Lipid bilayer composition modulates the unfolding free energy of a knotted α-helical membrane protein.

α-Helical membrane proteins have eluded investigation of their thermodynamic stability in lipid bilayers. Reversible denaturation curves have enabled some headway in determining unfolding free energies. However, these parameters have been limited to detergent micelles or lipid bicelles, which do not possess the same mechanical properties as lipid bilayers that comprise the basis of natural membranes. We establish reversible unfolding of the membrane transporter LeuT in lipid bilayers, enabling the comparison of apparent unfolding free energies in different lipid compositions. LeuT is a bacterial ortholog of neurotransmitter transporters and contains a knot within its 12-transmembrane helical structure. Urea is used as a denaturant for LeuT in proteoliposomes, resulting in the loss of up to 30% helical structure depending upon the lipid bilayer composition. Urea unfolding of LeuT in liposomes is reversible, with refolding in the bilayer recovering the original helical structure and transport activity. A linear dependence of the unfolding free energy on urea concentration enables the free energy to be extrapolated to zero denaturant. Increasing lipid headgroup charge or chain lateral pressure increases the thermodynamic stability of LeuT. The mechanical and charge properties of the bilayer also affect the ability of urea to denature the protein. Thus, we not only gain insight to the long-sought-after thermodynamic stability of an α-helical protein in a lipid bilayer but also provide a basis for studies of the folding of knotted proteins in a membrane environment.

Coercive parenting: modifiable and nonmodifiable risk factors in parents of children with developmental disabilities.

BACKGROUND: Parents of children with developmental or intellectual disabilities tend to report greater use of coercive parenting practices relative to parents of typically developing children, increasing the risk of adverse child outcomes. However, to date, there is limited research exploring the role and relative contribution of modifiable and nonmodifiable risk factors in parents of children with a disability. The present study aimed to explore the role of various modifiable and nonmodifiable parenting, family and sociodemographic factors associated with the use of coercive parenting practices in parents of children with a disability. METHODS: Caregivers (N = 1392) enrolled in the Mental Health of Young People with Developmental Disabilities (MHYPeDD) programme in Australia completed a cross-sectional survey about their parenting and their child aged 2-12 years with a disability. Measures covered a range of domains including relevant demographic and family background, use of coercive parenting practices, intensity of child behavioural difficulties and questions relating to parent and family functioning such as parental self-efficacy, adjustment difficulties and quality of family relationships. RESULTS: Parents of older children, those who were younger at the birth of their child, and parents who were co-parenting or working reported more use of coercive parenting practices. Greater intensity of child difficulties, poorer parental self-efficacy and parent-child relationships, and more parental adjustment difficulties were also significantly associated with more use of coercive parenting. Examination of the relative contribution of variables revealed parent-child relationship was a key contributing factor, followed by intensity of child behaviour problems, parent adjustment and parent confidence. CONCLUSIONS: These findings highlight a range of factors that should be targeted and modified through upstream prevention programmes and further inform our understanding of how coercive practices may be influenced through targeted parenting interventions.

Mechanisms Through Which Supportive Relationships with Parents and Peers Mitigate Victimization, Depression and Internalizing Problems in Children Bullied by Peers.

This study investigated how supportive relationships with peers and parents protect children against ongoing victimization, internalizing problems and depression. The longitudinal data set tracked progress of 111 children recruited for the trial of Resilience Triple P, and previously bullied by peers. Informants included children, parents and teachers. Higher levels of facilitative parenting (warm parenting that supports peer relationships) and peer acceptance predicted lower later levels of both depression and victimization over time. Higher levels of child friendedness predicted lower levels of child reports of internalizing problems. Children's friendships, acceptance by same sex peers and facilitative parenting all played moderating roles in protecting against ongoing victimization and internalizing problems. Peer acceptance mediated the relationships between facilitative parenting and victimization. Facilitative parenting mediated the relationship between peer acceptance and depression. It was concluded that supportive relationships with parents and peers play important and complementary roles in protecting children against ongoing victimization and depression.

Antecedents of Treatment Resistant Depression in Children Victimized by Peers.

Children victimized by peers are at increased risk of ongoing depression. This study investigates treatment resistant depression in children victimized by peers, following participation in a targeted cognitive behavioral family intervention. The sample comprised 39 children aged 6-12 years with elevated depression compared with a general sample, prior to the intervention. Six months after the intervention, 26 were no longer depressed and 13 were still depressed. This study investigated the differentiation of these two groups on the basis of parenting and child factors. Children with treatment resistant depression were discriminated from other children by lower levels of peer support and facilitative parenting immediately after the intervention. It was concluded that ongoing support from parents and peers is needed to reduce the risk of ongoing depression even if victimization has been reduced. Further research could develop a comprehensive profile of children at risk of depression following peer victimization.

Predictors of psychological adjustment, experienced parenting burden and chronic sorrow symptoms in parents of children with cerebral palsy.

AIM: To investigate the role of child behaviour, parental coping and experiential avoidance in predicting the psychological outcomes of: (i) psychological symptoms; (ii) chronic sorrow symptoms; and (iii) experienced parenting burden in parents of children with cerebral palsy (CP). METHOD: This study is a cross-sectional, correlational study. Ninety-four parents of children (aged 2-12 years) with CP (various levels of motor functioning GMFCS I-V) participated. RESULTS: Together, the three predictors of child behaviour, parental coping and experiential avoidance explained 36.8% of the variance in psychological symptoms with child behavioural problems and experiential avoidance as significant unique predictors. In addition, 15.8% of the variance in chronic sorrow symptoms was explained by the three predictors with experiential avoidance alone as a significant unique predictor. Lastly, the predictors together explained 24.3% of the variance in experienced parenting burden with child behavioural problems and experiential avoidance as significant unique predictors. CONCLUSIONS: This study demonstrates a relationship between child behavioural problems and parental psychological symptoms and experienced parenting burden as well as a relationship between experiential avoidance and parental psychological symptoms, experienced parenting burden and chronic sorrow symptoms.

Parenting knowledge and its role in the prediction of dysfunctional parenting and disruptive child behaviour.

BACKGROUND: There is a paucity of research on the relationship between parental knowledge, parenting and parenting self-efficacy, and some inconsistencies have been reported in the literature. METHOD: Parent knowledge of effective parenting strategies was assessed among 68 parents from a non-clinic sample, who also completed questionnaires relating to parenting confidence, quality of parenting and child behaviour. RESULTS: Parents with greater knowledge tended to be less dysfunctional, and reported significantly higher education and income levels. Parenting confidence explained a significant proportion of the variance in reported frequency of disruptive child behaviour while knowledge did not independently contribute to the prediction. However, the relationship between parenting confidence and dysfunctional parenting was moderated by the level of knowledge. There was a stronger negative relationship between confidence and dysfunctional parenting when knowledge level was low than when it was high. Post hoc analyses indicated that the relationship between parenting knowledge and disruptive child behaviour was moderated by the level of parenting dysfunction. Parenting knowledge and reported frequency of disruptive behaviour were positively related when the level of dysfunction was low, but were unrelated when it was high. CONCLUSIONS: Parents with low levels of knowledge and confidence in their parenting may be at greater risk of dysfunctional parenting and might benefit from interventions designed to enhance both knowledge and confidence. Results are interpreted in relation to inconsistencies with previous research and implications for future methodologies.

Trauma-informed care in the newborn intensive care unit: promoting safety, security and connectedness.

Both babies and their parents may experience a stay in the newborn intensive care unit (NICU) as a traumatic or a 'toxic stress,' which can lead to dysregulation of the hypothalamic-pituitary-adrenal axis and ultimately to poorly controlled cortisol secretion. Toxic stresses in childhood or adverse childhood experiences (ACEs) are strongly linked to poor health outcomes across the lifespan and trauma-informed care is an approach to caregiving based on the recognition of this relationship. Practitioners of trauma-informed care seek to understand clients' or patients' behaviors in light of previous traumas they have experienced, including ACEs. Practitioners also provide supportive care that enhances the client's or patient's feelings of safety and security, to prevent their re-traumatization in a current situation that may potentially overwhelm their coping skills. This review will apply the principles of trauma-informed care, within the framework of the Polyvagal Theory as described by Porges, to care for the NICU baby, the baby's family and their professional caregivers, emphasizing the importance of social connectedness among all. The Polyvagal Theory explains how one's unconscious awareness of safety, danger or life threat (neuroception) is linked through the autonomic nervous system to their behavioral responses. A phylogenetic hierarchy of behaviors evolved over time, leveraging the mammalian ventral or 'smart' vagal nucleus into a repertoire of responses promoting mother-baby co-regulation and the sense of safety and security that supports health and well-being for both members of the dyad. Fostering social connectedness that is mutual and reciprocal among parents, their baby and the NICU staff creates a critical buffer to mitigate stress and improve outcomes of both baby and parents. Using techniques of trauma-informed care, as explained by the Polyvagal Theory, with both babies and their parents in the NICU setting will help to cement a secure relationship between the parent-infant dyad, redirecting the developmental trajectory toward long-term health and well-being of the baby and all family members.

Prognostic significance of ventricular ectopic activity in survivors of acute myocardial infarction who receive propranolol.

Beta blockers are frequently prescribed for survivors of acute myocardial infarction (AMI). Although ventricular ectopic activity was found to be associated with mortality in several cohorts, there are no data on the relation of ventricular ectopic activity to mortality in patients with AMI who receive beta blockers. One thousand six hundred and fifty participants in the Beta-Blocker Heart Attack Trial who were randomized to receive propranolol (60 or 80 mg 3 times daily) had 24-hour ambulatory electrocardiography at baseline. By multivariate analysis considering 16 variables, ventricular ectopic activity was independently associated with sudden death (p = 0.02 to 0.001) and total mortality (p = 0.04 to 0.0001) for an average follow-up of 25 months. By univariate analysis, ventricular ectopic activity was associated with increased total mortality (odds ratios 2.13 to 3.54) and sudden death mortality (odds ratio 2.26 to 3.93). The association of ventricular ectopic activity with mortality was observed in both high- and low-risk patient subsets with odds ratios similar to the placebo group. Thus, treatment with propranolol does not alter the relation between ventricular ectopic activity and mortality.

Morning glory syndrome in children. Association with endocrine and central nervous system anomalies.

OBJECTIVE: To identify morning glory syndrome, an uncommon optic disc anomaly. Generally, it is an isolated ocular abnormality; however, some cranial facial and neurologic associations have been reported. PATIENTS: We herein report two patients with morning glory syndrome and associated pituitary dwarfism. In one patient, the pituitary insufficiency was secondary to compression of the pituitary gland by a basal encephalocele; in the second patient, causative factors were not identified. CONCLUSIONS: Patients with morning glory syndrome should have a complete general physical examination and growth evaluation so that early recognition and treatment of the patient with pituitary dwarfism can occur.

Children with persistent feeding difficulties: an observational analysis of the feeding interactions of problem and non-problem eaters.

This study examined the relationship between parent's feeding practices and the feeding behavior of toddlers and preschool-age children with (n = 19) or without (n = 29) persistent feeding difficulties. Specifically, patterns of parent-child interaction were assessed during standardized family mealtime observations in the clinic. Parents also kept observational records of their children's mealtime behavior at home and rated the degree of difficulty they experienced in feeding their child during each meal on a daily basis. Observational results showed that feeding-disordered children engaged in higher levels of disruptive mealtime behavior (food refusal, noncompliance, complaining, oppositional behavior, and playing with food) and lower levels of chewing during mealtime. There were several significant age effects, with younger children (under age 3) engaging in more vomiting and less aversive demanding and verbalizations. Parents of feeding-disordered children were more negative and coercive in their feeding practices and engaged in higher levels of aversive instruction giving, aversive prompting, and negative eating-related comments. There were several significant associations between coercive parental behaviors and children's food refusal and noncompliance in the sample as a whole. Measures of children's disruptiveness at mealtimes in the clinic were significantly correlated with measures of mealtime behavior in the home.

A comparison of the generalization of behavioral marital therapy and enhanced behavioral marital therapy.

This study examined the generalization of behavioral marital therapy (BMT) and enhanced behavioral marital therapy (EBMT), which added cognitive restructuring, affect exploration, and generalization training to BMT. Couples' communication and cognitions were assessed in the clinic and at home. Both BMT and EBMT were effective in decreasing negative communication behaviors and cognition across settings, but there was little evidence of differential generalization or change between the treatments. A series of regression equations showed no significant association between the extent of change in communication or cognitions and change in frequency of marital disagreements or marital satisfaction. It is concluded that BMT results in impressive generalization of communication and cognitive change, but it remains to be demonstrated that these changes are crucial to improvements in marital satisfaction.

The treatment of recurrent abdominal pain in children: a controlled comparison of cognitive-behavioral family intervention and standard pediatric care.

This study describes the results of a controlled clinical trial involving 44 7- to 14-year-old children with recurrent abdominal pain who were randomly allocated to either cognitive-behavioral family intervention (CBFI) or standard pediatric care (SPC). Both treatment conditions resulted in significant improvements on measures of pain intensity and pain behavior. However, the children receiving CBFI had a higher rate of complete elimination of pain, lower levels of relapse at 6- and 12-month follow-up, and lower levels of interference with their activities as a result of pain and parents reported a higher level of satisfaction with the treatment than children receiving SPC. After controlling for pretreatment levels of pain, children's active self-coping and mothers' caregiving strategies were significant independent predictors of pain behavior at posttreatment.

The use of inotropic agents in acute and chronic congestive heart failure.

This article reviews our current understanding of the physiology of myocardial contraction; recent research into its mechanical, macromolecular, and biochemical foundations; and its role in the clinical syndromes of congestive heart failure. This review serves as a background for discussing the mechanism of action and pharmacology of currently available and experimental inotropic agents. The clinical applications of these drugs are discussed and the successes and failures of the pharmacologic approach to patients with congestive heart failure analyzed.

The triple P-positive parenting program: a comparison of enhanced, standard, and self-directed behavioral family intervention for parents of children with early onset conduct problems.

Three variants of a behavioral family intervention (BFI) program known as Triple P were compared using 305 preschoolers at high risk of developing conduct problems. Families were randomly assigned to enhanced BFI (EBFI), standard BFI (SBFI), self-directed BFI (SDBFI), or wait list (WL). At postintervention, the 2 practitioner-assisted conditions were associated with lower levels of parent-reported disruptive child behavior, lower levels of dysfunctional parenting, greater parental competence, and higher consumer satisfaction than the SDBFI and WL conditions. Overall, children in EBFI showed greater reliable improvement than children in SBFI, SDBFI, and WL. By 1-year follow-up, children in all 3 conditions achieved similar levels of clinically reliable change in observed disruptive behavior. However, the EBFI and SBFI conditions showed greater reliable improvement on parent-observed disruptive child behavior.

Cognitive-behavioral treatment of recurrent nonspecific abdominal pain in children: an analysis of generalization, maintenance, and side effects.

From 10% to 15% of school-aged children experience recurring abdominal pain. This study evaluated the efficacy of a cognitive-behavioral program for the treatment of nonspecific recurrent abdominal pain (RAP) using a controlled group design. The multicomponent treatment program consisted of differential reinforcement of well behavior, cognitive coping skills training, and various generalization enhancement procedures. Multiple measures of pain intensity and pain behavior were conducted, including children's self-monitoring, parent observation, teacher observation, and observation by independent observers. Results showed that both the experimental and the control groups reduced their levels of pain. However, the treated group improved more quickly, the effects generalized to the school setting, and a larger proportion of subjects were completely pain-free by 3-months follow-up (87.5% vs. 37.5%). There was no evidence for any negative side effects of treatment.

Childhood depression and conduct disorder: I. Behavioral, affective, and cognitive aspects of family problem-solving interactions.

We assessed the family interactions of depressed, conduct-disordered, mixed depressed-conduct-disordered, and nonclinic children, ages 7-14 years, during a standardized family problem-solving discussion in the clinic. The child's and the mother's problem-solving proficiency, aversive behavior, and associated affective behavior (depressed and angry-hostile) were observed. The child and mother also rated each other's affect during the interaction for the dimensions sad, angry, critical, and happy on Likert-type scales. The child's and mother's cognitive constructions about the interaction were assessed using video-mediated recall. Although all clinic groups had lower levels of effective problem solving than did nonclinic children, their deficiencies were somewhat different. Mixed and depressed children displayed high levels of depressed affect and low levels of angry affect, whereas conduct-disordered children displayed both angry and depressed affect. In addition, conduct-disordered children had lower levels of positive problem solving and higher levels of aversive content than did non-conduct-disordered children. Depressed and conduct-disordered children had higher levels of self-referent negative cognitions than did mixed and comparison children, and depressed children also had higher other-referent negative cognitions than did all other groups. The study provides support for theories and treatment that stress the importance of family problem-solving and conflict resolution skills in child psychopathology.

Childhood depression and conduct disorder: II. An analysis of family interaction patterns in the home.

Few researchers have assessed family interaction patterns associated with childhood depression, especially using observations in natural settings. We directly sampled the interaction patterns of families with depressed, conduct-disordered, mixed depressed-conduct-disordered, and comparison children ages 7-14 years in their homes during the evening meal. Observational measures were taken of positive and aversive behaviors and affect expression for both parents, the referred children, and their siblings. Results replicated previous research showing that conduct-disordered children express high levels of aversive behavior and anger and are part of a family system marked by conflict and aggression. The depressed children were exposed to maternal aversiveness but did not show any evidence of elevated levels of anger or aversiveness in their own behavior. Surprisingly, this was also true for the mixed-disorder children. High levels of depression in both groups of depressed children were associated with low levels of conflict and anger in family members. Overall, siblings showed very similar patterns of behavior, and were exposed to similar patterns of parental behavior, as the referred children. Results are discussed in terms of family models that emphasize the function of aggression and depression in the maintenance of child psychopathology.

Perceptions of the limit of viability: neonatologists' attitudes toward extremely preterm infants.

Although recent technologic advances have dramatically improved the survival of preterm infants, little information exists regarding the attitudes of neonatologists toward their smallest patients, infants born at the "limit of viability." In this pilot study we sent a single mailing of a 25-question survey designed to provide information about the medical treatment of extremely preterm infants (< 22 to 27 weeks' gestational age) to 3056 neonatologists practicing in the United States in September 1992. The 1131 (37%) respondents were well distributed geographically and by nature of practice (i.e., academic, academic affiliate, and community hospitals). Most of the respondents counseled parents that all infants < or = 22 weeks' gestational age die and that at least 75% of infants born at 23 weeks' gestation die. Only for infants born at > or = 26 weeks' gestational age did most of the neonatologists counsel parents that mortality is < or = 50%. Nonintervention or compassionate care in the delivery room was believed to be appropriate for infants less than 23 weeks' gestational age by virtually all neonatologists, by 52% of respondents for infants 23 weeks' gestational age, and by only 1% of respondents for infants 25 weeks' gestational age. Approximately two thirds of neonatologists considered parental wishes regarding resuscitation, and one quarter considered parental parity/fertility history in their medical decision making for infants born at 23 to 24 weeks' gestation. If an infant who had been previously resuscitated decompensated in spite of maximal medical treatment, most of the neonatologists were not willing to provide full resuscitation for infants born at any gestation less than 27 weeks. However, the number of neonatologists who would actively encourage withdrawal of support in a decompensating infant decreased markedly for infants born at > or equal 25 weeks' gestation. Neonatologists who responded to this survey in 1992 considered 23 to 24 weeks of gestation the limit of viability and had great concerns regarding medical decision making for these infants.

Impact of the perception of viability on resource allocation in the neonatal intensive care unit.

OBJECTIVE: To understand how neonatologists' perceptions of viability impact their willingness to recommend or provide medical interventions for infants born at 23 to 24 weeks' gestation. STUDY DESIGN: A 25-question survey mailed to 3056 neonatologists in the United States in 1992 yielded 1131 responses. Seven hundred seventy-five (775 of 1131, 69%) reported they believed that the lower limit of viability was 23 to 24 weeks' gestation. These respondents were asked if they were willing to recommend or provide a series of medical interventions for infants born at 23 and 24 weeks' gestation. RESULTS: Most respondents would provide ventilation (82% and 95%) and surfactant (62% and 78%) for infants born at 23 and 24 weeks' gestation, respectively. The respondent's prediction of <100% mortality, infant factors, and parental wishes were significant predictors of willingness to resuscitate infants born at 23 weeks' gestation. CONCLUSION: There is considerable variation among neonatologists in their willingness to recommend or provide medical interventions for infants born at 23 to 24 weeks' gestation.

A comparison of the effects of child management and planned activities training in five parenting environments.

This study compared the effects of two procedures designed to enhance the extratraining effects of behavioral parent training. Twenty parents of oppositional children were randomly assigned to either a child management training condition or a combined child management plus planned activities condition. A further 10 nonproblem children and their parents served as a social validation group. Observations of both parent and child behavior were conducted in each of five home observation settings (breakfast time, kindy (kindergarten) or school exit, a structured playtime, bathtime, and bedtime). Both training procedures resulted in changes in both child oppositional and parent aversive behavior in all observation settings. In addition, desired positive parenting behaviors also improved in all settings. Treatment effects were maintained in all settings at 3-month follow-up. Comparisons between oppositional children following treatment and children in the social validation group showed that they each displayed similarly low levels of oppositional behavior in all settings. The implications of the results for facilitating generalized changes in behavioral parent training are discussed.