Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure

Noise induced hearing loss (NIHL) is a disease that affects millions of Americans. Identifying genetic pathways that influence recovery from noise exposure is an important step forward in understanding NIHL. The transcription factor Foxo3 integrates the cellular response to oxidative stress and plays a role in extending lifespan in many organisms, including humans. Here we show that Foxo3 is required for auditory function after noise exposure in a mouse model system, measured by ABR. Absent Foxo3, outer hair cells are lost throughout the middle and higher frequencies. SEM reveals persistent damage to some surviving outer hair cell stereocilia. However, DPOAE analysis reveals that some function is preserved in low frequency outer hair cells, despite concomitant profound hearing loss. Inner hair cells, auditory synapses and spiral ganglion neurons are all present after noise exposure in the Foxo3KO/KO fourteen days post noise (DPN). We also report anti-Foxo3 immunofluorescence in adult human outer hair cells. Taken together, these data implicate Foxo3 and its transcriptional targets in outer hair cell survival after noise damage. An additional role for Foxo3 in preserving hearing is likely, as low frequency auditory function is absent in noise exposed Foxo3KO/KOs even though all cells and structures are present

Home Is Where You Hang Your Hat: Host Town Identity, But Not Hometown Identity, Protects Against Mental Health Symptoms Associated with Financial Stress

Debt and financial insecurity are associated with stress, low self-worth, and poor health. Joining and identifying with social groups (social identification) promotes better health and higher self-esteem. Here, we examined whether identifying with one's local neighborhood protected people from developing mental health symptoms associated with financial stress. We analyzed data from a general population survey (Study 1, N = 4319) and a student mental health survey (Study 2, N = 612) conducted in the North West of England. We administered measures of financial stress, self-esteem, neighborhood identity, and mental health, and conducted moderated mediation analyses to test our predictions. Study 1 (population survey) demonstrated that stronger identification with one's local neighborhood attenuated the adverse effects of financial stress on self-esteem and subsequent mental health. Study 2 (student survey) showed that strong host town identities buffered students from mental health symptoms related to financial stress. Strong hometown identities, however, showed no buffering effect. The findings suggest that one way financial stress impacts mental health is by eroding self-esteem. Identifying with one's current place of residence appears to disrupt this pathway, while identifying with one's previous place of residence does not provide the same psychological protection. Read More: https://guilfordjournals.com/doi/10.1521/jscp.2018.37.3.15

Inward Rectifier Current Downregulation Promotes Spontaneous Calcium Release in a Novel Model of Rat Ventricular Electrophysiology

Aberrant intracellular calcium handling, as observed in diseases such as heart failure, promotes lethal ventricular arrhythmias and sudden cardiac death. Recent data from our laboratory suggests that reduced expression of the inward rectifier current in failing rat myocytes increases spontaneous calcium release, however existing computational models are unable to reproduce the underlying stochastic calcium cycling dynamics and so we have been unable to use simulation approaches to explore the cause of this pro-arrhythmic behaviour. Here, we develop a novel model of rat ventricular electrophysiology that reproduces normal spatio-temporal calcium dynamics. Simulations implementing a similar reduction in inward rectifier current to that observed experimentally show that spontaneous calcium release is promoted by action potential prolongation and sarcoplasmic reticulum loading in the presence of a depolarised resting membrane potential. Combined, these effects can result in triggered activity. The model therefore provides insight into arrhythmogenic mechanisms in failing ventricular myocytes and can be utilised to further explore pro-arrhythmic behaviour caused by abnormal calcium handling

A randomised controlled trial to assess the effectiveness of a single session of nurse administered massage for short term relief of chronic non-malignant pain

Background: Massage is increasingly used to manage chronic pain but its benefit has not been clearly established. The aim of the study is to determine the effectiveness of a single session of nurse-administered massage for the short term relief of chronic non-malignant pain and anxiety. Methods: A randomised controlled trial design was used, in which the patients were assigned to a massage or control group. The massage group received a 15 minute manual massage and the control group a 15 minute visit to talk about their pain. Adult patients attending a pain relief unit with a diagnosis of chronic pain whose pain was described as moderate or severe were eligible for the study. An observer blind to the patients' treatment group carried out assessments immediately before (baseline), after treatment and 1, 2, 3 and 4 hours later. Pain was assessed using 100 mm visual analogue scale and the McGill Pain Questionnaire. Pain Relief was assessed using a five point verbal rating scale. Anxiety was assessed with the Spielberger short form State-Trait Anxiety Inventory. Results: 101 patients were randomised and evaluated, 50 in the massage and 51 in the control group. There were no statistically significant differences between the groups at baseline interview. Patients in the massage but not the control group had significantly less pain compared to baseline immediately after and one hour post treatment. 95% confidence interval for the difference in mean pain reduction at one hour post treatment between the massage and control groups is 5.47 mm to 24.70 mm. Patients in the massage but not the control group had a statistically significant reduction in anxiety compared to baseline immediately after and at 1 hour post treatment. Conclusion: Massage is effective in the short term for chronic pain of moderate to severe intensity

The impact of interventions to promote healthier ready-to-eat meals (to eat in, to take away or to be delivered) sold by specific food outlets open to the general public: a systematic review.

INTRODUCTION: Ready-to-eat meals sold by food outlets that are accessible to the general public are an important target for public health intervention. We conducted a systematic review to assess the impact of such interventions. METHODS: Studies of any design and duration that included any consumer-level or food-outlet-level before-and-after data were included. RESULTS: Thirty studies describing 34 interventions were categorized by type and coded against the Nuffield intervention ladder: restrict choice = trans fat law (n = 1), changing pre-packed children's meal content (n = 1) and food outlet award schemes (n = 2); guide choice = price increases for unhealthier choices (n = 1), incentive (contingent reward) (n = 1) and price decreases for healthier choices (n = 2); enable choice = signposting (highlighting healthier/unhealthier options) (n = 10) and telemarketing (offering support for the provision of healthier options to businesses via telephone) (n = 2); and provide information = calorie labelling law (n = 12), voluntary nutrient labelling (n = 1) and personalized receipts (n = 1). Most interventions were aimed at adults in US fast food chains and assessed customer-level outcomes. More 'intrusive' interventions that restricted or guided choice generally showed a positive impact on food-outlet-level and customer-level outcomes. However, interventions that simply provided information or enabled choice had a negligible impact. CONCLUSION: Interventions to promote healthier ready-to-eat meals sold by food outlets should restrict choice or guide choice through incentives/disincentives. Public health policies and practice that simply involve providing information are unlikely to be effective

Behavior and Ecology of Silky Sharks Around the Chagos Archipelago and Evidence of Indian Ocean Wide Movement

Silky sharks (Carcharhinus falciformis) represent a major component of global shark catch, both directly and as bycatch, and populations are declining as a result. An improved understanding of their movement ecology is needed to support conservation efforts. We deployed satellite and acoustic tags (2013-2018) and analysed historical fisheries records (1997-2009), to investigate the spatial ecology of silky sharks in the central Indian Ocean and a large Marine Protected Area (MPA; 640,000 km2) around the Chagos Archipelago. We observed high fidelity to the MPA, and a sustained diurnal association with a seamount complex, with individuals moving off at night and returning at sunrise. Yet, we also observed large-scale divergent movements in two satellite tagged individuals and documented the furthest recorded displacement distance for the species to date, with one individual moving from the MPA to the Kenyan coast – a displacement distance of 3,549 km (track distance ~4,782 km). Silky sharks undertook diel vertical migrations and oscillatory diving behaviour, spending >99% of their time in the top 100 m, and diving to depths of greater than 300 m, overlapping directly with typical deployments of purse seine and longline sets in the Indian Ocean. One individual was recorded to a depth of 1,112 m, the deepest recorded silky shark dive to date. Individuals spent 96% of their time at liberty within water temperatures between 24-30 °C. Historic fisheries data revealed that silky sharks were a major component of the shark community around the archipelago, representing 13.7% of all sharks caught by longlines before the fishery closed in 2010. Over half (55.9%) of all individuals caught by longlines and purse seiners were juveniles. The large proportion of juveniles, coupled with the high site fidelity and residence observed in some individuals, suggests that the MPA could provide considerable conservation benefits for silky sharks, particularly during early life-history stages. However, their high mobility potential necessitates that large MPAs need to be considered in conjunction with fisheries regulations and conservation measures in adjacent EEZs and in areas beyond national jurisdiction

Multi-scale approaches for the simulation of cardiac electrophysiology: II - tissue-level structure and function

Computational models of the heart, from cell-level models, through one-, two- and three-dimensional tissue-level simplifications, to biophysically-detailed three-dimensional models of the ventricles, atria or whole heart, allow the simulation of excitation and propagation of this excitation, and have provided remarkable insight into the normal and pathological functioning of the heart. In this article we present equations for modelling cellular excitation (i.e. the cell action potential) from both a phenomenological and a biophysical perspective. Hodgkin-Huxley formalism is discussed, along with the current generation of biophysically-detailed cardiac cell models. Alternative Markovian formulations for modelling ionic currents are also presented. Equations describing propagation of this cellular excitation, through one-, two- and three-dimensional idealised or realistic tissues, are then presented. For all types of model, from cell to tissue, methods for discretisation and integration of the underlying equations are discussed. The article finishes with a discussion of two tissue-level experimental imaging techniques – diffusion tensor magnetic resonance imaging and optical imaging – that can be used to provide data for parameterisation and validation of cell- and tissue-level cardiac models

Electronic transport in polycrystalline graphene

Most materials in available macroscopic quantities are polycrystalline. Graphene, a recently discovered two-dimensional form of carbon with strong potential for replacing silicon in future electronics, is no exception. There is growing evidence of the polycrystalline nature of graphene samples obtained using various techniques. Grain boundaries, intrinsic topological defects of polycrystalline materials, are expected to dramatically alter the electronic transport in graphene. Here, we develop a theory of charge carrier transmission through grain boundaries composed of a periodic array of dislocations in graphene based on the momentum conservation principle. Depending on the grain boundary structure we find two distinct transport behaviours - either high transparency, or perfect reflection of charge carriers over remarkably large energy ranges. First-principles quantum transport calculations are used to verify and further investigate this striking behaviour. Our study sheds light on the transport properties of large-area graphene samples. Furthermore, purposeful engineering of periodic grain boundaries with tunable transport gaps would allow for controlling charge currents without the need of introducing bulk band gaps in otherwise semimetallic graphene. The proposed approach can be regarded as a means towards building practical graphene electronics.Comment: accepted in Nature Material

A geometric network model of intrinsic grey-matter connectivity of the human brain

Network science provides a general framework for analysing the large-scale brain networks that naturally arise from modern neuroimaging studies, and a key goal in theoretical neuro- science is to understand the extent to which these neural architectures influence the dynamical processes they sustain. To date, brain network modelling has largely been conducted at the macroscale level (i.e. white-matter tracts), despite growing evidence of the role that local grey matter architecture plays in a variety of brain disorders. Here, we present a new model of intrinsic grey matter connectivity of the human connectome. Importantly, the new model incorporates detailed information on cortical geometry to construct ‘shortcuts’ through the thickness of the cortex, thus enabling spatially distant brain regions, as measured along the cortical surface, to communicate. Our study indicates that structures based on human brain surface information differ significantly, both in terms of their topological network characteristics and activity propagation properties, when compared against a variety of alternative geometries and generative algorithms. In particular, this might help explain histological patterns of grey matter connectivity, highlighting that observed connection distances may have arisen to maximise information processing ability, and that such gains are consistent with (and enhanced by) the presence of short-cut connections