Elise Davis

The role of apoptosis in sexual differentiation of the rat sexually dimorphic nucleus of the preoptic area.

The sexually dimorphic nucleus of the preoptic area (SDN-POA) in the rat hypothalamus is larger in volume in males than in females due to a larger number of cells in the nucleus. Although the SDN-POA, and its development, have been extensively studied, the actual mechanism of its sexual differentiation has not been established. The results of previous studies have not supported a role for gonadal steroids in the regulation of neurogenesis or the determination of the migratory pathway perinatally. In this study, the role of cell death in the development of the sexual dimorphism in the SDN-POA was investigated using in situ end-labeling to visualize fragmented DNA in apoptotic cells. In the experiments described here, the incidence of apoptosis was determined in part of the SDN-POA, the central division of the medial preoptic nucleus (MPNc), over the first 13 days postnatally in male and female rats. There was a sex difference in the incidence of apoptosis in the MPNc between postnatal days 7 and 10; the incidence was higher in females. The role of testosterone (T) in regulating the incidence of apoptosis in the developing MPNc was examined in neonatally castrated males following T or vehicle injection. Testosterone had a profound inhibitory effect on the incidence of apoptosis between days 6 and 10. In a control region within the lateral preoptic area, there was no sex difference in the incidence of apoptosis, nor was there an effect of T. Thus, the data indicate that the regulation of apoptosis by T is one mechanism involved in the sexual differentiation of the SDN-POA.

Paediatric quality of life instruments: a review of the impact of the conceptual framework on outcomes.

With an increasing number of paediatric quality of life (QOL) instruments being developed, it is becoming difficult for researchers and clinicians to select the most appropriate instrument. Reviews of QOL instruments tend to report only basic properties of the instruments such as domains and psychometric properties. This paper seeks to appraise critically the conceptual underpinnings of paediatric QOL instruments. A systematic review was conducted to identify QOL instruments for children aged 0 to 12 years, and to examine and compare their conceptual frameworks, definitions employed, and structure. Both generic and condition‐specific measures were reviewed. Fourteen generic and 25 condition‐specific QOL instruments were identified. Eleven types of definition of QOL and health‐related QOL and three theories of QOL were identified. QOL was measured by a variety of domains including emotional, social and physical health, and well‐being. Items commonly assessed difficulties, or intensity/frequency of feelings/symptoms, in contrast to positive aspects of life and happiness. The findings highlight the diversity that is apparent in the conceptualization of paediatric QOL and draw attention to the lack of empirical evidence for many of the fundamental assumptions. The impact of the conceptual underpinnings of the instruments on the resulting QOL scores is discussed.

Parent-proxy and child self-reported health-related quality of life: using qualitative methods to explain the discordance

BackgroundAlthough parent-proxy reports of health-related quality of life (HRQOL) are only moderately correlated with child reported HRQOL, it remains unknown why these scores differ. The aim of this study was to use a qualitative methodology to examine why parents and children report different levels of HRQOL.MethodThe sample consisted of 15 parent–child pairs. A think-aloud technique was used where parents and children were given a generic HRQOL instrument (KIDSCREEN) and instructed to share their thoughts with the interviewer. Qualitative analyses were conducted to assess whether parents and children base their answer on different experiences or reasoning, have different response styles, or interpret the items differently.ResultsThere was discordance between parents and children, in terms of rating scale and in terms of the reasoning for their answer. Children tended to have different response styles to parents, where for example, children tended to provide extreme scores (highest or lowest score) and base their response on one single example, more than parents. Parents and children interpreted the meaning of the items very similarly.DiscussionThis study provides evidence to suggest that discordance among parent-child pairs on KIDSCREEN scores may be as a result of different reasoning and different response styles, rather than interpretation of items. These findings have important implications when parent-proxy reported HRQOL is used to guide clinical/treatment decisions.

Psychometric properties of the quality of life questionnaire for children with CP

This paper describes the development and psychometric properties of a condition‐specific quality of life instrument for children with cerebral palsy (CP QOL‐Child). A sample of 205 primary caregivers of children with CP aged 4 to 12 years (mean 8y 5mo) and 53 children aged 9 to 12 years completed the CP QOL‐Child. The children (112 males, 93 females) were sampled across Gross Motor Function Classification System (GMFCS) levels (Level I=18%, II=28%, III=14%, IV=11%, V=27%). Primary caregivers also completed other measures of child health (Child Health Questionnaire; CHQ), QOL (KIDSCREEN), and functioning (GMFCS). Internal consistency ranged from 0.74 to 0.92 for primary caregivers and from 0.80 to 0.90 for child self‐report. For primary caregivers, 2‐week test‐retest reliability ranged from 0.76 to 0.89. The validity of the CP QOL is supported by the pattern of correlations between CP QOL‐Child scales with the CHQ, KIDSCREEN, and GMFCS. Preliminary statistics suggest that the child self‐report questionnaire has acceptable psychometric properties. The questionnaire can be freely accessed at http://www.deakin.edu.ac/hmnbs/chase/cerebralpalsy/cp_qol_home.php

Structural Sexual Dimorphisms in the Anteroventral Periventricular Nucleus of the Rat Hypothalamus Are Sensitive to Gonadal Steroids Perinatally, but Develop Peripubertally

The volume of the anteroventral periventricular nucleus (AVPv) of the rat hypothalamus is larger in females than in males. A preliminary study from this laboratory found that this sexual dimorphism develops between days 30 and 91. The present study was designed to confirm and extend these findings and to determine the role of endogenous gonadal steroids in the development of the AVPv postnatally. The results indicate that the sexual dimorphism in AVPv volume arises between days 30 and 40 and that the length of the nucleus becomes sexually dimorphic between days 60 and 80. Additionally, both AVPv volume and length increased between days 30 and 80 in females. Castration of male rats on the day of birth sex-reversed AVPv volume in adulthood and AVPv length was sex-reversed by castration of males 5 days after birth; ovariectomy of females at these ages had no effect on either parameter. Moreover, in both males and females, AVPv volume and length were unaffected by gonadectomy at later ages. That the AVPv appears to be influenced by testicular hormones neonatally, but changes structurally around the time of puberty in females, clearly challenges current concepts of sexual differentiation that limit the process to the early postnatal period.

Quality of life instruments for children and adolescents with neurodisabilities: how to choose the appropriate instrument

Aim  There are many misconceptions about what constitutes ‘quality of life’ (QoL). It is often difficult for researchers and clinicians to determine which instruments will be most appropriate to their purpose. The aim of the current paper is to describe QoL instruments for children and adolescents with neurodisabilities against criteria that we think are important when choosing or developing a QoL instrument.

A randomized controlled trial of the impact of therapeutic horse riding on the quality of life, health, and function of children with cerebral palsy

This randomized controlled trial examined whether therapeutic horse riding has a clinically significant impact on the physical function, health and quality of life (QoL) of children with cerebral palsy (CP). Ninety‐nine children aged 4 to 12 years with no prior horse riding experience and various levels of impairment (Gross Motor Function Classification System Levels I−III) were randomized to intervention (10wks therapeutic programme; 26 males, 24 females; mean age 7y 8mo [SD 2y 5mo] or control (usual activities, 27 males, 22 females; mean age 8y 2mo [SD 2y 6mo]). Pre‐ and post‐measures were completed by 72 families (35 intervention and 37 control). Children’s gross motor function (Gross Motor Function Measure [GMFM]), health status (Child Health Questionnaire [CHQ]), and QoL (CP QoL‐Child, KIDSCREEN) were assessed by parents and QoL was assessed by children before and after the 10‐week study period. On analysis of covariance, there was no statistically significant difference in GMFM, CP QoL‐Child (parent report and child self‐report), and CHQ scores (except family cohesion) between the intervention and control group after the 10‐week study period, but there was weak evidence of a difference for KIDSCREEN (parent report). This study suggests that therapeutic horse riding does not have a clinically significant impact on children with CP. However, a smaller effect cannot be ruled out and the absence of evidence might be explained by a lack of sensitivity of the instruments since the QoL and health measures have not yet been demonstrated to be sensitive to change for children with CP.

The Relationship between Quality of Life and Functioning for Children with Cerebral Palsy.

Given that quality of life (QOL) is commonly confused with functioning, the aim of this study was to examine the association between functioning and QOL domains for children with cerebral palsy (CP). Two hundred and five parents of children aged 4 to 12 years with CP and 53 children aged 9 to 12 years with CP, completed the Cerebral Palsy Quality of Life Questionnaire for Children. Children were distributed reasonably evenly between sex (male, 54.6%) and Gross Motor Function Classification System levels (I 17.8%, II 28.3%, III 14.1%, IV 11.2%, and V 27.3%). For parent proxy‐report, all domains of QOL were significantly associated with functioning level except access to services. For child self‐report, feelings about functioning, participation and physical health, and pain and feelings about disability, were significantly associated with functioning level. Physical type domains of QOL accounted for more of the variance in functioning than psychosocial type domains. Children with CP have the potential to report a high psychosocial QOL score even if they have poor functioning.

A REVISED CRITICAL PERIOD FOR THE SEXUAL DIFFERENTIATION OF THE SEXUALLY DIMORPHIC NUCLEUS OF THE PREOPTIC AREA IN THE RAT

The volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of the rat is several times larger in males than in females. Several studies have established the importance of gonadal steroids perinatally in the sexual differentiation of the SDN-POA as well as a critical period for the permanent influences of exogenous androgen on the volume of the nucleus. Recent preliminary evidence from this laboratory had suggested, however, that the critical period for the effects of the removal of endogenous gonadal steroids on SDN-POA volume may not match that for the administration of exogenous gonadal steroids. A series of experiments was designed to examine further the effects of the removal of endogenous gonadal steroids on adult SDN-POA volume by castrating male rats at various ages. In spite of a rather clear definition of a postnatal critical period for the effects of exogenous steroid administration, the results of this study indicate that the volume of the SDN-POA is sensitive to the removal of endogenous gonadal steroids for a prolonged period of time, extending through at least day 29 postnatally. The data suggest that there may be multiple critical periods for the sexual differentiation of the SDN-POA and reinforce the concept that these critical periods are distinct from those for other sexually differentiated parameters.

Quality of life of adolescents with cerebral palsy: perspectives of adolescents and parents

Quality of life (QOL) has emerged over the past 20 years as an outcome for measuring the effectiveness of health‐improvement interventions. The Cerebral Palsy Quality of Life Questionnaire for Children (CPQOL‐Child) is well regarded and now integrated into research internationally. We describe the results of qualitative research, using grounded research in which we aimed to identify domains of QOL for adolescents with cerebral palsy (CP) from adolescent and parent perspectives to guide the development of an adolescent version. Seventeen adolescents (nine males, eight females) aged 13 to 18 years (mean=15.53 SD=1.74), with varying levels of impairment (Gross Motor Function Classification System levels I n=5, II n=2, III n=6, IV n=4, and V n=6) and their parents (n=23) participated in semi‐structured interviews. Questions included: ‘What do you think is important to your (child’s) QOL?’ and ‘How does CP impact on your (child’s) life?’ Fifteen themes were identified, including domains related to health issues in adolescence, participation, education, specific CP‐related issues (pain and discomfort, communication), family issues, practical issues (financial resources), and changes associated with adolescence (sexuality, independence). The composition of these QOL domains reflects the developmental concerns of adolescents with CP, adding to the views of children, and strongly supports adolescent participation in the development of self‐reported well‐being and QOL measures. Many of the domains are consistent with child reports of QOL and thus it appears feasible and valid to develop a measure that will be transferable across childhood and adolescence.