Optimizing Scripted Dialogues for an e-Health Intervention for Suicidal Veterans with Major Depression.

Suicide is a health concern among Veterans with depression. We had previously reported on scripted dialogues adapted for an e-health system that engages at-risk veterans with schizophrenia. Here we report a further adaptation of the dialogues for Veterans with depression. Usability was assessed with nine outpatients with a history of major depression and suicidality. We noted that participants preferred greater specificity in the wording of questions. Topics that elicited an emotional response dealt with questions on suicide, social isolation and family relationships. Based on feedback, dialogues were revised for patients with depression. We also compared responses between those with depression and those with schizophrenia who were previously tested. The two groups shared similar themes. Also, individuals with a history of major depression had less trouble with vocabulary comprehension but were less willing to answer more questions daily.

[Short Review of the History of Radiotherapy for Intraocular Tumours]. / Kurzer historischer Rückblick der Strahlentherapie intraokularer Tumoren.

For many decades, radiotherapy with its different modalities has proved to be the gold standard in the treatment of benign and malignant intraocular tumours. The various complicated therapeutic developments in this field cover a period of over 100 years and the present year deserves special mention because of the 100th anniversary of the first mention of a successful brachytherapy for a uveal melanoma by R. Deutschmann in Hamburg in 1915.

Using problem solving therapy to treat veterans with subsyndromal depression: a pilot study.

OBJECTIVE: We conducted a pilot study comparing problem solving therapy for primary care (PST-PC) to a dietary education control condition in middle-aged and older veterans with symptoms of emotional distress and subsyndromal depression. METHODS: This was a two-site study at the VA Pittsburgh Healthcare System and Philadelphia VA Medical Center. Participants included veterans >50 years of age referred from primary care clinics who were eligible if they obtained a pre-screen score >11 on the Centers for Epidemiologic Studies Depression (CES-D) scale. Exclusions were a DSM-IV Major Depressive Episode within the past year, active substance abuse/dependence within 1 month, current antidepressant therapy, and a Mini mental status exam score <24. Participants were randomized to receive one of two interventions--either PST-PC or an attention control condition consisting of dietary education (DIET)--each consisting of six to eight sessions within a 4-month period. RESULTS: Of 45 individuals randomized, 23 (11 PST-PC and 12 DIET) completed treatment. Using regression models in completers that examined outcomes at end of treatment while controlling for baseline scores, there were significant differences between treatment groups in SF-36 mental health component scores but not in depressive symptoms (as assessed with either the 17-item Hamilton Rating Scale for Depression or the Beck Depression Inventory), social problem solving skills, or physical health status (SF-36 physical health component score). CONCLUSIONS: These pilot study findings suggest that a six-to-eight session version of PST-PC may lead to improvements in mental health functioning in primary care veterans with subsyndromal depressive symptoms.

Risk of venous thrombosis in users of hormonal contraceptives in German gynaecological practices: a patient database analysis.

PURPOSE: Recent studies showed differences in the risk of venous thrombosis between different combined hormonal contraceptives. Database studies comprising large cohorts can add relevant aspects from daily clinical practice. The purpose of this study was to evaluate different progestogen in combination with ethinylestradiol on the risk of venous thrombosis in Germany. METHODS: Computerized data from 68,168 contraceptive users in gynecological practices throughout Germany (Disease Analyzer Database) were analyzed. The adjusted odds ratios for risk of thrombosis were estimated in users of different oral contraceptive (OC) formulations relative to users of levonorgestrel-containing preparations. RESULTS: In total, 38 (0.06 %) of the 68,168 contraceptive users had a recorded diagnosis of thrombosis within 365 days after the initial prescription. The adjusted risk was 1.95 for desogestrel (95 % CI 0.52-7.29), 2.97 for dienogest (95 % CI 0.96-9.24), 1.57 for drospirenone (95 % CI 0.46-5.38), 2.54 for chlormadinone (95 % CI 0.72-9.04), and 3.24 for norgestimate (95 % CI 0.59-17.75) compared to levonorgestrel. None of those findings reached statistical significance. The maximum absolute increase versus levonorgestrel was 6 cases per 10,000 women (n.s.). CONCLUSION: The study shows the low incidence rates of thrombosis in OC users. Since there is no significant difference, this study does not confirm an increased risk but shows only a tendency for this risk of third- and fourth-generation OC versus levonorgestrel-containing products.

Development of telehealth dialogues for monitoring suicidal patients with schizophrenia: consumer feedback.

Suicide is a health concern among individuals with schizophrenia. A telehealth system for monitoring suicidal patients with schizophrenia was developed using the Health Buddy©. The existing dialogues were improved using an expert panel; the new dialogues were tested in 10 consumers with schizophrenia and a history of suicidal behavior. Using qualitative editing, several themes emerged: (1) Certain topics elicited strong emotional responses; (2) There were concerns with confidentiality; (3) Some content was too vague and (4) There were problems with vocabulary and wording. The process yielded information for improving the intervention and demonstrated that the approach is feasible in this population.

Anhedonia in adolescents at transdiagnostic familial risk for severe mental illness: Clustering by symptoms and mechanisms of association with behavior.

BACKGROUND: Anhedonia is a transdiagnostic symptom of severe mental illness (SMI) and emerges during adolescence. Possible subphenotypes and neural mechanisms of anhedonia in adolescents at risk for SMI are understudied. METHODS: Adolescents at familial risk for SMI (N = 81) completed anhedonia (e.g., consummatory, anticipatory, social), demographic, and clinical measures and one year prior, a subsample (N = 46) completed fMRI scanning during a monetary reward task. Profiles were identified using k-means clustering of anhedonia type and differences in demographics, suicidal ideation, impulsivity, and emotional processes were examined. Moderation analyses were conducted to investigate whether levels of brain activation of reward regions moderated the relationships between anhedonia type and behaviors. RESULTS: Two-clusters emerged: a high anhedonia profile (high-anhedonia), characterized by high levels of all types of anhedonia, (N = 32) and a low anhedonia profile (low-anhedonia), characterized by low levels of anhedonia types (N = 49). Adolescents in the high-anhedonia profile reported more suicidal ideation and negative affect, and less positive affect and desire for emotional closeness than low-anhedonia profile. Furthermore, more suicidal ideation, less positive affect, and less desire for emotional closeness differentiated the familial high-risk, high-anhedonia profile adolescents from the familial high-risk, low-anhedonia profile adolescents. Across anhedonia profiles, moderation analyses revealed that adolescents with high dmPFC neural activation in response to reward had positive relationships between social, anticipatory, and consummatory anhedonia and suicidal ideation. LIMITATIONS: Small subsample with fMRI data. CONCLUSION: Profiles of anhedonia emerge transdiagnostically and vary on clinical features. Anhedonia severity and activation in frontostriatal reward areas have value for clinically important outcomes such as suicidal ideation.

Persistence in patients with breast cancer treated with tamoxifen or aromatase inhibitors: a retrospective database analysis.

Compliance and persistence are often underestimated in breast cancer (BC) treatment. The aim of our study was to analyze the persistence with tamoxifen (TAM) and aromatase inhibitors (AI) in postmenopausal women with hormone-receptor-positive BC and to identify determinants of non-persistence. We used data of the Disease Analyzer database (IMS HEALTH, Germany) including 2,067 general practices and 397 gynecological practices. Out of a dataset of 15 million patients, we identified BC patients with a first-time TAM or AI prescriptions from October 2001 to December 2010. For persistence analyses, 12,412 women on tamoxifen, 2,796 on anastrozole, 647 on exemestane, and 1,657 on letrozole met the inclusion/exclusion criteria. Within 3 years of follow-up, the discontinuation rates increased to 52.2 % for tamoxifen, 47 % for anastrozole, 55.1 % for exemestane, and 44.3 % for letrozole treated women. A minor proportion of patients switched to a different endocrine treatment; 33 % tamoxifen, 20 % anastrozole, 22.9 % exemestane, and 23 % letrozole. The multivariate hazard ratios of the cox regression models showed that patients younger than 50 were most likely to discontinue initial therapy when compared with the reference group of women over 70 (p < 0.001). In contrast, patients treated in gynecologist practice had significantly longer persistence than patients who obtained their prescriptions in general practitioner practice (p < 0.001). In addition, the presence of the co morbidities like diabetes (p < 0.001) or depression (p < 0.002) was also associated with decreased risk of treatment discontinuation. Persistence with all endocrine treatments in women with hormone-receptor-positive BC is low and needs to be significantly increased to improved outcome in clinical practice. Further research is required to understand this complex issue.

Structure guided mutagenesis of Henipavirus Receptor Binding Proteins reveals molecular determinants of receptor usage and antibody binding epitopes.

Nipah virus (NiV) is a highly lethal, zoonotic henipavirus (HNV) that causes respiratory and neurological signs and symptoms in humans. Similar to other paramyxoviruses, HNVs mediate entry into host cells through the concerted actions of two surface glycoproteins: a receptor binding protein (RBP) that mediates attachment and a fusion glycoprotein (F) that triggers fusion in an RBP-dependent manner. NiV uses ephrin-B2 (EFNB2) and ephrin-B3 (EFNB3) as entry receptors. Ghana virus (GhV), a novel HNV identified in a Ghanaian bat, use EFNB2 but not EFNB3. In this study, we employ a structure-informed approach to identify receptor interfacing residues and systematically introduce GhV-RBP residues into a NiV-RBP backbone to uncover the molecular determinants of EFNB3 usage. We reveal two regions that severely impair EFNB3 binding by NiV-RBP and EFNB3-mediated entry by NiV pseudotyped viral particles. Further analyses uncovered two point mutations (NiVN557SGhV and NiVY581TGhV) pivotal for this phenotype. Moreover, we identify NiV interaction with Y120 of EFNB3 as important for usage of this receptor. Beyond these EFNB3-related findings, we reveal two domains that restrict GhV binding of EFNB2, identify the HNV-head as an immunodominant target for polyclonal and monoclonal antibodies, and describe putative epitopes for GhV and NiV-specific monoclonal antibodies. Cumulatively, the work presented here generates useful reagents and tools that shed insight to residues important for NiV usage of EFNB3, reveals regions critical for GhV binding of EFNB2, and describes putative HNV antibody binding epitopes.

Comparative persistence and adherence to overactive bladder medications in patients with and without diabetes.

AIMS: This retrospective administrative claims-based study evaluated comparative persistence and adherence to overactive bladder (OAB) medications in US patients with and without diabetes. METHODS: Patients ≥ 18 years who initiated OAB medications between 1 January 2005 and 30 June 2008 were analysed from the Truven Health MarketScan Commercial and Medicare Supplemental databases. A 12-month baseline period prior to OAB medication initiation was used to classify patients into diabetes and non-diabetes cohorts, and measure demographic and clinical characteristics. Patients in each cohort were directly matched 1 : 1 based on index year, age, gender and geographic region. Multiple logistic regression was used to compare cohorts on outcomes of ≥ 80% adherence to OAB medications and refilling a second OAB medication prescription. Cox's proportional hazards model compared time to non-persistence with OAB medications between both cohorts. RESULTS: In total, 36,560 patients were included in each cohort. Compared with the non-diabetes cohort, the diabetes cohort had 21.5% higher odds of ≥ 80% adherence to OAB medications, 16.6% higher odds of filling a second OAB medication prescription and 10.3% lower hazard of non-persistence with OAB medications during a 12-month evaluation period. CONCLUSIONS: Patients with diabetes were more persistent and adherent to OAB medications and had higher odds of filling a second medication prescription than patients without diabetes. Further research is needed to identify factors responsible for these findings.

Development of a recovery manual for suicidal patients with schizophrenia: consumer feedback.

A recovery-oriented manual was developed for patients with schizophrenia and suicidality. It included psychoeducational information, vignettes, "workbook" sections and was reviewed by experts in suicidology, recovery, patient education, manual development and psychosocial interventions. The revised version was tested in 22 consumers with schizophrenia and a history of suicidality. Consumer-based focus groups yielded five key themes which were used to further refine the manual. A satisfaction survey indicated that 85% stated the manual was 'somewhat easy', 'easy' or 'very easy to read.' All stated it was 'very useful', 'useful' or 'somewhat useful. Thus, the manual appears to be acceptable and useful.

[Intraocular manifestations of systemic neoplasms]. / Intraokulare Manifestationen bei systemischen Tumorerkrankungen.

There are multiple possible intraocular manifestations in patients with systemic neoplasms. At first line there are uveal, retinal and vitreous metastases from carcinomas, melanomas and lymphomas. In patients with von Hippel Lindau syndrome or familiar adenomatous polyposis coli (FAP), Gardner or Turcot syndromes, fundus examinations can help in the primary diagnosis and thereby facilitate the early detection of systemic neoplasms such as cerebral and spinal haemangioblastoma, kidney or bowel cancer. Furthermore there are rare ocular paraneoplastic syndromes such as the cancer- or melanoma-associated retinopathies (CAR/MAR), the paraneoplastic optic neuropathy (PON) and the bilateral diffuse melanocytic proliferation (BDUMP) that develop secondary to systemic malignancies and can be the primary manifestation.

Suppression of the immune response in C3H/HeJ mice by protein-free lipopolysaccharides.

The experiments described herein demonstrate the plaque-forming cell response of C3H/HeJ mice can be suppressed by a Boivin type lipopolysaccharide (LPS) and a deproteinized glycolipid. Suppression was observed both in vivo and in vitro, and could be transferred to normal cells in coculture experiments. This newly discovered effect of LPS in C3H/HeJ mice indicates that the adjuvant and inhibitory action of LPS may be distinct phenomena which are under different genetic regulation. Thus, the C3H/HeJ strain provides a convenient animal model for study of immunosuppression independent of the adjuvant effect.

Immunoglobulin A1 protease, an exoenzyme of pathogenic Neisseriae, is a potent inducer of proinflammatory cytokines.

A characteristic of human pathogenic Neisseriae is the production and secretion of an immunoglobulin (Ig)A1-specific serine protease (IgA1 protease) that cleaves preferentially human IgA1 and other target proteins. Here we show a novel function for native IgA1 protease, i.e., the induction of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-8 from peripheral blood mononuclear cells. The capacity of IgA1 protease to elicit such cytokine responses in monocytes was enhanced in the presence of T lymphocytes. IgA1 protease did not induce the regulatory cytokine IL-10, which was, however, found in response to lipopolysaccharide and phytohemagglutinin. The immunomodulatory effects caused by IgA1 protease require a native form of the enzyme, and denaturation abolished cytokine induction. However, the proteolytic activity is not required for the cytokine induction by IgA1 protease. Our results indicate that IgA1 protease exhibits important immunostimulatory properties and may contribute substantially to the pathogenesis of neisserial infections by inducing large amounts of TNF-alpha and other proinflammatory cytokines. In particular, IgA1 protease may represent a key virulence determinant of bacterial meningitis.

Dysregulation of neurosteroids in obsessive compulsive disorder.

Alterations in hormone concentrations, including adrenocorticotropin, corticotropin releasing hormone, and cortisol have been reported in patients with obsessive compulsive disorder (OCD). Dehydroepiandrosterone (DHEA) and its sulfated metabolite, DHEA-S, have not been assessed in patients with OCD. We report 24-h serum DHEA, DHEA-S, and cortisol concentrations in a young man with OCD and 15 healthy young men. Circadian patterns of DHEA and cortisol were markedly different in the subject with OCD than in the control subjects. DHEA and DHEA-S concentrations were substantially higher in the OCD subject than in the control subjects. In contrast, cortisol concentrations were similar in the OCD subject and the control subjects. Future clinical studies are needed to evaluate the significance of DHEA and DHEA-S in OCD.

Enhanced activity and altered specificity of phospholipase A2 by deletion of a surface loop.

Protein engineering and x-ray crystallography have been used to study the role of a surface loop that is present in pancreatic phospholipases but is absent in snake venom phospholipases. Removal of residues 62 to 66 from porcine pancreatic phospholipase A2 does not change the binding constant for micelles significantly, but it improves catalytic activity up to 16 times on micellar (zwitterionic) lecithin substrates. In contrast, the decrease in activity on negatively charged substrates is greater than fourfold. A crystallographic study of the mutant enzyme shows that the region of the deletion has a well-defined structure that differs from the structure of the wild-type enzyme. No structural changes in the active site of the enzyme were detected.

Antimicrobial activity of lupulone against Clostridium perfringens in the chicken intestinal tract jejunum and caecum.

OBJECTIVES: Owing to the spread of antibiotic resistance among human infectious agents, there is a need to research antibiotic alternatives for use in animal agricultural systems. Antibiotic-free broiler chicken production systems are known to suffer from frequent outbreaks of necrotic enteritis due in part to pathogenic type A Clostridium perfringens. Hop (Humulus lupulus) bitter acids are known to possess potent antimicrobial activity. Lupulone was evaluated for in vivo antimicrobial activity to inhibit C. perfringens in a chick gastrointestinal colonization model. METHODS: Using a week-2 per os inoculated C. perfringens chicken colonization model, C. perfringens counts in mid-intestinal and caecal contents were compared between chickens administered lupulone at 62.5, 125 and 250 ppm in drinking water versus 0 ppm control. Results At day 22, post-hatch intestinal C. perfringens counts of lupulone-treated chickens were significantly lower (P < 0.05) than water-treated control groups in both jejunal and caecal sampling sites across all lupulone dosages tested. CONCLUSIONS: Lupulone administered through water inhibits gastrointestinal levels of inoculated pathogenic clostridia within the chicken gastrointestinal tract. Lupulone was effective within the chemically complex mixture of material within the gastrointestinal tract, thereby making this agent a target of further research as an antibiotic alternative for this and possibly other intestinal infections.

High performances, temperature resistant and stable OLED structures.

In the present work, a particular emphasis is put on the stability of the OLED devices obtained as well as on their ability to keep their good initial performances even in a severe environment. Moreover, the operation voltage of these devices turns out to be rather low.