Ventromedial prefrontal cortex activation and neurofeedback modulation during episodic future thinking for individuals with suicidal thoughts and behaviors.

Individuals experiencing suicidal thoughts and behaviors (STBs) show less specificity and positivity during episodic future thinking (EFT). Here, we present findings from two studies aiming to (1) further our understanding of how STBs may relate to neural responsivity during EFT and (2) examine the feasibility of modulating EFT-related activation using real-time fMRI neurofeedback (rtfMRI-nf). Study 1 involved 30 individuals with major depressive disorder (MDD; half with STBs) who performed an EFT task during fMRI, for which they imagined personally-relevant future positive, negative, or neutral events. Positive EFT elicited greater ventromedial prefrontal cortex (vmPFC) activation compared to negative EFT. Importantly, the MDD + STB group exhibited reduced vmPFC activation across all EFT conditions compared to MDD-STB; although EFT fluency and subjective experience remained consistent across groups. Study 2 included rtfMRI-nf focused on vmPFC modulation during positive EFT for six participants with MDD + STBs. Results support the feasibility and acceptability of the rtfMRI-nf protocol and quantitative and qualitative observations are provided to help inform future, larger studies aiming to examine similar neurofeedback protocols. Results implicate vmPFC blunting as a promising treatment target for MDD + STBs and suggest rtfMRI-nf as one potential technique to explore for enhancing vmPFC engagement.

What is wellness? Investigating the importance of different domains of wellness among laypeople and experts: A survey study.

AIMS: Lack of consensus on wellness has led to a vast number of different conceptualisations, which hinder international efforts to monitor individual-level wellness and social progress comparably. This study aimed to aid in the harmonisation of the concept by contributing to the scarce research on laypeople's views on wellness. The study investigates whether the importance of different areas of wellness varies depending on age, gender, education or socio-economic position. Furthermore, considering that wellness models are often constructed by expert panels, this study aimed to shed light on how experts' and laypeople's views on wellness vary. METHODS: Altogether, 1152 laypeople and 23 Finnish experts rated the importance of 61 systematic review-based wellness domains. Each domain received an ordinal number, which, together with the Mann-Whitney U-test or Kruskal-Wallis test, was used to examine the differences between the groups. RESULTS: Thirteen wellness domains were found at the top of the lists, regardless of whether the results were analysed based on gender, age, education or socio-economic position. When looking at the priority order of different domains, we were able to identify several differences between the expert panel and laypeople. CONCLUSIONS: To ensure the relevance of wellness models, it is vital to understand the areas that laypeople consider to be important for their comprehensive wellness. This study offers 13 domains that could be combined with an expert view on wellness and used as a starting point for creating a more comprehensive, inclusive and better-suited wellness instrument.

Acute outreach service to nursing homes: A systematic review with GRADE and triple aim approach.

BACKGROUND: People living in nursing homes face the risk of visiting the emergency department (ED). Outreach services are developing to prevent unnecessary transfers to ED. AIMS: We aim to assess the performance of acute care services provided to people living in nursing homes or long-term homecare, focusing on ED transfer prevention, safety, cost-effectiveness and experiences. MATERIALS & METHODS: This review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies were eligible for inclusion if they were peer-reviewed and examined acute outreach services dedicated to delivering care to people in nursing homes or long-term homecare. The service models could also have preventive components. The databases searched were Scopus and CINAHL. In addition, Robins-I and SIGN checklists were used. The primary outcomes of prevented ED transfers or hospitalisations and the composite outcome of adverse events (mortality/Emergency Medical Service or ED visit after outreach service contact related to the same clinical condition) were graded with GRADE. RESULTS: Fifteen relevant original studies were found-all were observational and focused on nursing homes. The certainty of evidence for acute outreach services with preventive components to prevent ED transfers or hospitalisations was low. Stakeholders were satisfied with these services. The certainty of evidence for solely acute outreach services to prevent ED transfers or hospitalisations was very low and inconclusive. Reporting of adverse events was inconsistent, certainty of evidence for adverse events was low. CONCLUSION: Published data might support adopting acute outreach services with preventive components for people living in nursing homes to reduce ED transfers, hospitalisations and possibly costs. If an outreach service is started, it is recommended that a cluster-randomised or quasi-experimental research design be incorporated to assess the effectiveness and safety of the service. More evidence is also needed on cost-effectiveness and stakeholders' satisfaction. Systematic review registration number: PROSPERO CRD42020211048, date of registration: 25.09.2020.

Skin Damage and Quality of Life among Healthcare Workers Providing Care during the COVID-19 Pandemic: A Multicenter Survey in Banten Province, Indonesia.

Background: Since the occurrence of the coronavirus disease-2019 pandemic, healthcare workers (HCWs) have been strictly adhering to infection control practices within healthcare facilities. However, regular use of personal protective equipment (PPE) and hand hygiene have led to increased prevalence of skin damage, subsequently impacting the quality of life (QoL). Objective: To analyse the connection between skin damage and the QoL among HCWs in a multicenter setting in Indonesia. Methods: A cross-sectional survey was conducted among HCWs working in hospitals in Banten Province, Indonesia. The data was obtained using a reliable self-reported questionnaire (Cronbach α 0.765) and a validated Indonesian version of the Dermatology Life Quality Index. Results: A total of 113 respondents (56.5%) who experienced at least one self-perceived PPE-related skin damage and had worn PPE of any level within the last 7 days were analysed. The mean age ± SD of respondents was 26.09 ± 6.22 years old, while the mean DLQI score ± SD was 5.46 ± 4.88, with a median of 4.0 (range, 0-24). The regression model showed that the level of PPE used (P < 0.05) to be a significant risk factor. Conclusions: Skin damage due to PPE affects HCWs physically and emotionally. It is crucial to recognise its impact on life and reinforce awareness, prevention, and treatment of skin damage. Dermatologist referral and intervention should be considered for optimum management.

Gelation Dynamics upon Pressure-Induced Liquid-Liquid Phase Separation in a Water-Lysozyme Solution.

Employing X-ray photon correlation spectroscopy, we measure the kinetics and dynamics of a pressure-induced liquid-liquid phase separation (LLPS) in a water-lysozyme solution. Scattering invariants and kinetic information provide evidence that the system reaches the phase boundary upon pressure-induced LLPS with no sign of arrest. The coarsening slows down with increasing quench depths. The g2 functions display a two-step decay with a gradually increasing nonergodicity parameter typical for gelation. We observe fast superdiffusive (γ ≥ 3/2) and slow subdiffusive (γ < 0.6) motion associated with fast viscoelastic fluctuations of the network and a slow viscous coarsening process, respectively. The dynamics age linearly with time τ ∝ tw, and we observe the onset of viscoelastic relaxation for deeper quenches. Our results suggest that the protein solution gels upon reaching the phase boundary.

Severe pulmonary toxicity associated with inhalation of pyrethroid-based domestic insecticides (Bop/Sapolio): a case series and literature review.

PURPOSE OF REVIEW: The current review focuses on serious pulmonary toxicity after inhalation of over the counter available pyrethroid-based insecticides. Pyrethroid is a synthetic product of pyrethrin, which in turn is the active ingredient of pyrethrum, a flower extract. RECENT FINDINGS: On the contrary, a large gap of knowledge exists in the association of interstitial lung disease (ILD) with pyrethroids. So far, two cases of ILD, one associated with pyrethrin and one associated with pyrethrum, were described. Existing literature on both other (pulmo)toxic effects of pyrethroids in human and animals is summarized. SUMMARY: We present three cases of severe pulmonary toxicity after inhalation of pyrethroid-based insecticides demanding hospitalization and oxygen therapy. One of these cases died. Although a causal relationship was hard to establish, these cases all demonstrated an obvious history of (repeated) pyrethroid exposure associated with ILD. Moreover, other causes of ILD as well as infections were excluded. Furthermore, studies in mammals as well as aquatic animals confirm (pulmonary) toxicity of pyrethroids. The occurrence of toxicity is dose-dependent but also associated with individual susceptibility. Therefore, we would like to acknowledge that awareness of potential hazards of commercially available insecticides containing pyrethroids to both medical physicians and the public is mandatory.

Electrophysiological investigation of reward anticipation and outcome evaluation during slot machine play.

Slot machines are a popular form of gambling, offering a tractable way to experimentally model reward processes. This study used a 3-reel slot paradigm to assess psychologically distinct phases of reward processing, reflecting anticipation, and early- and late-stage outcome processing. EEG measures of winning, nearly missing (a losing outcome revealed at the final, third reel), and "totally" missing (a losing outcome revealed earlier, at the second reel) were collected from healthy adults (n=54). Condition effects were evaluated in: i) event-related potential (ERP) components reflecting anticipatory attention (stimulus preceding negativity, SPN) and outcome processing (reward positivity, RewP and late-positive potential, LPP) and ii) total power and phase synchrony of theta and delta band oscillations. Behaviorally, trial initiation was fastest after a near miss outcome and slowest after a winning outcome. As expected, a significant SPN was observed for possible wins (AA) vs. total misses (AB), consistent with reward anticipation. Larger win (AAA) vs. near miss (AAB) amplitudes were observed for the RewP; LPP amplitudes were largest for wins (AAA), intermediate for near misses (AAB), and smallest for total misses (ABC), reflecting significant early (RewP) and late-stage (LPP) outcome processing effects. There was an effect of reel position on the RewP, with larger amplitude in the final reel (AAA-AAB) relative to the 2nd-reel locked difference waves (AA-AB). Across all outcomes, near misses elicited the largest and most phase-synchronized theta responses, while wins elicited larger and more phase-synchronized delta responses than total misses, with delta band measures not distinguishing between near misses and wins. . Phase locking measures contrasting win vs. near miss delta and theta synchronization, within time windows corresponding to ERP measurements, covaried with RewP, but not SPN or LPP, amplitude. Lastly, EEG measures showed differential relationships with age and self-reported consummatory pleasure. In the context of slot machine play, where reward anticipation and attainment place minimal demands on effort and skill, ERP and time-frequency methods capture distinct neurophysiological signatures of reward anticipation and outcome processing.

A general strategy to control antibody specificity against targets showing molecular and biological similarity: Salmonella case study.

The control of antibody specificity plays pivotal roles in key technological fields such as diagnostics and therapeutics. During the development of immunoassays (IAs) for the biosensing of pathogens in food matrices, we have found a way to rationalize and control the specificity of polyclonal antibodies (sera) for a complex analytical target (the Salmonella genus), in terms of number of analytes (Salmonella species) and potential cross-reactivity with similar analytes (other bacteria strains). Indeed, the biosensing of Salmonella required the development of sera and serum mixtures displaying homogeneous specificity for a large set of strains showing broad biochemical variety (54 Salmonella serovars tested in this study), which partially overlaps with the molecular features of other class of bacteria (like specific serogroups of E. coli). To achieve a trade-off between specificity harmonisation and maximization, we have developed a strategy based on the conversion of the specificity profiles of individual sera in to numerical descriptors, which allow predicting the capacity of serum mixtures to detect multiple bacteria strains. This approach does not imply laborious purification steps and results advantageous for process scaling-up, and may help in the customization of the specificity profiles of antibodies needed for diagnostic and therapeutic applications such as multi-analyte detection and recombinant antibody engineering, respectively.

Change in neural response during emotion regulation is associated with symptom reduction in cognitive behavioral therapy for anxiety disorders.

BACKGROUND: Anxiety disorders are debilitating conditions that can be treated with cognitive behavioral therapy (CBT). Increased understanding of the neurobiological correlates of CBT may inform treatment improvements and personalization. Prior neuroimaging studies point to treatment-related changes in anterior cingulate, insula, and other prefrontal regions during emotional processing, yet to date the impact of CBT on neural substrates of "top down" emotion regulation remains understudied. We examined the relationship between symptom changes assessed over the course of CBT treatment sessions and pre- to post-treatment neural change during an emotion regulation task. METHOD: In the current study, a sample of 30 participants with panic disorder or generalized anxiety disorder completed a reappraisal-based emotion regulation task while undergoing fMRI before and after completing CBT. RESULTS: Reduced activation in the parahippocampal gyrus was observed from pre- to post-treatment during periods of reducing versus maintaining emotion. Parahippocampal activation was associated with change in symptoms over the course of treatment and post-treatment responder status. Results suggest that, from pre- to post-CBT, participants demonstrated downregulation of neural responses during effortful cognitive emotion regulation. LIMITATIONS: Effects were not observed in frontoparietal systems as would be hypothesized based on prior literature, suggesting that treatment-related change could occur outside of fronto-parietal and limbic regions that are central to most models of neural functioning in anxiety disorders. CONCLUSIONS: Continued work is needed to better understand how CBT affects cognitive control and memory processes that are hypothesized to support reappraisal as a strategy for emotion regulation.

Protocol for a randomized controlled trial examining multilevel prediction of response to behavioral activation and exposure-based therapy for generalized anxiety disorder.

BACKGROUND: Only 40-60% of patients with generalized anxiety disorder experience long-lasting improvement with gold standard psychosocial interventions. Identifying neurobehavioral factors that predict treatment success might provide specific targets for more individualized interventions, fostering more optimal outcomes and bringing us closer to the goal of "personalized medicine." Research suggests that reward and threat processing (approach/avoidance behavior) and cognitive control may be important for understanding anxiety and comorbid depressive disorders and may have relevance to treatment outcomes. This study was designed to determine whether approach-avoidance behaviors and associated neural responses moderate treatment response to exposure-based versus behavioral activation therapy for generalized anxiety disorder. METHODS/DESIGN: We are conducting a randomized controlled trial involving two 10-week group-based interventions: exposure-based therapy or behavioral activation therapy. These interventions focus on specific and unique aspects of threat and reward processing, respectively. Prior to and after treatment, participants are interviewed and undergo behavioral, biomarker, and neuroimaging assessments, with a focus on approach and avoidance processing and decision-making. Primary analyses will use mixed models to examine whether hypothesized approach, avoidance, and conflict arbitration behaviors and associated neural responses at baseline moderate symptom change with treatment, as assessed using the Generalized Anxiety Disorder-7 item scale. Exploratory analyses will examine additional potential treatment moderators and use data reduction and machine learning methods. DISCUSSION: This protocol provides a framework for how studies may be designed to move the field toward neuroscience-informed and personalized psychosocial treatments. The results of this trial will have implications for approach-avoidance processing in generalized anxiety disorder, relationships between levels of analysis (i.e., behavioral, neural), and predictors of behavioral therapy outcome. TRIAL REGISTRATION: The study was retrospectively registered within 21 days of first participant enrollment in accordance with FDAAA 801 with ClinicalTrials.gov, NCT02807480. Registered on June 21, 2016, before results.

Experimental evidence for the relaxation coupling of all longitudinal 7Li magnetization orders in the superionic conductor Li10GeP2S12.

This contribution addresses the experimental proof of the relaxation coupling of the 7Li (I = 3/2) longitudinal magnetization orders in the solid-state electrolyte Li10GeP2S12 (LGPS). This effect was theoretically described by Korb and Petit in 1988 but has not yet been shown experimentally. In a 2D-T1/spin-alignment echo (SAE) experiment, the inverse Laplace transformation of the spectral component over two time dimensions revealed the asymmetric course of the spin-lattice relaxation following from the coupling of all longitudinal orders. These observations were supported by Multi-quantum-filter experiments and by simulations of the 2D-T1/SAE experiment with a lithium spin system. Since the asymmetric relaxation effects are directly dependent on the velocities and degrees of freedom of ion motion they could be used especially in fast Li-ion conductors as a separation tool for environments with different mobility processes.

Investigation of the Li-ion conduction behavior in the Li10GeP2S12 solid electrolyte by two-dimensional T1-spin alignment echo correlation NMR.

Li10GeP2S12 (LGPS) is the fastest known Li-ion conductor to date due to the formation of one-dimensional channels with a very high Li mobility. A knowledge-based optimization of such materials for use, for example, as solid electrolyte in all-solid-state batteries requires, however, a more comprehensive understanding of Li ion conduction that considers mobility in all three dimensions, mobility between crystallites and different phases, as well as their distributions within the material. The spin alignment echo (SAE) nuclear magnetic resonance (NMR) technique is suitable to directly probe slow Li ion hops with correlation times down to about 10-5 s, but distinction between hopping time constants and relaxation processes may be ambiguous. This contribution presents the correlation of the 7Li spin lattice relaxation (SLR) time constants (T1) with the SAE decay time constant τc to distinguish between hopping time constants and signal decay limited by relaxation in the τc distribution. A pulse sequence was employed with two independently varied mixing times. The obtained multidimensional time domain data was processed with an algorithm for discrete Laplace inversion that does not use a non-negativity constraint to deliver 2D SLR-SAE correlation maps. Using the full echo transient, it was also possible to estimate the NMR spectrum of the Li ions responsible for each point in the correlation map. The signal components were assigned to different environments in the LGPS structure.

Altered interoceptive activation before, during, and after aversive breathing load in women remitted from anorexia nervosa.

BACKGROUND: The neural mechanisms of anorexia nervosa (AN), a severe and chronic psychiatric illness, are still poorly understood. Altered body state processing, or interoception, has been documented in AN, and disturbances in aversive interoception may contribute to distorted body perception, extreme dietary restriction, and anxiety. As prior data implicate a potential mismatch between interoceptive expectation and experience in AN, we examined whether AN is associated with altered brain activation before, during, and after an unpleasant interoceptive state change. METHODS: Adult women remitted from AN (RAN; n = 17) and healthy control women (CW; n = 25) underwent functional magnetic resonance imaging during an inspiratory breathing load paradigm. RESULTS: During stimulus anticipation, the RAN group, relative to CW, showed reduced activation in right mid-insula. In contrast, during the aversive breathing load, the RAN group showed increased activation compared with CW in striatum and cingulate and prefrontal cortices (PFC). The RAN group also showed increased activation in PFC, bilateral insula, striatum, and amygdala after stimulus offset. Time course analyses indicated that RAN responses in interoceptive processing regions during breathing load increased more steeply than those of CW. Exploratory analyses revealed that hyperactivation after breathing load was associated with markers of past AN severity. CONCLUSIONS: Anticipatory deactivation with a subsequent exaggerated brain response during and after an aversive body state may contribute to difficulty predicting and adapting to internal state fluctuation. Because eating changes our interoceptive state, restriction may be one method of avoiding aversive, unpredictable internal change in AN.

Deletion of Pofut1 in Mouse Skeletal Myofibers Induces Muscle Aging-Related Phenotypes in cis and in trans.

Sarcopenia, the loss of muscle mass and strength during normal aging, involves coordinate changes in skeletal myofibers and the cells that contact them, including satellite cells and motor neurons. Here we show that the protein O-fucosyltransferase 1 gene (Pofut1), which encodes a glycosyltransferase required for NotchR-mediated cell-cell signaling, has reduced expression in aging skeletal muscle. Moreover, premature postnatal deletion of Pofut1 in skeletal myofibers can induce aging-related phenotypes in cis within skeletal myofibers and in trans within satellite cells and within motor neurons via the neuromuscular junction. Changed phenotypes include reduced skeletal muscle size and strength, decreased myofiber size, increased slow fiber (type 1) density, increased muscle degeneration and regeneration in aged muscles, decreased satellite cell self-renewal and regenerative potential, and increased neuromuscular fragmentation and occasional denervation. Pofut1 deletion in skeletal myofibers reduced NotchR signaling in young adult muscles, but this effect was lost with age. Increasing muscle NotchR signaling also reduced muscle size. Gene expression studies point to regulation of cell cycle genes, muscle myosins, NotchR and Wnt pathway genes, and connective tissue growth factor by Pofut1 in skeletal muscle, with additional effects on α dystroglycan glycosylation.

Polaron-induced lattice distortion of (In,Ga)As/GaAs quantum dots by optically excited carriers.

We report on a high resolution x-ray diffraction study unveiling the effect of carriers optically injected into (In,Ga)As quantum dots on the surrounding GaAs crystal matrix. We find a tetragonal lattice expansion with enhanced elongation along the [001] crystal axis that is superimposed on an isotropic lattice extension. The isotropic contribution arises from excitation induced lattice heating as confirmed by temperature dependent reference studies. The tetragonal expansion on the femtometer scale is tentatively attributed to polaron formation by carriers trapped in the quantum dots.

Early life stress and the anxious brain: evidence for a neural mechanism linking childhood emotional maltreatment to anxiety in adulthood.

BACKGROUND: Childhood emotional maltreatment (CEM) increases the likelihood of developing an anxiety disorder in adulthood, but the neural processes underlying conferment of this risk have not been established. Here, we test the potential for neuroimaging the adult brain to inform understanding of the mechanism linking CEM to adult anxiety symptoms. METHOD: One hundred eighty-two adults (148 females, 34 males) with a normal-to-clinical range of anxiety symptoms underwent structural and functional magnetic resonance imaging while completing an emotion-processing paradigm with facial expressions of fear, anger, and happiness. Participants completed self-report measures of CEM and current anxiety symptoms. Voxelwise mediation analyses on gray-matter volumes and activation to each emotion condition were used to identify candidate brain mechanisms relating CEM to anxiety in adulthood. RESULTS: During processing of fear and anger faces, greater amygdala and less right dorsolateral prefrontal (dlPFC) activation partially mediated the positive relationship between CEM and anxiety symptoms. Greater right posterior insula activation to fear also partially mediated this relationship, as did greater ventral anterior cingulate (ACC) and less dorsal ACC activation to anger. Responses to happy faces in these regions did not mediate the CEM-anxiety relationship. Smaller right dlPFC gray-matter volumes also partially mediated the CEM-anxiety relationship. CONCLUSIONS: Activation patterns of the adult brain demonstrate the potential to inform mechanistic accounts of the CEM conferment of anxiety symptoms. Results support the hypothesis that exaggerated limbic activation to negative valence facial emotions links CEM to anxiety symptoms, which may be consequent to a breakdown of cortical regulatory processes.

Left hemisphere EEG coherence in infancy predicts infant declarative pointing and preschool epistemic language.

Pointing plays a central role in preverbal communication. While imperative pointing aims at influencing another person's behavior, declarative gestures serve to convey epistemic information and to share interest in an object. Further, the latter are hypothesized to be a precursor ability of epistemic language. So far, little is known about their underlying brain maturation processes. Therefore, the present study investigated the relation between brain maturation processes and the production of imperative and declarative motives as well as epistemic language in N = 32 infants. EEG coherence scores were measured at 14 months, imperative and declarative point production at 15 months and epistemic language at 48 months. Results of correlational analyses suggest distinct behavioral and neural patterns for imperative and declarative pointing, with declarative pointing being associated with the maturation of the left hemisphere. Further, EEG coherence measures of the left hemisphere at 14 months and declarative pointing at 15 months are related to individual differences in epistemic language skills at 48 months, independently of child IQ. In regression analyses, coherence measures of the left hemisphere prove to be the most important predictor of epistemic language skills. Thus, neural processes of the left hemisphere seem particularly relevant to social communication.

Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder.

Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13-18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder.

Deletion of Galgt2 (B4Galnt2) reduces muscle growth in response to acute injury and increases muscle inflammation and pathology in dystrophin-deficient mice.

Transgenic overexpression of Galgt2 (official name B4Galnt2) in skeletal muscle stimulates the glycosylation of α dystroglycan (αDG) and the up-regulation of laminin α2 and dystrophin surrogates known to inhibit muscle pathology in mouse models of congenital muscular dystrophy 1A and Duchenne muscular dystrophy. Skeletal muscle Galgt2 gene expression is also normally increased in the mdx mouse model of Duchenne muscular dystrophy compared with the wild-type mice. To assess whether this increased endogenous Galgt2 expression could affect disease, we quantified muscular dystrophy measures in mdx mice deleted for Galgt2 (Galgt2(-/-)mdx). Galgt2(-/-) mdx mice had increased heart and skeletal muscle pathology and inflammation, and also worsened cardiac function, relative to age-matched mdx mice. Deletion of Galgt2 in wild-type mice also slowed skeletal muscle growth in response to acute muscle injury. In each instance where Galgt2 expression was elevated (developing muscle, regenerating muscle, and dystrophic muscle), Galgt2-dependent glycosylation of αDG was also increased. Overexpression of Galgt2 failed to inhibit skeletal muscle pathology in dystroglycan-deficient muscles, in contrast to previous studies in dystrophin-deficient mdx muscles. This study demonstrates that Galgt2 gene expression and glycosylation of αDG are dynamically regulated in muscle and that endogenous Galgt2 gene expression can ameliorate the extent of muscle pathology, inflammation, and dysfunction in mdx mice.

Increased anterior insula activity in anxious individuals is linked to diminished perceived control.

Individuals with high-trait anxiety frequently report decreased perceived control. However, it is unclear how these processes are instantiated at a neural level. Prior research suggests that individuals prone to anxiety may have exaggerated activity in the anterior insula and altered activity in the cingulate cortex during anticipation of aversive events. Thus, we hypothesized that anxiety proneness influences anterior insula activation during anticipation of unpredictable threat through decreased perceived control. Forty physically healthy adults underwent neuroimaging while they explored computer-simulated contexts associated either with or without the threat of an unpredictable shock. Skin conductance, anxiety ratings and blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging were used to assess responses to threat versus no threat. Perceived control was measured using the Anxiety Control Questionnaire-Revised. Mediation analysis examined how anxiety proneness influenced BOLD activity. Anticipation of unpredictable threat resulted in increased skin conductance responses, anxiety ratings and enhanced activation in bilateral insula, anterior midcingulate cortex (aMCC) and bed nucleus of the stria terminalis. Individuals with greater anxiety proneness and less perceived control showed greater activity in dorsal anterior insula (dAI). Perceived control mediated the relationship between anxiety proneness and dAI activity. Increased dAI activity was associated with increased activity in aMCC, which correlated with increased exploratory behavior. Results provide evidence that exaggerated insula activation during the threat of unpredictable shock is directly related to low perceived control in anxiety-prone individuals. Perceived control thus may constitute an important treatment target to modulate insula activity during anxious anticipation in anxiety-disordered individuals.