Motor learning without physical practice: The effects of combined action observation and motor imagery practice on cup-stacking speed.

In this study we explored training effects for combined action observation and motor imagery (AO + MI) instructions on a complex cup-stacking task, without physical practice. Using a Graeco-Latin Square design, we randomly assigned twenty-six participants into four groups. This counterbalanced the within-participant factor of practice condition (AO + MI, AO, MI, Control) across four cup-stacking tasks, which varied in their complexity. On each of the three consecutive practice days participants experienced twenty trials under each of the three mental practice conditions. On each trial, a first-person perspective video depicted bilateral cup-stacking performed by an experienced model. During AO, participants passively observed this action, responding only to occasional colour cues. For AO + MI, participants imagined performing the observed action and synchronised their concurrent MI with the display. For MI, a sequence of pictures cued imagery of each stage of the task. Analyses revealed a significant main effect of practice condition both at the 'surprise' post-test (Day 3) and at the one-week retention test. At both time points movement execution times were significantly shorter for AO + MI compared with AO, MI and the Control. Execution times were also shorter overall at the retention compared with the post-test. These results demonstrate that a complex novel motor task can be acquired without physical training. Practitioners can therefore use AO + MI practice to supplement physical practice and optimise skill learning.

A Multi-Disciplinary Approach for the Management of Prosthetic Joint Infections: An Australian Perspective.

Introduction: Prosthetic joint infections (PJI) are a major complication of hip and knee arthroplasty, imposing significant morbidity and mortality. Orthopaedic oncology units have utilised a multi-disciplinary team (MDT) approach for some time. PJI is not only an equally life-threatening condition, it also requires input from multiple healthcare personnel and treatment can vary significantly between individuals given the diversity in microbiological, surgical and host factors. Our arthroplasty service established an MDT meeting to manage this complex patient group. This study describes the philosophy and implementation of an MDT approach to the management of PJIs at a tertiary hospital in Australia. Materials and methods: A retrospective review of all patients that presented to the MDT PJI meeting from October 2017 to April 2020 was performed. Patient characteristics, microbiological profile and management were reviewed. Results: One hundred and one patients were reviewed over 2.5 years with a mean age of 69.2 years (SD 11.9). Patients presenting predominantly had a primary TKR (32%) or primary THR (22%). Results of Microbiology cultures varied, with 42% Gram-positive organisms, 13% Gram-negative organisms, 2% fungus and 1% yeast origin. Management mainly consisted of two-stage revision (28%), debridement-antibiotics-and-implant retention (22%) and antibiotic suppression (14%). A total of 91.5% of patients who underwent surgical management were considered cured at one year. Conclusion: PJIs are complex and require coordinated care by a number of healthcare personnel. The MDT process has allowed collaboration between Orthopaedic, Infectious Disease and Microbiology departments and aims to improve the quality of care provided to patients, potentially reducing morbidity and mortality of patients with PJI.

Absolute Quantification of Phosphorylated ERß Amino Acids in the Hippocampus of Women and in A Rat Model of Menopause.

The rapid decline of circulating 17ß-estradiol (E2) at menopause leads to negative neurological consequences, although hormone therapy paradoxically has both harmful and positive effects depending on the age at which it is delivered. The inconsistent response to E2 suggests unappreciated regulatory mechanisms for estrogen receptors (ERs), and we predicted it could be due to age-related differences in ERß phosphorylation. We assessed ERß phosphorylation using a sensitive mass spectrometry approach that provides absolute quantification (AQUA-MS) of individually phosphorylated residues. Specifically, we quantified phosphorylated ERß in the hippocampus of women (aged 21-83 years) and in a rat model of menopause at 4 residues with conserved sequence homology between the 2 species: S105, S176, S200, and Y488. Phosphorylation at these sites, which spanned all domains of ERß, were remarkably consistent between the 2 species, showing high levels of S105 phosphorylation (80%-100%) and low levels of S200 (20%-40%). Further, S200 phosphorylation decreased with aging in humans and loss of E2 in rats. Surprisingly, Y488 phosphorylation, which has been linked to ERß ligand-independent actions, exhibited approximately 70% phosphorylation, unaltered by species, age, or E2, suggesting ERß's primary mode of action may not require E2 binding. We further show phosphorylation at 2 sites directly altered ERß DNA-binding efficiency, and thus could affect its transcription factor activity. These findings provide the first absolute quantification of ERß phosphorylation in the human and rat brain, novel insights into ERß regulation, and a critical foundation for providing more targeted therapeutic options for menopause in the future.

Epigenomic control of gonadotrophin-releasing hormone neurone development and hypogonadotrophic hypogonadism.

Mammalian reproductive success depends on gonadotrophin-releasing hormone (GnRH) neurones to stimulate gonadotrophin secretion from the anterior pituitary and activate gonadal steroidogenesis and gametogenesis. Genetic screening studies in patients diagnosed with Kallmann syndrome (KS), a congenital form of hypogonadotrophic hypogonadism (CHH), identified several causal mutations, including those in the fibroblast growth factor (FGF) system. This signalling pathway regulates neuroendocrine progenitor cell proliferation, fate specification and cell survival. Indeed, the GnRH neurone system was absent or abrogated in transgenic mice with reduced (ie, hypomorphic) Fgf8 and/or Fgf receptor (Fgfr) 1 expression, respectively. Moreover, we found that GnRH neurones were absent in the embryonic olfactory placode of Fgf8 hypomorphic mice, the putative birthplace of GnRH neurones. These observations, together with those made in human KS/CHH patients, indicate that the FGF8/FGFR1 signalling system is a requirement for the ontogenesis of the GnRH neuronal system and function. In this review, we discuss how epigenetic factors control the expression of genes such as Fgf8 that are known to be critical for GnRH neurone ontogenesis, fate specification, and the pathogenesis of KS/CHH.

Neurodevelopmental wiring deficits in the Ts65Dn mouse model of Down syndrome.

Down syndrome is the most common genetic cause of intellectual disability and occurs due to the trisomy of human chromosome 21. Adolescent and adult brains from humans with Down syndrome exhibit various neurological phenotypes including a reduction in the size of the corpus callosum, hippocampal commissure and anterior commissure. However, it is unclear when and how these interhemispheric connectivity defects arise. Using the Ts65Dn mouse model of Down syndrome, we examined interhemispheric connectivity in postnatal day 0 (P0) Ts65Dn mouse brains. We find that there is no change in the volume of the corpus callosum or anterior commissure in P0 Ts65Dn mice. However, the volume of the hippocampal commissure is significantly reduced in P0 Ts65Dn mice, and this may contribute to the impaired learning and memory phenotype of this disorder. Interhemispheric connectivity defects that arise during development may be due to disrupted axon growth. In line with this, we find that developing hippocampal neurons display reduced axon length in vitro, as compared to neurons from their euploid littermates. This study is the first to report the presence of defective interhemispheric connectivity at the time of birth in Ts65Dn mice, providing evidence that early therapeutic intervention may be an effective time window for the treatment of Down syndrome.

TET1 regulates fibroblast growth factor 8 transcription in gonadotropin releasing hormone neurons.

Fibroblast growth factor 8 (FGF8) is a potent morphogen that regulates the ontogenesis of gonadotropin-releasing hormone (GnRH) neurons, which control the hypothalamus-pituitary-gonadal (HPG) axis, and therefore reproductive success. Indeed, FGF8 and FGFR1 deficiency severely compromises vertebrate reproduction in mice and humans and is associated with Kallmann Syndrome (KS), a congenital disease characterized by hypogonadotropic hypogonadism associated with anosmia. Our laboratory demonstrated that FGF8 signaling through FGFR1, both of which are KS-related genes, is necessary for proper GnRH neuron development in mice and humans. Here, we investigated the possibility that non-genetic factors, such as the epigenome, may contribute to KS onset. For this purpose, we developed an embryonic explant model, utilizing the mouse olfactory placode (OP), the birthplace of GnRH neurons. We show that TET1, which converts 5-methylcytosine residues (5mC) to 5-hydroxymethylated cytosines (5hmC), controls transcription of Fgf8 during GnRH neuron ontogenesis. Through MeDIP and ChIP RT-qPCR we found that TET1 bound to specific CpG islands on the Fgf8 promoter. We found that the temporal expression of Fgf8 correlates with not only TET1 binding, but also with 5hmC enrichment. siRNA knockdown of Tet1 reduced Fgf8 and Fgfr1 mRNA expression. During this time period, Fgf8 also switched histone status, most likely via recruitment of EZH2, a major component of the polycomb repressor complex-2 (PRC2) at E13.5. Together, these studies underscore the significance of epigenetics and chromatin modifications to temporally regulated genes involved in KS.

Predicting responses to inhibitory synaptic input in substantia nigra pars reticulata neurons.

The changes in firing probability produced by a synaptic input are usually visualized using the poststimulus time histogram (PSTH). It would be useful if postsynaptic firing patterns could be predicted from patterns of afferent synaptic activation, but attempts to predict the PSTH from synaptic potential waveforms using reasoning based on voltage trajectory and spike threshold have not been successful, especially for inhibitory inputs. We measured PSTHs for substantia nigra pars reticulata (SNr) neurons inhibited by optogenetic stimulation of striato-nigral inputs or by matching artificial inhibitory conductances applied by dynamic clamp. The PSTH was predicted by a model based on each SNr cell's phase-resetting curve (PRC). Optogenetic activation of striato-nigral input or artificial synaptic inhibition produced a PSTH consisting of an initial depression of firing followed by oscillatory increases and decreases repeating at the SNr cell's baseline firing rate. The phase resetting model produced PSTHs closely resembling the cell data, including the primary pause in firing and the oscillation. Key features of the PSTH, including the onset rate and duration of the initial inhibitory phase, and the subsequent increase in firing probability could be explained from the characteristic shape of the SNr cell's PRC. The rate of damping of the late oscillation was explained by the influence of asynchronous phase perturbations producing firing rate jitter and wander. Our results demonstrate the utility of phase-resetting models as a general method for predicting firing in spontaneously active neurons and their value in interpretation of the striato-nigral PSTH. NEW & NOTEWORTHY The coupling of patterned presynaptic input to sequences of postsynaptic firing is a Gordian knot, complicated by the multidimensionality of neuronal state and the diversity of potential initial states. Even so, it is fundamental for even the simplest understanding of network dynamics. We show that a simple phase-resetting model constructed from experimental measurements can explain and predict the sequence of spike rate changes following synaptic inhibition of an oscillating basal ganglia output neuron.

Comparison of quartz crystallographic preferred orientations identified with optical fabric analysis, electron backscatter and neutron diffraction techniques.

Three techniques are used to measure crystallographic preferred orientations (CPO) in a naturally deformed quartz mylonite: transmitted light cross-polarized microscopy using an automated fabric analyser, electron backscatter diffraction (EBSD) and neutron diffraction. Pole figure densities attributable to crystal-plastic deformation are variably recognizable across the techniques, particularly between fabric analyser and diffraction instruments. Although fabric analyser techniques offer rapid acquisition with minimal sample preparation, difficulties may exist when gathering orientation data parallel with the incident beam. Overall, we have found that EBSD and fabric analyser techniques are best suited for studying CPO distributions at the grain scale, where individual orientations can be linked to their source grain or nearest neighbours. Neutron diffraction serves as the best qualitative and quantitative means of estimating the bulk CPO, due to its three-dimensional data acquisition, greater sample area coverage, and larger sample size. However, a number of sampling methods can be applied to FA and EBSD data to make similar approximations.

The Regulation and Function of Fibroblast Growth Factor 8 and Its Function during Gonadotropin-Releasing Hormone Neuron Development.

Over the last few years, numerous studies solidified the hypothesis that fibroblast growth factor (FGF) signaling regulates neuroendocrine progenitor cell proliferation, fate specification, and cell survival and, therefore, is critical for the regulation and maintenance of homeostasis of the body. One important example that underscores the involvement of FGF signaling during neuroendocrine cell development is gonadotropin-releasing hormone (GnRH) neuron ontogenesis. Indeed, transgenic mice with reduced olfactory placode (OP) Fgf8 expression do not have GnRH neurons. This observation indicates the requirement of FGF8 signaling for the emergence of the GnRH neuronal system in the embryonic OP, the putative birth place of GnRH neurons. Mammalian reproductive success depends on the presence of GnRH neurons to stimulate gonadotropin secretion from the anterior pituitary, which activates gonadal steroidogenesis and gametogenesis. Together, these observations are critical for understanding the function of GnRH neurons and their control of the hypothalamus-pituitary-gonadal (HPG) axis to maintain fertility. Taken together, these studies illustrate that GnRH neuron emergence and hence HPG function is vulnerable to genomic and molecular signals that abnormally modify Fgf8 expression in the developing mouse OP. In this short review, we focus on research that is aimed at unraveling how androgen, all-trans retinoic acid, and how epigenetic factors modify control mouse OP Fgf8 transcription in the context of GnRH neuronal development and mammalian reproductive success.

The ionic mechanism of membrane potential oscillations and membrane resonance in striatal LTS interneurons.

Striatal low-threshold spiking (LTS) interneurons spontaneously transition to a depolarized, oscillating state similar to that seen after sodium channels are blocked. In the depolarized state, whether spontaneous or induced by sodium channel blockade, the neurons express a 3- to 7-Hz oscillation and membrane impedance resonance in the same frequency range. The membrane potential oscillation and membrane resonance are expressed in the same voltage range (greater than -40 mV). We identified and recorded from LTS interneurons in striatal slices from a mouse that expressed green fluorescent protein under the control of the neuropeptide Y promoter. The membrane potential oscillation depended on voltage-gated calcium channels. Antagonism of L-type calcium currents (CaV1) reduced the amplitude of the oscillation, whereas blockade of N-type calcium currents (CaV2.2) reduced the frequency. Both calcium sources activate a calcium-activated chloride current (CaCC), the blockade of which abolished the oscillation. The blocking of any of these three channels abolished the membrane resonance. Immunohistochemical staining indicated anoctamin 2 (ANO2), and not ANO1, as the CaCC source. Biophysical modeling showed that CaV1, CaV2.2, and ANO2 are sufficient to generate a membrane potential oscillation and membrane resonance, similar to that in LTS interneurons. LTS interneurons exhibit a membrane potential oscillation and membrane resonance that are both generated by CaV1 and CaV2.2 activating ANO2. They can spontaneously enter a state in which the membrane potential oscillation dominates the physiological properties of the neuron.

Perinatal midline astrocyte development is impaired in fibroblast growth factor 8 hypomorphic mice.

Our previous studies showed that Fgf8 mutations can cause Kallmann syndrome (KS), a form of congenital hypogonadotropic hypogonadism, in which patients do not undergo puberty and are infertile. Interestingly, some KS patients also have agenesis of the corpus callosum (ACC) suggesting that KS pathology is not limited to reproductive function. Here, we asked whether FGF8 dysfunction is the underlying cause of ACC in some KS patients. Indeed, early studies in transgenic mice with Fgf8 mutations reported the presence of failed or incomplete corpus callosum formation. Additional studies in transgenic mice showed that FGF8 function most likely prevents the prenatal elimination of glial fibrillary acidic protein (GFAP)-immunoreactive (IR) glial cells in the indusium griseum (IG) and midline zipper (MZ), two anterior-dorsal midline regions required for corpus callosum formation (i.e., between embryonic days (E) 15.5-18.5). Here, we tested the hypothesis that FGF8 function is critical for the survival of the GFAP-IR midline glial cells. First, we measured the incidence of apoptosis in the anterior-dorsal midline region in Fgf8 hypomorphic mice during embryonic corpus callosum formation. Second, we quantified the GFAP expression in the anterior-dorsal midbrain region during pre- and postnatal development, in order to study: 1) how Fgf8 hypomorphy disrupts prenatal GFAP-IR midline glial cell development, and 2) whether Fgf8 hypomorphy continues to disrupt postnatal GFAP-IR midline glial cell development. Our results indicate that perinatal FGF8 signaling is important for the timing of the onset of anterior-dorsal Gfap expression in midline glial cells suggesting that FGF8 function regulates midline GFAP-IR glial cell development, which when disrupted by Fgf8 deficiency prevents the formation of the corpus callosum. These studies provide an experimentally-based mechanistic explanation as to why corpus callosum formation may fail in KS patients with deficits in FGF signaling.

Fibroblast Growth Factor 8 Expression in GT1-7 GnRH-Secreting Neurons Is Androgen-Independent, but Can Be Upregulated by the Inhibition of DNA Methyltransferases.

Fibroblast growth factor 8 (FGF8) is a potent morphogen that regulates the embryonic development of hypothalamic neuroendocrine cells. Indeed, using Fgf8 hypomorphic mice, we showed that reduced Fgf8 mRNA expression completely eliminated the presence of gonadotropin-releasing hormone (GnRH) neurons. These findings suggest that FGF8 signaling is required during the embryonic development of mouse GnRH neurons. Additionally, in situ hybridization studies showed that the embryonic primordial birth place of GnRH neurons, the olfactory placode, is highly enriched for Fgf8 mRNA expression. Taken together these data underscore the importance of FGF8 signaling for GnRH emergence. However, an important question remains unanswered: How is Fgf8 gene expression regulated in the developing embryonic mouse brain? One major candidate is the androgen receptor (AR), which has been shown to upregulate Fgf8 mRNA in 60-70% of newly diagnosed prostate cancers. Therefore, we hypothesized that ARs may be involved in the regulation of Fgf8 transcription in the developing mouse brain. To test this hypothesis, we used chromatin-immunoprecipitation (ChIP) assays to elucidate whether ARs interact with the 5'UTR region upstream of the translational start site of the Fgf8 gene in immortalized mouse GnRH neurons (GT1-7) and nasal explants. Our data showed that while AR interacts with the Fgf8 promoter region, this interaction was androgen-independent, and that androgen treatment did not affect Fgf8 mRNA levels, indicating that androgen signaling does not induce Fgf8 transcription. In contrast, inhibition of DNA methyltransferases (DNMT) significantly upregulated Fgf8 mRNA levels indicating that Fgf8 transcriptional activity may be dependent on DNA methylation status.

Long-term effects of very low-carbohydrate and high-carbohydrate weight-loss diets on psychological health in obese adults with type 2 diabetes: randomized controlled trial.

BACKGROUND/OBJECTIVE: Very low-carbohydrate, high-fat (LC) diets are used for type 2 diabetes (T2DM) management, but their effects on psychological health remain largely unknown. This study examined the long-term effects of an LC diet on psychological health. METHODS: One hundred and fifteen obese adults [age: 58.5 ± 7.1 years; body mass index: 34.6 ± 4.3 kg m(-2) ; HbA1c : 7.3 ± 1.1%] with T2DM were randomized to consume either an energy-restricted (~6 to 7 MJ), planned isocaloric LC or high-carbohydrate, low-fat (HC) diet, combined with a supervised exercise programme (3 days week(-1) ) for 1 year. Body weight, psychological mood state and well-being [Profile of Mood States (POMS), Beck Depression Inventory (BDI) and Spielberger State Anxiety Inventory (SAI)] and diabetes-specific emotional distress [Problem Areas in Diabetes (PAID) Questionnaire] and quality of life [QoL Diabetes-39 (D-39)] were assessed. RESULTS: Overall weight loss was 9.5 ± 0.5 kg (mean ± SE), with no difference between groups (P = 0.91 time × diet). Significant improvements occurred in BDI, POMS (total mood disturbance and the six subscales of anger-hostility, confusion-bewilderment, depression-dejection, fatigue-inertia, vigour-activity and tension-anxiety), PAID (total score) and the D-39 dimensions of diabetes control, anxiety and worry, sexual functioning and energy and mobility, P < 0.05 time. SAI and the D-39 dimension of social burden remained unchanged (P ≥ 0.08 time). Diet composition had no effect on the responses for the outcomes assessed (P ≥ 0.22 time × diet). CONCLUSION: In obese adults with T2DM, both diets achieved substantial weight loss and comparable improvements in QoL, mood state and affect. These results suggest that either an LC or HC diet within a lifestyle modification programme that includes exercise training improves psychological well-being.

Fibroblast growth factor 8 regulates postnatal development of paraventricular nucleus neuroendocrine cells.

BACKGROUND: Fibroblast growth factors (FGFs) are crucial signaling molecules that direct the development of the vertebrate brain. FGF8 gene signaling in particular, may be important for the development of the hypothalamus-pituitary-adrenal (HPA)-axis. Indeed, newborn Fgf8 hypomorphic mice harbor a major reduction in the number of vasopressin (VP) neurons in the paraventricular nucleus (PVN), the central output component of the HPA-axis. Additionally, recent studies indicated that adult heterozygous ((+/neo)) Fgf8 hypomorphic mice exhibit more anxiety-like behaviors than wildtype (WT) mice. These studies led us to investigate whether Fgf8 hypomorphy abrogated VP and/or corticotropin-releasing hormone (CRH) neuronal development in the postnatal day (PN) 21 and adult mouse PVN. Furthermore, we studied whether Fgf8 hypomorphy disrupted HPA responsiveness in these mice. METHODS: Using immunohistochemistry, we examined the development of VP and CRH neurons located in the PVN of PN 21 and adult Fgf8 (+/neo) mice. Moreover, we used a restraint stress (RS) paradigm and measured corticosterone levels with enzyme immunoassays in order to assess HPA axis activation. RESULTS: The number of VP neurons in the PVN did not differ between WT and Fgf8 (+/neo) mice on PN 21 and in adulthood. In contrast, CRH immunoreactivity was much higher in Fgf8 (+/neo) mice than in WT mice on PN 21, this difference was no longer shown in adult mice. RS caused a higher increase in corticosterone levels in adult Fgf8 (+/neo) mice than in WT mice after 15 min, but no difference was seen after 45 min. CONCLUSIONS: First, Fgf8 hypomorphy did not eliminate VP and CRH neurons in the mouse PVN, but rather disrupted the postnatal timing of neuropeptide expression onset in PVN neurons. Second, Fgf8 hypomorphy may, in part, be an explanation for affective disorders involving hyperactivity of the HPA axis, such as anxiety.

Alignment Analyses in the Varus Osteoarthritic Knee Using Computer Navigation.

Osteoarthritic (OA) knees with severe extension varus deformity seem to have correspondingly more severe flexion varus, especially beyond a certain tibiofemoral angle. Clinical measurement of flexion varus and fixed flexion deformity (FFD), which had been difficult to perform because of the spatial alignment of the knee in flexion, was recently made possible with computer navigation. We conducted a study to evaluate the relationship of extension and flexion varus in OA knees and to determine whether severity of FFD in the sagittal plane correlates with severity of coronal plane varus deformity. The study included 317 consecutive cases of computer-navigated total knee arthroplasty performed on OA knees with varus deformities. Three sets of values were extracted from the navigation data: varus angle at maximal knee extension, 90° knee flexion, and maximal knee extension. Correlation analyses were performed for extension and flexion varus, FFD, and coronal plane deformity. OA knees with extension varus of more than 10° had an incremental likelihood of more severe flexion varus. When the extension varus angle exceeded 20°, probability became almost certainty. There was no correlation between FFD and coronal plane varus deformity.

Making EBSD on water ice routine.

Electron backscatter diffraction (EBSD) on ice is a decade old. We have built upon previous work to select and develop methods of sample preparation and analysis that give >90% success rate in obtaining high-quality EBSD maps, for the whole surface area (potentially) of low porosity (<15%) water ice samples, including very fine-grained (<10 µm) and very large (up to 70 mm by 30 mm) samples. We present and explain two new methods of removing frost and providing a damage-free surface for EBSD: pressure cycle sublimation and 'ironing'. In general, the pressure cycle sublimation method is preferred as it is easier, faster and does not generate significant artefacts. We measure the thermal effects of sample preparation, transfer and storage procedures and model the likelihood of these modifying sample microstructures. We show results from laboratory ice samples, with a wide range of microstructures, to illustrate effectiveness and limitations of EBSD on ice and its potential applications. The methods we present can be implemented, with a modest investment, on any scanning electron microscope system with EBSD, a cryostage and a variable pressure capability.

Sun-related behaviours among young Australians with Asian ethnic background: differences according to sociocultural norms and skin tone perceptions.

Deliberate tanning, poor sun protection and sun exposure increase an individual's risk for skin cancer. Recent evidence suggests that individuals of Asian heritage have lower incidence of skin cancer than Caucasians but that their post-diagnosis outcomes are often worse. In Western cultures tanning behaviours are often motivated by a desire for 'attractive' tanned skin. Conversely, a light complexion is desired in a number of Asian cultures and may consequently serve to protect this group from excessive and risky sun exposure behaviours. This possibility is yet to be tested, with little known about the sun-related behaviours of Asian people residing in Australia. The present study involves 140 South Australian young adults who report having Asian heritage. Results show that the majority of female participants, and significantly fewer males, reported participating in deliberate outdoor tanning behaviour. Perceptions of family, peer and media tanning norms influenced behaviour, with peer norms being the strongest predictor. The desire for a lighter skin tone was associated with increased sun-protective behaviour and a lower number of previous severe sunburns. As a significant proportion of participants engaged in deliberate tanning behaviour, it is recommended that future research continue to explore factors associated with tanning, including an explicit measure of culture.

The relationship between sun protection policies and practices in schools with primary-age students: the role of school demographics, policy comprehensiveness and SunSmart membership.

Schools can implement evidence-based sun protection policies that guide practices to help protect children from harmful sun exposure. This national study assessed the relationship between the existence and comprehensiveness of written policies and the comprehensiveness of sun protection practices. The impact of school demographics on the strength of the relationship was also examined, as was the possibility that 'SunSmart' membership would have an additional impact on practices, beyond having any formal policy. In 2011-12, staff members of 1573 schools catering to primary-age students completed a self-administered survey about sun protection policies and practices (response rate of 57%). Results showed that schools with a written policy had more comprehensive practices than schools without a written policy. The relationship between having a written policy and sun protection practices was stronger for remote schools compared with metropolitan and regional schools, and for schools catering to both primary and secondary students compared with primary students only. In addition, policy comprehensiveness was associated with practice comprehensiveness, and SunSmart membership was indirectly related to practice comprehensiveness via policy comprehensiveness. These results indicate that written policies relate to practice comprehensiveness, but the strength of the association can vary according to the characteristics of the organization.

Active decorrelation in the basal ganglia.

The cytoarchitecturally-homogeneous appearance of the globus pallidus, subthalamic nucleus and substantia nigra has long been said to imply a high degree of afferent convergence and sharing of inputs by nearby neurons. Moreover, axon collaterals of neurons in the external segment of the globus pallidus and the substantia nigra pars reticulata arborize locally and make inhibitory synapses on other cells of the same type. These features suggest that the connectivity of the basal ganglia may impose spike-time correlations among the cells, and it has been puzzling that experimental studies have failed to demonstrate such correlations. One possible solution arises from studies of firing patterns in basal ganglia cells, which reveal that they are nearly all pacemaker cells. Their high rate of firing does not depend on synaptic excitation, but they fire irregularly because a dense barrage of synaptic inputs normally perturbs the timing of their autonomous activity. Theoretical and computational studies show that the responses of repetitively-firing neurons to shared input or mutual synaptic coupling often defy classical intuitions about temporal synaptic integration. The patterns of spike-timing among such neurons depend on the ionic mechanism of pacemaking, the level of background uncorrelated cellular and synaptic noise, and the firing rates of the neurons, as well as the properties of their synaptic connections. Application of these concepts to the basal ganglia circuitry suggests that the connectivity and physiology of these nuclei may be configured to prevent the establishment of permanent spike-timing relationships between neurons. The development of highly synchronous oscillatory patterns of activity in Parkinson's disease may result from the loss of pacemaking by some basal ganglia neurons, and accompanying breakdown of the mechanisms responsible for active decorrelation.

Ontogenesis of gonadotropin-releasing hormone neurons: a model for hypothalamic neuroendocrine cell development.

The vertebrate hypothalamo-pituitary-gonadal axis is the anatomical framework responsible for reproductive competence and species propagation. Essential to the coordinated actions of this three-tiered biological system is the fact that the regulatory inputs ultimately converge on the gonadotropin-releasing hormone (GnRH) neuronal system, which in rodents primarily resides in the preoptic/hypothalamic region. In this short review we will focus on: (1) the general embryonic temporal and spatial development of the rodent GnRH neuronal system, (2) the origin(s) of GnRH neurons, and (3) which transcription - and growth factors have been found to be critical for GnRH neuronal ontogenesis and cellular fate-specification. Moreover, we ask the question whether the molecular and cellular mechanisms involved in GnRH neuronal development may also play a role in the development of other hypophyseal secreting neuroendocrine cells in the hypothalamus.