Investigating the Efficacy of Genetic, Environmental, and Multifactorial Risk Information When Communicating Obesity Risk to Parents of Young Children.

BACKGROUND: Effectively communicating with parents about children's obesity risk is of critical importance for preventive medicine and public health. PURPOSE: The current study investigates the efficacy of communications focused on two primary causes of obesity: genes and environment. METHODS: We compared parental feeding responses to messages focused on (i) genetics alone, (ii) family environment alone, (iii) genetics-family environment interaction (G × FE), and (iv) no causal message. We also examined whether parental guilt mediates the effect of message type on feeding. Our sample consisted of 190 parents, half mothers and half fathers, of children 3-7 years old. After receiving one of the four types of messages, parents chose foods for their child using the Virtual Reality Buffet measure. Parents responded to questionnaires in the lab and at 1-week follow-up. RESULTS: In the VR Buffet, parents did not feed their children differently in message provision conditions versus control. There were, however, differences among message provision conditions wherein mothers who received any genetic information chose higher-calorie meals in the VR Buffet. At 1-week follow-up, parents who received information about genetics alone reported feeding their child more junk food and fatty meat on self-report food frequency assessments; there were no such differences for sugary beverages, sugary foods, or fast foods. Parental guilt was typically higher for participants who received family environment information alone but did not mediate the relation between information provision and feeding outcomes. CONCLUSIONS: While none of the messages improved feeding above the control condition, GxFE messages were associated with a better overall profile of outcomes. As such, it may be beneficial for messaging for parents about children's obesity risk to include content that reflects the complexity of genetic and environmental contributions to obesity risk.

X-linked markers in the Duchenne muscular dystrophy gene associated with oral clefts.

As part of an international consortium, case-parent trios were collected for a genome-wide association study of isolated, non-syndromic oral clefts, including cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP). Non-syndromic oral clefts have a complex and heterogeneous etiology. Risk is influenced by genes and environmental factors, and differs markedly by gender. Family-based association tests (FBAT) were used on 14,486 single nucleotide polymorphisms (SNPs) spanning the X chromosome, stratified by type of cleft and racial group. Significant results, even after multiple-comparisons correction, were obtained for the Duchenne muscular dystrophy (DMD) gene, the largest single gene in the human genome, among CL/P (i.e., both CL and CLP combined) trios. When stratified into groups of European and Asian ancestry, stronger signals were obtained for Asian subjects. Although conventional sliding-window haplotype analysis showed no increase in significance, selected combinations of the 25 most significant SNPs in the DMD gene identified four SNPs together that attained genome-wide significance among Asian CL/P trios, raising the possibility of interaction between distant SNPs within the DMD gene.

Combining evidence-based practices for improved behavioral outcomes: a demonstration project.

This article describes a demonstration project carried out by a special team at a mental health agency serving adults with a serious psychiatric condition. The project consisted of combining the evidence-based practices of cognitive therapy, Motivational Interviewing and Stages of Change with Social Role Theory and the Chronic Care Model that were the organizing concepts of the agency's assessment and treatment program. Measures of the results of clients' improved mental health and social functioning indicated the successful use of this combination.

Continuum of readiness for collaboration, ICWA compliance, and reducing disproportionality.

From 2008-2010, a California Breakthrough Series Collaborative (BSC) addressed the disproportionality of African American and American Indian/Alaska Native (AI/AN) children in public child welfare services in partnership with the Annie E. Casey Foundation, Casey Family Program, the Child and Family Policy Institute of California, and the California Department of Social Services. The result was the development of the Continuum of Readiness, to be utilized by California counties to make strategic decisions to achieve Indian Child Welfare Act (ICWA) compliance and address AI/AN dis-proportionality through collaboration with tribes and urban Indian communities.

Aneurysmal subarachnoid hemorrhage: an update on the medical complications and treatments strategies seen in these patients.

PURPOSE OF REVIEW: Aneurysmal subarachnoid hemorrhage (SAH) remains a devastating condition with high mortality and poor outcome among survivors. Early surgical or endovascular securing of the aneurysm is the norm, and management of these patients is precarious due to their unstable intracranial physiology and the severe systemic medical complications common in SAH. RECENT FINDINGS: New research into biomarkers and clinical factors with their association to outcome in SAH can help us to identify patients at risk. New evidence questions the benefit of broad application of the current SAH treatment mainstays, and re-examines agents previously failing clinical trials. SUMMARY: Growing knowledge of the physiologic derangements associated with poor outcomes in SAH can improve our understanding of the widespread physiologic changes occurring with SAH and with further research, may provide clinicians with a direction for increasingly meaningful intervention. Ongoing investigation of our current therapeutics enable clinicians to apply them more judiciously to suitable patients, thereby enhancing the benefit and minimizing the complications of such treatments. Furthermore, by re-evaluating previously disproved treatments through the use of novel regimens or administration routes, promising treatment options are emerging.

Welfare phenotyping of genetically-modified mice.

Technologies that enable the targeted manipulation of the genome have created new opportunities to study the role and interplay of specific genes in both the regulation and function of physiological and behavioural processes and in the development of pathological conditions. Despite the potential benefits, there are ethical issues in relation to the application of these technologies, some of which relate to the impact on the welfare of the animals involved. Matters of concern include the methods involved in the derivation and production of genetically-modified (GM) animals and resulting phenotypes, where animal welfare is compromised. In the case of the latter, this may be the predicted consequence of the genetic modification, but the occurrence of unforeseen animal welfare complications is a major challenge in the management of GM animals. There has been a rapid escalation in the development of new GM lines, most of them involving mice. Databases of available lines have been developed by national and international consortia, and researchers have developed standard protocols to describe the phenotype of a new line; increasingly, such data are entered into these databases. The inclusion of animal welfare assessments with these data would provide a powerful and sophisticated tool to promote refinement. The scope, level and frequency of monitoring would facilitate the identification of unpredicted effects and the management of humane endpoints, and would identify opportunities to manage the animals so as to ameliorate negative impacts. Furthermore, by highlighting the subtleties of gene-environment interactions, such data have wider implications in achieving the goals of refinement.

Diabetes causal attributions among affected and unaffected individuals.

Objective: The present study aims to describe and compare causal attributions for type 1 diabetes (T1D) and type 2 diabetes (T2D) among affected and unaffected individuals and to investigate the relationships among attributions, attitudes, and beliefs. Research design and methods: Adults with no diabetes (N=458), T1D (N=192), or T2D (N=207) completed an online survey. Measures assessed diabetes conceptual knowledge, causal attributions for T1D and T2D, perceived control over diabetes onset, and favorability judgements of individuals affected by each type. Results: Results indicate general agreement on causal attributions for T1D and T2D among all respondent groups, with some divergences by disease status. All respondents attributed both T1D and T2D to genetics, and genetic attributions were positively associated with favorability judgements of individuals with T2D, but not those with T1D. Conclusions: This report sets the stage for investigations into how and why attributions for T1D and T2D differ and the implications of these differences including stigmatization of individuals with diabetes and diabetes-related self-concept. Additionally, this work can inform efforts towards clinical and public health education to prevent and optimize treatment of T1D and T2D.

Animal Research, Accountability, Openness and Public Engagement: Report from an International Expert Forum.

In November 2013, a group of international experts in animal research policy (n = 11) gathered in Vancouver, Canada, to discuss openness and accountability in animal research. The primary objective was to bring together participants from various jurisdictions (United States, Sweden, Australia, New Zealand, Germany, Canada and the United Kingdom) to share practices regarding the governance of animals used in research, testing and education, with emphasis on the governance process followed, the methods of community engagement, and the balance of openness versus confidentiality. During the forum, participants came to a broad consensus on the need for: (a) evidence-based metrics to allow a "virtuous feedback" system for evaluation and quality assurance of animal research, (b) the need for increased public access to information, together with opportunities for stakeholder dialogue about animal research, (c) a greater diversity of views to be represented on decision-making committees to allow for greater balance and (d) a standardized and robust ethical decision-making process that incorporates some sort of societal input. These recommendations encourage aspirations beyond merely imparting information and towards a genuine dialogue that represents a shared agenda surrounding laboratory animal use.

Validation of Matrix Metalloproteinase-9 (MMP-9) as a Novel Target for Treatment of Diabetic Foot Ulcers in Humans and Discovery of a Potent and Selective Small-Molecule MMP-9 Inhibitor That Accelerates Healing.

Diabetic foot ulcers (DFUs) are a significant health problem. A single existing FDA-approved drug for this ailment, becaplermin, is not standard-of-care. We previously demonstrated that upregulation of active matrix metalloproteinase (MMP)-9 is the reason that the diabetic wound in mice is recalcitrant to healing and that MMP-8 participates in wound repair. In the present study, we validate the target MMP-9 by identifying and quantifying active MMP-8 and MMP-9 in human diabetic wounds using an affinity resin that binds exclusively to the active forms of MMPs coupled with proteomics. Furthermore, we synthesize and evaluate enantiomerically pure ( R)- and ( S)-ND-336, as inhibitors of the detrimental MMP-9, and show that the ( R)-enantiomer has superior efficacy in wound healing over becaplermin. Our results reveal that the mechanisms of pathology and repair are similar in diabetic mice and diabetic humans and that ( R)-ND-336 holds promise for the treatment of DFUs as a first-in-class therapeutic.

Consensus Statement for Clinical Pathway Development for Perioperative Pain Management and Care Transitions.

The perioperative surgical home (PSH) model has been created with the intention to reduce costs and to improve efficiency of care and patient experience in the perioperative period. The PSH is a comprehensive model of care that is team-based and patient-centric. The team in each facility should be multidisciplinary and include the input of perioperative services leadership, surgical services, and support personnel in order to provide seamless care for the patient from the preoperative period when decision to undergo surgery is initially made to discharge and, if needed after discharge from the hospital, until full recovery is achieved. PSH is discussed in this consensus article with the emphasis on perioperative care coordination of patients with chronic pain conditions. Preoperative optimization can be successfully undertaken through patient evaluation, screening, and education. Many important positive implications in the PSH model, in particular for those patients with increased potential morbidity, mortality, and high-risk populations, including those with a history of substance abuse or anxiety, reflect a more modern approach to health care. Newer strategies, such as preemptive and multimodal analgesic techniques, have been demonstrated to reduce opioid consumption and to improve pain relief. Continuous catheters, ketamine, methadone, buprenorphine, and other modalities can be best delivered with the expertise of an anesthesiologist and a support team, such as an acute pain care coordinator. A physician-led PSH is a model of care that is patient-centered with the integration of care from multiple disciplines and is ideally suited for leadership from the anesthesia team. Optimum pain control will have a significant positive impact on the measures of the PSH, including lowering of complication rates, lowering of readmissions, improved patient satisfaction, reduced morbidity and mortality, and shortening of hospital stays. All stakeholders should work together and consider the PSH model to ensure the best quality of health care for patients undergoing surgery in the future. The pain management physician's role in the postoperative period should be focused on providing optimal analgesia associated with improved patient satisfaction and outcomes that result in reduced health care costs.

Challenges to the Development and Implementation of Public Policies to Achieve Animal Welfare Outcomes.

Although there is a long-established tradition of concern for the welfare of animals, it was not until the mid 1800's that governments sought to enact legislation to protect animals from cruelty. In the 1950's, questions concerning animal welfare re-emerged and in the ensuing years have been an on-going focus of government activities. These developments occurred against a backdrop of significant social change but there are important differences in what now underpins and informs these considerations. In the formulation and implementation of public policies, governments look for a course of action that represents and protects the interests of the community; the process may be challenging with competing interests but the final determination seeks a middle ground that best meets the needs and interests of the community as a whole. When policy development concerns our relationship with other animals, the complexity of this relationship presents particular challenges not only to the formulation of policies but also to the evaluation of outcomes. Notably, the depth of feelings and diversity of views in our community reflect the complex social, cultural and personal dimensions of this relationship. The use of animals for scientific purposes remains one of the most contentious animal welfare issues primarily because when animals are used for these purposes, accepted animal welfare benchmarks cannot always be met. Based on the Australian experience, this paper will discuss the influences in and on-going challenges to the development and implementation of public policy when animals are used for these purposes.

Development and implementation of a carboplatin desensitization protocol for children with neurofibromatosis, type 1 and hypersensitivity reactions in an outpatient oncology clinic.

Neurofibromatosis, type 1 (NF 1), is a relatively common disorder. Children with NF 1 are at much greater risk for the development of optic pathway tumors, which are sometimes treated with chemotherapy. As a result, many oncology centers and clinics are now seeing and treating NF patients. One of the most frequently used drugs is carboplatin. However, as many as 30% of NF patients may develop a reaction to carboplatin, which can include anaphylaxis. This often results in the cessation of the medication and treatment protocol. At the Children's Hospital of Philadelphia a desensitization protocol has been instituted with children who have had such reactions and whose tumors have demonstrated a positive response to the treatment. The desensitization process is quite complex and requires an interdisciplinary approach. However, it is the nursing personnel that are key to the successful coordination and delivery of such a protocol in an oncology outpatient clinic on a regular basis.