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Enriched environment (EE), characterized by multi-sensory stimulation, represents a non-invasive alternative for alleviating epileptic seizures. However, the mechanism by which EE exerts its therapeutic impact remains incompletely understood. Here, it is elucidated that EE mitigates seizure susceptibility through the augmentation of adult neurogenesis within the entorhinal cortex (EC) circuit. A substantial upregulation of adult hippocampal neurogenesis concomitant with a notable reduction in seizure susceptibility has been found following exposure to EE. EE-enhanced adult-born dentate granule cells (abDGCs) are functionally activated during seizure events. Importantly, the selective activation of abDGCs mimics the anti-seizure effects observed with EE, while their inhibition negates these effects. Further, whole-brain c-Fos mapping demonstrates increased activity in DG-projecting EC CaMKIIα + neurons in response to EE. Crucially, EC CaMKIIα + neurons exert bidirectional modulation over the proliferation and maturation of abDGCs that can activate local GABAergic interneurons; thus, they are essential components for the anti-seizure effects mediated by EE. Collectively, this study provides compelling evidence regarding the circuit mechanisms underlying the effects of EE treatment on epileptic seizures, shedding light on the involvement of the EC-DG circuit in augmenting the functionality of abDGCs. This may help for the translational application of EE for epilepsy management., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: The most recent edition of the International Clinical Practice Guideline for the Prevention and Treatment of Pressure Ulcers/Injuries was released in 2019. Shortly after, in 2020, the first edition of the SECURE Prevention expert panel report, focusing on device-related pressure ulcers/injuries, was published as a special issue in the Journal of Wound Care . A second edition followed in 2022. This article presents a comprehensive summary of the current understanding of the causes of pressure ulcers/injuries (PU/Is) as detailed in these globally recognised consensus documents., Method: The literature reviewed in this summary specifically addresses the impact of prolonged soft tissue deformations on the viability of cells and tissues in the context of PU/Is related to bodyweight or medical devices., Results: Prolonged soft tissue deformations initially result in cell death and tissue damage on a microscopic scale, potentially leading to development of clinical PU/Is over time. That is, localised high tissue deformations or mechanical stress concentrations can cause microscopic damage within minutes, but it may take several hours of continued mechanical loading for this initial cell and tissue damage to become visible and clinically noticeable. Superficial tissue damage primarily stems from excessive shear loading on fragile or vulnerable skin. In contrast, deeper PU/Is, known as deep tissue injuries, typically arise from stress concentrations in soft tissues at body regions over sharp or curved bony prominences, or under stiff medical devices in prolonged contact with the skin., Conclusion: This review promotes deeper understanding of the pathophysiology of PU/Is, indicating that their primary prevention should focus on alleviating the exposure of cells and tissues to stress concentrations. This goal can be achieved either by reducing the intensity of stress concentrations in soft tissues, or by decreasing the exposure time of soft tissues to such stress concentrations.

Aims: In patients with colitis, the high comorbidity of depressive disorders is well-known, but the detailed mechanisms remain unresolved. In this study, we examined whether colitis induced by dextran sulfate sodium (DSS) increased the susceptibility to chronic unpredictable mild stress (CUMS) in C57BL/6J mice with resilience to CUMS., Main Methods: To induce experimental colitis and depressive-like behaviors, male 7-weeks old C57BL/6J mice were administered ad libitum 1% DSS solution for 11 days, and subjected to various mild stressors in a chronic, inevitable and unpredictable way according to a random schedule for 21 days, respectively., Key Findings: In naïve mice exposed to CUMS, their immobility times in a forced swim (FS) test were almost equal to those in control mice. The DSS administration to naïve mice induced colitis without depressive-like behavior, and at 18 days after termination of the DSS administration, the colitis had recovered to control levels, while altered diversity and composition of bacterial genera such as Bacteroides spp., Alistipes spp., etc., were found in the gut microbiota. Exposure of mice with DSS-induced colitis to CUMS (DSS + CUMS) significantly increased the immobility times in the FS test. In the gut microbiota of DSS + CUMS mice, the alteration profile of the relative abundance of bacterial genera differed from in the DSS ones., Significance: These findings indicate that mice with colitis exhibit increased susceptibility to psychological stress, resulting in induction of depressive-like behavior, and this might be due, at least in part, to altered characteristics of the gut microbiota., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Major negative life events, such as trauma exposure, can play a key role in igniting or exacerbating psychopathology. However, few disorders are diagnosed with respect to precipitating events, and the role of these events in the unfolding of new psychopathology is not well understood. The authors conducted a multisite transdiagnostic longitudinal study of trauma exposure and related mental health outcomes to identify neurobiological predictors of risk, resilience, and different symptom presentations., Methods: A total of 146 participants (discovery cohort: N=69; internal replication cohort: N=77) were recruited from emergency departments within 72 hours of a trauma and followed for the next 6 months with a survey, MRI, and physiological assessments., Results: Task-based functional MRI 2 weeks after a motor vehicle collision identified four clusters of individuals based on profiles of neural activity reflecting threat reactivity, reward reactivity, and inhibitory engagement. Three clusters were replicated in an independent sample with a variety of trauma types. The clusters showed different longitudinal patterns of posttrauma symptoms., Conclusions: These findings provide a novel characterization of heterogeneous stress responses shortly after trauma exposure, identifying potential neuroimaging-based biotypes of trauma resilience and psychopathology.

Abstract: Pain sensitization leading to polyalgia can be observed during infectious diseases. The blood pressure cuff-evoked pain threshold (BPCEPT) has been used in previous studies as a screening tool for fibromyalgia.We aimed to use the BPCEPT as a screening test for detecting pain sensitization in patients suffering from infectious diseases. We also investigated whether specific factors were associated with pain sensitization.We performed a prospective comparative study including all patients of our infectious diseases center in a 1-year period. We created a positive control group of patients suffering from fibromyalgia and a negative control group of "apparently healthy" patients consulting for vaccination.The blood pressure (BP) cuff was inflated until the patient signaled that they experienced pain, and this pressure value was noted.A total of 2355 patients were included. The positive control group had significantly lower values of the BPCEPT than all other groups. Among hospitalized patients with infectious diseases, a low BPCEPT was significantly associated with high temperature (P < .0001), older age (P = .002), being a woman (P = .004), high serum glutamic-oxaloacetic transaminase (P = .007), and high C reactive protein levels (P = .02). Moreover, in multivariate analysis, respiratory infection, meningitis, urinary tract infection, febrile neutropenia, and Q fever were independently associated with a low BPCEPT. A significant negative dynamic correlation between the BPCEPT and temperature was also observed (P < .001).We demonstrated for the first time in a large sample of patients that the BPCEPT method can be used to detect pain susceptibility. We observed a significant dynamic correlation between pain sensitization and temperature. Additionally, pain sensitization was associated with some diseases, suggesting that they trigger pain sensitivity., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Resilience is the capacity to maintain normal psychological and physical functions in the face of stress and adversity. Understanding how one can develop and enhance resilience is of great relevance to not only promoting coping mechanisms but also mitigating maladaptive stress responses in psychiatric illnesses such as depression. Preclinical studies suggest that GABA(B) receptors (GABA(B1) and GABA(B2)) are potential targets for the treatment of major depression. In this study, we assessed the functional role of GABA(B) receptors in stress resilience and vulnerability by using a chronic unpredictable stress (CUS) model in mice. As the medial prefrontal cortex (mPFC) plays a key role in the top-down modulation of stress responses, we focused our study on this brain structure. Our results showed that only approximately 41.9% of subjects exhibited anxiety- or despair-like behaviors after exposure to CUS. The vulnerable mice showed higher c-Fos expression in the infralimbic cortex (IL) subregion of the mPFC when exposed to a social stressor. Moreover, the expression of GABA(B1) but not GABA(B2) receptors was significantly downregulated in IL subregion of susceptible mice. Finally, we found that intra-IL administration of baclofen, a GABA(B) receptor agonist, rapidly relieved the social avoidance symptoms of the "stress-susceptible" mice. Taken together, our results show that the GABA(B1) receptor within the IL may play an important role in stress resilience and vulnerability, and thus open an avenue to develop novel, personalized approaches to promote stress resilience and treat stress-related psychiatric disorders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was recognised by the WHO as a pandemic in 2020. Host preparation to combat the virus is an important strategy to avoid COVID-19 severity. Thus, the relationship between eating habits, nutritional status and their effects on the immune response and further implications in viral respiratory infections is an important topic discussed in this review. Malnutrition causes the most diverse alterations in the immune system, suppressing of the immune response and increasing the susceptibility to infections such as SARS-CoV-2. On the other hand, obesity induces low-grade chronic inflammation caused by excess adiposity, which increases angiotensin-converting enzyme 2. It decreases the immune response favouring SARS-CoV-2 virulence and promoting respiratory distress syndrome. The present review highlights the importance of food choices considering their inflammatory effects, consequently increasing the viral susceptibility observed in malnutrition and obesity. Healthy eating habits, micronutrients, bioactive compounds and probiotics are strategies for COVID-19 prevention. Therefore, a diversified and balanced diet can contribute to the improvement of the immune response to viral infections such as COVID-19.

Addiction is a chronic brain disease that has dramatic health and socioeconomic consequences worldwide. Multiple approaches have been used for decades to clarify the neurobiological basis of this disease and to identify novel potential treatments. This review summarizes the main brain networks involved in the vulnerability to addiction and specific innovative technological approaches to investigate these neural circuits. First, the evolution of the definition of addiction across the Diagnostic and Statistical Manual of Mental Disorders (DSM) is revised. We next discuss several innovative experimental techniques that, combined with behavioral approaches, have allowed recent critical advances in understanding the neural circuits involved in addiction, including DREADDs, calcium imaging, and electrophysiology. All these techniques have been used to investigate specific neural circuits involved in vulnerability to addiction and have been extremely useful to clarify the neurobiological basis of each specific component of the addictive process. These novel tools targeting specific brain regions are of great interest to further understand the different aspects of this complex disease. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Prolonged fever-induced seizures (febrile status epilepticus [FSE]) during early childhood increase the risk for later epilepsy, but the underlying mechanisms are incompletely understood. Experimental FSE (eFSE) in rats successfully models human FSE, recapitulating the resulting epileptogenesis in a subset of affected individuals. However, the powerful viral and genetic tools that may enhance mechanistic insights into epileptogenesis and associated comorbidities, are better-developed for mice. Therefore, we aimed to determine if eFSE could be generated in mice and if it provoked enduring changes in hippocampal-network excitability and the development of spontaneous seizures., Methods: We employed C57BL/6J male mice, the strain used most commonly in transgenic manipulations, and examined if early life eFSE could be sustained and if it led to hyperexcitability of hippocampal networks and to epilepsy. Outcome measures included vulnerability to the subsequent administration of the limbic convulsant kainic acid (KA) and the development of spontaneous seizures. In the first mouse cohort, adult naive and eFSE-experiencing mice were exposed to KA. A second cohort of control and eFSE-experiencing young adult mice was implanted with bilateral hippocampal electrodes and recorded using continuous video-electroencephalography (EEG) for 2 to 3 months to examine for spontaneous seizures (epileptogenesis)., Results: Induction of eFSE was feasible and eFSE increased the susceptibility of adult C57BL/6J mice to KA, thereby reducing latency to seizure onset and increasing seizure severity. Of 24 chronically recorded eFSE mice, 4 (16.5%) developed hippocampal epilepsy with a latent period of ~3 months, significantly different from the expectation by chance (P = .04). The limbic epilepsy that followed eFSE was progressive., Significance: eFSE promotes pro-epileptogenic network changes in a majority of C57BL/6J male mice and frank "temporal lobe-like" epilepsy in one sixth of the cohort. Mouse eFSE may thus provide a useful tool for investigating molecular, cellular, and circuit changes during the development of temporal lobe epilepsy and its comorbidities., (© 2021 International League Against Epilepsy.)

Background and Aims: Internet addiction (IA) is common among young students. This study aimed to examine the influence and mechanisms of IA and susceptible personality traits on the impact of suicidal ideation in adolescent students in China., Methods: This cross-sectional study (09/2012-09/2015) used stratified cluster sampling with "school type" for stratification; 136,266 students from 63 schools completed the questionnaire. Logistic regression analysis was performed to estimate the effect of IA (Young's Internet Addiction Test) and susceptible personality (Barratt impulsiveness scale, Buss & Perry Aggression Questionnaire; and Eysenck Personality Questionnaire-R Short Scale) on suicidal ideation (Scale of Suicidal Ideation)., Results: Suicidal ideation was observed in 20,218 (14.77%) of the students, and IA was detected in 28,836 (21.16%) subjects. Compared with those without IA, students with IA had a higher prevalence of suicidal ideation (P < 0.0001). No planning impulsiveness had a predictive effect on suicidal ideation in the impulsive personality trait, while in the aggressive personality trait, hostility and self-aggression had a predictive effect on suicidal ideation (all P < 0.0001). High psychoticism and neuroticism were impact factors for suicidal ideation, but extroversion was a protective factor (all P < 0.0001)., Discussion: These results highlight the importance of assessing personality traits and reducing IA as a possible means of lessening suicidal ideation. Susceptible personality (such as high psychoticism, high neuroticism, and low extroversion) play a prominent role in influencing the probability of having suicidal behavior among those recently exposed to IA., Conclusions: IA and susceptible personality traits were significantly correlated with suicidal and self-harm ideation among adolescent students.

Background: There is currently no concise systematic review or meta-analysis addressing cardio-metabolic risk factors in women experiencing infertility., Objectives: To determine whether infertile women have higher levels of cardiovascular risk factors compared with fertile women., Search Strategy: We performed a systematic literature search using PubMed, Embase and CINAHL, Scopus and additional manual and bibliographic searches for relevant articles (end search date 6 November 2019)., Selection Criteria: We selected studies that compared cardio-metabolic risk factors in fertile and infertile women of reproductive age., Data Collection and Analysis: At least two authors independently screened potentially eligible studies., Main Results: There was an increased presence of several cardio-metabolic risk factors in infertile women compared with fertile women. Infertile women had statistically significant higher body mass index (BMI), increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) compared with fertile women. Fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and mean arterial pressure were not found to be different between fertile and infertile women. A subgroup analysis revealed that TC, fasting glucose and fasting insulin were increased, and high-density lipoprotein was decreased only in women with polycystic ovarian syndrome compared with fertile women, whereas BMI, TG and LDL-C were statistically significantly increased in women with any indication of infertility compared with fertile women., Conclusions: Infertile women have a higher level of cardio-metabolic risk factors compared with fertile women. This finding has clinical implications for infertile women in general, and those attempting to conceive through medically assisted reproduction., Tweetable Abstract: Infertile women appear to have a higher level of cardio-metabolic risk factors compared with fertile women., (© 2020 Royal College of Obstetricians and Gynaecologists.)

Shoulder surgery is a primary intervention for shoulder pain, yet many individuals experience persistent postoperative pain. Previously, we found individuals categorized as having a high-risk phenotype (comprised of COMT variation and pain catastrophizing) had approximately double the chance of not reaching a 12-month pain recovery criterion. As a means to better understand the development of persistent postoperative shoulder pain, this study advanced our previous work by examining temporal ordering of postoperative shoulder recovery based on potential mediating factors, and expansion of outcomes to include movement-evoked pain and shoulder active range of motion. Before surgery, individuals were categorized as either high-risk (high pain catastrophizing, COMT-genotype linked to low enzyme activity [n = 41]) or low-risk (low pain catastrophizing, COMT-genotype linked to normal enzyme activity [n = 107]). We then compared potential mediating variables at 3, 6, and 12 months postoperatively 1) endogenous pain modulation defined by a conditioned pain modulation paradigm; and 2) and emotion factors such as anxiety, fear of movement, and depressive symptoms. At 3 months, the high-risk subgroup had higher fear and movement-evoked pain, and causal mediation analysis confirmed the direct effect of risk subgroup on 12-month movement evoked pain. However, baseline to 12-month change in depressive symptoms were found to mediate 53% of the total effect of risk subgroup on 12-month movement-evoked pain. This study introduces potential temporal components and relationships to the development of persistent postoperative shoulder pain, which future studies will confirm and assess for potential therapeutic targets. PERSPECTIVE: This study expands upon postoperative shoulder recovery measures to include movement-evoked pain and depressive symptoms, and provides preliminary indication of temporal ordering to postoperative shoulder recovery for a preidentified high-risk subgroup. Future studies will distinguish temporal components of shoulder surgery that may optimize treatment targets of postoperative recovery., (Copyright © 2019 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Developmental dyslexia, a severe deficit in literacy learning, is a neurodevelopmental learning disorder. Yet, it is not clear whether existing neurobiological accounts of dyslexia capture potential predispositions of the deficit or consequences of reduced reading experience. Here, we longitudinally followed 32 children from preliterate to school age using functional and structural magnetic resonance imaging techniques. Based on standardised and age-normed reading and spelling tests administered at school age, children were classified as 16 dyslexic participants and 16 controls. This longitudinal design allowed us to disentangle possible neurobiological predispositions for developing dyslexia from effects of individual differences in literacy experience. In our sample, the disorder can be predicted already before literacy learning from auditory cortex gyrification and aberrant downstream connectivity within the speech processing system. These results provide evidence for the notion that dyslexia may originate from an atypical maturation of the speech network that precedes literacy instruction., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous findings suggested deficits in pleasure experience in schizophrenia, but little is known in psychosis risk prodrome, especially in adolescence. Aim of this study was (1) to assess anhedonia in distinct help-seeking subgroups of adolescents identified through the ultra-high risk (UHR) criteria, (2) to explore any association of anhedonia with other psychopathological aspects in the UHR group, and (3) to monitor longitudinally the stability of anhedonia in UHR individuals across 1-year follow-up period. 123 participants (13-18 years) completed the Comprehensive Assessment of At-Risk Mental States (CAARMS), the Beck Depression Inventory-II, the Schizotypal Personality Questionnaire-Brief version, the Brief-O-LIFE questionnaire (BOL), and the Brief version of the World Health Organization Quality of Life scale (WHOQOL-BREF). Two different indexes of anhedonia were used: CAARMS "Anhedonia" item 4.3 and BOL "Introvertive Anhedonia" subscale scores. No difference in anhedonia levels between UHR and First Episode Psychosis (FEP) groups was found. UHR adolescents showed higher CAARMS and BOL anhedonia scores than non-UHR/FEP. After 1-year follow-up period, UHR adolescents had a significant decrease in severity only in CAARMS anhedonia subscores. In UHR subgroup, CAARMS anhedonia measures showed significant correlations with impaired role functioning and negative symptoms, while BOL anhedonia was significantly correlated with specific schizotypal personality traits concerning interpersonal deficits. Anhedonia is prominent in the psychosis prodrome, also in adolescence. Its severity is not statistically different from that of FEP adolescents and is related to more severe functioning impairment and a worse quality of life.

Defective spleen function increases susceptibility to bacterial infections which can be prevented by vaccine prophylaxis. Splenic hypofunction can be found in a number of autoimmune disorders; however, no data are available regarding autoimmune atrophic gastritis (AAG), autoimmune enteropathy (AIE) and autoimmune liver disease (AILD). Peripheral blood samples from patients with AAG (n = 40), AIE (n = 3) and AILD (n = 40) were collected. Patients affected by autoimmune disorders already known to be associated with splenic hypofunction, i.e. coeliac disease (CD) and ulcerative colitis (UC), were included as disease controls, while splenectomised patients and healthy subjects were evaluated as positive and negative controls, respectively. Counting of erythrocytes with membrane abnormalities, i.e. pitted red cells, was used as an indicator of spleen function (normal upper limit 4%). Defective splenic function was observed in 22 of the 40 patients with AAG (55.0%), in two of the three patients with AIE (66.6%) and in 35 of the 40 patients with AILD (87.5%). As expected, in untreated CD, refractory CD and UC there was a high prevalence of hyposplenism (43.7%, 88.2% and 54.4%, respectively). Due to the high prevalence of splenic hypofunction, patients with AAG, AILD and AIE should undergo pitted red cell evaluation and, if hyposplenic, they should be candidate to vaccine prophylaxis against encapsulated bacteria.

Patients with psychiatric disorders, such as gambling and substance use, tend to exhibit maladaptive decision-making. In this study, we assessed individual differences in risk-taking behaviors using a rat gambling task (GT) and investigated the relationship between risk-taking behaviors and vulnerability to drug dependence using methamphetamine (METH)-induced conditioned place preference (CPP). In the GT using a radial arm maze, male Long-Evans rats were trained to choose one of three choice arms (a low-risk/low reward (L-L), a high-risk/high reward (H-H), and an empty arm) in 16 trials per day for 14 days. METH-induced CPP consisted of 6 sessions: habituation, conditioning, preference test (Test I), extinction, extinction test (Test II), and reinstatement test (Test III). Results demonstrated that the percentage of choosing the H-H arm was significantly positively correlated with the percentage of time spent in the METH-paired compartment in the preference test, but not with the extinction and reinstatement tests, suggesting that risk-taking rats are more vulnerable to drug dependence., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Individuals seem to be differently susceptible to motion-related sickness (motion sickness, visually induced sickness etc.). Investigations of the reasons for these different susceptibilities have revealed many potential factors that could predict individual susceptibility to motion-related sickness., Objective: This paper attempts to conduct a comprehensive literature review on inter-individual predictors of susceptibility to motion-related sickness using systematic approaches., Methods: After a systematic literature research, titles and abstracts of 1778 publications were screened for relevance. Reference lists of selected publications were searched for additional studies. This procedure yielded 184 relevant publications., Results: The identified predictors were clustered into demographic, physiological and psychological aspects. Among these predictors, the factors gender, length of velocity storage and anxiety showed the greatest predictive power. In addition, individual susceptibility to motion-related sickness is also to a large extent dependent on the degree of habituation to the aversive stimulus., Conclusions: Some of the identified influencing factors seem to have different effects on physically and visually induced motion sickness. More research is needed to close gaps, especially on predictive factors of visually induced motion sickness.

Social cognition refers to the mental operations governing social interactions. Recent research has highlighted the importance of social cognition in determining functional outcome in patients with schizophrenia and in psychosis risk populations. The aim of this review is to investigate the neural correlates of social cognition in different psychosis risk populations, potentially representing different levels of risk i.e. high schizotypy (SR), familial risk (FR) and clinical high risk (CHR). PsychINFO, Web of Science and PubMed were systematically searched, and 39 papers were included in the final review. Results in FR samples were highly inconclusive. In SR samples, findings showed a tendency towards increased task related activity in frontal cortex regions. The most consistent results come from CHR samples, where findings suggest increased task related activity in frontal and cingulate cortices. Interestingly, all studies of CHR populations also report increased activity in temporal cortex and abnormal response to neutral stimuli during emotional processing tasks. These findings are discussed in relation to dopamine models of psychosis due to temporal cortex abnormality., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To determine whether the susceptibility value in the deep gray matter obtained by quantitative susceptibility mapping (QSM) provides additive value to the morphometric index for differentiating progressive supranuclear palsy (PSP) from Parkinson's disease (PD)., Materials and Methods: PSP- (n = 8) and PD patients (n = 18) and 18 age-matched healthy controls who underwent QSM and 3D magnetization-prepared rapid gradient echo (MPRAGE) sequences. The mean susceptibility values (MSVs) of the deep gray matter structures on QSM- and areas of the midbrain (morphometric index, MI) on 3D MPRAGE images were measured by two neuroradiologists. Analysis of variance, the Scheffe test and receiver operating characteristic (ROC) analysis were conducted to assess differences and discriminate among PSP, PD and controls by the MSVs and the MI. Using the MSV of a structure with the best area under the curve (AUC) and the MI, we created a decision tree to differentiate between PSP and PD., Results: The MSVs of the globus pallidus (GP) and substantia nigra (SN) were significantly higher in PSP than PD and the controls (p < .05). By ROC analysis (PSP vs PD), AUC was greatest (0.903) for the GP. The MI was significantly smaller in PSP than PD and the controls (p < .05); AUC (PSP vs PD) was 0.917. The decision tree using cutoff values of 244 parts per billion for MSV of the GP and 74.0 mm 2 for MI served to completely differentiate between PSP and PD., Conclusion: The MSV in the GP on QSM images adds value to the MI for differentiating PSP from PD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

It is increasingly suggested that personality traits are critical to understanding patterns of cardiovascular stress adaptation. However, studies have focused on higher-order traits with no research having examined underlying facet effects to repeated stress. The examination of facets provides a more granular examination, which has the potential to identify specific personality components that are relevant within the context of psychophysiological stress adaptation. This study objective was to determine if the underlying facets which encapsulate the dimension of emotional stability, are associated with cardiovascular adaptation to recurring stress. Continuous cardiovascular monitoring and psychometric measures were collated from 79 healthy young male and female adults, across a protocol of recurring active stress tasks. Multiple regression analysis revealed that the facet of vulnerability was associated with systolic and diastolic blood pressure adaptation across the protocol. More specifically, vulnerability was negatively associated with adaptation to recurring stress, such that those highest in vulnerability displayed a sensitization to the recurring stressor. No significant effects emerged for any other facet. Importantly, this research adds to the existing literature examining stress adaptation and has implications for future research on the relevance of examining facet effects. This study is the first to implicate the personality facet of vulnerability which encapsulates an individual's tendency to feel unable to cope with stress and becoming hopeless when faced with emergency situations, in the context of cardiovascular stress adaptation. Taken together, this study suggests that the facet of vulnerability is a critical component to consider in the context of cardiovascular stress adaptation., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Some argue that physiological and psychological stress sensitivities contribute causally to schizophrenia. Indeed, evidence shows that those with or at risk for schizophrenia have highly sensitive stress responses. However, it is unclear how psychological stress sensitivity develops. Our aim was to test whether psychological stress sensitization develops longitudinally in association with major life events and components of schizophrenia liability. We expected schizophrenia liability to predict higher psychological stress sensitivity; life events to predict subsequent increases in psychological stress sensitivity; and schizophrenia liability to moderate this relationship., Methods: In a prospective study, undergraduates (n = 184) completed a measure of schizophrenia liability at baseline. Then at 2-month intervals over 6 months, they reported on the occurrence of major life events and completed measures of psychological stress sensitivity., Results: Latent variable growth modelling showed that stress sensitivity increased following incident life events when controlling for baseline life events. Higher cognitive-perceptual and interpersonal scores predicted higher baseline sensitivity. Higher cognitive-perceptual features predicted larger increases in psychological stress sensitivity following life events whereas greater disorganization reduced growth., Conclusions: This evidence is consistent with the idea that psychological sensitization is involved in the development of schizophrenia and suggests an important link between positive features of schizophrenia liability and the magnification of psychological stress sensitivity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Amphibians worldwide continue to battle an emerging infectious disease, chytridiomycosis, caused by Batrachochytrium dendrobatidis ( Bd ). Southern leopard frogs, Rana sphenocephala , are known to become infected with this pathogen, yet they are considered 'of least concern' for declines due to chytridiomycosis. Previous studies have shown that R. sphenocephala secretes four antimicrobial peptides (AMPs) onto their skin which may play an important role in limiting susceptibility to chytridiomycosis. Here, we examined (1) the effects of temperature and AMP depletion on infections with Bd and (2) the effects of temperature and Bd infection on the capacity to secrete AMPs in juvenile leopard frogs. Pathogen burden and mortality were greater in frogs exposed to Bd at low temperature but did not increase following monthly AMP depletion. Both low temperature and Bd exposure reduced the capacity of juvenile frogs to restore peptides after monthly depletions. Frogs held at 14°C were poorly able to restore peptides in comparison with those at 26°C. Frogs held at 26°C were better able to restore their peptides, but when exposed to Bd , this capacity was significantly reduced. These results strongly support the hypothesis that both colder temperatures and Bd infection impair the capacity of juvenile frogs to produce and secrete AMPs, an important component of their innate defense against chytrid fungi and other pathogens. Thus, in the face of unpredictable climate changes and enzootic pathogens, assessments of disease risk should consider the potential for effects of environmental variation and pathogen exposure on the quality of host defenses., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

The nucleus accumbens (NAc) plays critical roles in motivated behaviors, including food seeking and feeding. Differences in NAc function contribute to overeating that drives obesity, but the underlying mechanisms are poorly understood. In addition, there is a fair degree of variation in individual susceptibility versus resistance to obesity that is due in part to differences in NAc function. For example, using selectively bred obesity-prone and obesity-resistant rats, we have found that excitability of medium spiny neurons (MSNs) within the NAc core is enhanced in obesity-prone versus -resistant populations, before any diet manipulation. However, it is unknown whether consumption of sugary, fatty "junk food" alters MSN excitability. Here whole cell patch-clamp recordings were conducted to examine MSN intrinsic excitability in adult male obesity-prone and obesity-resistant rats with and without exposure to a sugary, fatty junk food diet. We replicated our initial finding that basal excitability is enhanced in obesity-prone versus obesity-resistant rats and determined that this is due to a lower fast transient potassium current ( I A ) in prone versus resistant groups. In addition, the junk food diet had opposite effects on excitability in obesity-prone versus obesity-resistant rats. Specifically, junk food enhanced excitability in MSNs of obesity-resistant rats; this was mediated by a reduction in I A . In contrast, junk food reduced excitability in MSNs from obesity-prone rats; this was mediated by an increase in inward-rectifying potassium current. Thus individual differences in obesity susceptibility influence both basal excitability and how MSN excitability adapts to junk food consumption. NEW & NOTEWORTHY Medium spiny neurons (MSNs) in the nucleus accumbens of obesity-prone rats are hyperexcitable compared with MSNs from obesity-resistant rats. We found that 10 days of "junk food" exposure reduces MSN excitability in obesity-prone rats by increasing inward-rectifying potassium current and increases MSN excitability in obesity-resistant rats by decreasing fast transient potassium current. These data show that there are basal and junk food diet-induced differences in MSN excitability in obesity-prone and obesity-resistant individuals; this may contribute to previously observed differences in incentive motivation.

Xanthomonas campestris pv. campestris (Xcc)- responsive soluble and cell wall-bound hydroxycinnamic acids (HAs) and flavonoids accumulation in relation to hormonal changes in two Brassica napus cultivars contrasting disease susceptibility were interpreted with regard to the disease resistance. At 14-day post inoculation with Xcc, disease resistance in cv. Capitol was distinguished by an accumulation of specific (HAs) and flavonoids particularly in cell-wall bound form, and was characterized by higher endogenous jasmonic acid (JA) resulting in a decrease of JA-based balance with other hormones, as well as enhanced expression of JA signaling that was concurrently based on upregulation of PAP1 (production of anthocyanin pigment 1), MYB transcription factor, and phenylpropanoid biosynthetic genes. Fourier transform infrared spectra confirmed higher amounts of esterified phenolic acids in cv. Capitol. These results indicate that enhanced JA levels and signaling in resistant cultivar was associated with a higher accumulation of HAs and flavonoids, particularly in the cell wall-bound form, and vice versa in the susceptible cultivar (cv. Mosa) with enhanced SA-, ABA-, and CK- levels and signaling. Thus the JA-mediated phenolic metabolites accumulation is an important feature for the management and breeding program to develop disease-resistant B. napus cultivar., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Recent studies suggest that people with diabetes or who are at risk of developing diabetes, i.e. prediabetic (preDM), are potentially susceptible to air pollution, but the underlying mechanisms remain unclear because the existing epidemiological studies did not include healthy control groups and only focused on limited health outcomes. We hypothesized that acute exposure to ambient fine particles (PM 2.5 ) will lead to enhanced pulmonary and cardiometabolic changes in preDM than healthy individuals., Methods: We recruited 60 preDM and 60 healthy individuals from a community of 22,343 adults in Beijing China, and arranged each subject to complete up to seven repeated clinical visits with measures of 6 cardiopulmonary biomarkers, 6 cytokines, 4 blood pressure and endothelial function outcomes and 4 glucose metabolism biomarkers.. Moving averaged daily ambient PM 2.5 in preceding 1-14 days was matched to each subject and the PM 2.5 associated effect on multiple biomarkers was estimated and compared between PreDM and healthy subjects based on linear mixed effect model., Results: All the subjects exhibited significant acute elevation of exhaled nitric oxide, white blood cells, neutrophils, interleukin-1α, and glycated haemoglobin with increased exposure to PM 2.5 . PreDM subjects had significant stronger adverse changes compared to healthy subjects in 6 cardiometabolic biomarkers, namely, interleukin-2, interleukin-8, systolic and diastolic blood pressure, augmentation pressure, and glucose. The maximum elevation of these 6 biomarkers in PreDM subjects were 8.6% [CI: 4.1-13.3%], 10.0% [CI: 3.9-16.4%], 1.9% [CI: 0.2-3.6%], 1.2% [CI: - 0.1-2.4%], 5.7% [CI: - 0.1-11.8%], 2.4% [CI: 0.7-4.2%], respectively, per an interquartile increase of ambient PM 2.5 (61.4 μg m - 3 ) throughout the exposure window of the preceding 1-14 days. No significant difference was observed for the changes in pulmonary biomarkers between the two groups., Conclusions: PreDM individuals are more susceptible to the acute cardiometabolic effect of air pollution than the healthy individuals. A considerable public health burden can be inferred, given the high prevalence of prediabetes and the ubiquity of air pollution in China and worldwide.

Although depressive disorders are among the most common disorders in youth, highly efficacious treatments for childhood affective disorders are lacking. There is significant need to better understand the factors that contribute to the development and maintenance of depression in youth so that treatments can be targeted at optimal mechanisms. The aim of the current paper was to synthesize research on cognitive and neurobiological factors associated with youth depression, guided by De Raedt and Koster's model (2010) for vulnerability to depression in adults. Consistent with model predictions, there is evidence that attentional impairments are greatest in the context of negative information, relative to positive or neutral information, and some evidence that attentional deficits are associated with rumination in depressed youth. However, we found little evidence for the model's assumption that attentional bias is an etiological and maintenance factor for depression. There are several other model predictions that require additional study as current data are lacking. Overall, De Raedt and Koster's (2010) integrative cognitive and biological framework has tremendous potential to move the field forward in understanding the development of depression in youth. Additional longitudinal studies incorporating measures across biological and cognitive levels of analysis are needed., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Neuroticism, a dispositional trait of heightened negative emotionality, is a vulnerability factor for psychopathology. Given neuroticism's strong association with rumination, a repetitive thought pattern that intensifies and prolongs emotions, some question whether these constructs capture the same or unique information about vulnerability for psychopathology. The present study examined whether neuroticism is genetically and environmentally distinct from two clinically relevant ruminative subtypes-anger and depressive rumination-and whether genetic and environmental influences specific to rumination versus shared with neuroticism overlap with internalizing and externalizing psychopathology. These analyses were conducted on 439 same-sex twin pairs in the Colorado Longitudinal Twin study. Rumination and neuroticism latent variables were created from multiple rumination questionnaires administered at age 23 and shortened Eysenck Personality Questionnaires administered at ages 17 and 21, respectively. Lifetime psychopathology symptoms, assessed by two structured clinical interviews, were used to create ordinal composite variables. Multivariate Cholesky decompositions indicated that neuroticism, anger rumination, and depressive rumination have common genetic and nonshared environmental influences but are differentiated by nonshared environmental influences specific to each ruminative subtype. Genetic influences common to rumination and neuroticism explained considerable variance in internalizing psychopathology, suggesting possible genetic mediation or common genetic causes. Genetic and environmental influences on externalizing psychopathology did not substantially overlap with those on neuroticism and rumination. These findings suggest that rumination and neuroticism share most genetic influences yet are influenced by distinct environmental influences. Furthermore, our results indicate that a comprehensive understanding of transdiagnostic risk factors must include an examination of both genetic and environmental influences. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

1. The objective of the study was to investigate the susceptibility of young and older laying hens to fatty liver-haemorrhagic syndrome (FLHS) and to evaluate the reliability of different blood lipid fractions for predicting or diagnosing FLHS. 2. Forty young hens and 40 older hens were caged individually. Each group of hens was randomly allotted to four treatments for 21 days: either a control, an oestradiol group, a high energy-low protein diet (HELPD) group or a HELPD + oestradiol group. Blood levels of oestradiol, triglyceride (TG), cholesterol (CHOL), high density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C), liver total lipids, hepatic haemorrhagic scores and productive performance were assessed. 3. In older hens, β -oestradiol increased ( P < 0.05) liver total lipids, hepatic haemorrhagic scores and the incidence of FLHS but reduced ( P < 0.05) productive performance; however, such changes were not observed in young hens. 4. In two groups of hens, serum TG, CHOL and HDL-C levels were increased ( P < 0.001) by β -oestradiol. Hens with FLHS had higher serum TG, CHOL and HDL-C ( P < 0.001) than non-FLHS birds in the older layer group of hens. 5. An interaction ( β -oestradiol × HELPD) ( P < 0.05) for LDL-C levels was observed in both groups of hens. In young hens, β -oestradiol induced a decrease ( P = 0.004) in serum LDL-C levels but the effect was attenuated by HELPD. In older hens, HELPD caused an increase ( P = 0.02) in serum LDL-C although the effect depended on the presence of β -oestradiol. 6. In conclusion, older layers were more susceptible to FLHS than young layers after oestradiol treatment. Blood TG, CHOL and HDL-C rather than LDL-C levels can be used as a prediction tool for the overall susceptibility to FLHS in older rather than young layers. There were interactions between oestradiol and HELPD on blood LDL-C levels in laying hens.

Background and Objective: Obesity produces restrictive effects on lung function. We previously reported that obese patients with asthma exhibit a propensity towards small airway closure during methacholine challenge which improved with weight loss. We hypothesized that increased abdominal adiposity, a key contributor to the restrictive effects of obesity on the lung, mediates this response. This study investigates the effect of body mass index (BMI) versus waist circumference (WC) on spirometric lung function, sensitivity to airway narrowing and closure, and airway closure during bronchoconstriction in patients with asthma., Methods: Participants underwent spirometry and methacholine challenge. Sensitivity to airway closure and narrowing was assessed from the dose-response slopes of the forced vital capacity (FVC) and the ratio of forced expiratory volume in 1 s (FEV 1 ) to FVC, respectively. Airway closure during bronchoconstriction (closing index) was computed as the percent reduction in FVC divided by the percent reduction in FEV 1 at maximal bronchoconstriction., Results: A total of 116 asthmatic patients (56 obese) underwent methacholine challenge. Spirometric lung function was inversely related to WC (P < 0.05), rather than BMI. Closing index increased significantly during bronchoconstriction in obese patients and was related to increasing BMI (P = 0.01), but not to WC. Sensitivity to airway closure and narrowing was not associated with BMI or WC., Conclusion: Although WC is associated with restrictive effects on baseline lung function, increased BMI, rather than WC, predisposes to airway closure during bronchoconstriction. These findings suggest that obesity predisposes to airway closure during bronchoconstriction through mechanisms other than simple mass loading., (© 2019 Asian Pacific Society of Respirology.)

Very little is known about marine mammal susceptibility to primary blast injury (PBI) except in rare cases of opportunistic studies. As a result, traditional analysis techniques relied on methods developed more than 30 years ago using terrestrial mammals as surrogates. Modeling tools available today have the computing power to vastly improve calculation of safe ranges and injury zones from underwater explosions (UNDEX) employing morphologically accurate proxies with material properties similar to marine mammal tissues. The Dynamic System Mechanics Advanced Simulation (DYSMAS) fluid-structure interaction (FSI) software is being used to simulate the complex phenomena of UNDEX, shock wave, and bubble pulse propagation through the water and transmission of energy to a cetacean focusing on the dynamic response of the thoracic cavity and air-filled lungs to a shock wave. The approach integrates fluid and structural analyses with the material properties of blubber, bone, and muscle using marine mammal morphometrics to eliminate unnecessary assumptions made during more traditional approaches to analysis developed before these types of data and computational power were available. DYSMAS analyses of a 1D gas bubble surrounded by water was found to closely match the classical bubble dynamics models. Further, DYSMAS models of a spherical gas bubble surrounded by tissue and rib structure demonstrate a global radial oscillation of the gas bubble, but also show significant local deflection and material strain in response to the UNDEX loading. The intended result of the investigation is an improved and scientifically defensible understanding of the effects of UNDEX on marine mammals. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. Anat Rec, 302:718-734, 2019. Published 2018. This article is a U.S. Government work and is in the public domain in the USA., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

The 22q11.2 deletion is one of the most common copy number variants in humans. Carriers of the deletion have a markedly increased risk for neurodevelopmental brain disorders, including schizophrenia, autism spectrum disorders, and attention deficit hyperactivity disorder. The high risk of psychiatric disorders associated with 22q11.2 deletion syndrome offers a unique possibility to identify the functional abnormalities that precede the emergence of psychosis. Carriers of a 22q11.2 deletion show a broad range of sensory processing and cognitive abnormalities similar as in schizophrenia, such as auditory and visual sensory processing, response inhibition, working memory, social cognition, reward processing and arithmetic processing. All these processes have a significant negative impact on daily life if impaired and have been studied extensively in schizophrenia using task-based functional neuroimaging. Here, we review task-related functional brain mapping studies that have used electroencephalography or functional magnetic resonance imaging to identify functional alterations in carriers with 22q11.2 deletion syndrome within the above mentioned cognitive and sensory domains. We discuss how the identification of functional changes at the brain system level can advance the general understanding of which neurobiological alterations set the frame for the emergence of neurodevelopmental disorders in the human brain. The task-based functional neuroimaging literature shows conflicting results in many domains. Nevertheless, consistent similarities between 22q11.2 deletion syndrome and schizophrenia have been found for sensory processing, social cognition and working memory. We discuss these functional brain alterations in terms of potential biomarkers of increased risk for psychosis in the general population., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Active adaptation to acute stress is essential for coping with daily life challenges. The stress hormone cortisol, as well as large scale re-allocations of brain resources have been implicated in this adaptation. Stress-induced shifts between large-scale brain networks, including salience (SN), central executive (CEN) and default mode networks (DMN), have however been demonstrated mainly under task-conditions. It remains unclear whether such network shifts also occur in the absence of ongoing task-demands, and most critically, whether these network shifts are predictive of individual variation in the magnitude of cortisol stress-responses. In a sample of 335 healthy participants, we investigated stress-induced functional connectivity changes (delta-FC) of the SN, CEN and DMN, using resting-state fMRI data acquired before and after a socially evaluated cold-pressor test and a mental arithmetic task. To investigate which network changes are associated with acute stress, we evaluated the association between cortisol increase and delta-FC of each network. Stress-induced cortisol increase was associated with increased connectivity within the SN, but with decreased coupling of DMN at both local (within network) and global (synchronization with brain regions also outside the network) levels. These findings indicate that acute stress prompts immediate connectivity changes in large-scale resting-state networks, including the SN and DMN in the absence of explicit ongoing task-demands. Most interestingly, this brain reorganization is coupled with individuals' cortisol stress-responsiveness. These results suggest that the observed stress-induced network reorganization might function as a neural mechanism determining individual stress reactivity and, therefore, it could serve as a promising marker for future studies on stress resilience and vulnerability., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The Forkhead Box G1 (FOXG1) gene encodes a transcription factor with an essential role in mammalian telencephalon development. FOXG1-related disorders, caused by deletions, intragenic mutations or duplications, are usually associated with severe intellectual disability, autistic features, and, in 87% of subjects, epileptiform manifestations. In a subset of patients with FoxG1 mutations, seizures remain intractable, prompting the need for novel therapeutic options. To address this issue, we took advantage of a haploinsufficient animal model, the FoxG1 +/- mouse. In vivo electrophysiological analyses of FoxG1 +/- mice detected hippocampal hyperexcitability, which turned into overt seizures upon delivery of the proconvulsant kainic acid, as confirmed by behavioral observations. These alterations were associated with decreased expression of the chloride transporter KCC2. Next, we tested whether a triheptanoin-based anaplerotic diet could have an impact on the pathological phenotype of FoxG1 +/- mice. This manipulation abated altered neural activity and normalized enhanced susceptibility to proconvulsant-induced seizures, in addition to rescuing altered expression of KCC2 and increasing the levels of the GABA transporter vGAT. In conclusion, our data show that FoxG1 haploinsufficiency causes dysfunction of hippocampal circuits and increases the susceptibility to a proconvulsant insult, and that these alterations are rescued by triheptanoin dietary treatment., (Copyright © 2019. Published by Elsevier Ltd.)

Chronic obstructive pulmonary disease, a disease of increasing incidence, is related mainly to smoking. Although symptoms only appear at adulthood, the disease can develop from early life events. For example, bronchopulmonary dysplasia, which occurs in preterm infants, is characterized by airspace enlargement and could lead to late lung consequences. Once the lesions are established, no curative treatment is available. Stimulating lung regeneration from endogenous stem cells is therefore an exciting research domain, particularly through the activation of the mesenchymal contingent located in the lung stem cell niche., (Copyright © 2019. Published by Elsevier Masson SAS.)

Cellular parabiosis is tissue-based phenotypic suppression of cellular dysfunction by intercellular molecular traffic keeping initiated age-related diseases and conditions in long latency. Interruption of cellular parabiosis (e.g. by chronic inflammation) promotes the onset of initiated pathologies. The stability of initiated latent cancers and other age-related diseases (ARD) hints to phenotypically silent genome alterations. I propose that latency in the onset of ageing and ARD is largely due to phenotypic suppression of cellular dysfunctions via molecular traffic among neighbouring cells. Intercellular trafficking ranges from the transfer of ions and metabolites (via gap junctions) to entire organelles (via tunnelling nanotubes). Any mechanism of cell-to-cell communication resulting in functional cross-complementation among the cells is called cellular parabiosis. Such 'cellular solidarity' creates tissue homeostasis by buffering defects and averaging cellular functions within the tissues. Chronic inflammation is known to (i) interrupt cellular parabiosis by the activity of extracellular proteases, (ii) activate dormant pathologies and (iii) shorten disease latency, as in tumour promotion and inflammaging. Variation in cellular parabiosis and protein oxidation can account for interspecies correlations between body mass, ARD latency and longevity. Now, prevention of ARD onset by phenotypic suppression, and healing by phenotypic reversion, become conceivable.

Ageing is considered as a snowballing phenotype of the accumulation of damaged dysfunctional or toxic proteins and silent mutations (polymorphisms) that sensitize relevant proteins to oxidative damage as inborn predispositions to age-related diseases. Ageing is not a disease, but it causes (or shares common cause with) age-related diseases as suggested by similar slopes of age-related increase in the incidence of diseases and death. Studies of robust and more standard species revealed that dysfunctional oxidatively damaged proteins are the root cause of radiation-induced morbidity and mortality. Oxidized proteins accumulate with age and cause reversible ageing-like phenotypes with some irreversible consequences (e.g. mutations). Here, we observe in yeast that aggregation rate of damaged proteins follows the Gompertz law of mortality and review arguments for a causal relationship between oxidative protein damage, ageing and disease. Aerobes evolved proteomes remarkably resistant to oxidative damage, but imperfectly folded proteins become sensitive to oxidation. We show that α-synuclein mutations that predispose to early-onset Parkinson's disease bestow an increased intrinsic sensitivity of α-synuclein to in vitro oxidation. Considering how initially silent protein polymorphism becomes phenotypic while causing age-related diseases and how protein damage leads to genome alterations inspires a vision of predictive diagnostic, prognostic, prevention and treatment of degenerative diseases.

Extracellular proteolysis initiated by the binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) regulates the development of inhibitory neuronal circuits in the cerebral cortex and tissue remodeling after epileptogenic brain injury. To study the function of different components of the uPA-uPAR system on behavior and epileptogenesis, and to complement our previous studies on naïve and injured mice deficient in the uPA-encoding gene Plau or the uPAR-encoding gene Plaur, we analyzed the behavioral phenotype, seizure susceptibility, and perineuronal nets surrounding parvalbumin-positive inhibitory interneurons in Plau and Plaur (double knockout dKO) mice. In a climbing test, dKO mice showed reduced interest towards the environment as compared with Wt mice (p < 0.01). In a social approach test, however, dKO mice spent more time than Wt mice exploring the compartment containing a stranger mouse than the empty compartment (p < 0.05). Moreover, in a social interaction test, dKO mice exhibited increased contact time (p < 0.01). Compared with Wt mice, the dKO mice also had a longer single contact duration (p < 0.001) with the stranger mouse. In the elevated plus-maze, grooming, and marble burying tests, the anxiety level of dKO mice did not differ from that of Wt mice. Rearing time in an exploratory activity test, and spatial learning and memory in the Morris swim navigation task were also comparable between dKO and Wt mice. In the pentylenetetrazol (PTZ) seizure-susceptibility test, dKO mice had a shorter latency to the first epileptiform spike (p = 0.0001) and a greater total number of spikes (p < 0.001) than Wt mice. The dKO genotype did not affect the number of cortical perineuronal nets. Our findings indicate that Plau/Plaur-deficiency leads to a more social phenotype toward other mice with diminished interest in the surrounding environment, and increased seizure susceptibility., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Since the circadian system seems to modulate stress responses, this study aimed to evaluate if the combination of circadian strain and stress amplifies changes expected from each factor alone. Control Balb/c mice (12:12-NS) kept in standard 12:12 light:dark cycles (LD) and submitted to no stress procedures (NS) were compared to groups submitted to shortened LD (10:10-NS), chronic mild stress (CMS) but no circadian strain (12:12-CMS), or shortened LD followed by CMS (10:10-CMS). Rest-activity/temperature rhythms and body weight were assessed throughout the experiments. In Experiment 1 mice were submitted to 3 weeks of CMS; in Experiment 2 sucrose preference and light-dark tests were performed. Also, blood samples were collected at the end of Experiment 2 to assess metabolic parameters. Relative amplitude of temperature after CMS was increased only in the 10:10-CMS group, while body weight change was reduced during CMS regardless of LD intervention. During the CMS, the relative amplitude of temperature was negatively correlated with body weight gain. No differences in behavior and metabolic parameters were seen among groups. Identifying suitable research designs to investigate our hypothesis that circadian disturbances may increase vulnerability to stress-induced depression and anxiety is warranted., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Reduced reward responsiveness (RR) may contribute to depression vulnerability. At the neurophysiological level, RR is reliably and validly assessed using the reward positivity (RewP) event-related potential component. We previously identified a blunted RewP in 9-year-old children at high risk for depression due to maternal depression, but the role of RR in pathways from parental history to the development of depressive symptoms has not been examined., Methods: At age 9, never-depressed children (N = 369) completed a task in which RewP was measured in response to monetary reward and loss feedback. Parental history of depression was assessed using semistructured interviews, and children reported on their depressive symptoms. At age 12, youth depressive symptoms were reassessed, along with a self-report measure of RR. We tested RR as a moderator of the effects of parental depression on depressive symptoms at age 12, using both neurophysiological and self-report measures and controlling for age 9 symptoms., Results: Main effects of RR and interactions with maternal depression were significant. Maternal depression predicted greater depressive symptoms in youth with blunted and average RewP but was not a significant predictor in youth with an enhanced RewP. A similar pattern was observed for self-reported RR. The two measures of RR were not correlated with each other and accounted for unique variance in symptoms. Interactions between RR and paternal depression were not significant., Conclusions: Reduced RR, as measured by neurophysiology and self-report, moderates the effects of maternal depression on depressive symptoms in offspring. Assessment of RR along with risk factors such as parental depression may aid in identifying children at greatest risk and enhancing RR could be a potential target for prevention. Results highlight the utility of multimethod approaches for advancing understanding of depression risk., (© 2018 Association for Child and Adolescent Mental Health.)

Non-communicable diseases (NCDs) are a major problem as they are the leading cause of death and represent a substantial economic cost. The 'Developmental Origins of Health and Disease Hypothesis' proposes that adverse stimuli at different life stages can increase the predisposition to these diseases. In fact, adverse in utero programming is a major origin of these diseases due to the high malleability of embryonic development. This review provides a comprehensive analysis of the scientific literature on in utero programming and NCDs highlighting potential medical strategies to prevent these diseases based upon this programming. We fully address the concept and mechanisms involved in this programming (anatomical disruptions, epigenetic modifications and microbiota alterations). We also examine the negative role of in utero programming on the increased predisposition of NCDs in the offspring, which introduces the passive medical approach that consists of avoiding adverse stimuli including an unhealthy diet and environmental chemicals. Finally, we extensively discuss active medical approaches that target the causes of NCDs and have the potential to significantly and rapidly reduce the incidence of NCDs. These approaches can be classified as direct in utero programming modifications and personalized lifestyle pregnancy programs; they could potentially provide transgenerational NCDs protection. Active strategies against NCDs constitute a promising tool for the reduction in NCDs.

Background and Objectives: Trigger warnings notify people of the distress that written, audiovisual, or other material may evoke, and were initially used to provide for the needs of those with posttraumatic stress disorder (PTSD). Since their inception, trigger warnings have become more widely applied throughout contemporary culture, sparking intense controversy in academia and beyond. Some argue that they empower vulnerable individuals by allowing them to psychologically prepare for or avoid disturbing content, whereas others argue that such warnings undermine resilience to stress and increase vulnerability to psychopathology while constraining academic freedom. The objective of our experiment was to investigate the psychological effects of issuing trigger warnings., Methods: We randomly assigned online participants to receive (n = 133) or not receive (n = 137) trigger warnings prior to reading literary passages that varied in potentially disturbing content., Results: Participants in the trigger warning group believed themselves and people in general to be more emotionally vulnerable if they were to experience trauma. Participants receiving warnings reported greater anxiety in response to reading potentially distressing passages, but only if they believed that words can cause harm. Warnings did not affect participants' implicit self-identification as vulnerable, or subsequent anxiety response to less distressing content., Limitations: The sample included only non-traumatized participants; the observed effects may differ for a traumatized population., Conclusions: Trigger warnings may inadvertently undermine some aspects of emotional resilience. Further research is needed on the generalizability of our findings, especially to collegiate populations and to those with trauma histories., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Cognitive and emotional functions are supported by the coordinated activity of a distributed network of brain regions. This coordinated activity may be disrupted by psychosocial stress, resulting in the dysfunction of cognitive and emotional processes. Graph theory is a mathematical approach to assess coordinated brain activity that can estimate the efficiency of information flow and determine the centrality of brain regions within a larger distributed neural network. However, limited research has applied graph-theory techniques to the study of stress. Advancing our understanding of the impact stress has on global brain networks may provide new insight into factors that influence individual differences in stress susceptibility. Therefore, the present study examined the brain connectivity of participants that completed the Montreal Imaging Stress Task (Goodman et al., 2016; Wheelock et al., 2016). Salivary cortisol, heart rate, skin conductance response, and self-reported stress served as indices of stress, and trait anxiety served as an index of participant's disposition toward negative affectivity. Psychosocial stress was associated with a decrease in the efficiency of the flow of information within the brain. Further, the centrality of brain regions that mediate emotion regulation processes (i.e., hippocampus, ventral prefrontal cortex, and cingulate cortex) decreased during stress exposure. Interestingly, individual differences in cortisol reactivity were negatively correlated with the efficiency of information flow within this network, whereas cortisol reactivity was positively correlated with the centrality of the amygdala within the network. These findings suggest that stress reduces the efficiency of information transfer and leaves the function of brain regions that regulate the stress response vulnerable to disruption. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Purpose of Review: This review offers a perspective of the utility of rodent models of stress for identifying sources of individual vulnerability to depression and cardiovascular disease comorbidity., Recent Findings: Differential stress susceptibility is found in rodents exposed to repeated social defeat as a function of their coping style. Specifically, passive coping rodents show an increase in inflammatory processes within the brain that favour the development of depressive-like symptoms and cardiovascular abnormalities. Similarly, only a sub-group of rats develops depressive-like symptoms following chronic mild stress exposure. Cardiovascular changes differ depending on individual stress susceptibility and may be related to an imbalance in the autonomic regulation of cardiac function in stress vulnerable subjects. Rodent models of stress that take into account individual phenotypic variations are useful for a better understanding of the role of neuroinflammatory and autonomic processes in the development of comorbid depression and cardiovascular disease under stressful conditions.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and causes up to 200,000 infant deaths a year worldwide. The average rate of hospitalization for severe RSV infection is 5 per 1000 children, and the rate is three-times higher in those with congenital heart disease (CHD). Palivizumab, a monoclonal antibody, reduces hospitalization rates and intensive care admissions. It is used prophylactically and is administered as monthly doses during the RSV season. Hemodynamically unstable CHD is the most susceptible CHD to a severe episode of RSV infection. This review explores current evidence surrounding therapies, patterns of infection and identifies groups which may still be vulnerable to severe RSV infection.

Background: Rheumatoid arthritis (RA) patients may suffer cardiovascular (CV) events much more than the general population, and CV disease is the leading cause of death in patients with RA. Our hypothesis was that impaired function of endothelial progenitor cells may contribute to endothelial dysfunction and the clinical CV events of patients with RA., Methods: About 27 RA patients (9 males and 18 females) with an active disease and 13 healthy subjects who served as the control group (nine males and four females) were enrolled to this prospective study. The ability to grow in culture colony-forming units of endothelial progenitor cells (CFU-EPCs) was measured, as well as their endothelial function using high-resolution ultrasonography of the brachial artery, and levels of C reactive protein (CRP) in the serum. For statistical analysis, we used the Student's t-test., Results: As a group, patients with RA were older (P < 0.0001), had severe endothelial dysfunction (P<0.0001), with impaired ability to grow CFU-EPCs (P<0.0001), and a higher inflammatory state (P = 0001). No difference was observed in BMI. All RA patients had an active disease (DAS28 3.9 ± 0.9) for 9.2 ± 6.5 years. The same differences were observed in both genders., Conclusions: Patients with RA had an impaired ability to grow EPCs and severe endothelial dysfunction. Inability to grow colonies of EPCs reflects the impaired regenerative capacity of patients with RA and may explain the endothelial dysfunction and the high CV event rate among patients with RA., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Pneumonia is a complex pulmonary disease in need of new clinical approaches. Although triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune resistance and tissue resilience then dictate whether and how pneumonia progresses or resolves. Inadequate or inappropriate host responses lead to more severe outcomes such as acute respiratory distress syndrome and to organ dysfunction beyond the lungs and over extended time frames after pathogen clearance, some of which increase the risk for subsequent pneumonia. Improved understanding of such host responses will guide the development of novel approaches for preventing and curing pneumonia and for mitigating the subsequent pulmonary and extrapulmonary complications of pneumonia. The NHLBI assembled a working group of extramural investigators to prioritize avenues of host-directed pneumonia research that should yield novel approaches for interrupting the cycle of unhealthy decline caused by pneumonia. This report summarizes the working group's specific recommendations in the areas of pneumonia susceptibility, host response, and consequences. Overarching goals include the development of more host-focused clinical approaches for preventing and treating pneumonia, the generation of predictive tools (for pneumonia occurrence, severity, and outcome), and the elucidation of mechanisms mediating immune resistance and tissue resilience in the lung. Specific areas of research are highlighted as especially promising for making advances against pneumonia.

Background and Objectives: Diminished heart rate variability has been found to be associated with high anxiety symptomatology. Since adolescence is the period of onset for many anxiety disorders, this study aimed to determine sex- and anxiety-related differences in heart rate variability and complexity in adolescents., Methods: We created four groups according to sex and anxiety symptomatology: high-anxiety girls (n = 24) and boys (n = 25), and low-anxiety girls (n = 22) and boys (n = 24) and recorded their cardiac function while they performed regular school activities. A series of two-way (sex and anxiety) MANOVAs were performed on time domain variability, frequency domain variability, and non-linear complexity., Results: We obtained no multivariate interaction effects between sex and anxiety, but highly anxious participants had lower heart rate variability than the low-anxiety group. Regarding sex, girls showed lower heart rate variability and complexity than boys., Conclusions: The results suggest that adolescent girls have a less flexible cardiac system that could be a marker of the girls' vulnerability to developing anxiety disorders.