Effects of neonatal monocular enucleation on the number of GAD-positive puncta in rat visual cortex.

Rats that had one eye removed on the day of birth were examined at various postnatal ages with immunocytochemical methods to determine the effect on the development of the GABAergic axonal plexus in the visual cortex. The monocular segment of visual cortex contralateral to the enucleated orbit had 20-30% fewer GABAergic axon terminals than the monocular segment of visual cortex contralateral to the normal eye. Other cortical areas did not show any significant changes. These findings suggest that sensory deprivation of the visual cortex interferes with the normal development of GABAergic neurons

Electron microscopic localization of acetylcholinesterase in the dentate gyrus of young and adult rats.

Acetylcholinesterase (AChE) histochemical staining occurred in neurons of the dentate gyrus at the day of birth and steadily increased in intensity and distribution during the first 3 postnatal weeks until the adult pattern was reached. Granule cells failed to display AChE staining; however, the somata of most non-principal cells in these regions showed AChE activity. It is interesting that most hilar neurons in the dentate gyrus were AChE-positive, but molecular layer local circuit neurons and pyramidal basket cells associated with the granule cell layer did not display AChE staining. AChE reaction product was localized to the nuclear envelope and cisternae of the granular endoplasmic reticulum in the labeled neuronal somata. In addition, the neuropil in the dentate gyrus displayed AChE staining associated with membranes. The possible cholinoceptive role of the AChE somata in the hilus is discussed

A decision aid for nutrition support is acceptable in the pediatric hospital setting

Purpose: Incorporating a Decision Aid (DA) about nutrition support into the general pediatric healthcare setting may improve parent and patient understanding about the risks and benefits of nutrition support options. We aimed to evaluate the acceptability and usability of our newly developed DA for parents of children in the general pediatric healthcare setting who require nutrition support. Design and methods: Participants were 18 parents with a child who had received nutrition support; and 12 Healthcare Professionals (HCPs) involved in pediatric nutrition support discussions. Parents' and HCPs' ratings of acceptability and feasibility of the booklet, and parents' perceived knowledge acquisition after reading the booklet were assessed. Results: Parents were satisfied with the DA, reporting that it was an appropriate length and unbiased. Most parents felt the DA was relevant to their decision-making, improved understanding, and would recommend it to other parents. HCPs felt that the booklet clearly described the essential information for nutrition support options, but less certain of the booklets' impact on parent decision-making. Regardless, most HCPs would recommend the booklet to other clinicians. Conclusion: Our decision aid appears to be acceptable and useful for parents deciding on nutrition support for their child in the general pediatric hospital setting. Practice implications: A DA may facilitate shared decision-making through improved understanding of the risks and benefits of different nutrition support options in the pediatric setting. Further evaluation is required with specific pediatric conditions, to determine the effectiveness for parents actively deciding on their child's nutrition support

Decision-making in childhood cancer: parents’ and adolescents’ views and perceptions

Purpose: Few studies have addressed the way in which families of children with cancer make treatment decisions, and how we can meet parents’ and young peoples’ decisional involvement needs. We aimed to explore parents’ and adolescents’ views and perceptions of making medical decisions in pediatric oncology. Methods: We conducted semi-structured interviews with 25 parents of children diagnosed with cancer in the past 12 months, and 5 adolescents diagnosed in the past 12 months. Our interview schedule was underpinned by Elwyn and Miron-Shatz’s decision-making model. The model acknowledges the deliberation (process of coming to a decision) and determination (making a choice) phases of decision-making. We conducted a thematic analysis. Results: Our findings indicate that information provision is not enough to facilitate parents’ decision-making involvement. Many parents sought additional information to meet their individual needs and preferences. While many parents and young people desired decisional involvement, they trusted the doctors to make treatment decisions. Feelings of distress, inadequacy, and lack of choice impacted decision-making participation. Regardless, many parents in our study were satisfied with treatment decisions, but this was largely dependent on positive treatment outcomes. Conclusion: Our study contributes to understanding how families of a child with cancer make treatment decisions. Families tend to rely on doctors to make treatment decisions, but often seek additional information to help them feel involved in the decision process. Findings highlight that decision-making in pediatric oncology should focus on involving families in the deliberation phase, rather than just determination of choice

An inbred epilepsy-prone substrain of BALB/c mice shows absence of the corpus callosum, an abnormal projection to the basal forebrain, and bilateral projections to the thalamus.

BALB/c mice lack a corpus callosum in about 11% of the population. Two inbred substrains of BALB/c mice, epilepsy-prone (EP) and epilepsy-resistant (ER), have been examined to determine whether these substrains differ in regard to corpus callosum morphology. Further, this study addressed the issue of whether misrouted cortical axons form an aberrant pathway instead of the corpus callosum. Initial studies that examined fresh brain tissue of adult animals revealed normal corpora callosa in all ER mice but deficient or absent corpora callosa in all EP mice. Subsequently, Dil crystals were placed in the motor cortices of aldehyde-fixed brains of 2-week-old animals to investigate cortical projections in both inbred substrains of mice. Fluorescent microscopy revealed that all of the ER animals had normal corpora callosa, whereas all EP animals exhibited either reduced corpora callosa (partially callosal) or an absence (acallosal) of this structure. Both acallosal and partially callosal EP mice displayed an extensive, aberrant projection to the basal forebrain as well as bilateral projections to midline and intralaminar thalamic nuclei. The fibers projecting to the basal forebrain arose from the cortex, coursed toward the midline before turning ventrally along the midline, and appeared to terminate in the medial septal nucleus and the nucleus of the diagonal band. ER animals lacked this aberrant cortical projection to the basal forebrain. Electron microscopic results obtained from EP mice indicated that labeled axons in this aberrant pathway formed axosomatic, axodendritic, and axospinous synapses with the neurons in the medial septal/diagonal band complex. The function of the aberrant projection to the basal forebrain remains unknown but it may provide an abnormal excitatory input to a region that provides cholinergic and GABAergic input to the cerebral cortex and hippocampus. The additional projections to midline and contralateral intralaminar thalamic nuclei in EP mice may function to intensify the synchronization of bilateral discharges

Piloting a parent and patient decision aid to support clinical trial decision making in childhood cancer

Objective: Families of a child with cancer can find the decision to enrol in a clinical trial challenging and often misunderstand key concepts that underpin trials. We pilot tested “Delta,” an online and booklet decision aid for parents with a child with cancer, and adolescents with cancer, deciding whether or not to enrol in a clinical trial. Methods: We developed Delta in accordance with the International Patient Decision Aid Standards. We conducted a pre-post pilot with parents with a child, and adolescents, who had enrolled in a paediatric phase III clinical trial for newly diagnosed acute lymphoblastic leukaemia. Parents (n = 37) and adolescents (n = 3) completed a questionnaire before and after using Delta (either the website or booklet, based on their preference). Results: Twenty-three parents (62.2%) and three adolescents (100%) reviewed the Delta website. Parents rated Delta as highly acceptable in regard to being clearly presented, informative, easy to read, useful, visually appealing, and easy to use. All participants reported that they would recommend Delta to others and that it would have been useful when making their decision. Parents' subjective (Mdiff=10.8, SDdiff = 15.69, P <.001) and objective (OR = 2.25, 95% CI, 1.66-3.04; P <.001) clinical trial knowledge increased significantly after reviewing Delta. Conclusions: To our knowledge, Delta is the first reported decision aid, available online and as a booklet, for parents and adolescents deciding whether or not to enrol in a paediatric oncology clinical trial. Our study suggests that Delta is acceptable, feasible, and potentially useful

The simple, conventional markers of fatigue - variations in neuromuscular performance, creatine kinase and hydration status in elite soccer players over a season.

Background and Purpose: Fixture congestion, game-intensities and limited recovery negatively influence physical/ physiological responses during a competitive soccer season. Therefore, the aim of the investigation was to examine weekly alterations in neuromuscular performance markers, creatine kinase and hydration in elite soccer players throughout a season. Study Design: Longitudinal Observational Study. Methods: Sixteen male professional soccer players competing in the English Football League Championship were assessed over the course of a season. All players provided a urine sample, a blood sample to assess creatine-kinase concentration and performed a countermovement jump test at the start of the season, in-season, pre-and post-match over 38 weeks. Results: Jump height was the most common marker of performance to be significantly reduced in season compared to baseline (-5.4 to -11.3%, P <0.05) with 45.2% of the time-points affected. Measures of FT:CT (-7.5 to -12.4%) and AP (-9.4 to -11.5%), also showed significant deteriorations throughout the season compared to baseline (P<0.05) at several time-points. Max force (MF) significantly increased in-season (+5.1 to 7.0%) in 20% of the observed time-points compared to baseline. CK concentration significantly increased during 19% of the time-points (P<0.05; 62 to 159%). Urine osmolality demonstrated significant differences in-season compared to baseline, but none to levels of dehydration. Conclusion: Monitoring elite soccer players over the course of a competitive season shows alterations in neuromuscular performance and hydration status. These data suggest that assessing counter-movement jump performance may be a useful marker for monitoring responses to training/competition, while creatine-kinase and hydration status may be limited

Statistical challenges in assessing potential efficacy of complex interventions in pilot or feasibility studies

Early phase trials of complex interventions currently focus on assessing the feasibility of a large RCT and on conducting pilot work. Assessing the efficacy of the proposed intervention is generally discouraged, due to concerns of underpowered hypothesis testing. In contrast, early assessment of efficacy is common for drug therapies, where phase II trials are often used as a screening mechanism to identify promising treatments. In this paper we outline the challenges encountered in extending ideas developed in the phase II drug trial literature to the complex intervention setting. The prevalence of multiple endpoints and clustering of outcome data are identified as important considerations, having implications for timely and robust determination of optimal trial design parameters. The potential for Bayesian methods to help to identify robust trial designs and optimal decision rules is also explored

What’s in a Name? Parents’ and Healthcare Professionals’ Preferred Terminology for Pathogenic Variants in Childhood Cancer Predisposition Genes

Current literature/guidelines regarding the most appropriate term to communicate a cancer-related disease-causing germline variant in childhood cancer lack consensus. Guidelines also rarely address preferences of patients/families. We aimed to assess preferences of parents of children with cancer, genetics professionals, and pediatric oncologists towards terminology to describe a disease-causing germline variant in childhood cancer. Using semi-structured interviews we asked participants their most/least preferred terms from; ‘faulty gene,’ ‘altered gene,’ ‘gene change,’ and ‘genetic variant,’ analyzing responses with directed content analysis. Twenty-five parents, 6 genetics professionals, and 29 oncologists participated. An equal number of parents most preferred ‘gene change,’ ‘altered gene,’ or ‘genetic variant’ (n = 8/25). Parents least preferred ‘faulty gene’ (n = 18/25). Half the genetics professionals most preferred ‘faulty gene’ (n = 3/6); however this was least preferred by the remaining genetics professionals (n = 3/6). Many oncologists most preferred ‘genetic variant’ (n = 11/29) and least preferred ‘faulty gene’ (n = 19/29). Participants across all groups perceived ‘faulty gene’ as having negative connotations, potentially placing blame/guilt on parents/children. Health professionals described challenges selecting a term that was scientifically accurate, easily understood and not distressing to families. Lack of consensus highlights the need to be guided by families’ preferred terminology, while providing accurate explanations regarding implications of genetic findings