Advanced glycation end products cause increased CCN family and extracellular matrix gene expression in the diabetic rodent retina

Aims/hypothesis: Referred to as CCN, the family of growth factors consisting of cystein-rich protein 61 (CYR61, also known as CCN1), connective tissue growth factor (CTGF, also known as CCN2), nephroblastoma overexpressed gene (NOV, also known as CCN3) and WNT1-inducible signalling pathway proteins 1, 2 and 3 (WISP1, -2 and -3; also known as CCN4, -5 and -6) affects cellular growth, differentiation, adhesion and locomotion in wound repair, fibrotic disorders, inflammation and angiogenesis. AGEs formed in the diabetic milieu affect the same processes, leading to diabetic complications including diabetic retinopathy. We hypothesised that pathological effects of AGEs in the diabetic retina are a consequence of AGE-induced alterations in CCN family expression.

Materials and methods: CCN gene expression levels were studied at the mRNA and protein level in retinas of control and diabetic rats using real-time quantitative PCR, western blotting and immunohistochemistry at 6 and 12 weeks of streptozotocin-induced diabetes in the presence or absence of aminoguanidine, an AGE inhibitor. In addition, C57BL/6 mice were repeatedly injected with exogenously formed AGE to establish whether AGE modulate retinal CCN growth factors in vivo.

Results: After 6 weeks of diabetes, Cyr61 expression levels were increased more than threefold. At 12 weeks of diabetes, Ctgf expression levels were increased twofold. Treatment with aminoguanidine inhibited Cyr61 and Ctgf expression in diabetic rats, with reductions of 31 and 36%, respectively, compared with untreated animals. Western blotting showed a twofold increase in CTGF production, which was prevented by aminoguanidine treatment. In mice infused with exogenous AGE, Cyr61 expression increased fourfold and Ctgf expression increased twofold in the retina.

Conclusions/interpolation: CTGF and CYR61 are downstream effectors of AGE in the diabetic retina, implicating them as possible targets for future intervention strategies against the development of diabetic retinopathy.

Association Study of SNAP25 and Schizophrenia in Irish Family and Case-Control Samples

SNAP25 occurs on chromosome 20p12.2, which has been linked to schizophrenia in some samples, and recently linked to latent classes of psychotic illness in our sample. SNAP25 is crucial to synaptic functioning, may be involved in axonal growth and dendritic sprouting, and its expression may be decreased in schizophrenia. We genotyped 18 haplotype-tagging SNPs in SNAP25 in a sample of 270 Irish high-density families. Single marker and haplotype analyses were performed in FBAT and PDT. We adjusted for multiple testing by computing q values. Association was followed up in an independent sample of 657 cases and 411 controls. We tested for allelic effects on the clinical phenotype by using the method of sequential addition and 5 factor-derived scores of the OPCRIT. Nine of 18 SNPs had Pvalues

Christian Gottlob Neefe and the Bonn National Theatre, with New Light on the Beethoven Family

When the Bonn stage was closed after the death of Elector Max Friedrich in 1784, the director of its theatre company, Gustav Friedrich Wilhelm Großmann, decided to leave the city to further his career elsewhere in the Rhinelands. During the next few years, he was kept informed about developments in Bonn by two of his erstwhile colleagues, Christian Gottlob Neefe and Nikolaus Simrock, whose correspondence paints a vivid picture of musical life in the city during the later 1780s. The new Elector, Maximilian Franz, permitted a visiting troupe to perform during Carnival each year, but repeatedly delayed the decision to re-establish a resident troupe. In 1787 Christoph Brandt, a singer in the Bonn Hofkapelle, attempted a home-grown initiative, perhaps to test the market for a new permanent company. Although this failed almost immediately, a single, well-attended public rehearsal of Monsigny’s Le Déserteur was given, in which Johann van Beethoven made what was probably his last stage appearance. In a letter dated 14 May 1787, Simrock rated his performance ‘zimlich gut’. In the event, a new Bonn troupe was not recruited until 1789, when it featured the young singer Magdalena Willmann. Neefe and his musical colleagues were relieved finally to be able to resume their theatrical careers.

A Family Booklet About Comfort Care in Advanced Dementia:Three-Country Evaluation

Objectives: To evaluate a booklet on comfort care in dementia from the perspective of family with relevant experience, and assess nursing home resident and family factors associated with evaluations. Design: Retrospective study. Setting: Long term care facilities in French-speaking Canada, and the Netherlands and Italy.
Participants: Bereaved family (n = 138).
Measurements: An 8-item scale assessed the booklet's acceptability. Usefulness was rated on a 0 to 10 scale, and perceived usefulness referred to usefulness if family had had the booklet during the resident's stay. Families indicated preferred ways of obtaining, and the most appropriate time to get the booklet.
Results: Almost all families (94%) perceived the booklet as useful. Canadian and Dutch families evaluated the booklet's contents and format favorably, whereas Italian families' evaluations were less favorable. Almost all families endorsed roles for physicians or nurses and about half additionally accepted availability through own initiative, in print or through the Internet. Preference of timing was highly variable. Better acceptability, usefulness, and availability through own initiative were independently associated with non-Italian nationality, presence of more physical signs discussed in the booklet, feeling ill-prepared, and higher satisfaction with care. A preference of receiving the booklet early was more likely in Italian families, those without university education, and those involved with older residents.
Conclusion: The booklet is suitable to inform Dutch and Canadian families on comfort care in dementia, but implementation in Italy requires further consideration. The booklet may be integrated in advance care planning in long term care, and made available outside long term care settings to serve families who wish to be informed early. © 2012 American Medical Directors Association, Inc.
Keywords: Decision aid; decision making; advance care planning; palliative care; nursing homes; dementia.

Physicians' and Nurses' Perceived Usefulness and Acceptability of a Family Information Booklet about Comfort Care in Advanced Dementia

Background: Families of patients with advanced dementia need to be informed about the course of the dementia and comfort care. Conditional for health care providers educating families is their knowledge and comfort in family education. Methods: Perceived usefulness and acceptability of a Canadian family booklet explaining possible complications and comfort care in dementia was assessed by physicians and nurses caring for dementia patients in 14 nursing homes in Lombardy, Italy and 21 in the Netherlands. The practitioners received a questionnaire and translated versions adapted to local practice where needed. In 10 of 21 Dutch homes, physicians evaluated only the original Canadian version in English. A 15-item scale assessed the booklet's acceptability, for example, to inform families, or for educational purposes. Perceived usefulness referred to proportion of families of dementia patients for whom the booklet would be useful. A total of 168 evaluations were available for multivariable regression analyses. Results: The practitioners anticipated that the booklet would be useful for most families. Evaluation of the Dutch translation of the booklet was similar to the English version. Country (Netherlands) and profession (nurses) were independently associated with better acceptability. Usefulness was perceived as better by Italian respondents and nurses, but only in analyses unadjusted for the higher educational needs of these respondents. Conclusion: Overall, the concept of written information on comfort care was appreciated by practitioners of European countries differing in attitudes toward end-of-life care. A booklet may help practitioners, and in particular nurses, in providing comfort care for dementia patients and their families. © Copyright 2011, Mary Ann Liebert, Inc. 2011.

Educating families about end-of-life care in advanced dementia:Acceptability of a Canadian family booklet to nurses from Canada, France, and Japan

Background: The families of people with late-stage dementia need to be informed about the course of the dementia and the comfort/ palliative care option. A booklet was written for that purpose and can be provided to family members by physicians and nurses. Methods: The acceptability of the booklet for nurses was tested in Canada (French and English version), France (French Canadian version) and Japan (translated and adapted version). Results: Overall, 188 nurses completed a survey questionnaire. The booklet was accepted best in Canada and less so in France and Japan. Despite regional variation, the majority of the nurses perceived the booklet as useful for families. The French and Japanese nurses also reported a greater need for palliative care education in advanced dementia. Conclusion: The booklet may help nurses educate families about end-of-life issues in dementia palliative care, but local adaptation of the booklet content and physician engagement are necessary.

Interleukin 3 and schizophrenia:the impact of sex and family history

Chromosome 5q21-33 has been implicated in harboring risk genes for schizophrenia. In this paper, we report evidence that multiple single nucleotide polymorphisms in and around interleukin 3 (IL3) are associated with the disease in the Irish Study of High-Density Schizophrenia Families (ISHDSF), the Irish Case-Control Study of Schizophrenia (ICCSS) and the Irish Trio Study of Schizophrenia (ITRIO). The associations are sex-specific and depend on the family history (FH) of schizophrenia. In all three samples, rs31400 shows female-specific and FH-dependent associations (P=0.0062, 0.0647 and 0.0284 for the ISHDSF, ICCSS and ITRIO, respectively). Several markers have similar associations in one or two of the three samples. In haplotype analyses, identical risk and protective haplotypes are identified in the ISHDSF and ITRIO samples in several multimarker combinations. For ICCSS, the same haplotypes are implicated; however, the risk haplotypes observed in the family samples become protective. Several significant markers, rs440970, rs31400 and rs2069803, are located in and around known estrogen response elements, promoter and enhancer of the IL3 gene. They may explain the sex-specific associations and be functional for the expression of IL3 gene.