Attitudes of Parents at risk of inheriting Li-Fraumeni Syndrome towards predictive genetic testing in their minor-aged children.

Li-Fraumeni Syndrome (LFS) is a hereditary cancer syndrome which predisposes individuals to cancer beginning in childhood. These risks are spread across a lifetime, from early childhood to adulthood. Mutations in the p53 tumor suppressor gene are known to cause the majority of cases of LFS. The risk for early onset cancer in individuals with Li-Fraumeni Syndrome is high. Studies have shown that individuals with LFS have a 90% lifetime cancer risk. Children under 18 have up to a 15% chance of cancer development. Effectiveness of cancer screening and management in individuals with Li-Fraumeni Syndrome is unclear. Screening for LFS-associated cancers has not been shown to reduce mortality. Due to the lack of effective screening techniques for childhood cancers, institutions vary with regard to their policies on testing children for LFS. There are currently no national guidelines regarding predictive testing of children who are at risk of inheriting LFS. No studies have looked at parental attitudes towards predictive p53 genetic testing in their children. This was a cross-sectional pilot study aimed at describing these attitudes. We identified individuals whose children were at risk for inheriting p53 genetic mutations. These individuals were provided with surveys which included validated measures addressing attitudes and beliefs towards genetic testing. The questionnaire included qualitative and quantitative measures. Six individuals completed and returned the questionnaire with a response rate of 28.57%. In general, respondents agreed that parents should have the opportunity to obtain p53 genetic testing for their child. Parents vary in regard to their attitudes towards who should be involved in the decision making process and at what time and under what considerations testing should occur. Testing motivations cited most important by respondents included family history, planning for the future and health management. Concern for insurance genetic discrimination was cited as the most important “con” to genetic testing. Although limited by a poor response rate, this study can give health care practitioners insight into testing attitudes and beliefs of families considering pediatric genetic testing.

Impact of dental caries and trauma on quality of life among 5- to 6-year-old children: perceptions of parents and children.

OBJECTIVE To assess the impact of dental caries and traumatic dental injuries (TDI) on the oral health-related quality of life (OHRQoL) of 5- to 6-year-olds according to both self- and parental reports. METHODS A total of 335 pairs of parents and children who sought dental screening at the Dental School, University of São Paulo, completed the Scale of Oral Health Outcomes for 5-year-old children (SOHO-5), which consists of a child self-report and a parental proxy-report version. Three calibrated examiners assessed the experience of caries according to primary teeth that were decayed, indicated for extraction due to caries, or filled (def-t). TDI were classified into uncomplicated and complicated injuries. Poisson regression models were used to associate the different clinical and sociodemographic factors to the outcome. RESULTS Overall, 74.6% of children reported an oral impact, and the corresponding estimate for parental reports was 70.5%. The mean (standard deviation) SOHO-5 scores in child self-report and parental versions were 3.32(3.22) and 5.18(6.28), respectively. In both versions, caries was associated with worse children's OHRQoL, for the total score and all SOHO-5 items (P < 0.001). In contrast, TDI did not have a negative impact on children's OHRQoL, with the exception of two items of the parental version and one item of the child self-report version. In the final multivariate adjusted models, there was a gradient in the association between caries experience and child's OHRQoL with worse SOHO-5 score at each consecutive level with more severe caries experience, for both child and parental perceptions [RR (CI 95%) = 6.37 (4.71, 8.62) and 10.81 (7.65, 15.27)], respectively. A greater family income had a positive impact on the children's OHRQoL for child and parental versions [RR (CI 95%) = 0.68 (0.49, 0.94) and 0.70 (0.54, 0.90)], respectively. CONCLUSIONS Dental caries, but not TDI, is associated with worse OHRQoL of 5- to 6-year-old children in terms of perceptions of both children and their parents. Families with higher income report better OHRQoL at this age, independent of the presence of oral diseases.

Stimulant medication and psychotic symptoms in offspring of parents with mental illness

BACKGROUND: Stimulants, such as methylphenidate, are among the most commonly used medications in children and adolescents. Psychotic symptoms have been reported as rare adverse reactions to stimulants but have not been systematically inquired about in most previous studies. Family history of mental illness may increase the vulnerability to drug-induced psychotic symptoms. We examined the association between stimulant use and psychotic symptoms in sons and daughters of parents with major mood and psychotic disorders. METHODS: We assessed psychotic symptoms, psychotic-like experiences, and basic symptoms in 141 children and youth (mean ± SD age: 11.8 ± 4.0 years; range: 6–21 years), who had 1 or both parents with major depressive disorder, bipolar disorder, or schizophrenia, and of whom 24 (17.0%) had taken stimulant medication. RESULTS: Psychotic symptoms were present in 62.5% of youth who had taken stimulants compared with 27.4% of participants who had never taken stimulants. The association between stimulant use and psychotic experiences remained significant after adjustment for potential confounders (odds ratio: 4.41; 95% confidence interval: 1.82–10.69; P = .001) and was driven by hallucinations occurring during the use of stimulant medication. A temporal relationship between use of stimulants and psychotic symptoms was supported by an association between current stimulant use and current psychotic symptoms and co-occurrence in cases that were assessed on and off stimulants. CONCLUSIONS: Psychotic symptoms should be monitored during the use of stimulants in children and adolescents. Family history of mood and psychotic disorders may need to be taken into account when considering the prescription of stimulants.

Employment Situation of Parents of Long-Term Childhood Cancer Survivors.

BACKGROUND Taking care of children diagnosed with cancer affects parents' professional life. The impact in the long-term however, is not clear. We aimed to compare the employment situation of parents of long-term childhood cancer survivors with control parents of the general population, and to identify clinical and socio-demographic factors associated with parental employment. METHODS As part of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to parents of survivors aged 5-15 years, who survived ≥5 years after diagnosis. Information on control parents of the general population came from the Swiss Health Survey (restricted to men and women with ≥1 child aged 5-15 years). Employment was categorized as not employed, part-time, and full-time employed. We used generalized ordered logistic regression to determine associations with clinical and socio-demographic factors. Clinical data was available from the Swiss Childhood Cancer Registry. RESULTS We included 394 parent-couples of survivors and 3'341 control parents (1'731 mothers; 1'610 fathers). Mothers of survivors were more often not employed (29% versus 22%; ptrend = 0.007). However, no differences between mothers were found in multivariable analysis. Fathers of survivors were more often employed full-time (93% versus 87%; ptrend = 0.002), which remained significant in multivariable analysis. Among parents of survivors, mothers with tertiary education (OR = 2.40, CI:1.14-5.07) were more likely to be employed. Having a migration background (OR = 3.63, CI: 1.71-7.71) increased the likelihood of being full-time employed in mothers of survivors. Less likely to be employed were mothers of survivors diagnosed with lymphoma (OR = 0.31, CI:0.13-0.73) and >2 children (OR = 0.48, CI:0.30-0.75); and fathers of survivors who had had a relapse (OR = 0.13, CI:0.04-0.36). CONCLUSION Employment situation of parents of long-term survivors reflected the more traditional parenting roles. Specific support for parents with low education, additional children, and whose child had a more severe cancer disease could improve their long-term employment situation.

Perceptions of work engagement of nurses in Taiwan

Purpose. The purpose of this study was to determine the perceptions of work engagement of Taiwanese nurses with 3 specific aims: (1) understand Taiwanese nurses' perceptions of work engagement; (2) explore the factors influencing work engagement, and (3) examine how work engagement impacts nursing care for patients. ^ Design. The study used an ethnographic approach with participant observation and semi-structured interviews with RNs. ^ Setting. The study was conducted in the highest and lowest nurse turnover medical surgical units at a regional teaching hospital in southwestern Taiwan. ^ Sample. Purposive sampling resulted in 28 formal interviews with RNs who provided direct patient care, had at least 3 months experience in nursing, and were full-time employees. ^ Methods. Descriptive data were collected through participant observation in each unit. Observations were made while attending meetings, continuing education sessions, and informal conversations with RNs. Field notes and audio recorded semi-structured interviews were analyzed using qualitative thematic analytic techniques. ^ Findings. Findings revealed perceptions of work engagement spanned four domains: patients ("wholehearted care"), work (positive attitude), self (fulfillment and happiness), and others (relationships with colleagues). Providing "wholehearted care" toward patients was the foundation of work engagement for nurses in Taiwan. Engaged nurses felt fulfilled, happy, and found "meaning" through the process of patient care. The study revealed five factors that influenced work engagement: personal, organizational, social, patient, and professional. The impact of work engagement on nurse and patient outcomes are confirmed. ^ Conclusions. Taiwanese nurses connect work engagement with patients, the job, oneself, and colleagues. "Wholehearted patient care" is the core manifestation of work engagement among these nurses. In contrast, studies in western business only focused on work attitudes. Losing interest and "heart" lead to work routines which can lead to individual unhappiness. Findings from this study validate the multiple factors contributing to work engagement of nurses. Job demands and resources can only partially explain what hinders work engagement. Work disengagement and burnout share some commonality but should be measured differently. An understanding of RNs' perceptions of work engagement may provide direction for strategies that improve work engagement leading to decreased RN turnover. ^

Engagement of p75/AIRM1 or CD33 inhibits the proliferation of normal or leukemic myeloid cells

P75/AIRM1 is a recently identified surface molecule that belongs to the sialoadhesin family and displays homology with the myeloid cell antigen CD33. In lymphoid cells, p75/AIRM1 is confined to natural killer cells and mediates inhibition of their cytolytic activity. In this study, we show that p75/AIRM1 is also expressed by cells of the myelomonocytic cell lineage, in which it appears at a later stage as compared with CD33. In vitro proliferation and differentiation of cord blood-derived CD34+ cells (induced by stem cell factor and granulocyte–macrophage colony-stimulating factor) were consistently inhibited by the addition of anti-p75/AIRM1 mAb. Engagement of CD33 led to inhibition in some experiments. A sharp decrease of cell proliferation/survival was detected in all three p75/AIRM1+ chronic myeloid leukemias analyzed when cultured in the presence of either anti-p75/AIRM1 or anti-CD33 mAbs. Thus, the present study suggests that p75/AIRM1 and CD33 may play a regulatory role in normal myelopoiesis and may be viewed as suitable target molecules to counteract the proliferation/survival of chronic myeloid leukemias.

Cytoskeletal Reorganization Induced by Engagement of the NG2 Proteoglycan Leads to Cell Spreading and Migration

Cells expressing the NG2 proteoglycan can attach, spread, and migrate on surfaces coated with NG2 mAbs, demonstrating that engagement of NG2 can trigger the cytoskeletal rearrangements necessary for changes in cell morphology and motility. Engagement of different epitopes of the proteoglycan results in distinct forms of actin reorganization. On mAb D120, the cells contain radial actin spikes characteristic of filopodial extension, whereas on mAb N143, the cells contain cortical actin bundles characteristic of lamellipodia. Cells that express NG2 variants lacking the transmembrane and cytoplasmic domains are unable to spread or migrate on NG2 mAb-coated surfaces, indicating that these portions of the molecule are essential for NG2-mediated signal transduction. Cells expressing an NG2 variant lacking the C-terminal half of the cytoplasmic domain can still spread normally on mAbs D120 and N143, suggesting that the membrane-proximal cytoplasmic segment is responsible for this process. In contrast, this variant migrates poorly on mAb D120 and exhibits abnormal arrays of radial actin filaments decorated with fascin during spreading on this mAb. The C-terminal portion of the NG2 cytoplasmic domain, therefore, may be involved in regulating molecular events that are crucial for cell motility.

Surface expression and function of p75/AIRM-1 or CD33 in acute myeloid leukemias: Engagement of CD33 induces apoptosis of leukemic cells

p75/AIRM-1 is a recently identified inhibitory receptor expressed by natural killer and myeloid cells displaying high homology with CD33. Crosslinking of p75/AIRM-1 or CD33 has been shown to sharply inhibit the in vitro proliferation of both normal myeloid cells and chronic myeloid leukemias. In this study, we analyzed acute myeloid leukemic cells for the expression of p75/AIRM-1. p75/AIRM-1 marked the M5 (11/12) and M4 (2/2) but not the M1, M2, and M3 subtypes according to the French–American–British classification. Cell samples from 12 acute myeloid leukemias were cultured in the presence of granulocyte/macrophage colony-stimulating factor. Addition to these cultures of anti-CD33 antibody resulted in ≈70% inhibition of cell proliferation as assessed by [3H]thymidine uptake or by the recovery of viable cells. Anti-p75/AIRM-1 antibody exerted a strong inhibitory effect only in two cases characterized by a high in vitro proliferation rate. After crosslinking of CD33 (but not of p75/AIRM-1), leukemic cells bound Annexin V and displayed changes in their light-scattering properties and nucleosomal DNA fragmentation, thus providing evidence for the occurrence of apoptotic cell death. Remarkably, when anti-CD33 antibody was used in combination with concentrations of etoposide insufficient to induce apoptosis when used alone, a synergistic effect could be detected in the induction of leukemic cell death. These studies provide the rationale for new therapeutic approaches in myeloid leukemias by using both chemotherapy and apoptosis-inducing mAbs.

Antibody-induced engagement of beta 2 integrins on adherent human neutrophils triggers activation of p21ras through tyrosine phosphorylation of the protooncogene product Vav.

It is known that beta 2 integrins are crucial for leukocyte cell-cell and cell-matrix interactions, and accumulating evidence now suggests that integrins serve not only as a structural link but also as a signal-transducing unit that controls adhesion-induced changes in cell functions. In the present study, we plated human neutrophils on surface-bound anti-beta 2 (CD18) antibodies and found that the small GTP-binding protein p21ras is activated by beta 2 integrins. Pretreatment of the cells with genistein, a tyrosine kinase inhibitor, led to a complete block of p21ras activation, an effect that was not achieved with either U73122, which abolishes the beta 2 integrin-induced Ca2+ signal, or wortmannin, which totally inhibits the phosphatidylinositol 3-kinase activity. Western blot analysis revealed that antibody-induced engagement of beta 2 integrins causes tyrosine phosphorylation of several proteins in the cells. One of these tyrosine-phosphorylated proteins had an apparent molecular mass of 95 kDa and was identified as the protooncogene product Vav, a p21ras guanine nucleotide exchange factor that is specifically expressed in cells of hematopoietic lineage. A role for Vav in the activation of p21ras is supported by the observations that antibody-induced engagement of beta 2 integrins causes an association of Vav with p21ras and that the effect of genistein on p21ras activation coincided with its ability to inhibit both the tyrosine phosphorylation of Vav and the Vav-p21ras association. Taken together, these results indicate that antibody-induced engagement of beta 2 integrins on neutrophils triggers tyrosine phosphorylation of Vav and, possibly through its association, a downstream activation of p21ras.

NMR studies of muscle glycogen synthesis in insulin-resistant offspring of parents with non-insulin-dependent diabetes mellitus immediately after glycogen-depleting exercise.

To examine the impact of insulin resistance on the insulin-dependent and insulin-independent portions of muscle glycogen synthesis during recovery from exercise, we studied eight young, lean, normoglycemic insulin-resistant (IR) offspring of individuals with non-insulin-dependent diabetes mellitus and eight age-weight matched control (CON) subjects after plantar flexion exercise that lowered muscle glycogen to approximately 25% of resting concentration. After approximately 20 min of exercise, intramuscular glucose 6-phosphate and glycogen were simultaneously monitored with 31P and 13C NMR spectroscopies. The postexercise rate of glycogen resynthesis was nonlinear. Glycogen synthesis rates during the initial insulin independent portion (0-1 hr of recovery) were similar in the two groups (IR, 15.5 +/- 1.3 mM/hr and CON, 15.8 +/- 1.7 mM/hr); however, over the next 4 hr, insulin-dependent glycogen synthesis was significantly reduced in the IR group [IR, 0.1 +/- 0.5 mM/hr and CON, 2.9 +/- 0.2 mM/hr; (P < or = 0.001)]. After exercise there was an initial rise in glucose 6-phosphate concentrations that returned to baseline after the first hour of recovery in both groups. In summary, we found that following muscle glycogen-depleting exercise, IR offspring of parents with non-insulin-dependent diabetes mellitus had (i) normal rates of muscle glycogen synthesis during the insulin-independent phase of recovery from exercise and (ii) severely diminished rates of muscle glycogen synthesis during the subsequent recovery period (2-5 hr), which has previously been shown to be insulin-dependent in normal CON subjects. These data provide evidence that exercise and insulin stimulate muscle glycogen synthesis in humans by different mechanisms and that in the IR subjects the early response to stimulation by exercise is normal.

Kids Alive! Support for Children of Parents with Cancer: An Exemplar Program for Children of Parents with Cancer

Cancer in a parent or caregiver is an event that affects the whole family. The roles and responsibilities of the diagnosed parent, as well as those of each family member, are affected at the time of diagnosis and throughout the progression of the illness. According to the American Cancer Society, there will be an estimated 1,665,540 new cancer cases diagnosed and 585,720 cancer deaths in 2014. This staggering statistic means there are a number of cancer diagnoses that will directly affect thousands of parents and their children. Past research suggests this upheaval in the system is particularly stressful on children and can lead to a number of responses including anxiety, depression, distress, and other negative reactions. Despite the large number of parents and caregivers diagnosed with cancer in the United States each year, there are relatively few support groups aimed at supporting children affected by parental cancer. Support groups provide opportunities to serve this population in a number of advantageous ways by providing safety, support, and a sense of community. Additionally, support groups allow this population of young people to express their fears and worries, connect to others going through similar circumstances, and explore their parent's diagnosis in a context that is helpful and developmentally appropriate. Past research has found that children who do not receive support during this life-changing event can be negatively affected throughout the life span. On the other hand, this event can be a time to build a child's resilience and provide the structure through which they may thrive in adversity. Support groups offer the opportunity to address this difficult event and lead to positive results. Kids Alive! is one such group that has been proactive in support for children of parents diagnosed with cancer since 1995. Kids Alive!, a support group that runs out of Porter Hospital in Denver Colorado, uses Joseph Campbell's Hero's Journey to structure monthly groups. The Hero's Journey, described in Campbell's The Hero with a Thousand Faces (1949), focuses on a set pattern that all heroes must go through during their journey towards an ultimate victory and self-discovery. Kids Alive! incorporates this journey into a curriculum aimed at helping children explore their thoughts and feelings around their parent's cancer and leads to a realization that they are not alone on this journey. Over the course of eight months, children in Kids Alive! receive support and solidarity that leads to life-changing experiences and an understanding of what a diagnosis of cancer in a parent can mean. Kids Alive! consists of professionals and volunteers who take time to recognize and support this underserved population. The program has led to positive outcomes for nearly two decades and consistently increases the numbers of children and families served. The purpose of this paper is to describe the Kids Alive! program as an exemplar program that addresses these problems by utilizing protective factors research has found in this population. Further, this paper will discuss areas of future research while providing the model of an effective program aimed at serving an important population. Additionally, the model of Kids Alive! will be described through this paper in a way that allows for other oncology settings to consider this relatively simple program that provides consistently positive results.

Examining the Impact of Child Psychologists' Stigmatization of Parents on Treatment Outcomes Through a Developmental Lens

The purpose of this paper is to examine how child psychologists' specialized training inhuman development may make them more prone to stigmatize the parents of their young clients. The stigmatization of parents may lead to fewer parents seeking treatment for their children and to poorer treatment outcomes for those who work with a child psychologist. The process of stigmatization is summarized to provide context for the method through which parents receive stigma. A commonly used theory of child development, Erik Erikson's stages of ego development, is outlined to provide background on how child psychologists may interpret and evaluate a child'sdevelopment. Child psychologists' may identify parenting practices that seem to hinder or stunt children's emotional development, which would make the psychologist more aptto stigmatize and isolate parents from the treatment process. To demonstrate the unique ways in which a child psychologist may stigmatize parents of children at different developmental stages two case studies are included. Finally, a theoretical model of treatment is described that may be more inclusive, and less stigmatizing of parents. This model outlines how the parents' concerns about and observations of their children should be validated and reflected in the treatment process. This treatment modality would allow for child psychologists to more actively involve parents in treatment and provide more education and support around their children's unique emotional development needs. Through this treatment model and child psychologists' awareness of and attempts to reduce the stigmatization of parents, treatment outcomes for young clients may improve.