Sex Differences in Number Magnitude Processing Strategies Are Mediated by Spatial Navigation Strategies: Evidence From the Unit-Decade Compatibility Effect

The hybrid model of number magnitude processing suggests that multi-digit numbers are simultaneously processed holistically (whole number magnitudes) and in a decomposed manner (digit magnitudes). Thus, individual tendencies and situational factors may affect which type of processing becomes dominant in a certain individual in a given situation. The unit-decade compatibility effect has been described as indicative of stronger decomposed number processing. This effect occurs during the comparison of two-digit numbers. Compatible items in which the larger number contains the larger unit digit are easier to solve than incompatible items in which the larger number contains the smaller unit digit. We have previously described women show a larger compatibility effect than men. Furthermore, the compatibility effect is modulated by situational factors like the vertical spacing of the presented numbers. However, it has not been addressed whether situational factors and sex affect the unit-decade compatibility effect interactively. We have also demonstrated that the unit-decade compatibility effects relates to global-local processing, which in turn also affects spatial processing strategies. However, a link between spatial processing strategies and the unit-decade compatibility effect has not yet been established. In the present study we investigate, whether sex differences in the unit-decade compatibility effect (i) depend on the vertical spacing between numbers, (ii) are mediated via sex hormone levels of participants, and (iii) relate to sex differences in spatial processing strategies. 42 men and 41 women completed a two-digit number comparison task as well as a spatial navigation task. The number comparison task modulates compatibility and vertical spacing in a 2 × 2 design. The results confirm a larger compatibility effect in women compared to men and with dense compared to sparse spacing. However, no interactive effect was observed, suggesting that these factors modulate number magnitude processing independently. The progesterone/testosterone ratio was related to the compatibility effect, but did not mediate the sex difference in the compatibility effect. Furthermore, spatial processing strategies were related to the compatibility effect and did mediate the sex difference in the compatibility effect. Participants with a stronger focus on landmarks in the spatial navigation task showed a larger compatibility effect

Contrasting alterations to synaptic and intrinsic properties in upper-cervical superficial dorsal horn neurons following acute neck muscle inflammation

Background: Acute and chronic pain in axial structures, like the back and neck, are difficult to treat, and have incidence as high as 15%. Surprisingly, most preclinical work on pain mechanisms focuses on cutaneous structures in the limbs and animal models of axial pain are not widely available. Accordingly, we developed a mouse model of acute cervical muscle inflammation and assessed the functional properties of superficial dorsal horn (SDH) neurons.<p></p> Results: Male C57/Bl6 mice (P24-P40) were deeply anaesthetised (urethane 2.2?g/kg i.p) and the rectus capitis major muscle (RCM) injected with 40??l of 2% carrageenan. Sham animals received vehicle injection and controls remained anaesthetised for 2?hrs. Mice in each group were sacrificed at 2?hrs for analysis. c-Fos staining was used to determine the location of activated neurons. c-Fos labelling in carrageenan-injected mice was concentrated within ipsilateral (87% and 63% of labelled neurons in C1 and C2 segments, respectively) and contralateral laminae I - II with some expression in lateral lamina V. c-Fos expression remained below detectable levels in control and sham animals. In additional experiments, whole cell recordings were obtained from visualised SDH neurons in transverse slices in the ipsilateral C1 and C2 spinal segments. Resting membrane potential and input resistance were not altered. Mean spontaneous EPSC amplitude was reduced by ~20% in neurons from carrageenan-injected mice versus control and sham animals (20.63???1.05 vs. 24.64???0.91 and 25.87???1.32 pA, respectively). The amplitude (238???33 vs. 494???96 and 593???167 pA) and inactivation time constant (12.9???1.5 vs. 22.1???3.6 and 15.3???1.4?ms) of the rapid A type potassium current (IAr), the dominant subthreshold current in SDH neurons, were reduced in carrageenan-injected mice.<p></p> Conclusions: Excitatory synaptic drive onto, and important intrinsic properties (i.e., IAr) within SDH neurons are reduced two hours after acute muscle inflammation. We propose this time point represents an important transition period between peripheral and central sensitisation with reduced excitatory drive providing an initial neuroprotective mechanism during the early stages of the progression towards central sensitisation

Feasibility and Compliance with Daily Home ECG Monitoring of the QT Interval in Heart Transplant Recipients

Background: Recent evidence suggests that acute allograft rejection after heart transplantation causes an increased QT interval on electrocardiogram (ECG). The aims of this pilot study were to (1) determine whether heart transplant recipients could achieve compliance in transmitting a 30-second ECG every day for 1 month using a simple ECG device and their home telephone, (2) evaluate the ease of device use and acceptability by transplant recipients, and (3) evaluate the quality of transmitted ECG tracings for QT-interval measurement. Methods: A convenience sample of adult heart transplant recipients were recruited and trained to use the device (HeartOne, Aerotel Medical Systems, Holon, Israel). Lead II was used with electrodes that were easy to slip on and off (expandable metal wrist watch-type electrode for right wrist and C-shaped band electrode for left ankle). Patients used a toll-free number with automated voice prompts to guide their ECG transmission to the core laboratory for analysis. Results: Thirty-one subjects (72% were male; mean age of 52 ± 17 years; 37% were nonwhite) achieved an ECG transmission compliance of 73.4% (daily) and 100% (weekly). When asked, how difficult do you think it was to record and transmit your ECG by phone, 90% of subjects replied “somewhat easy” or “extremely easy.” Of the total 644 ECGs that were transmitted by subjects, 569 (89%) were acceptable quality for QT-interval measurement. The mean QTc was 448 ± 44 ms (440 ± 41 ms for male subjects and 471 ± 45 ms for female subjects). Eleven subjects (35%) had an extremity tremor, and 19 subjects (55%) had ≥ 1+ left leg edema. Neither of these conditions interfered with ECG measurements. Conclusion: Transplant recipients are compliant with recording and transmitting daily and weekly ECGs

Managed moves: schools collaborating for collective gain

Government guidance in the United Kingdom encourages groups of schools to take collective responsibility for supporting and making provision for excluded pupils and those at risk of exclusion. Managed-moves are one way that some schools and authorities are enacting such guidance. This paper presents the results of an evaluation of one such scheme. The scheme, involving seven neighbouring secondary schools, was nearing its first year of completion. The paper draws primarily on interview data with pupils, parents and school staff to describe a number of positive outcomes associated with the scheme and to explore how these were achieved. We found that while some of these could be attributed directly to the managed-move, others arose from the more inclusive ethos and practices of particular schools. The concepts of tailored support, care and commitment emerged as strong themes that underpinned the various practical ways in which some schools in the cluster were able to re-engage 'at-risk' pupils. As managed moves become more widely practiced it will be important to remember that it is how the move proceeds and develops rather than the move itself that will ultimately make the difference for troubled and troublesome pupils

Mouse H6 Homeobox 1 (Hmx1) mutations cause cranial abnormalities and reduced body mass

<p>Abstract</p> <p>Background</p> <p>The H6 homeobox genes <it>Hmx1</it>, <it>Hmx2</it>, and <it>Hmx3 </it>(also known as <it>Nkx5-3</it>; <it>Nkx5-2 </it>and <it>Nkx5-1</it>, respectively), compose a family within the NKL subclass of the ANTP class of homeobox genes. Hmx gene family expression is mostly limited to sensory organs, branchial (pharyngeal) arches, and the rostral part of the central nervous system. Targeted mutation of either <it>Hmx2 </it>or <it>Hmx3 </it>in mice disrupts the vestibular system. These tandemly duplicated genes have functional overlap as indicated by the loss of the entire vestibular system in double mutants. Mutants have not been described for <it>Hmx1</it>, the most divergent of the family.</p> <p>Results</p> <p>Dumbo (<it>dmbo</it>) is a semi-lethal mouse mutation that was recovered in a forward genetic mutagenesis screen. Mutants exhibit enlarged ear pinnae with a distinctive ventrolateral shift. Here, we report on the basis of this phenotype and other abnormalities in the mutant, and identify the causative mutation as being an allele of <it>Hmx1</it>. Examination of dumbo skulls revealed only subtle changes in cranial bone morphology, namely hyperplasia of the gonial bone and irregularities along the caudal border of the squamous temporal bone. Other nearby otic structures were unaffected. The semilethality of <it>dmbo/dmbo </it>mice was found to be ~40%, occured perinatally, and was associated with exencephaly. Surviving mutants of both sexes exhibited reduced body mass from ~3 days postpartum onwards. Most dumbo adults were microphthalmic. Recombinant animals and specific deletion-bearing mice were used to map the <it>dumbo </it>mutation to a 1.8 Mb region on Chromosome 5. DNA sequencing of genes in this region revealed a nonsense mutation in the first exon of H6 Homeobox 1 (<it>Hmx1</it>; also <it>Nkx5-3</it>). An independent spontaneous allele called misplaced ears (<it>mpe</it>) was also identified, confirming <it>Hmx1 </it>as the responsible mutant gene.</p> <p>Conclusion</p> <p>The divergence of <it>Hmx1 </it>from its paralogs is reflected by different and diverse developmental roles exclusive of vestibular involvement. Additionally, these mutant <it>Hmx1 </it>alleles represent the first mouse models of a recently-discovered Oculo-Auricular syndrome caused by mutation of the orthologous human gene.</p

Integrated analysis of the molecular pathogenesis of FDXR-associated disease.

The mitochondrial flavoprotein ferredoxin reductase (FDXR) is required for biogenesis of iron-sulfur clusters and for steroidogenesis. Iron-sulfur (Fe-S) clusters are ubiquitous cofactors essential to various cellular processes, and an increasing number of disorders are associated with disruptions in the synthesis of Fe-S clusters. Our previous studies have demonstrated that hypomorphic mutations in FDXR cause a novel mitochondriopathy and optic atrophy in humans and mice, attributed in part to reduced function of the electron transport chain (ETC) as well as elevated production of reactive oxygen species (ROS). Inflammation and peripheral neuropathy are also hallmarks of this disease. In this paper, we demonstrate that FDXR mutation leads to significant optic transport defects that are likely to underlie optic atrophy, a major clinical presentation in FDXR patients, as well as a neurodegenerative loss of cells in the central nervous system (CNS). Molecular analysis indicates that FDXR mutation also leads to mitochondrial iron overload and an associated depolarization of the mitochondrial membrane, further supporting the hypothesis that FDXR mutations cause neurodegeneration by affecting FDXR\u27s critical role in iron homeostasis

An allelic series of spontaneous Rorb mutant mice exhibit a gait phenotype, changes in retina morphology and behavior, and gene expression signatures associated with the unfolded protein response.

The Retinoid-related orphan receptor beta (RORβ) gene encodes a developmental transcription factor and has 2 predominant isoforms created through alternative first exon usage; one specific to the retina and another present more broadly in the central nervous system, particularly regions involved in sensory processing. RORβ belongs to the nuclear receptor family and plays important roles in cell fate specification in the retina and cortical layer formation. In mice, loss of RORβ causes disorganized retina layers, postnatal degeneration, and production of immature cone photoreceptors. Hyperflexion or high-stepping of rear limbs caused by reduced presynaptic inhibition by Rorb-expressing inhibitory interneurons of the spinal cord is evident in RORβ-deficient mice. RORβ variants in patients are associated with susceptibility to various neurodevelopmental conditions, primarily generalized epilepsies, but including intellectual disability, bipolar, and autism spectrum disorders. The mechanisms by which RORβ variants confer susceptibility to these neurodevelopmental disorders are unknown but may involve aberrant neural circuit formation and hyperexcitability during development. Here we report an allelic series in 5 strains of spontaneous Rorb mutant mice with a high-stepping gait phenotype. We show retinal abnormalities in a subset of these mutants and demonstrate significant differences in various behavioral phenotypes related to cognition. Gene expression analyses in all 5 mutants reveal a shared over-representation of the unfolded protein response and pathways related to endoplasmic reticulum stress, suggesting a possible mechanism of susceptibility relevant to patients

Creating political will for action on health equity: practical lessons for public health policy actors

Background Despite growing evidence on the social determinants of health and health equity, political action has not been commensurate. Little is known about how political will operates to enact pro-equity policies or not. This paper examines how political will for pro-health equity policies is created through analysis of public policy in multiple sectors. Methods Eight case studies were undertaken of Australian policies where action was either taken or proposed on health equity or where the policy seemed contrary to such action. Telephone or face-to-face interviews were conducted with 192 state and non-state participants. Analysis of the cases was done through thematic analysis and triangulated with document analysis. Results Our case studies covered: trade agreements, primary healthcare (PHC), work conditions, digital access, urban planning, social welfare and Indigenous health. The extent of political will for pro-equity policies depended on the strength of path dependency, electoral concerns, political philosophy, the strength of economic and biomedical framings, whether elite interests were threatened and the success or otherwise of civil society lobbying. Conclusion Public health policy actors may create political will through: determining how path dependency that exacerbates health inequities can be broken, working with sympathetic political forces committed to fairness; framing policy options in a way that makes them more likely to be adopted, outlining factors to consider in challenging the interests of elites, and considering the extent to which civil society will work in favour of equitable policies. A shift in norms is required to stress equity and the right to health.This research was funded by the Australian National Health & Medical Research Council Centre for Research Excellence Grant APP107804