SLPI and elafin: multifunctional antiproteases of the WFDC family

SLPI (secretory leucoprotease inhibitor) and elafin represent the archetypal members of the WFDC [WAP (whey acidic protein) four disulfide core] family of proteins, and were originally characterized as protease inhibitors but have since been shown to possess a wider repertoire of activities. These functions include antimicrobial and immunomodulatory properties, suggesting that these proteins may play key roles in the innate immune response, and indicate the potential to develop some of these proteins as novel therapeutics. Susceptibility to host and bacterial protease cleavage may, however, limit the efficacy of recombinant protein therapies in diseases with a high protease burden such as CF (cystic fibrosis) lung disease. To overcome this problem, further refinement of the native proteins will be required to provide effective treatment strategies.

Added complexity in Ras and Rho family GTPase function:Added complexity in Ras and Rho family GTPase function

The regulation of the small GTPases leading to their membrane localization has long been attributed to processing of their C-terminal CAAX box. As deregulation of many of these GTPases have been implicated in cancer and other disorders, prenylation and methylation of this CAAX box has been studied in depth as a possibility for drug targeting, but unfortunately, to date no drug has proved clinically beneficial. However, these GTPases also undergo other modifications that may be important for their regulation. Ubiquitination has long been demonstrated to regulate the fate of numerous cellular proteins and recently it has become apparent that many GTPases, along with their GAPs, GeFs and GDis, undergo ubiquitination leading to a variety of fates such as re-localization or degradation. in this review we focus on the recent literature demonstrating that the regulation of small GTPases by ubiquitination, either directly or indirectly, plays a considerable role in controlling their function and that targeting these modifications could be important for disease treatment.

Early pain experience, child and family factors, as precursors of somatization:a prospective study of extremely premature and fullterm children

In a prospective study of 36 children who were extremely low birthweight (ELBW: <1000 g) preterm infants and 36 matched full-term controls, differences were found in somatization at age 4 1/2 years. Only children who had been extremely premature, and thereby experienced prolonged hospitalization and repeated medical intervention in infancy, had clinically high somatization scores on the Personality Inventory for Children. The combination of family relations at age 4 1/2 years, neonatal intensive care experience, poor maternal sensitivity to child cues in mother-child interaction observed at age 3 years, and child avoidance of touch or holding at age 3, predicted somatization scores, prior to school entry. Due to the known higher incidence of actual medical problems among children with a history of extreme prematurity, the high somatization ELBW children were compared with the normal somatization ELBW children. There were no differences in prevalence of actual medical problems between the 2 ELBW groups, and the importance of maternal factors in relation to somatization was confirmed. Child temperament at age 3, but not personality at 4 1/2, was related to somatization. The etiology of recurrent physical complaints of no known medical cause appears to be a multi-dimensional problem. Non-optimal parenting may contribute to the development of inappropriate strategies for coping with common pains of childhood, or of chronic pain patterns, in some children who have experienced prolonged or repeated pain as neonates.

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.

Family caregivers' ideal expectations of Canada's Compassionate Care Benefit

We present the findings of 57 interviews conducted in 2007-2008 with Canadians who have cared for a dying family member to examine their ideal expectations of the Compassionate Care Benefit (CCB) - a social programme providing job security and income support for workers caring for a dying person. Our aims are to (1) appreciate how intended users and other family caregivers view the programme's very nature; (2) identify programme challenges and improvements that emerge from considering family caregivers' ideal expectations; and (3) contribute to a larger evaluative study designed to make policy-relevant recommendations for CCB improvement. Review of transcripts across three respondent groups reveals four categories of ideal expectations: (1) eligibility, (2) informational, (3) timing and (4) financial. Ideal expectations were typically derived from respondents' experiences of care-giving, their knowledge of the programme and, for some, of applying for and/or receiving the CCB. Findings reveal that there are gaps between respondents' ideal expectations and their experienced realities. Such gaps may lead to disappointment being experienced by those who believe they should be eligible for the programme but are not, or should be entitled to receive some form of support that is not presently available. This analysis plays an important role in identifying potential changes for the CCB that may better support family caregivers, in that the ideal expectations serve as a starting point for articulating desirable programme amendments. This analysis also has wider relevance. For jurisdictions looking to create new social programmes to support caregivers based upon labour policy strategies and legislation, this analysis identifies considerations that should be made at the outset of development. For jurisdictions that already have employment-based caregiver support programmes, this analysis demonstrates that programme challenges may not always be met through legislative changes alone but also through measures such as increasing awareness. © 2011 Blackwell Publishing Ltd.

The influence of culture on home-based family caregiving at end-of-life: A case study of Dutch reformed family care givers in Ontario, Canada

Families are facing increased pressure to provide care to their terminally-ill or dying kin in the home. It is known that balancing care with other personal and social roles can adversely affect family caregivers' (FCGs) health, yet access to supportive services which can mitigate burden is often inadequate. Cultural factors are known to shape the experience of caregiving; however, most research to date tends to neglect the experiences of FCGs from different cultural groups. This understanding is necessary to ensure that supportive services are both meaningful and culturally-appropriate. Using qualitative methods, we undertook longitudinal research with a sample of Dutch Reformed FCGs (n = 5) to understand their experiences of caregiving and bereavement. The results of the study are suggestive of a cultural specificity with respect to caregiving that impacts both responsibilities and reactions to care. Three themes were salient to this group as a cultural entity: cultural attitudes towards care, religious beliefs and coping, and c. ulturally-informed care-seeking behaviours. These three themes were seen to be a function of their religious and ethnic identities and were reinforced by ties to the communities in which they resided. Cultural identity provided a framework through which to understand and make sense of the experience, while group membership provided access to networks of informal support. This research contributes to the geographical literature on care/caregiving by providing insight into the social, cultural and religious context of informal family caregiving with a population who live in close geographic proximity. On a practical level, this case study indicates the importance of considering how these factors may operate in other settings in order to implement timely and appropriate interventions to better support FCGs who are caring for their terminally-ill loved-ones at home.

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.

Who is responsible?:The role of family physicians in the provision of supportive cancer care

Purpose: Patients living with cancer identify family physicians (FPs; ie, primary care physicians) as a preferred resource for supportive cancer care (SCC), either through direct provision or referral. However, little research exists on the specific role FPs play in addressing these needs. Methods: A mailed survey was sent to all FPs in a health care region in Ontario, Canada, to determine their current and preferred roles in the specific provision of SCC to patients with cancer who have been newly diagnosed or are at the end of life. Results: Completed surveys were received from 84 (64%) of 183 eligible FPs. Most practitioners reported providing for their patients' various SCC needs. However, clear gaps were demonstrated in psychosocial and nutritional counseling and in providing information about SCC services. FPs were satisfied with their current role reported in SCC coordination, although the type of role varied; FPs who were asked about their end-of-life patients tended to see themselves as part of coordinating teams, whereas FPs asked about their recently diagnosed patients were more likely to defer this responsibly to a third party. Conclusion: This study identified gaps in the provision of psychosocial and informational care to patients with cancer that may result in unmet needs. In general, FPs do not see themselves as primarily responsible for coordinating patients' SCC and do not wish to assume this role. Accordingly, models that involve FPs as team members in SCC coordination are more feasible for reducing patient need. Copyright © 2010 by American Society of Clinical Oncology.

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.

Meeting the supportive needs of family caregivers in palliative care:challenges for health professionals

Caring for a dying relative is demanding, and family caregivers have acknowledged many unmet needs associated with their caregiver role. Consistently, caregivers of dying patients with cancer have reported that they need more support and information from health care professionals. Moreover, a number of palliative care clinicians and researchers have called for interventions to enhance the support offered to family caregivers. However, before researchers can develop and test palliative care interventions directed to families, it is important to identify barriers that may confront health care professionals with regard to the provision of supportive family care. For new interventions to be feasible they must be applicable within the constraints of current palliative care service delivery environments. This paper provides an account of issues that may impinge on optimal transference of supportive strategies from health care professionals to family caregivers of patients receiving palliative care. By acknowledging these barriers to supportive care, researchers and health care professionals can begin to design and implement interventions that are clinically relevant and more likely to be effective.

Reducing the psychological distress of family caregivers of home based palliative care patients: Longer term effects from a randomised controlled trial.

Background: Palliative care incorporates comprehensive support of family caregivers because many of them experience burden and distress. However, evidence-based support initiatives are few.

Purpose: We evaluated a one-to-one psychoeducational intervention aimed at mitigating the distress of caregivers of patients with advanced cancer receiving home-based palliative care. We hypothesised that caregivers would report decreased distress as assessed by the General Health Questionnaire (GHQ).

Method: A randomised controlled trial comparing two versions of the delivery of the intervention (one face-to-face home visit plus telephone calls versus two visits) plus standard care to a control group (standard care only) across four sites in Australia.

Results: Recruitment to the one visit condition was 57, the two visit condition 93, and the control 148. We previously reported non-significant changes in distress between times 1 (baseline) and 2 (1-week post-intervention) but significant gains in competence and preparedness. We report here changes in distress between times 1 and 3 (8-week post-death). There was significantly less worsening in distress between times 1 and 3 in the one visit intervention group than in the control group; however, no significant difference was found between the two visit intervention and the control group.

Conclusions: These results are consistent with the aim of the intervention, and they support existing evidence demonstrating that relatively short psychoeducational interventions can help family caregivers who are supporting a dying relative. The sustained benefit during the bereavement period may also have positive resource implications, which should be the subject of future inquiry. © 2014 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.

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.

A pilot study of a family focused, psychosocial intervention with war-exposed youth at risk of attack and abduction in north-eastern Democratic Republic of Congo

Rural communities in the Haut-Uele Province of northern Democratic Republic of Congo live in constant danger of attack and/or abduction by units of the Lord's Resistance Army operating in the region. This pilot study sought to develop and evaluate a community-participative psychosocial intervention involving life skills and relaxation training and Mobile Cinema screenings with this war-affected population living under current threat. 159 war-affected children and young people (aged 7-18) from the villages of Kiliwa and Li-May in north-eastern DR Congo took part in this study. In total, 22% of participants had been abduction previously while 73% had a family member abducted. Symptoms of post-traumatic stress reactions, internalising problems, conduct problems and pro-social behaviour were assessed by blinded interviewers at pre- and post-intervention and at 3-month follow-up. Participants were randomised (with an accompanying caregiver) to 8 sessions of a group-based, community-participative, psychosocial intervention (n=79) carried out by supervised local, lay facilitators or a wait-list control group (n=80). Average seminar attendance rates were high: 88% for participants and 84% for caregivers. Drop-out was low: 97% of participants were assessed at post-intervention and 88% at 3 month follow-up. At post-test, participants reported significantly fewer symptoms of post-traumatic stress reactions compared to controls (Cohen's d=0.40). At 3 month follow up, large improvements in internalising symptoms and moderate improvements in pro-social scores were reported, with caregivers noting a moderate to large decline in conduct problems among the young people. Trial Registration clinicalTrials.gov, Identifier: NCT01542398.

Exploring molecular recognition pathways within a family of gelators with different hydrogen bonding motifs

We report the synthesis of a family of gelators in which alkyl chains are connected to the amino groups of L-lysine methyl ester using a range of different hydrogen bonding linking groups (carbamate, amide, urea, thiourea and diacylhydrazine) using simple synthetic methodology based on isocyanate or acid chloride chemistry. The ability of these compounds to gelate organic solvents such as toluene or cyclohexane can be directly related to the ability of the linking group to form intermolecular hydrogen bonds. In general terms, the ability to structure solvents can be considered as: thiourea <carbamate <amide <urea similar to diacylhydrazine. This process has been confirmed by thermal measurements, scanning electron microscopy (SEM) and infrared and circular dichroism spectroscopies. By deprotecting the methyl ester group, we have demonstrated that a balance between hydrophobic and hydrophilic groups is essential-if the system has too much hydrophilicity (e. g., diacylhydrazine, urea) it will not form gels due to low solubility in the organic media. However, the less effective gelators based on amide and carbamate linkages are enhanced by converting the methyl ester to a carboxylic acid. Furthermore, subsequent mixing of the acid with a second component (diaminododecane) further enhances the ability to form networks, and, in the case of the amide, generates a two-component gel, which can immobilise a wide range of solvents of industrial interest including petrol and diesel (fuel oils), olive oil and sunflower oil (renewable food oils) and ethyl laurate, isopropyl myristate and isopropyl palmitate (oils used in pharmaceutical formulation). The gels are all thermoreversible, and may therefore be useful in controlled release/formulation applications.

Trajectories of Adolescent Aggression and Family Cohesion: The Potential to Perpetuate or Ameliorate Political Conflict

Correlations between intergroup violence and youth aggression are often reported. Yet longitudinal research is needed to understand the developmental factors underlying this relation, including between-person differences in within-person change in aggression through the adolescent years. Multilevel modeling was used to explore developmental and contextual influences related to risk for youth aggression using 4 waves of a prospective, longitudinal study of adolescent/mother dyad reports (N = 820; 51% female; 10–20 years old) in Belfast, Northern Ireland, a setting of protracted political conflict. Experience with sectarian (i.e., intergroup) antisocial behavior predicted greater youth aggression; however, that effect declined with age, and youth were buffered by a cohesive family environment. The trajectory of aggression (i.e., intercepts and linear slopes) related to more youth engagement in sectarian antisocial behavior; however, being female and having a more cohesive family were associated with lower levels of youth participation in sectarian acts. The findings are discussed in terms of protective and risk factors for adolescent aggression, and more specifically, participation in sectarian antisocial behavior. The article concludes with clinical and intervention implications, which may decrease youth aggression and the perpetuation of intergroup violence in contexts of ongoing conflict.