerbation and remission. During remission of AD, NPY concentration was higher than during exacerbation. [source] Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose,response studyALLERGY, Issue 2 2006T. Werfel Background:, The effect of specific immunotherapy (SIT) on eczema in atopic dermatitis is not known. Therefore, a multi-centre, randomized dose,response trial, double-blind with respect to the efficacy of a biologically standardized depot house dust mite preparation was performed. Methods:, Eighty-nine adults with a chronic course of atopic dermatitis, SCORAD ,40 and allergic sensitization to house dust mites [CAP-FEIA ,3] were included, of whom 51 completed the study. Subcutaneous SIT with a house dust mite preparation (Dermatophagoides pteronyssinus/D. farinae) applying maintenance doses of 20, 2000 and 20 000 SQ-U in weekly intervals for 1 year. The main outcome measures addressed the change of the SCORAD as average of the values after 9 and 12 months of SIT in comparison with the value at baseline. Results:, The SCORAD declined in the three dose groups in a dose-dependent manner (P = 0.0368, Jonckheere,Terpstra test) and was significantly lower in the two high-dose groups (2000, 20000 SQ-U) compared with the low-dose group of 20 SQ-U (P = 0.0379, U -test) after 1 year of SIT. The use of topical corticosteroids was significantly reduced with higher doses (P = 0.0007, Mantel,Haenszel chi-square test). Conclusions:, Allergen-SIT for 1 year with a house dust mite preparation is able to improve the eczema in patients with atopic dermatitis who are sensitized to house dust mite allergens and reduces the need for topical corticosteroids. SIT may be valuable in the treatment of this chronic skin disease. [source] Neutrophilic Figurate Erythema of InfancyPEDIATRIC DERMATOLOGY, Issue 2 2008ANNALISA PATRIZI M.D. Neutrophilic figurate erythema of infancy is a rare inflammatory dermatosis which is part of the figurate inflammatory dermatoses of infancy and is considered a variant of annular erythema of infancy. The disease is clinically characterized by annular erythematous lesions, sometimes with a polycyclic configuration, and histologically by a dermal neutrophilic infiltration with leukocytoclasia. Differential diagnosis mainly includes clear-cut severe diseases with a well-known etiology, such as neonatal lupus erythematosus and its variant erythema gyratum atrophicans transiens neonatale, erythema chronicum migrans and erythema marginatum rheumaticum, and diseases of unknown origin and with less clear limits, such as erythema annulare centrifugum and its variant familial annular erythema. Anamnesis, laboratory findings, clinical features, and histology allow the correct diagnosis and therefore, having excluded severe diseases, parents should be reassured as neutrophilic figurate erythema of infancy, as the annular erythema of infancy, is a benign disease, in most cases unassociated with other conditions and usually self-limiting over a few months, even though a chronic course may rarely occur. Our case was characterized by a chronic persistent course and by a complete resolution of the lesions only during febrile episodes. [source] Childhood Discoid Lupus Erythematosus: A Tunisian Retrospective Study of 16 CasesPEDIATRIC DERMATOLOGY, Issue 4 2003Faïka Cherif The clinical features of childhood DLE are similar to those of adult DLE in presentation and chronic course. However, children have a particularly high level of transition to systemic disease. We undertook a retrospective study of 16 children with DLE ranging in age from 2 to 15 years, seen over a 9-year period. Six were less than 10 years old at the onset of the disease. The sex ratio was equal. The frequency of childhood DLE was about 7% of the total number of DLE patients seen in our department. Photosensitivity was defined as a clinical history of induction or exacerbation of discoid lesions following sun exposure, and was present in 81% of patients. There was no progression to systemic lupus erythematosus (SLE); an average follow-up time was 10.5 months (2,30 months). We would like to emphasize the increased frequency of childhood DLE in our country and the importance of photosensitivity. However, follow-up data regarding transition to SLE is lacking, therefore we are unable to offer a prognosis to our patients. [source] Increased positive thought disorder with illness duration in patients with schizophreniaPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 6 2007KEIKO MAEDA ma Abstract It is unclear whether the severity of positive formal thought disorder, a core clinical feature of schizophrenia, is stable or worsening through the chronic course of the illness. The neurocognitive basis for positive thought disorder also remains unclear. The aim of the present paper was to examine the relationship between thought disorder as measured by the Thought Disorder Index (TDI) and duration of illness and neuropsychological indices in 79 patients with schizophrenia. TDI scores increased in proportion to illness duration. TDI scores were not associated with verbal memory or executive functioning. These results indicate an ongoing worsening of positive thought disorder through the course of illness in schizophrenia. [source] Predicting the course of juvenile dermatomyositis: Significance of early clinical and laboratory featuresARTHRITIS & RHEUMATISM, Issue 11 2008Elizabeth Stringer Objective Juvenile dermatomyositis (DM) is a rare chronic inflammatory disease of childhood. The clinical course of juvenile DM appears to be variable, and little is known about predictors of the disease course. The aims of this study were to describe the clinical course of juvenile DM and to determine whether early clinical and laboratory features can be used to predict the time to remission and/or the disease course. Methods Clinical and laboratory data from a cohort of 84 patients with juvenile DM were prospectively entered into a database (1990,2005). Remission was defined as a clinical state of no active skin rash, weakness, or elevated muscle enzyme levels for 6 months off medication. The disease course was defined as monophasic, polyphasic, or chronic. Data were reviewed at the time of diagnosis and at 3 months and 6 months after the diagnosis to determine predictors of the time to remission and/or the disease course. Results The median time to remission was 4.67 years. Sixty percent of patients had a chronic course, 37% a monophasic course, and 3% a polyphasic course. The presence of rash (most strongly indicated by Gottron's papules) at 3 months was the earliest predictor of a longer time to remission (relative risk [RR] 0.55 [95% confidence interval (95% CI) 0.37,0.81], P = 0.002). At 6 months, the presence of nailfold abnormalities and rash also predicted a longer time to remission (RR 0.35 [95% CI 0.14,0.74], P = 0.003). We were unable to determine a prediction model of disease course. Conclusion The majority of patients in our cohort had a chronic disease course. The persistence of Gottron's papules and nailfold abnormalities early in the disease course was associated with a longer time to remission. [source] The epidemiology of bipolar disorder: sociodemographic, disability and service utilization data from the Australian National Study of Low Prevalence (Psychotic) DisordersBIPOLAR DISORDERS, Issue 4 2005Vera A Morgan Objectives:, Data from the Australian National Study of Low Prevalence (Psychotic) Disorders were used to describe the clinical and sociodemographic profile of individuals with bipolar disorder, their levels of impairment and disability, and use of medication and treatment services. Methods:, A 1-month census of contacts with mental health services, private psychiatric and general practices, as well as contact points in marginalized settings, was conducted in a national catchment of 1.1 million adults. The census yielded 3,800 individuals who screened positive for psychosis, of whom a random sample of 980 were administered a comprehensive semi-structured interview schedule. Results are presented on 112 persons with an ICD-10 diagnosis of bipolar disorder. Results:, Overall, 69.6% of the 112 persons who met the ICD-10 criteria for bipolar disorder reported a recurrent episodic illness, 25.0% had a chronic course without clear remissions, and 5.4% had a single episode of mania. Assessed on a lifetime basis, suicidal ideation was common (78.6%) and levels of drug and alcohol abuse/dependence were high (32.1%). The majority (84.8%) had had at least one contact with inpatient, outpatient or emergency services in the previous year. Those with serious impairment had levels of service utilization similar to the rest of the sample, but were more likely to report a poorer quality of life and unmet service needs. While the percentage experiencing social and occupational dysfunction was substantial and similar for both sexes, women appeared to be better integrated socially than men. Comparisons with schizophrenia patients within the same survey sample highlighted less chronic impairment but equal or greater utilization of services by bipolar patients. Conclusions:, Despite low levels of chronicity, the burden of social disablement associated with bipolar disorder is high. The data suggest a number of important gaps in the provision of services for this predominantly treated population. [source] The expression pattern of interferon-inducible proteins reflects the characteristic histological distribution of infiltrating immune cells in different cutaneous lupus erythematosus subsetsBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2007J. Wenzel Summary Background, Plasmacytoid dendritic cells and type I interferons (IFNs) are supposed to play a central proinflammatory role in the pathogenesis of cutaneous lupus erythematosus (LE). The IFN-inducible chemokines CXCL9 and CXCL10 are involved in recruiting CXCR3+ effector lymphocytes from the peripheral blood into skin lesions of LE. We hypothesized that the expression pattern of IFN-inducible proteins reflects the characteristic distribution of the inflammatory infiltrate in different subsets of cutaneous LE. Objectives, To test this hypothesis in patients with LE. Methods, Lesional skin biopsies taken from patients with different subsets of LE [chronic discoid LE (CDLE), n = 12; subacute cutaneous LE (SCLE), n = 5; LE tumidus (LET), n = 4; LE profundus (LEP), n = 6] were investigated by immunohistochemistry using monoclonal antibodies to the lymphocyte surface markers CD3, CD4, CD8, CD20 and CD68, the cytotoxic proteins Tia1 and granzyme B, the chemokine receptor CXCR3, the specifically type I IFN-inducible protein myxovirus protein A (MxA) and the chemokines CXCL9 and CXCL10. Results, The expression pattern of MxA followed the distribution of the inflammatory infiltrate typically seen in the investigated cutaneous LE subsets. In CDLE and SCLE, expression was focused in the epidermis and upper dermis, while in LET a perivascular and in LEP a subcutaneous pattern was found. Similar findings were obtained for CXCL9 and CXCL10. Conclusions, Our results demonstrate a close morphological association between the expression pattern of IFN-inducible proteins and the distribution of CXCR3+ CD3+ lymphocytes in all investigated subsets of cutaneous LE. This supports the importance of an IFN-driven inflammation in this condition. Infiltrating lymphocytes carrying CXCL10 in their granules might amplify the lesional inflammation and be responsible for the chronic course of this disease. [source] Post-varicella thrombocytopenic purpuraACTA PAEDIATRICA, Issue 9 2010Achiya Amir Abstract Aims:, The aim of the study was to characterize the clinical course of post-varicella idiopathic thrombocytopenic purpura (ITP) and to asses the risk of acquiring ITP after varicella infection. Methods:, A retrospective study of all children diagnosed with ITP in a tertiary medical centre during 1998,2008. Findings were compared with the Intercontinental Childhood ITP Study Group database. The risk of acquiring ITP after a varicella infection was assessed. Results:, Ten children were diagnosed with post-varicella ITP. The incidence of post-varicella ITP was 1.9% amongst children diagnosed with ITP and 1.1% amongst children hospitalized for varicella. ITP was diagnosed, on average, 8.5 days after the onset of the varicella rash. The female-to-male ratio was 1:1.5. The average minimal platelet count was 9.5 × 109 platelets/L. Post-varicella ITP had an acute course in 80% of cases and a chronic course in the remaining 20%. Bleeding episodes occurred in three patients. During the follow-up period, 11 patients with previously diagnosed ITP developed varicella. The infection had no apparent affect on the platelet count of the children with acute ITP, but caused a relapse in 71% of the patients with chronic ITP. Conclusions: Post-varicella ITP has similar clinical features and course to non-varicella associated ITP. The calculated risk of ITP as a complication of varicella infections is approximately 1:25 000. [source] Continuous generation of colitogenic CD4+ T cells in persistent colitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2008Takayuki Tomita Abstract Inflammatory bowel diseases take chronic courses due to the expansion of colitogenic CD4+ cells. However, it is unclear whether the persistent disease is driven by continuous reactivation of colitogenic memory CD4+ cells to generate effector CD4+ cells or by continuous generation of effector CD4+ cells from naïve cells. To clarify this issue, we performed a series of sequential adoptive transfers of Ly5.2+ and Ly5.1+ CD4+CD45RBhigh cells into RAG-2,/, mice at different time points. We show here that the secondarily transferred CD4+CD45RBhigh cells can be converted to CD4+CD44highCD62L,IL-7R,high effector-memory T cells even in the presence of pre-existing effector-memory CD4+ cells. Although the total cell numbers of CD4+ cells in established colitic mice were consistently equivalent irrespective of the number of primarily transferred cells, the ratio of primarily and secondarily transferred cells was dependent on the ratio of the transferred cell numbers, but not on the order of the transfer. Of note, we found that primarily transferred CD4+ cells produced significantly lower amounts of IFN-, and IL-17 than CD4+ cells arising from secondary transfer. In conclusion, the continuous generation of colitogenic CD4+ cells that compensate for exhausted CD4+ cells may be one of the mechanisms involved in the persistence of colitis. [source] | ||||||||||||||||||||||