ABSTRACT
Rates of family violence, including intimate partner violence (IPV) and child maltreatment, remain high in the U.S. and contribute to substantial health and economic costs. How neighborhood environment may influence family violence remains poorly understood. We examine the association between neighborhood vacant and abandoned properties and family violence, and the role collective efficacy may play in that relationship. Data were used from a longitudinal cohort of 218 maternal-child dyads in a southern U.S. city known for elevated rates of violence. Women were matched on their propensity score, for living in a neighborhood with elevated vacant and cited properties. Analyses accounting for clustering in neighborhood and matched groups were conducted to examine the association between neighborhood vacant and abandoned property and family violence, and the potential mediating relationship of collective efficacy. The likelihood of experiencing child maltreatment at 12-months of age was more than twice as high for children living in neighborhoods with a high vacant and cited property rates compared to women living in neighborhoods with fewer vacant and cited properties (OR=2.11, 95% CI=1.03, 4.31). Women living in neighborhoods characterized by high levels of vacant and cited properties were also more than twice as likely to report IPV (OR=2.52, 95% CI=1.21, 5.25). Associations remained mostly stable after controlling for key covariates. Collective efficacy did not act as a mediator in the relationship between vacant and cited properties and family violence. Reducing neighborhood vacant and cited properties may be an important target for interventions focused on reducing family violence.
ABSTRACT
Extracellular vesicles (EVs) are membrane-bound nanoparticles that carry DNA, RNA, and protein cargoes and are found in a variety of biofluids. EVs, along with cell-free DNA (cfDNA), have attracted interest as a source of biomarker material for liquid biopsy, a process in which a sample of body fluid is used for the detection or monitoring of disease. The Vn96 synthetic peptide facilitates the isolation of both EVs and cfDNA from multiple body fluids, including human plasma, placing it as a versatile tool for the capture of multiple biomarker materials for disease detection and/or treatment monitoring. In this chapter, we describe an optimized protocol for Vn96-mediated isolation of EVs and cfDNA from human plasma samples, as well as downstream methods for EV enumeration and DNA, RNA, and protein extraction from the material captured by Vn96 for use in biomarker discovery or detection.
Subject(s)
Cell-Free Nucleic Acids , Extracellular Vesicles , Biomarkers/metabolism , Cell-Free Nucleic Acids/metabolism , DNA/metabolism , Extracellular Vesicles/metabolism , Humans , Peptides/metabolism , Proteins/metabolism , RNA/metabolismABSTRACT
Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues such as 177-lutetium DOTATATE is an effective treatment modality for neuroendocrine tumours, paragangliomas, and neuroblastomas. However, renal and haematopoietic toxicities are the major limitations of this therapeutic approach. The renal toxicity of PRRT is mediated by renal proximal tubular reabsorption and interstitial retention of the radiolabelled peptides resulting in excessive renal irradiation that can be dose-limiting. To protect the kidneys from PRRT-induced radiation nephropathy, basic amino acids are infused during PRRT as they competitively bind to the proximal tubular cells and prevent uptake of the radionuclide. In adults, 1 L of a basic amino acid solution consisting of arginine and lysine is infused over 4 h commencing 30 min prior to PRRT. However, this volume of amino acids infused over 4 h is excessive in small children and can result in hemodynamic overload. This is all the more relevant in paediatric oncology, as many of the children may have been heavily pretreated and so may have treatment-related renal and or cardiac impairment. We have therefore developed the following guidelines for safe paediatric dosing of renal protective amino acid infusions during PRRT. Our recommendations have been made taking into consideration the renal physiology in small children and the principles of safe fluid management in children.
Subject(s)
Positron-Emission Tomography , Radionuclide ImagingABSTRACT
Extracellular vesicles (EVs) have been recognized as a rich material for the analysis of DNA, RNA, and protein biomarkers. A remaining challenge for the deployment of EV-based diagnostic and prognostic assays in liquid biopsy testing is the development of an EV isolation method that is amenable to a clinical diagnostic lab setting and is compatible with multiple types of biomarker analyses. We have previously designed a synthetic peptide, known as Vn96 (ME kit), which efficiently isolates EVs from multiple biofluids in a short timeframe without the use of specialized lab equipment. Moreover, it has recently been shown that Vn96 also facilitates the co-isolation of cell-free DNA (cfDNA) along with EVs. Herein we describe an optimized method for Vn96 affinity-based EV and cfDNA isolation from plasma samples and have developed a multiparametric extraction protocol for the sequential isolation of DNA, RNA, and protein from the same plasma EV and cfDNA sample. We are able to isolate sufficient material by the multiparametric extraction protocol for use in downstream analyses, including ddPCR (DNA) and 'omic profiling by both small RNA sequencing (RNA) and mass spectrometry (protein), from a minimum volume (4 mL) of plasma. This multiparametric extraction protocol should improve the ability to analyse multiple biomarker materials (DNA, RNA and protein) from the same limited starting material, which may improve the sensitivity and specificity of liquid biopsy tests that exploit EV-based and cfDNA biomarkers for disease detection and monitoring.
Subject(s)
Cell-Free Nucleic Acids , Extracellular Vesicles , Biomarkers, Tumor , Humans , Liquid Biopsy , RNAABSTRACT
OBJECTIVE: To assess US pediatricians' preparedness, motivation, and barriers related to educating parents about corporal punishment (CP) and effective child discipline. METHODS: A random sample of 1500 pediatricians was drawn from a nationwide database in the United States. A self-administered questionnaire was sent via mail in 2016. The response rate (53%; n = 787) was maximized via repeated survey mailings and use of cash incentives. RESULTS: The majority of respondents were White (69%), female (59%) and were members of the American Academy of Pediatrics (85%). Most pediatricians felt somewhat prepared to advise parents about child discipline, particularly CP, and perceived their colleagues to be slightly less prepared than themselves. Although most (72%) respondents believed it was "extremely/very" likely that parents valued their advice about child discipline, only 36% believed parents were "extremely/very" likely to follow their advice. Most respondents were highly motivated to participate in activities designed to change norms regarding CP. The most common strategy pediatricians identified for improving child behavior was being consistent with rules (71%). Perceived barriers to providing child discipline advice to parents included lack of time (90%), lack of insurance reimbursement (48%), and lack of training and educational resources (47%). CONCLUSIONS: Pediatricians are a key source of professional advice for parents about how to discipline children safely. Given this, along with strong approval and use of CP in the United States and its harm for children, the current findings suggest a strong need for pediatricians to receive additional training on how to advise parents about child discipline along with removal of barriers to providing such advice.
Subject(s)
Motivation , Punishment , Child , Child Rearing , Female , Humans , Parents , Pediatricians , United StatesABSTRACT
While collecting high quality data from physicians is critical, response rates for physician surveys are frequently low. A proven method for increasing response in mail surveys is to provide a small, prepaid monetary incentive in the initial mailing. More recently, researchers have begun experimenting with adding a second cash incentive in a follow-up contact in order to increase participation among more reluctant respondents. To assess the effects of sequential incentives on response rates, data quality, sample representativeness, and costs, physicians (N = 1,500) were randomly assigned to treatments that crossed the amount of a first ($5 or $10) and second ($0, $5, or $10) incentive to form the following groups: Group $5/$5; Group $5/$10; Group $10/$0; Group $10/$5; and Group $10/$10. Overall, second incentives were associated with higher response rates and lower costs per completed survey, and while they had no effect on item nonresponse, they increased sample representativeness.
Subject(s)
Motivation , Physicians , Data Accuracy , Humans , Postal Service , Surveys and QuestionnairesABSTRACT
The use of corporal punishment (CP) is a strong risk factor for many poor outcomes for children including child maltreatment. The use of CP occurs within social contexts which are important to understand. Although it is known that perceived social norms regarding CP are related to its use, the specific role that a mother's primary support person plays in influencing attitudes toward and use of CP remains unknown. The current study assessed linkages between maternal perceived social support in parenting and perceived injunctive norms of CP from her primary source of support, with maternal attitudes toward and use of CP. Survey data were collected from female primary caregivers (N = 436) of children age 2 to 7 years (mean age = 3.7) enrolled in Special Supplemental Nutrition Program for Women, Infants and Children (WIC) clinics in Southeastern Louisiana. Most frequently, the biological father of the child (37.9%) and the maternal grandmother of the child (24.2%) were identified as the participant's primary source of social support in parenting. Perceived injunctive norms of this support person toward CP use were significantly and positively associated with attitudes toward, AOR = 5.97, 95% CI = [4.04, 8.82], and use of CP, AOR = 3.77, 95% CI = [2.55, 5.59]. However, perceived social support was not associated with these outcomes and also did not moderate these associations. Findings suggest that efforts to reduce maternal risk for child physical abuse and use of CP must include the mother's primary source of social support if they are to be successful.
Subject(s)
Attitude to Health , Child Abuse/psychology , Physical Abuse/psychology , Punishment/psychology , Social Norms , Adolescent , Adult , Aged , Caregivers/psychology , Child , Child, Preschool , Female , Humans , Infant , Male , Mothers/psychology , Parenting/psychology , Risk Factors , Social Support , Surveys and Questionnaires , Young AdultABSTRACT
OBJECTIVE: To assess United States pediatricians' attitudes, beliefs, and perceived professional injunctive norms regarding spanking. METHOD: A self-administered questionnaire was mailed to a nationwide random sample of 1500 pediatricians in the US, drawn from a database maintained by IMS Health. Four survey mailings were conducted and cash incentives of up to $20 were provided. The response rate was 53% (N = 787). RESULTS: Most respondents were members of the American Academy of Pediatrics (85%), had been practicing physicians for 15 years or more (66%), and were white (69%) and female (59%). All US regions were represented. About 3-quarters of pediatricians did not support the use of spanking, and most perceived that their colleagues did not support its use either. Pediatricians who were male, black, and/or sometimes spanked as children had more positive attitudes toward spanking and expected more positive outcomes from spanking than their counterparts. Nearly 80% of pediatricians never or seldom expected positive outcomes from spanking, and a majority (64%) expected negative outcomes some of the time. CONCLUSION: The majority of pediatricians in the US do not support the use of spanking with children and are aware of the empirical evidence linking spanking with increased risk of poor health outcomes for children. Pediatricians are a key, trusted professional source in advising parents about child discipline. These findings suggest that most pediatricians will discourage the use of spanking with children, which over time could reduce its use and associated harms in the population. This is of clinical relevance because, despite strong and consistent evidence of the harms that spanking raises for children, spanking is still broadly accepted and practiced in the US.
Subject(s)
Attitude of Health Personnel , Child Rearing , Pediatricians/statistics & numerical data , Punishment , Adult , Child , Female , Humans , Male , Middle Aged , United StatesABSTRACT
This study used a pre/post design to evaluate the implementation of a hospital-wide No Hit Zone (NHZ) bystander intervention around parent-to-child hitting. A total of 2,326 staff completed the pre-NHZ survey and received training about the NHZ policy; 623 staff completed the post-test survey 10 months later. A group of 225 parents participated in the pre-NHZ survey and a second group of 180 participated in the post-NHZ survey, also 10 months later. Compared to staff in the pre-NHZ group, staff in the post-NHZ group had more negative attitudes about spanking and more positive attitudes about intervention when parents hit children in the hospital. Few differences were found among the parent pre- and post-groups. This study demonstrated that NHZs are a feasible way to inform and train hospital staff in ways to intervene during incidents of parent-to-child hitting to promote a safe and healthy medical environment.
ABSTRACT
OBJECTIVE: To test whether experiencing childhood corporal punishment is linked to later perpetration of dating violence. STUDY DESIGN: Young adults (n = 758; 61% female; mean age of 20 years), originally recruited for a longitudinal study as 9th- and 10th-grade Texas high school students, were asked about their childhood experiences with corporal punishment and physical abuse, as well as current experiences with dating violence. A path model was used to determine whether childhood corporal punishment was related to recent perpetration of physical dating violence, while controlling for childhood physical abuse, age, sex, ethnicity, and socioeconomic status. RESULTS: In all, 19% of participants (n = 134) reported physical dating violence perpetration and 68% reported experiencing corporal punishment as children (n = 498). Analysis showed a significant positive association between corporal punishment and physical perpetration of dating violence (OR 1.30, 95% CI 1.07-1.59). Even after controlling for sex, ethnicity, age, parental education, and child physical abuse, childhood corporal punishment was associated significantly with physical dating violence perpetration (aOR 1.29, 95% CI 1.02-1.62). CONCLUSIONS: The finding that childhood corporal punishment was associated with perpetration of young adult physical dating violence, even after controlling for several demographic variables and childhood physical abuse, adds to the growing literature demonstrating deleterious outcomes associated with corporal punishment.
Subject(s)
Child Abuse/statistics & numerical data , Intimate Partner Violence/statistics & numerical data , Physical Abuse/statistics & numerical data , Punishment , Adolescent , Adult , Child , Female , Humans , Longitudinal Studies , Male , Risk Factors , Young AdultABSTRACT
Despite the risk it poses to children's mental and physical health, approval and use of corporal punishment (CP) remains high in the United States. Informed by the Theory of Planned Behavior, we examined potential predictors of attitudes supportive of CP while assessing the moderating effects of parents' (N=500) chosen primary professional source of advice regarding child discipline: pediatricians (47.8%), religious leaders (20.8%), mental health professionals (MHPs) (n=18.4%), or other identified professionals (13.0%). We conducted a random-digit-dial telephone survey among parents ages 18 and over within New Orleans, LA. The main outcome measure was derived from the Attitudes Toward Spanking scale (ATS). The main "predictors" were: perceived injunctive norms (i.e., perceived approval of CP by professionals; and by family and friends), perceived descriptive norms of family and friends regarding CP, and expected outcomes of CP use. We used multivariate OLS models to regress ATS scores on the predictor variables for each subset of parents based on their chosen professional source of advice. Perceived approval of CP by professionals was the strongest predictor of parental attitudes supportive of CP, except for those seeking advice from MHPs. Perceived injunctive and descriptive norms of family and friends were important, but only for those seeking advice from pediatricians or religious leaders. Positive expected outcomes of CP mattered, but only for those seeking advice from religious leaders or MHPs. In conclusion, the strength and relevance of variables predicting attitudes toward CP varied according to the professional from which the parent was most likely to seek advice.
ABSTRACT
Hitting children for disciplinary purposes (i.e., spanking or corporal punishment [CP]) is a strong risk factor for child physical abuse and is highly prevalent in the U.S. Yet, little is currently known about the relevant attitudes, beliefs, or training needs of key professionals who often advise parents regarding child discipline strategies. A survey of the American Professional Society on the Abuse of Children (APSAC) membership, comprised of mental health professionals, physicians, child welfare professionals, and other professionals in the child maltreatment field, was conducted to assess attitudes, beliefs, perceived norms, training needs, and motivations to change norms regarding CP (N=571, response rate=51%). Most respondents agreed that spanking is a bad disciplinary technique (82%), is harmful for children (74%), and leads to negative outcomes (M=3.0, SD=0.6) more frequently than positive outcomes (M=2.1, SD=0.6; t=20.8; p<0.0001) for children. Professionals reported perceiving that their colleagues' level of endorsement of CP (M=2.4, SD=1.0) was higher than their own (M=1.9, SD=1.0; t(568)=-10.7, p<0.0001) though still below the midpoint. Professionals reported high levels of preparedness to effectively advise parents on non-physical child discipline strategies, but reported perceiving lower levels of preparedness amongst their colleagues. They reported highly valuing giving such advice to parents and being very motivated to participate in activities designed to change social norms regarding CP. Most APSAC members are poised to change these norms and, in doing so, to help reduce rates of child physical abuse in the U.S.
Subject(s)
Attitude , Culture , Physical Abuse/prevention & control , Physical Abuse/psychology , Punishment/psychology , Social Norms , Societies, Scientific , Adolescent , Child , Child Abuse/prevention & control , Child Abuse/psychology , Child Rearing/psychology , Child Welfare , Child, Preschool , Education, Nonprofessional , Female , Humans , Infant , Male , Risk Factors , United StatesABSTRACT
Adverse Childhood Experiences (ACEs) such as child abuse are related to poor health outcomes. Spanking has indicated a similar association with health outcomes, but to date has not been considered an ACE. Physical and emotional abuse have been shown in previous research to correlate highly and may be similar in nature to spanking. To determine if spanking should be considered an ACE, this study aimed to examine 1): the grouping of spanking with physical and emotional abuse; and 2) if spanking has similar associations with poor adult health problems and accounts for additional model variance. Adult mental health problems included depressive affect, suicide attempts, moderate to heavy drinking, and street drug use. Data were from the CDC-Kaiser ACE study (N=8316, response rate=65%). Spanking loaded on the same factor as the physical and emotional abuse items. Additionally, spanking was associated with increased odds of suicide attempts (Adjusted Odds Ratios (AOR)=1.37; 95% CI=1.02 to1.86), moderate to heavy drinking (AOR)=1.23; 95% CI=1.07 to 1.41), and the use of street drugs (AOR)=1.32; 95% CI=1.4 to 1.52) in adulthood over and above experiencing physical and emotional abuse. This indicates spanking accounts for additional model variance and improves our understanding of these outcomes. Thus, spanking is empirically similar to physical and emotional abuse and including spanking with abuse adds to our understanding of these mental health problems. Spanking should also be considered an ACE and addressed in efforts to prevent violence.
Subject(s)
Child Abuse/psychology , Life Change Events , Mental Disorders/psychology , Physical Abuse/psychology , Adult , Alcoholism/epidemiology , Alcoholism/psychology , Child , Child Abuse/statistics & numerical data , Female , Humans , Male , Manitoba , Mental Disorders/epidemiology , Odds Ratio , Physical Abuse/statistics & numerical data , Risk Factors , Statistics as Topic , Substance-Related Disorders/epidemiology , Suicide, Attempted/psychology , Suicide, Attempted/statistics & numerical dataABSTRACT
OBJECTIVE: Physical punishment of children is a prevalent practice that is condemned by most medical professionals given its link with increased risk of child physical abuse and other adverse child outcomes. This study examined the prevalence of parent-to-child hitting in medical settings and the intervention behaviors of staff who witness it. METHOD: Staff at a children's medical center and a general medical center completed a voluntary, anonymous survey. We used descriptive statistics to examine differences in the experiences of physicians, nurses, and other medical staff. We used logistic regression to predict intervention behaviors among staff who witnessed parent-to-child hitting. RESULTS: Of the hospital staff who completed the survey (N = 2863), we found that 50% of physicians, 24% of nurses, 27% of other direct care staff, and 17% of nondirect care staff witnessed parent-to-child hitting at their medical center in the past year. A majority of physicians, nurses, and other direct care staff reported intervening sometimes or always. Nondirect care staff rarely intervened. Believing staff have the responsibility to intervene, and having comfortable strategies with which to intervene were strongly predictive of intervention behavior. Staff who did not intervene commonly reported that they did not know how to respond. CONCLUSION: Many medical center staff witness parent-to-child hitting. Although some of the staff reported that they intervened when they witnessed this behavior, the findings indicate that staff may need training to identify when and how they should respond.
Subject(s)
Attitude of Health Personnel , Parent-Child Relations , Personnel, Hospital/statistics & numerical data , Punishment , Adult , Child , HumansABSTRACT
Several medical professional organizations, including the American Academy of Pediatrics, recommend that parents avoid hitting children for disciplinary purposes (e.g., spanking) and that medical professionals advise parents to use alternative methods. The extent to which medical professionals continue to endorse spanking is unknown. This study is the first to examine attitudes about spanking among staff throughout medical settings, including non-direct care staff. A total of 2580 staff at a large general medical center and 733 staff at a children's hospital completed an online survey; respondents were roughly divided between staff who provide direct care to patients (e.g., physicians, nurses) and staff who do not (e.g., receptionists, lab technicians). Less than half (44% and 46%) of staff at each medical center agreed that spanking is harmful to children, although almost all (85% and 88%) acknowledged that spanking can lead to injury. Men, staff who report being religious, and staff who held non-direct care positions at the medical center reported stronger endorsement of spanking and perceived their co-workers to be more strongly in favor of spanking. Non-direct care staff were more supportive of spanking compared with direct care staff on every item assessed. All staff underestimated the extent to which their co-workers held negative views of spanking. If medical centers and other medical settings are to lead the charge in informing the community about the harms of spanking, comprehensive staff education about spanking is indicated.
Subject(s)
Attitude of Health Personnel , Attitude to Health , Medical Staff, Hospital/psychology , Punishment/psychology , Adolescent , Adult , Aged , Child , Female , Hospitals, Pediatric , Humans , Male , Medical Staff, Hospital/statistics & numerical data , Middle Aged , Parents , Surveys and Questionnaires , Texas , Young AdultABSTRACT
The objective of this study was to examine the association between externalizing behaviors and indirect violence exposure, assessed both within the household and at the community level, as well as the interaction effect of indirect and direct violence exposure. A sample of parents of children ages 4-15 who have not been referred or enrolled in child welfare (n = 82) were recruited from the greater New Orleans community. Externalizing behavior was assessed with the Child Behavior Checklist (CBCL). The child's indirect exposure to violence included witnessing community violence, witnessing physical assault, and witnessing fighting or domestic violence at home. Direct exposure to violence included the child experiencing physical aggression from a caregiver. All assessments were based on caregiver reports. To decrease potential for confounding, children were matched for analysis based on age, Hurricane Katrina exposure, and their propensity to be exposed to high indirect violence. Cumulative indirect exposure to violence was significantly positively correlated with CBCL scores. After controlling for key covariates, CBCL externalizing T score increased significantly by approximately 1.25 points for each level increase in indirect violence exposure (ß = 1.25, SE = 0.57, p = 0.027). There also was a significant interaction between indirect and direct exposure to violence in the association with CBCL score (ß = -0.08, SE = 0.03, p = 0.002). These findings extend previous research by demonstrating that exposure to both direct and cross-contextual indirect violence influences externalizing behaviors in children. Additionally, the findings suggest that community and household social environments are both important targets for interventions designed to decrease externalizing behaviors and improve long-term outcomes for youth at risk of exposure to violence.
Subject(s)
Child Behavior , Exposure to Violence/psychology , Adolescent , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Interviews as Topic , Male , New Orleans , Qualitative ResearchABSTRACT
Using data from couples (N = 1,195) who participated in a large community-based study of families, we used maternal reports of parental discipline to examine mothers' and fathers' use of and patterns related to aggressive and nonviolent discipline of their 3-year-old child. First, we separately examined mothers' and fathers' patterns, or classes, of disciplinary behaviors. Second, we identified joint mother-father class profiles. Maternal reports indicated that the patterns among fathers and mothers were similar, but fathers were more likely to be in the low-aggression classes than mothers; and mothers were more likely to be in the high-aggression classes than fathers. Dyads in which both parents employed high levels of aggressive discipline were characterized by higher parenting stress, poorer parental relationship, and lower quality community context. The majority (81.2%) of dyads used congruent disciplinary behaviors. Discordant dyads were similar to dyads in which both parents were high in aggressive discipline, in that these groups had children with the highest levels of aggressive behavior. Implications highlight the need to target both mothers and fathers with parent education efforts to reinforce positive parenting.
ABSTRACT
The purpose of this review was to better understand the impact of universal campaign interventions with a media component aimed at preventing child physical abuse (CPA). The review included 17 studies featuring 15 campaigns conducted from 1989 to 2011 in five countries. Seven studies used experimental designs, but most were quasi-experimental. CPA incidence was assessed in only three studies and decreased significantly in two. Studies also found significant reductions in relevant outcomes such as dysfunctional parenting, child problem behaviors and parental anger as well as increases in parental self-efficacy and knowledge of concepts and actions relevant to preventing child abuse. The following risk factors were most frequently targeted in campaigns: lack of knowledge regarding positive parenting techniques, parental impulsivity, the stigma of asking for help, inadequate social support and inappropriate expectations for a child's developmental stage. The evidence base for universal campaigns designed to prevent CPA remains inconclusive due to the limited availability of rigorous evaluations; however, Triple-P is a notable exception. Given the potential for such interventions to shift population norms relevant to CPA and reduce rates of CPA, there is a need to further develop and rigorously evaluate such campaigns.
Subject(s)
Child Abuse/prevention & control , Health Promotion , Australia , Canada , Child , Humans , Japan , New Zealand , Program Evaluation , United Kingdom , United StatesABSTRACT
The high rates of recurrence and low median survival in many B-cell cancers highlight a need for new targeted therapeutic modalities. In dividing cells, eukaryotic translation initiation factor 5A (eIF5A) is hypusinated and involved in regulation of protein synthesis and proliferation, whereas the non-hypusinated form of eIF5A is a potent inducer of cell death in malignant cells. Here, we demonstrate the potential of modulating eIF5A expression as a novel approach to treating B-cell cancers. SNS01-T is a nonviral polyethylenimine-based nanoparticle, designed to induce apoptosis selectively in B-cell cancers by small interfering RNA-mediated suppression of hypusinated eIF5A and plasmid-based overexpression of a non-hypusinable eIF5A mutant. In this study, we show that SNS01-T is preferentially taken up by malignant B cells, inhibits tumor growth in multiple animal models of B-cell cancers without damaging normal tissues, and synergizes with the current therapies bortezomib and lenalidomide to inhibit tumor progression. The results collectively demonstrate the potential of SNS01-T as a novel therapeutic for treatment of a diverse range of B-cell malignancies.
Subject(s)
Boronic Acids/therapeutic use , Lymphoproliferative Disorders/therapy , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Peptide Initiation Factors/antagonists & inhibitors , Pyrazines/therapeutic use , RNA, Small Interfering/administration & dosage , RNA-Binding Proteins/antagonists & inhibitors , Thalidomide/analogs & derivatives , Animals , Bortezomib , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Synergism , Humans , Lenalidomide , Lymphoproliferative Disorders/genetics , Lymphoproliferative Disorders/pathology , Mice , Nanoparticles/therapeutic use , Neoplasm Transplantation , Polyethyleneimine/chemistry , RNA, Small Interfering/therapeutic use , Thalidomide/therapeutic use , Xenograft Model Antitumor Assays , Eukaryotic Translation Initiation Factor 5AABSTRACT
This study examined separate and combined maternal and paternal use of spanking with children at age 3 and children's subsequent aggressive behavior at age 5. The sample was derived from a birth cohort study and included families (n = 923) in which both parents lived with the child at age 3. In this sample, 44% of 3-year-olds were spanked 2 times or more in the past month by either parent or both parents. In separate analyses, being spanked more than twice in the prior month at age 3, by either mother or father, was associated with increased child aggression at 5 years. In combined analyses, there was a dose-response association; the greatest risk for child aggression was reported when both parents spanked more than twice in the prior month (adjusted odds ratio: 2.01; [confidence interval: 1.03-3.94]). Violence prevention initiatives should target and engage mothers and fathers in anticipatory guidance efforts aimed at increasing the use of effective and non-aggressive child discipline techniques and reducing the use of spanking.