Gene editing of SAMHD1 in macrophage-like cells reveals complex relationships between SAMHD1 phospho-regulation, HIV-1 restriction, and cellular dNTP levels.

IMPORTANCE: We introduce BLaER1 cells as an alternative myeloid cell model in combination with CRISPR/Cas9-mediated gene editing to study the influence of sterile α motif and HD domain-containing protein 1 (SAMHD1) T592 phosphorylation on anti-viral restriction and the control of cellular dNTP levels in an endogenous, physiologically relevant context. A proper understanding of the mechanism of the anti-viral function of SAMHD1 will provide attractive strategies aiming at selectively manipulating SAMHD1 without affecting other cellular functions. Even more, our toolkit may inspire further genetic analysis and investigation of restriction factors inhibiting retroviruses and their cellular function and regulation, leading to a deeper understanding of intrinsic anti-viral immunity.

Adaptation and Psychometric Evaluation of the Parenting Concerns Questionnaire-Advanced Disease.

PURPOSE: When patients with advanced cancer have minor children (age < 18), their health-related quality of life is closely linked to their concerns about the impact of progressive illness and death on their children. The Parenting Concerns Questionnaire (PCQ), a validated measure for parents with cancer, does not capture the full range of concerns in advanced cancer. The aim of this was study was to adapt and establish psychometrics for the PCQ for advanced disease (PCQ-AD). METHODS: After generating an initial item-bank, we conducted concept elicitation interviews with clinicians (n = 8) and cognitive interviews with patients (n = 23) for face validity. New items addressed concerns about impact of parental death, making every moment count, communication, and financial impact of cancer on children. We administered 21 candidate items to 151 parents with advanced cancer. We conducted confirmatory factor analysis (CFA), calculated internal consistency, and assessed convergent and known-groups validity. RESULTS: We removed 8 redundant items due to residual covariation between items. CFA of the 13-item PCQ-AD demonstrated satisfactory fit (CFI = 0.971, TLI = 0.966, RMSEA = 0.081) and high internal consistency (Cronbach's alpha = 0.94, composite reliability = 0.95). The PCQ-AD demonstrated convergent validity and known-groups validity; patients with poor functional status reported higher scores than patients with better functional status (Cohen's d = 0.56, p = 0.002). CONCLUSION: Adaptation of the PCQ yielded the addition of constructs important in advanced cancer. The PCQ-AD appears to be a reliable and valid measure of parenting concerns in advanced cancer, but future studies are needed to examine measure performance in diverse populations and responsiveness of the PCQ-AD to interventions.

Talking With Children About Prognosis: The Decisions and Experiences of Mothers With Metastatic Cancer.

PURPOSE: Parents with metastatic cancer report unique concerns and challenges when discussing their illness with their minor children. Greater understanding of parents' communication experiences can facilitate these discussions. This study aimed to describe the challenges, approaches, and decisions related to discussing prognosis among a sample of mothers with metastatic cancer. METHODS: We conducted a web-based cross-sectional survey assessing the psychosocial concerns of 224 women with metastatic cancer who had minor children. This analysis focused on participant responses to structured and open-ended questions addressing communication with their children. We used descriptive statistics to summarize responses to the structured questions and qualitative content analysis for responses to open-ended questions. RESULTS: Nearly 80% (n = 176) reported they had discussed their prognosis with at least one of their children; 79% identified at least one barrier to these discussions. The most common obstacles were participants' uncertainty about their illness trajectory (43%) and emotional distress associated with these conversations (41%). Qualitative analyses revealed three principles that guided mothers' communication decisions: commitment to honesty and protection; child developmental readiness; and beliefs about the right time. Approaches to discussing prognosis included total honesty, using the language of chronic illness, gradual disclosure, waiting for questions, and emphasizing hope, love, and reassurance. CONCLUSION: This study provides further evidence of the complexity and challenges of parental communication with their children about metastatic cancer. There is a need for both clinicians and researchers to identify, test, and implement evidence-based strategies to assist ill parents with their communication concerns.

Maternal breast cancer and communicating with children: A qualitative exploration of what resources mothers want and what health professionals provide.

OBJECTIVE: To explore the communication and resource needs of mothers diagnosed with breast cancer treated with curative intent in communicating with their young children and to identify gaps in the resources and support provided to these women. METHODS: Data were collected via semi-structured telephone interviews from 13 mothers who were diagnosed with breast cancer while parenting a young child (age 3-12 years), and 10 health professionals in Victoria, Australia. Data were analysed qualitatively using the Framework Method. RESULTS AND CONCLUSION: Mothers and health professionals prioritised communication with children about the cancer diagnosis; however, health professionals and mothers differed in their views of parents' communication needs both in terms of the nature of the support/information needed and the delivery of this support/information. Mothers wanted easily accessible resources that were both instructive and practical. Mothers also emphasised quality over quantity of support. Health professionals were mostly aware of mothers' needs, however, emphasised less instructive support and information. This study highlights the need for improved coordination and tailoring of psychosocial resources and supports for these parents and families communicating about a cancer diagnosis with their young children.

Preventative Health and Risk Behaviors Among Adolescent Girls With and Without Family Histories of Breast Cancer.

PURPOSE: To compare health behaviors (smoking, alcohol use, fruit and vegetable intake, and exercise frequency) and breast self-exam (BSE) between girls with breast cancer family history (BCFH+) and without (BCFH-) and assess associates of behaviors across all girls. METHODS: A total of 208 BCFH+ girls (11-19 years old), with first- or second-degree relatives with breast cancer or a mother with a BRCA1/2 mutation, and 112 BCFH- peers reported their health behaviors, beliefs, and psychosocial function. RESULTS: Despite higher BCFH+ girls' greater perceived breast cancer risk, there were no differences between BCFH+ and BCFH- girls on diet, exercise, alcohol initiation, or BSE. BCFH+ girls were slightly more likely to report trying cigarettes (11% vs. 5%, p = .04). In multivariable models with all girls, categorical associations with behaviors included the following: developmental and demographic factors with smoking, alcohol, diet, and exercise; family breast cancer history and experience with smoking, alcohol, and diet; psychosocial factors with smoking; girls perceptions of cancer controllability and mother support for health behaviors with alcohol, diet, exercise, and BSE; and mother behaviors with diet. CONCLUSIONS: Adolescent girls from BCFH+ families reported similar health behaviors to BCFH- peers, signaling that they are not translating their higher perceived risk into cancer control behaviors. Both uncontrollable (i.e., breast cancer experiences) and modifiable factors relate to health behaviors and warrant further investigation. Results indicate that interventions with teens and parents that target modifiable variables such as controllability perceptions, maternal modeling, and communication may relate to better health behaviors and reduced future breast cancer risk.

Study protocol for Enhancing Parenting In Cancer (EPIC): development and evaluation of a brief psycho-educational intervention to support parents with cancer who have young children.

BACKGROUND: Parents with cancer have high rates of psychological morbidity, and their children are at risk of poor psychosocial outcomes, particularly in the context of parental distress and poor family communication. Parents express concerns about the impact of cancer on their children and report a lack of professional guidance in meeting their children's needs. Few parenting interventions exist and current interventions have extensive infrastructure demands making them unsuitable for routine use in most health settings. The aims of this study are to develop and establish the feasibility and acceptability of a novel and accessible psycho-educational intervention to improve parenting efficacy and decrease parental stress among adults with cancer who have children aged 3-12 years. The intervention will be suitable for parents with cancer who are receiving treatment with a view to longer term survival, irrespective of cancer diagnosis, and their respective co-parents. METHODS/DESIGN: This study comprises two phases using the UK Medical Research Council framework for developing complex interventions. In the development phase, intervention content will be iteratively developed and evaluated in consultation with consumers, and in the piloting phase, feasibility will be tested in a clinical sample of 20 parents with cancer and their co-parents using a single arm, pre-test post-test design. The intervention will comprise an audiovisual resource (DVD), a question prompt list, and a telephone call with a clinical psychologist. Questionnaires administered pre- and 1 month post-intervention will assess parental stress, psychological morbidity, quality of life, self-efficacy and perceptions of child adjustment, and family functioning. Intervention feasibility will be determined by mixed-method participant evaluation of perceived usefulness, benefits, and acceptability. DISCUSSION: This new initiative will translate existing descriptive evidence into an accessible intervention that supports parenting during cancer treatment and meets the information needs of parents with cancer and their families. This is an important advance: despite increasing recognition of the impact of parental cancer on the family, intervention research lags behind the descriptive literature. This low-intensity, accessible, and targeted intervention places minimal burden on infrastructure and promotes patient autonomy and self-management. If feasible, this style of intervention may be a template for future interventions with similar populations.

Psychosocial Adjustment and Perceived Risk Among Adolescent Girls From Families With BRCA1/2 or Breast Cancer History.

PURPOSE: To evaluate the impact of breast cancer family history and maternal BRCA1/2 mutation on the psychosocial adjustment and perceived risk in girls age 11 to 19 years old. MATERIALS AND METHODS: Girls age 11 to 19 years old with one or more relatives with breast cancer or a familial BRCA1/2 mutation (breast cancer family history [BCFH] positive, n = 208; n = 69 with BRCA1/2-positive mother), peers (BCFH negative, n = 112), and their mothers completed assessments of psychosocial adjustment, breast cancer-specific distress, and perceived risk of breast cancer. RESULTS: General psychosocial adjustment did not differ significantly between BCFH-positive and BCFH-negative girls, either by self-report or mother report, except for higher self-esteem among BCFH-positive girls (P = .01). BCFH-positive girls had higher breast cancer-specific distress than BCFH-negative girls (P < .001), but girls from BRCA1/2-positive families did not differ from other BCFH-positive peers. BCFH-positive girls were more likely to report themselves at increased self-risk for breast cancer in adulthood than BCFH-negative peers (74% v 33%, respectively; P ≤ .001). Girls from BRCA1/2-positive families were more likely than other BCFH-positive and BCFH-negative peers to report themselves at increased risk (P < .001). In all groups, perceived risk of breast cancer was associated with older age. Higher breast cancer-specific distress among adolescent girls was associated with higher self-perceived risk of breast cancer and higher maternal breast cancer-specific distress. CONCLUSION: Adolescent girls from BRCA1/2-positive and breast cancer families have higher self-esteem and do not have poorer psychosocial adjustment than peers. However, they do experience greater breast cancer-specific distress and perceived risk of breast cancer, particularly among older girls. Understanding the impact is important to optimize responses to growing up in families at familial and genetic risk for breast cancer, particularly given the debate over the genetic testing of children for cancer susceptibility in adulthood.

Psychosocial Adjustment in School-age Girls With a Family History of Breast Cancer.

OBJECTIVE: Understanding how young girls respond to growing up with breast cancer family histories is critical given expansion of genetic testing and breast cancer messaging. We examined the impact of breast cancer family history on psychosocial adjustment and health behaviors among >800 girls in the multicenter LEGACY Girls Study. METHODS: Girls aged 6 to 13 years with a family history of breast cancer or familial BRCA1/2 mutation (BCFH+), peers without a family history (BCFH-), and their biological mothers completed assessments of psychosocial adjustment (maternal report for 6- to 13-year-olds, self-report for 10- to 13-year-olds), breast cancer-specific distress, perceived risk of breast cancer, and health behaviors (10- to 13-year-olds). RESULTS: BCFH+ girls had better general psychosocial adjustment than BCFH- peers by maternal report. Psychosocial adjustment and health behaviors did not differ significantly by self-report among 10- to 13-year-old girls. BCFH+ girls reported higher breast cancer-specific distress (P = .001) and were more likely to report themselves at increased breast cancer risk than BCFH- peers (38.4% vs 13.7%, P < .001), although many girls were unsure of their risk. In multivariable analyses, higher daughter anxiety was associated with higher maternal anxiety and poorer family communication. Higher daughter breast cancer-specific distress was associated with higher maternal breast cancer-specific distress. CONCLUSIONS: Although growing up in a family at risk for breast cancer does not negatively affect general psychosocial adjustment among preadolescent girls, those from breast cancer risk families experience greater breast cancer-specific distress. Interventions to address daughter and mother breast cancer concerns and responses to genetic or familial risk might improve psychosocial outcomes of teen daughters.

Parenting changes in adults with cancer.

BACKGROUND: Children whose parents have cancer are at risk for psychosocial difficulties; however, the mechanisms are not well understood. This cross-sectional study sought support for a model connecting parental cancer to child distress through its impact on parenting self-efficacy beliefs and parenting behaviors by examining relations among parental illness, quality of life/parent functioning, parenting efficacy beliefs, and concerns about children's emotional distress. METHODS: One hundred ninety-four adult oncology outpatients with children who were 18 years old or younger completed questionnaires assessing their health-related quality of life (Functional Assessment of Cancer Therapy-General), depression and anxiety symptoms (Hospital Anxiety and Depression Scale), overall distress (Distress Thermometer), and parenting efficacy beliefs and parenting concerns (Parenting Concerns Questionnaire). RESULTS: Parenting efficacy scores for parents and coparents declined significantly after diagnosis. This decline correlated with more visits to a medical clinic, treatment with intravenous chemotherapy in the past month, poorer health-related quality of life, and more depression and distress. Parents experiencing the most concern about the impact of mood, physical limitations, and changes in routines on their children experienced the biggest declines in their own sense of efficacy as parents and in their belief in their coparent's efficacy. Finally, declines in parenting efficacy beliefs correlated with parental concerns about children's emotional distress about aspects of the parent's illness. CONCLUSIONS: This study highlights the importance of identifying and addressing parenting concerns to alleviate patient distress, and it may help to guide future intervention efforts.

NCCN roundtable: talking to children about cancer.

A roundtable presentation at the NCCN 19th Annual Conference focused on the child's experience when a parent has cancer and concluded that honest communication, appropriate to the child's age and temperament, is essential, and that oncology providers should institute programs that help families deal with the illness.

Knowledge and perceptions of familial and genetic risks for breast cancer risk in adolescent girls.

Evidence suggests early events might modify adult breast cancer risk and many adolescents learn of familial and genetic risks for breast cancer. Little is known about how adolescent girls understand and respond to breast cancer risk. Semi-structured interviews with 11-19 year-old girls at high-risk and population-risk for breast cancer evaluated knowledge and perceptions of breast cancer risk and risk modification. Framework analysis and descriptive statistics were utilized to analyze open-ended responses. Risk group and age differences were evaluated by Fisher's exact and McNemar's tests. Fifty-four girls (86 % of invited), 35 high-risk (65 %), and 19 population-risk (35 %) completed interviews. The most frequently reported risk for breast cancer was family history/hereditary predisposition (66 %). Only 17 % of girls were aware of BRCA1/2 genes. The majority (76 %) of high-risk girls perceive themselves to be at increased risk for breast cancer, compared to 22 % of population-risk girls (p = 0.001). Half of girls reported that women can get breast cancer before 20-years-old. The majority believe there are things women (70 %) and girls (67 %) can do to prevent breast cancer. Mother was the most frequently reported source of information for breast cancer among both high-risk (97 %) and population-risk (89 %) girls. In this study, many high-risk girls perceive themselves to be at increased risk for breast cancer, and many girls believe that breast cancer can occur in teens. Yet, most girls believe there are things women and girls can do to prevent breast cancer. Research evaluating the impact of awareness and perceptions of breast cancer risk on psychosocial, health, and risk behaviors is needed to develop strategies to optimize responses to cancer risk.

Measuring psychosocial distress and parenting concerns among adults with cancer: the Parenting Concerns Questionnaire.

BACKGROUND: A 2-phase, mixed methods study was conducted to develop a Parenting Concerns Questionnaire (PCQ) for adults with cancer. Limited information about this area of psychosocial distress highlights the need for a measurement tool that can identify adult oncology patients with heightened parenting concerns who could benefit from additional intervention. METHODS: Telephone focus groups were conducted with 16 oncology patients who had children 18 years old and younger. Group interview transcripts were analyzed to generate qualitative themes and candidate items for the PCQ. A 38-item version of the questionnaire was completed by 173 oncology outpatients who had children 18 years old and under. Participants also completed the Distress Thermometer, HADS (Hospital Anxiety and Depression Scale), and FACT-G (Functional Assessment of Cancer Therapy-General). Exploratory factor analyses revealed the emergence of 3 subscales of 5 items each, yielding a 15-item questionnaire. Associations between total PCQ scores, standardized measures of distress, depression, anxiety, quality of life, and demographic and illness characteristics were examined. RESULTS: The 15-item PCQ demonstrates good internal consistency (Cronbach's α = .83). PCQ scores were significantly associated (P < .01) with standardized measures of psychosocial distress (Distress Thermometer, HADS, and FACT-G) in the expected directions. Higher PCQ scores were associated with female sex, single parenthood, metastatic or recurrent cancer, subjective understanding of incurable disease, comorbid chronic health condition, and current mental health treatment. CONCLUSIONS: The PCQ proved a reliable and valid measure of parenting distress among cancer patients, and thus merits further study.

Children facing the death of a parent: the experiences of a parent guidance program at the massachusetts general hospital cancer center.

Children facing the death of a parent are facing a major upheaval, a loss that will bring them emotional pain and will resonate in different ways at important points throughout their lives. Given the proper supports, most children can expect to adjust well to this enormous change and live happy,productive, and meaningful lives. Although some risk factors for poor adjustment are fixed, the parents themselves often can address others effectively. Clinicians can help the parents of these children facilitate their children's best possible adjustment by emphasizing the principles of facilitating communication, minimizing disruption, preserving family time, and at-tending to their legacy. Clinicians place their children's behaviors within the context of their developmental stage and help the parents find language and an approach that feels comfortable to them. The goal is to help parents re-locate their bearings and realize they can use the parenting skills they al-ready have. Guided by the goal of protecting their children, these parents can find purpose and strength. Reframing their circumstances as a painful and unavoidable challenge, but one that they can actively face, is organizing and fortifying for these families buffeted by loss.

The importance of parenting concerns among patients with cancer.

Almost one quarter of all cancer patients in the United States is estimated to have children under 18-years-old living with them. However, there is limited research on how children's functioning is affected by parental cancer, and the impact of parenting concerns on treatment decisions. This paper will review the literature and hypothesize about why addressing the needs of the children has not been part of routine cancer care. In addition, we will make a case for the importance of including parenting issues in cancer care, and in assessments of treatment decision-making and quality of life. We also describe a clinical program that is attempting to address these issues, and offer practical recommendations for oncologists who want to help parents with cancer and their partners support their children through the challenges of cancer treatment.