Mental health and wellbeing coordinators in primary schools to support student mental health: protocol for a quasi-experimental cluster study.

BACKGROUND: Half of mental health disorders begin before the age of 14, highlighting the importance of prevention and early-intervention in childhood. Schools have been identified globally by policymakers as a platform to support good child mental health; however, the majority of the research is focused on secondary schools, with primary schools receiving very little attention by comparison. The limited available evidence on mental health initiatives in primary schools is hindered by a lack of rigorous evaluation. This quasi-experimental cluster study aims to examine the implementation and effectiveness of a Mental Health and Wellbeing Co-ordinator role designed to build mental health capacity within primary schools. METHODS: This is a primary (ages 5-12) school-based cluster quasi-experimental study in Victoria, Australia. Before baseline data collection, 16 schools selected by the state education department will be allocated to intervention, and another 16 matched schools will continue as 'Business as Usual'. In intervention schools, a mental health and well-being coordinator will be recruited and trained, and three additional school staff will also be selected to receive components of the mental health training. Surveys will be completed by consenting staff (at 2-, 5-, 10- and 17-months post allocation) and by consenting parents/carers (at 3-, 10- and 17-months post allocation) in both intervention and business as usual schools. The primary objective is to assess the change in teacher's confidence to support student mental health and wellbeing using the School Mental Health Self-Efficacy Teacher Survey. Secondary objectives are to assess the indirect impact on systemic factors (level of support, prioritisation of child mental health), parent and teachers' mental health literacy (stigma, knowledge), care access (school engagement with community-based services), and student mental health outcomes. Implementation outcomes (feasibility, acceptability, and fidelity) and costs will also be evaluated. DISCUSSION: The current study will examine the implementation and effectiveness of having a trained Mental Health and Wellbeing Coordinator within primary schools. If the intervention increases teachers' confidence to support student mental health and wellbeing and builds the capacity of primary schools it will improve student mental health provision and inform large-scale mental health service reform. TRIAL REGISTRATION: The trial was retrospectively registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) on July 6, 2021. The registration number is ACTRN12621000873820 .

Aorto-left atrial fistula secondary to infective aortic endocarditis and endarteritis in a cat with valvular aortic stenosis.

A cat previously diagnosed with valvular aortic stenosis developed acute respiratory distress. A new continuous heart murmur was noted on physical exam. Echocardiographic examination revealed vegetative lesions on the aortic valve and continuously shunting blood flow from the aorta into the left atrium. Despite initial treatment for left-sided congestive heart failure, the cat died suddenly. In addition to confirming aortic valve endocarditis and an acquired aorto-left atrial shunt, pathological examination identified vegetative lesions on the luminal surface of the ascending aorta. Although antemortem aerobic blood culture, 16s bacterial ribosomal DNA PCR, and Bartonella PCR failed to identify causative organisms, Escherichia coli was identified on postmortem tissue culture of the aortic lesion. This represented a unique case of primary valvular aortic stenosis with secondary infective aortic endocarditis, infective aortic endarteritis, and aorto-left atrial fistula in a cat. It highlighted potential adverse outcomes of aortic stenosis that are more commonly recognized in humans and dogs.

Universal dynamics of coarsening during polymer-polymer thin-film spinodal dewetting kinetics.

The dewetting dynamics of a supported bilayer polymer thin film on a solid substrate is investigated using grazing incidence x-ray photon correlation spectroscopy. We find that the top layer dewets via the spinodal mechanism. The kinetics of the dewetting is studied by monitoring the time evolution of the surface diffuse x-ray scattering intensity. We study the time evolution of fluctuations about the average surface structure by measuring the two-time x-ray intensity fluctuation correlation functions. Using these two-time correlation functions we quantify the crossover from early-time diffusive dynamics to hydrodynamics. The early diffusive regime satisfies dynamic universality. The two-time correlation functions also quantify the onset of hydrodynamic effects. The hydrodynamic regime is observed during the spinodal dewetting process as these interactions are not screened.

The deubiquitylase Ataxin-3 restricts PTEN transcription in lung cancer cells.

The phosphatidylinositol-3-kinase (PI3K) pathway is commonly hyperactivated in cancer. One mechanism by which this occurs is by silencing of the phosphatase and tensin homolog (PTEN), a tumor suppressor and major antagonist of the pathway, through genetic, epigenetic or posttranscriptional mechanisms. Here, we used an unbiased siRNA screen in non-small-cell lung cancer cells to identify deubiquitylases (DUBs) that have an impact on PI3K signaling by regulating the abundance of PTEN. We found that PTEN expression was induced by depleting any of three members of the Josephin family DUBs: ataxin 3 (ATXN3), ataxin 3-like (ATXN3L) and Josephin domain containing 1 (JOSD1). However, this effect is not mediated through altered PTEN protein stability. Instead, depletion of each DUB increases expression of both the PTEN transcript and its competing endogenous RNA, PTENP1. In ATXN3-depleted cells, under conditions of transcriptional inhibition, PTEN and PTENP1 mRNAs rapidly decay, suggesting that ATXN3 acts primarily by repressing their transcription. Importantly, the PTEN induction observed in response to ATXN3 siRNA is sufficient to downregulate Akt phosphorylation and hence PI3K signaling. Histone deacetylase inhibitors (HDACi) have been suggested as potential mediators of PTEN transcriptional reactivation in non-small-cell lung cancer. Although PTEN exhibits a very limited response to the broad-spectrum HDACi Vorinostat (SAHA) in A549 cells, we find that combination with ATXN3 depletion enhances PTEN induction in an additive manner. Similarly, these interventions additively decrease cell viability. Thus, ATXN3 provides an autonomous, complementary therapeutic target in cancers with epigenetic downregulation of PTEN.

Estimating a mosquito repellent's potential to reduce malaria in communities.

BACKGROUND & OBJECTIVES: Probability models for assessing a mosquito repellent's potential to reduce malaria transmission are not readily available to public health researchers. To provide a means for estimating the epidemiological efficacy of mosquito repellents in communities, we developed a simple mathematical model. STUDY DESIGN: A static probability model is presented to simulate malaria infection in a community during a single transmission season. The model includes five parameters- sporozoite rate, human infection rate, biting pressure, repellent efficacy, and product-acceptance rate. INTERVENTIONS: The model assumes that a certain percentage of the population uses a personal mosquito repellent over the course of a seven-month transmission season and that this repellent maintains a constant rate of protective efficacy against the bites of malaria vectors. MAIN OUTCOME MEASURES: This model measures the probability of evading infection in circumstances where vector biting pressure, repellent efficacy, and product acceptance may vary. [corrected] RESULTS & CONCLUSION: Absolute protection using mosquito repellents alone requires high rates of repellent efficacy and product acceptance. [corrected] Using performance data from a highly effective repellent, the model estimates an 88.9% reduction of infections over a seven- month transmission season. A corresponding reduction in the incidence of super-infection in community members not completely evading infection can also be presumed. Thus, the model shows that mass distribution of a repellent with >98% efficacy and >98% product acceptance would suppress new malaria infections to levels lower than those achieved with insecticide treated nets (ITNs). A combination of both interventions could create synergies that result in reductions of disease burden significantly greater than with the use of ITNs alone.

Crossover behavior in the hydrogen sensing mechanism for palladium ultrathin films.

Palladium has been extensively studied as a material for hydrogen sensors because of the simplicity of its reversible resistance change when exposed to hydrogen gas. Various palladium films and nanostructures have been used, and different responses have been observed with these diverse morphologies. In some cases, such as with nanowires, the resistance will decrease, whereas in others, such as with thick films, the resistance will increase. Each of these mechanisms has been explored for several palladium structures, but the crossover between them has not been systematically investigated. Here we report on a study aimed at deciphering the nanostructure-property relationships of ultrathin palladium films used as hydrogen gas sensors. The crossover in these films is observed at a thickness of approximately 5 nm. Ramifications for future sensor developments are discussed.

The role of metal nanoparticles and nanonetworks in alloy degradation.

Oxide scale, which is essential to protect structural alloys from high-temperature degradation such as oxidation, carburization and metal dusting, is usually considered to consist simply of oxide phases. Here, we report on a nanobeam X-ray and magnetic force microscopy investigation that reveals that the oxide scale actually consists of a mixture of oxide materials and metal nanoparticles. The metal nanoparticles self-assemble into nanonetworks, forming continuous channels for carbon transport through the oxide scales. To avoid the formation of these metallic particles in the oxide scale, alloys must develop a scale without spinel phase. We have designed a novel alloy that has been tested in a high-carbon-activity environment. Our results show that the incubation time for carbon transport through the oxide scale of the new alloy is more than an order of magnitude longer compared with commercial alloys with similar chromium content.

Neuropsychological evidence for separating components of visuo-spatial working memory.

There is increasing evidence to support the idea that visuo-spatial working memory can be segregated into separate cognitive subsystems. However, the nature of these systems remains unclear. In this paper we report data from two brain injured patients suggesting that information about visual appearance is retained in a different subsystem from information about spatial location, and that this differential processing can be observed when the style of presentation (sequential or simultaneous) is controlled.

Surface vibrations in alkanethiol self-assembled monolayers of varying chain length.

The effect of chain length on the low-energy vibrations of alkanethiol striped phase self-assembled monolayers on Au(111) was studied. We have examined the low-energy vibrational structure of well-ordered, low-density 1-decanethiol (C10), 1-octanethiol (C8), and 1-hexanethiol (C6) to further understand the interaction between adsorbate and substrate. Dispersionless Einstein mode phonons, polarized perpendicularly to the surface, were observed for the striped phases of C10, C8, and C6 at 8.0, 7.3, and 7.3 meV, respectively. An overtone at 12.3 meV was also observed for C6/Au(111). These results, in concert with molecular dynamics simulations, indicate that the forces between the adsorbate and substrate can be described using simple van der Waals forces between the hydrocarbon chains and the Au substrate with the sulfur chemisorbed in the threefold hollow site.

Hierarchical assembly and compliance of aligned nanoscale polymer cylinders in confinement.

We report a combined top-down/bottom-up hierarchical approach to fabricate massively parallel arrays of aligned nanoscale domains by means of the self-assembly of asymmetric polystyrene-block-poly(ethylene-alt-propylene) diblock copolymers. Silicon nitride grating substrates of various depths and periodicities are used to template the alignment of the high-aspect-ratio cylindrical polymer domains. Alignment is nucleated by polystyrene preferentially wetting the trough sidewalls and is thermally extended throughout the polymer film by defect annihilation. Topics discussed include a detailed analysis of the capacity of this system to accommodate lithographic defects and observations of alignment beyond the confined channel volumes. This graphoepitaxial methodology can be exploited in hybrid hard/soft condensed matter systems for a variety of applications.

The role of NMDA receptors in neonatal cocaine-induced neurotoxicity.

The present study assessed the ability of N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine (MK-801), to modulate neonatal cocaine-induced neurobehavioral changes in the rat. Sprague-Dawley rats were randomly assigned on postnatal day 0 (PND 0) to one of four treatment groups. Treatments began on PND 4 and continued until PND 10. Treatments consisted of an oral bolus of either cocaine HCl (40 mg/kg), (+)MK-801 (0.4 mg/kg), (+)MK-801 (0.4 mg/kg) followed 30 min later with cocaine HCl (40 mg/kg) or 0.9% saline. On PND 21, 30, 40 and 60, males and females were examined for stress response using the cold-water swim test. Cocaine-treated male and female rats exhibited significantly diminished tolerance to cold-water stress compared to control and MK-801/cocaine-treated groups. In addition, neonatal exposure to cocaine was associated with increased severity of motor symptoms (tail twitches, wet dog shaking and convulsions) following the administration of NMDA (35 mg/kg). Treatment groups were also tested for pain sensitivity using the tail flick (TF) and hot plate (HP) methods. The results indicated that neonatal cocaine exposure altered pain sensitivity in both tests. NMDA receptor binding studies showed a significant increase in receptor densities in the hippocampus and hypothalamus of the cocaine-treated group compared to control. MK-801 administered to rat pups before cocaine treatment blocked the increase in receptor density. The results indicated that neonatal cocaine exposure was associated with altered responses to NMDA, stress tolerance and pain sensitivity. Moreover, the pretreatment with NMDA receptor antagonist, MK-801, abolished or attenuated these cocaine-induced neurobehavioral changes.

A strategy for the assembly of multiple porphyrin arrays based on the coordination chemistry of Ru-centered porphyrin pentamers.

An approach which employs pentameric porphyrin arrays as building blocks toward larger porphyrin arrays is described. Two flexible, and one relatively rigid, Ru-centered porphyrin pentamers (1-3) were synthesized and fully characterized. Their potential as building blocks toward larger porphyrin arrays has been studied via their coordination chemistry using bidentate and tetradentate ligands. DABCO (diazabicyclo[2.2.2]octane) can bind two monomeric porphyrins but was found to be too small to allow the complete formation of a 10-porphyrin array. On the other hand, titration of a larger bridging dipyridyl porphyrin ligand 17 (0.5 equiv) with 1 or 2 and tetrapyridyl ligand 18 (0.25 equiv) with 3 results in the formation of the 11-porphyrin and 21-porphyrin arrays, respectively, with the 21-porphyrin array containing porphyrins in three different metalation states. Changes in the chemical shift of the inner NH protons as well as the ortho- and meso-protons of the pyridyl groups of the porphyrin ligand clearly indicate the formation of large multiple porphyrin complexes. These studies demonstrate that by use of carefully designed building blocks and suitable bridging ligands, porphyrin arrays can be constructed with a dramatic increase in size in relatively few steps. Exploiting the fact that the strength of binding of pyridyl ligands is Ru > Zn > Ni, intra- vs intermolecular competition has been used to investigate aspects of the folding of the array. The photophysical properties of 3 are also described.

Effect of antioxidants on L-glutamate and N-methyl-4-phenylpyridinium ion induced-neurotoxicity in PC12 cells.

The neuropathology associated with Parkinson's disease within and around the substantia nigra is thought to involve excessive production of free radicals, dopamine autoxidation, defects in the expression of glutathione peroxidase, attenuated levels of reduced glutathione, altered calcium homeostasis, excitotoxicity and genetic defects in mitochondrial complex I activity. While the neurotoxic mechanisms are vastly different for excitotoxins and N-methyl-4-phenylpyridinium ion (MPP+), both are thought to involve free radical production, compromised mitochondrial activity and excessive lipid peroxidation. In the present study, several dietary antioxidant compounds, monoamine oxidase inhibitors and ergogenic compounds were examined for protective action against neurotoxicity induced by L-glutamate (15 mM) or MPP+-HCl (5 mM) in a plastic adhering variant of murine pheochromocytoma cells. The results show no significant protective effects exhibited by azulene, (+)-catechin, curcrumin, (-)-epigallocatechin gallate, green tea, morin, pygnogenol, silymarin, clove oil, garlic oil or rosemary, extract. Compounds, which were effective in providing protection against L-glutamate-induced cell death, were coenzyme Q-0, coenzyme Q-10, L-deprenyl and N-acetyl-L-cysteine. Compounds, which provided protection against MPP+-HCl toxicity, were allopurinol, coenzyme Q-10, L-deprenyl, N-acetyl-L-cysteine and sesame oil. In both models, significant protection was achieved in the presence of coenzyme Q-10, L-deprenyl and N-acetyl-L-cysteine. These results indicate that the mechanism of cell death in both of these toxicity models is most likely not related to the destructive effects of free radicals.

Altered responsiveness to stress and NMDA following prenatal exposure to cocaine.

Pregnant Sprague--Dawley rats were treated once daily with 40-mg/kg cocaine or saline from gestation days (GD) 12 to 21. A third group of pregnant dams was used as a pairfed control. Male and female offspring were examined for stress endurance response as determined by the cold-water swim test on postnatal days (PND) 21, 30, 40, and 60. Male and female offspring exposed to cocaine in utero were found to have diminished tolerance and altered hormonal response to stress. Moreover, prenatal cocaine exposure has been associated with significant increases in severity of N-methyl-D-aspartate (NMDA; 35 mg/kg) behavioral responses (tail twitches, wetdog shaking, and convulsion) as compared to control. Examining the experimental groups for pain sensitivity using the tail-flick and the hot-plate methods indicated that prenatal cocaine exposure altered pain sensitivity. NMDA receptor binding studies showed an increase in receptor density in the hippocampus and hypothalamus of the cocaine-treated group. These results indicate that gestational cocaine exposure is associated with long-term alterations in response to stress, NMDA receptor, and pain sensitivity in the rat offspring.

The role of inducible nitric oxide synthase in cocaine-induced locomotor sensitization.

Experimentally naive male Sprague-Dawley rats (weighing 85-110 g) were used to examine the role of inducible nitric oxide synthase (iNOS) in cocaine-induced locomotor sensitization. Repeated administration of cocaine (15 mg/kg, ip) for 7 consecutive days produced locomotor sensitization. Pretreatment with iNOS inhibitors, L-N(6)-(1-iminoethyl) lysine (NIL) or (-)-epigallocatechin gallate (EGCG; 10 mg/kg, ip), 30 min before cocaine (15 mg/kg, ip) administration totally blocked the development of cocaine-induced locomotor sensitization. Dopamine (DA) receptor binding in the nucleus accumbens (NAC) showed a significant decrease in the density of D(2) receptor and the affinity of D(1) receptor after cocaine treatment. Pretreatment with EGCG or NIL abolished the cocaine-induced changes in these parameters. These results suggest that iNOS may participate in the process of development of locomotor sensitization through the modulation of DA receptors in the NAC.

Altered expression of insulin-like growth factor-1 and insulin like growth factor binding proteins-2 and 5 in the mouse mutant Hypodactyly (Hd) correlates with sites of apoptotic activity.

Insulin-like growth factor-I (IGF-I) mediated signalling has been implicated to be of significant importance during vertebrate embryonic development. IGF-I signalling has also been shown to be modulated by a number of IGF binding proteins that are thought to act as either agonists or antagonists of IGF activity. IGF-I has been implicated in a number of cellular processes, including cell division and programmed cell death (apoptosis). We have used the mouse mutant Hypodactyly (Hd) as a tool to determine the role of IGF-I and two key IGF binding proteins (IGFBP-2 and IGFBP-5) during embryonic development. The Hd mutant is a good model with which to study developmental cascades, since it has a distinct phenotype in the limb where cellular and molecular circuits have been thoroughly investigated. The distinctive pointed limb buds observed in Hd mutant embryos have been shown to be the result of a massive increase in apoptosis. We show that all three genes, IGF-1, IGFBP-2 and IGFBP-5, display restricted expression patterns during limb development. Indeed, IGFBP-5 shows a remarkable similarity to the expression of Engrailed-1, which is the vertebrate homologue of the Drosophila selector gene Engrailed. We show that there is downregulation in the expression of IGFBP-2 in the entire apical ectodermal ridge (AER) in homozygous Hd/Hd limb buds, whereas IGFBP-5 is downregulated in specific regions in the mutant AER. IGF-I expression is downregulated in Hd limb buds in regions undergoing high levels of cell death, consistent with its proposed role as an anti-apoptotic factor, while IGFBP-5 is found at higher levels in regions of cell death, consistent with reports of its association with apoptosis in adult tissues. We propose that these three components of the IGF axis could be involved in the manifestation of the mutant phenotype in Hypodactyly, and that this is probably a result of their ability to regulate cell survival and cell death.

Abnormal baroreflex responses in patients with idiopathic orthostatic intolerance.

BACKGROUND: Patients diagnosed with idiopathic orthostatic intolerance report symptoms of lightheadedness, fatigue, and nausea accompanied by an exaggerated tachycardia when assuming the upright posture. Often, these symptoms are present in the absence of any decrease in arterial pressure. We hypothesized that patients with idiopathic orthostatic intolerance would have impaired cardiac vagal and integrated baroreflex function, lower blood volume, and increased venous compliance. METHODS AND RESULTS: Sixteen patients and 14 healthy control subjects underwent the modified Oxford technique to assess cardiac vagal baroreflex sensitivity. Progressive lower-body negative pressure (to -50 mm Hg; LBNP) was used to examine the integrated baroreflex response to progressive hypovolemic stimuli. Blood volume and venous compliance were also assessed. Patients with idiopathic orthostatic intolerance had lower cardiac vagal baroreflex sensitivity (12+/-1 versus 25+/-4 ms/mm Hg; P

Gender differences in knee cartilage volume as measured by magnetic resonance imaging.

OBJECTIVE: The aim of this study was to analyze sex differences in knee cartilage volume. METHODS: Articulate cartilage volumes were determined by processing images acquired in the sagittal plane using T1-weighted fat saturation magnetic resonance on an independent work station. The knees of 28 subjects (17 male, 11 female) who underwent MRI for clinical indications (pain <3 months) but who had a normal X-ray and structurally normal MRI were examined. RESULTS: Males had significantly larger cartilage volumes than females, with difference in cartilage volume remaining statistically significant after adjusting for age, height, weight and bone volume. The differences for males relative to females were: femoral cartilage volume [4.1 ml 95% CI (2.0, 6.1)]; and patella cartilage volume [1.4 ml (0.2, 2.7)]. Although not statistically significant, the tibial cartilage volume also showed these sex differences. Exploratory analysis indicated an increasing gender difference with increasing age for patellar cartilage volume. CONCLUSION: Men have significantly larger knee cartilage volume than women, independent of body and bone size. The mechanisms for this will need to be determined.

Shh, Fgf4 and Hoxd gene expression in the mouse limb mutant hypodactyly.

The semidominant mouse mutation hypodactyly (Hd), caused by a deletion within the Hoxa13 gene, results in reduced digits; heterozygotes lack digit I in the hindlimb and homozygotes have only one digit on each limb. We investigated expression of Shh and Fgf4 signaling molecules involved in digit specification in mutant limb buds. Shh and Fgf4 are expressed in the posterior part of the limb buds as normal but expression may be slightly prolonged. The extent of digit reduction in hypodactyly is much more severe than in the Hoxa13 deficient mouse and resembles that in the Hoxa13(-/-)/Hoxd13(-/-) double mutant mouse. We found that the pattern of Hoxd13 and Hoxd11 transcripts was not markedly different in the mutant compared with the normal limbs even though the mutant limbs are narrower. Therefore Hoxd genes are transcribed as normal in the mutant. This makes it likely that the severe digit reductions in hypodactyly are caused by interference with Hoxd13 function at the protein level. Similar interactions between mutant and normal HOX gene products have been suggested to occur in the human semidominant disorder, synpolydactyly, caused by mutations in HOXD13.