Abstract Background Disturbed sleep may confer risk for suicidal behaviors. Polysomnographic (PSG) sleep parameters have not been systematically evaluated in association with suicidal ideation (SI) ...among individuals with treatment-resistant depression (TRD). Methods This secondary data analysis included 54 TRD individuals (N=30 with major depressive disorder (MDD) and N=24 with bipolar depression (BD)). PSG sleep parameters included Sleep Efficiency (SE), Total Sleep Time (TST), Wakefulness After Sleep Onset (WASO), REM percent/latency, and non-REM (NREM) Sleep Stages 1–4. The Hamilton Depression Rating Scale (HAM-D) was used to group participants according to presence or absence of SI. Sleep abnormalities were hypothesized among those with current SI. ANOVA analyses were conducted before (Model 1) and after adjusting for depression (Model 2) and diagnostic variables (Model 3). Results Significant differences in PSG parameters were observed in Model 1; those with SI had less NREM Stage 4 sleep (p<.05). After adjusting for central covariates, Models 2 and 3 revealed significantly less NREM Stage 4 sleep, lower SE (P<.05), and higher WASO (P<.05) among those with SI. BD participants with SI also had less NREM Stage 4 and more NREM Stage 1 sleep. Limitations 1) a predominantly white sample; 2) exclusion of imminent suicide risk; 3) concomitant mood stabilizer use among BD patients; and 4) single-item SI assessment. Conclusions Independent of depression severity, SI was associated with less NREM Stage 4 sleep, and higher nocturnal wakefulness across diagnostic groups. Sleep may warrant further investigation in the pathogenesis of suicide risk, particularly in TRD, where risk may be heightened.
Young adults attempt suicide at disproportionately high rates relative to other groups and demonstrate high rates of sleep disturbance. No study has yet prospectively evaluated disturbed sleep as an ...acute indicator of risk using an objective index of sleep. We investigated objective and subjective parameters of disturbed sleep as a warning sign of suicidal ideation among young adults over an acute period.
A longitudinal study across a 21-day observation period and 3 time points. Fifty of 4,847 participants (aged 18-23 years) were prescreened from a university undergraduate research pool (February 2007-June 2008) on the basis of suicide attempt history and recent suicidal ideation. Actigraphic and subjective sleep parameters were evaluated as acute predictors of suicidal ideation (Beck Scale for Suicide Ideation), with adjustment for baseline symptoms. Hierarchical regression analyses were employed to predict residual change scores.
Ninety-six percent of participants (n = 48) endorsed a suicide attempt history. Mean actigraphy values revealed objectively disturbed sleep parameters; 78% (n = 39) and 36% (n = 18) endorsed clinically significant insomnia and nightmares, respectively. When results were controlled for baseline suicidal and depressive symptoms, actigraphic and subjective sleep parameters predicted suicidal ideation residual change scores at 7- and 21-day follow-ups (P < .001). Specifically, actigraphy-defined variability in sleep timing, insomnia, and nightmares predicted increases in suicidal ideation (P < .05). In a test of competing risk factors, sleep variability outperformed depressive symptoms in the longitudinal prediction of suicidal ideation across time points (P < .05).
Objectively and subjectively measured sleep disturbances predicted acute suicidal ideation increases in this population, independent of depressed mood. Self-reported insomnia and nightmares and actigraphically assessed sleep variability emerged as acute warning signs of suicidal ideation. These findings highlight the potential utility of sleep as a proposed biomarker of suicide risk and a therapeutic target.
Increasing research indicates that sleep disturbances may confer increased risk for suicidal behaviors, including suicidal ideation, suicide attempts, and death by suicide. Despite increased ...investigation, a number of methodological problems present important limitations to the validity and generalizability of findings in this area, which warrant additional focus. To evaluate and delineate sleep disturbances as an evidence-based suicide risk factor, a systematic review of the extant literature was conducted with methodological considerations as a central focus. The following methodologic criteria were required for inclusion: the report (1) evaluated an index of sleep disturbance; (2) examined an outcome measure for suicidal behavior; (3) adjusted for presence of a depression diagnosis or depression severity, as a covariate; and (4) represented an original investigation as opposed to a chart review. Reports meeting inclusion criteria were further classified and reviewed according to: study design and timeframe; sample type and size; sleep disturbance, suicide risk, and depression covariate assessment measure(s); and presence of positive versus negative findings. Based on keyword search, the following search engines were used: PubMed and PsycINFO. Search criteria generated
N
= 82 articles representing original investigations focused on sleep disturbances and suicide outcomes. Of these,
N
= 18 met inclusion criteria for review based on systematic analysis. Of the reports identified,
N
= 18 evaluated insomnia or poor sleep quality symptoms, whereas
N
= 8 assessed nightmares in association with suicide risk. Despite considerable differences in study designs, samples, and assessment techniques, the comparison of such reports indicates preliminary, converging evidence for sleep disturbances as an empirical risk factor for suicidal behaviors, while highlighting important, future directions for increased investigation.
Intake of trans fatty acids (TFA), which are consumed by eating foods made from partially hydrogenated vegetable oils, is associated with a higher risk of cardiovascular disease. This relation can be ...explained by many factors including TFA's negative effect on endothelial function and reduced nitric oxide (NO) bioavailability. In this study we investigated the effects of three different TFA (2 common isomers of C18 found in partially hydrogenated vegetable oil and a C18 isomer found from ruminant-derived-dairy products and meat) on endothelial NF-κB activation and nitric oxide (NO) production. Human endothelial cells were treated with increasing concentrations of Elaidic (trans-C18:1 (9 trans)), Linoelaidic (trans-C18:2 (9 trans, 12 trans)), and Transvaccenic (trans-C18:1 (11 trans)) for 3 h. Both Elaidic and Linoelaidic acids were associated with increasing NF-κB activation as measured by IL-6 levels and phosphorylation of IκBα, and impairment of endothelial insulin signaling and NO production, whereas Transvaccenic acid was not associated with these responses. We also measured superoxide production, which has been hypothesized to be necessary in fatty acid-dependent activation of NF-κB. Both Elaidic acid and Linoelaidic acid are associated with increased superoxide production, whereas Transvaccenic acid (which did not induce inflammatory responses) did not increase superoxide production. We observed differential activation of endothelial superoxide production, NF-κB activation, and reduction in NO production by different C18 isomers suggesting that the location and number of trans double bonds effect endothelial NF-κB activation.
A Drug-Eluting Contact Lens Ciolino, Joseph B; Hoare, Todd R; Iwata, Naomi G ...
Investigative ophthalmology & visual science,
07/2009, Letnik:
50, Številka:
7
Journal Article
Recenzirano
Odprti dostop
To formulate and characterize a drug-eluting contact lens designed to provide extended, controlled release of a drug.
Prototype contact lenses were created by coating PLGA (polylactic-co-glycolic ...acid) films containing test compounds with pHEMA (polyhydroxyethyl methacrylate) by ultraviolet light polymerization. The films, containing encapsulated fluorescein or ciprofloxacin, were characterized by scanning electron microscopy. Release studies were conducted in phosphate-buffered saline at 37 degrees C with continuous shaking. Ciprofloxacin eluted from the contact lens was studied in an antimicrobial assay to verify antimicrobial effectiveness.
After a brief and minimal initial burst, the prototype contact lenses demonstrated controlled release of the molecules studied, with zero-order release kinetics under infinite sink conditions for over 4 weeks. The rate of drug release was controlled by changing either the ratio of drug to PLGA or the molecular mass of the PLGA used. Both the PLGA and the pHEMA affected release kinetics. Ciprofloxacin released from the contact lenses inhibited ciprofloxacin-sensitive Staphylococcus aureus at all time-points tested.
A prototype contact lens for sustained drug release consisting of a thin drug-PLGA film coated with pHEMA could be used as a platform for ocular drug delivery with widespread therapeutic applications.
To collect clinical information and
mutation data on patients with Blau syndrome and to evaluate their prognosis.
Fifty patients with
mutations were analysed. The activity of each
mutant was ...evaluated in HEK293 cells by reporter assay. Clinical information was collected from medical records through the attending physicians.
The study population comprised 26 males and 24 females aged 0-61 years. Thirty-two cases were sporadic, and 18 were familial from 9 unrelated families. Fifteen different mutations in
were identified, including 2 novel mutations (p.W490S and D512V); all showed spontaneous nuclear factor kappa B activation, and the most common mutation was p.R334W. Twenty-six patients had fever at relatively early timepoints in the disease course. Forty-three of 47 patients had a skin rash. The onset of disease in 9 patients was recognised after BCG vaccination. Forty-five of 49 patients had joint lesions. Thirty-eight of 50 patients had ocular symptoms, 7 of which resulted in blindness. After the diagnosis of Blau syndrome, 26 patients were treated with biologics; all were antitumour necrosis factor agents. Only 3 patients were treated with biologics alone; the others received a biologic in combination with methotrexate and/or prednisolone. None of the patients who became blind received biologic treatment.
In patients with Blau syndrome, severe joint contractures and blindness may occur if diagnosis and appropriate treatment are delayed. Early treatment with a biologic agent may improve the prognosis.
Summary Background Systemic-onset juvenile idiopathic arthritis does not always respond to available treatments, including antitumour necrosis factor agents. We investigated the efficacy and safety ...of tocilizumab, an anti-interleukin-6-receptor monoclonal antibody, in children with this disorder. Methods 56 children (aged 2–19 years) with disease refractory to conventional treatment were given three doses of tocilizumab 8 mg/kg every 2 weeks during a 6-week open-label lead-in phase. Patients achieving an American College of Rheumatology Pediatric (ACR Pedi) 30 response and a C-reactive protein concentration (CRP) of less than 5 mg/L were randomly assigned to receive placebo or to continue tocilizumab treatment for 12 weeks or until withdrawal for rescue medication in a double-blind phase. The primary endpoint of the double-blind phase was an ACR Pedi 30 response and CRP concentration of less than 15 mg/L. Patients responding to tocilizumab and needing further treatment were enrolled in an open-label extension phase for at least 48 weeks. The analysis was done by intention to treat. This study is registered with ClinicalTrials.gov , numbers NCT00144599 (for the open-label lead-in and double-blind phases) and NCT00144612 (for the open-label extension phase). Findings At the end of the open-label lead-in phase, ACR Pedi 30, 50, and 70 responses were achieved by 51 (91%), 48 (86%), and 38 (68%) patients, respectively. 43 patients continued to the double-blind phase and were included in the efficacy analysis. Four (17%) of 23 patients in the placebo group maintained an ACR Pedi 30 response and a CRP concentration of less than 15 mg/L compared with 16 (80%) of 20 in the tocilizumab group (p<0·0001). By week 48 of the open-label extension phase, ACR Pedi 30, 50, and 70 responses were achieved by 47 (98%), 45 (94%), and 43 (90%) of 48 patients, respectively. Serious adverse events were anaphylactoid reaction, gastrointestinal haemorrhage, bronchitis, and gastroenteritis. Interpretation Tocilizumab is effective in children with systemic-onset juvenile idiopathic arthritis. It might therefore be a suitable treatment in the control of this disorder, which has so far been difficult to manage. Funding Chugai Pharmaceuticals.
Abstract
Objective
To investigate the clinical significance of serum IL-18 levels for the diagnosis of systemic JIA (s-JIA) and to predict the disease course of s-JIA.
Methods
Overall, 116 patients ...with s-JIA, 151 with other diseases and 20 healthy controls were analysed. Serum IL-18 levels were measured longitudinally in 41 patients with s-JIA from active phase through remission phase. Serum IL-18 levels were quantified via enzyme-linked immunosorbent assay and the results were compared with clinical features and the disease course of s-JIA.
Results
The serum IL-18 level cut-off value for differentiation of s-JIA from other diseases was 4800 pg/ml. In patients with a monocyclic course, serum IL-18 levels steadily decreased during the inactive phase and low levels were sustained during remission. In contrast, in patients with a chronic course, elevated serum IL-18 levels were sustained even during the inactive phase. In patients with a polycyclic course, serum IL-18 levels were elevated during disease flares and normalized during the inactive phase. The serum IL-18 level cut-off value for diagnosis of remission in s-JIA was 595 pg/ml,
Conclusion
Serum IL-18 levels of >4800 pg/ml may be useful for differentiating between s-JIA and other diseases. Monitoring of serum IL-18 levels might be useful for predicting the disease course and assessing remission in s-JIA.
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