Altered intrinsic functional connectivity of the cingulate cortex in children with severe temper outbursts

Severe temper outbursts (STO) in children are associated with impaired school and family functioning and may contribute to negative outcomes. These outbursts can be conceptualized as excessive frustration responses reflecting reduced emotion regulation capacity. The anterior cingulate cortex (ACC) has been implicated in negative affect as well as emotional control, and exhibits disrupted function in children with elevated irritability and outbursts. This study examined the intrinsic functional connectivity (iFC) of a region of the ACC, the anterior midcingulate cortex (aMCC), in 5- to 9-year-old children with STO (n = 20), comparing them to children with attention-deficit/hyperactivity disorder (ADHD) without outbursts (ADHD; n = 18). Additional analyses compared results to a sample of healthy children (HC; n = 18) and examined specific associations with behavioral and emotional dysregulation. Compared to the ADHD group, STO children exhibited reduced iFC between the aMCC and surrounding regions of the ACC, and increased iFC between the aMCC and precuneus. These differences were also seen between the STO and HC groups; ADHD and HC groups did not differ. Specificity analyses found associations between aMCC-ACC connectivity and hyperactivity, and between aMCC-precuneus iFC and emotion dysregulation. Disruption in aMCC networks may underlie the behavioral and emotional dysregulation characteristic of children with STO

Nonthermal Hard X-ray Emission and Iron Kalpha Emission from a Superflare on II Pegasi

We report on an X-ray flare detected on the active binary system II~Pegasi with the Swift telescope. The trigger had a 10-200 keV luminosity of 2.2$\times10^{32}$ erg s$^{-1}$-- a superflare, by comparison with energies of typical stellar flares on active binary systems. The trigger spectrum indicates a hot thermal plasma with T$\sim$180 $\times10^{6}$K. X-ray spectral analysis from 0.8--200 keV with the X-Ray Telescope and BAT in the next two orbits reveals evidence for a thermal component (T$>$80 $\times10^{6}$K) and Fe K 6.4 keV emission. A tail of emission out to 200 keV can be fit with either an extremely high temperature thermal plasma (T$\sim3\times10^{8}$K) or power-law emission. Based on analogies with solar flares, we attribute the excess continuum emission to nonthermal thick-target bremsstrahlung emission from a population of accelerated electrons. We estimate the radiated energy from 0.01--200 keV to be $\sim6\times10^{36}$ erg, the total radiated energy over all wavelengths $\sim10^{38}$ erg, the energy in nonthermal electrons above 20 keV $\sim3\times10^{40}$ erg, and conducted energy $<5\times10^{43}$ erg. The nonthermal interpretation gives a reasonable value for the total energy in electrons $>$ 20 keV when compared to the upper and lower bounds on the thermal energy content of the flare. This marks the first occasion in which evidence exists for nonthermal hard X-ray emission from a stellar flare. We investigate the emission mechanism responsible for producing the 6.4 keV feature, and find that collisional ionization from nonthermal electrons appears to be more plausible than the photoionization mechanism usually invoked on the Sun and pre-main sequence stars.Comment: 41 pages, 7 figures, accepted for publication in the Astrophysical Journa

Mapping cortical activations underlying covert and overt language production using high-density diffuse optical tomography

Gold standard neuroimaging modalities such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and more recently electrocorticography (ECoG) have provided profound insights regarding the neural mechanisms underlying the processing of language, but they are limited in applications involving naturalistic language production especially in developing brains, during face-to-face dialogues, or as a brain-computer interface. High-density diffuse optical tomography (HD-DOT) provides high-fidelity mapping of human brain function with comparable spatial resolution to that of fMRI but in a silent and open scanning environment similar to real-life social scenarios. Therefore, HD-DOT has potential to be used in naturalistic settings where other neuroimaging modalities are limited. While HD-DOT has been previously validated against fMRI for mapping the neural correlates underlying language comprehension and covert (i.e., silent ) language production, HD-DOT has not yet been established for mapping the cortical responses to overt (i.e., out loud ) language production. In this study, we assessed the brain regions supporting a simple hierarchy of language tasks: silent reading of single words, covert production of verbs, and overt production of verbs in normal hearing right-handed native English speakers (n = 33). First, we found that HD-DOT brain mapping is resilient to movement associated with overt speaking. Second, we observed that HD-DOT is sensitive to key activations and deactivations in brain function underlying the perception and naturalistic production of language. Specifically, statistically significant results were observed that show recruitment of regions in occipital, temporal, motor, and prefrontal cortices across all three tasks after performing stringent cluster-extent based thresholding. Our findings lay the foundation for future HD-DOT studies of imaging naturalistic language comprehension and production during real-life social interactions and for broader applications such as presurgical language assessment and brain-machine interfaces

Amygdala and Nucleus Accumbens Activation to Emotional Facial Expressions in Children and Adolescents at Risk for Major Depression

Objective. Offspring of parents with major depressive disorder (MDD) face three-fold higher risk for MDD than offspring without a family history. Although MDD is a major cause of morbidity and mortality, neural correlates of risk for MDD remain poorly understood. This study compares amygdala and nucleus accumbens activation in children and adolescents at high and low risk for MDD under varying attentional and emotional conditions. Methods. Thirty-nine juveniles, 17 offspring of parents with MDD (high-risk group) and 22 offspring of parents without histories of MDD, anxiety or psychotic disorders (low-risk group) completed a functional magnetic resonance imaging study. During imaging, subjects viewed faces that varied in intensity of emotional expressions across blocks of trials; while attention was unconstrained (passive viewing), and constrained (rate nose width on face; rate subjective fear while viewing face). Results. When attention was unconstrained, high-risk, relative to low-risk, subjects showed greater amygdala and nucleus accumbens (NAcc) activation to fearful faces, and lower NAcc activation to happy faces (p values \u3c .05, small volume corrected for the amygdala and NAcc). No group differences emerged in amygdala or NAcc activation during constrained attention. Exploratory analysis showed that constraining attention was associated with greater medial prefrontal cortex activation in the high-risk than low-risk group. Conclusions. Amygdala and NAcc responses to affective stimuli may reflect vulnerability for MDD. Constraining attention may normalize emotion-related neural function, possibly via engagement of the medial prefrontal cortex; face-viewing with unconstrained attention may engage aberrant processes associated with risk for MDD

The role of lumbar puncture in children with suspected central nervous system infection

BACKGROUND: The use of the lumbar puncture in the diagnosis of central nervous system infection in acutely ill children is controversial. Recommendations have been published but it is unclear whether they are being followed. METHODS: The medical case notes of 415 acute medical admissions in a children's hospital were examined to identify children with suspected central nervous system infection and suspected meningococcal septicaemia. We determined whether lumbar punctures were indicated or contraindicated, whether they had been performed, and whether the results contributed to the patients' management. RESULTS: Fifty-two children with suspected central nervous system infections, and 43 with suspected meningococcal septicaemia were identified. No lumbar punctures were performed in patients with contraindications, but only 25 (53%) of 47 children with suspected central nervous system infection and no contraindications received a lumbar puncture. Lumbar puncture findings contributed to the management in 18 (72%) of these patients, by identifying a causative organism or excluding bacterial meningitis. CONCLUSION: The recommendations for undertaking lumbar punctures in children with suspected central nervous system infection are not being followed because many children that should receive lumbar punctures are not getting them. When they are performed, lumbar puncture findings make a useful contribution to the patients' management

Highlights from the 3rd international HIV/viral hepatitis Co-infection meeting - HIV/viral hepatitis: improving diagnosis, antiviral therapy and access

The International AIDS Society convened the 3rd International HIV/Viral Hepatitis Co-Infection Meeting on 17 July 2016 as part of the pre-conference program preceding the 21st International AIDS Conference held in Durban, South Africa. The meeting brought together a diversity of scientific, technical and community interests to discuss opportunities and challenges for increased prevention, diagnosis and treatment of viral hepatitis in people living with HIV, particularly in low- and middle-income settings. The objectives of the meeting were: i. To review the latest therapeutic developments in viral hepatitis; ii. To identify challenges such as high cost of medications for hepatitis C virus (HCV) and risk of developing viral resistance, and successes, such as the provision of HCV treatment in community-based settings, movements to reduce drug costs and increasing access, in relation to scaling up diagnosis, screening, antiviral treatment and prevention of viral hepatitis; iii. To advance the agenda for elimination of viral hepatitis as a public health problem. Discussions centred around the six key interventions outlined by the World Health Organization Global Health Sector Strategy on Viral Hepatitis 2016–2021: hepatitis B virus (HBV) vaccination (including birth dose); safe injection practices plus safe blood; harm reduction among people who inject drugs; safer sex practices; hepatitis B treatment; and hepatitis C cure. This article summarizes the main issues and findings discussed during the pre-conference meeting. One of the recommendations from the meeting delegates is universal implementation of birth dose vaccination for HBV without further delay to prevent mother-to-child transmission of infection. There is also the need to implement screening and treatment of hepatitis among pregnant women. A call was made for concerted efforts to be put together by all stakeholders towards addressing some of the structural barriers, including criminalization of drug use, discrimination and stigma that people living with viral hepatitis face. Finally, the need for greater advocacy was highlighted to enable access to therapy of viral hepatitis at lower cost than currently prevails. Implementation of these resolutions will help in achieving the target of eliminating viral hepatitis as a public health threat

Impairments in psychological functioning in refugees and asylum seekers

© 2024 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Refugees are at increased risk for developing psychological impairments due to stressors in the pre-, peri- and post-migration periods. There is limited knowledge on how everyday functioning is affected by migration experience. In a secondary analysis of a study in a sample of refugees and asylum seekers, it was examined how aspects of psychological functioning were differentially affected. 1,101 eligible refugees and asylum seekers in Europe and Türkiye were included in a cross-sectional analysis. Gender, age, education, number of relatives and children living nearby, as well as indicators for depressive and posttraumatic symptoms, quality of life, psychological well-being and functioning, and lifetime potentially traumatic events were assessed. Correlations and multiple regression models with World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) 12-item version’s total and six subdomains’ scores (‘mobility’, ‘life activities’, ‘cognition’, ‘participation’, ‘self-care’, ‘getting along’) as dependent variables were calculated. Tests for multicollinearity and Bonferroni correction were applied. Participants reported highest levels of impairment in ‘mobility’ and ‘participation’, followed by ‘life activities’ and ‘cognition’. Depression and posttraumatic symptoms were independently associated with overall psychological functioning and all subdomains. History of violence and abuse seemed to predict higher impairment in ‘participation’, while past events of being close to death were associated with fewer issues with ‘self-care’. Impairment in psychological functioning in asylum seekers and refugees was related to current psychological symptoms. Mobility and participation issues may explain difficulties arising after resettlement in integration and exchange with host communities in new contexts.Peer reviewe

Association of Coding Variants in Hydroxysteroid 17-beta Dehydrogenase 14 (HSD17B14) with Reduced Progression to End Stage Kidney Disease in Type 1 Diabetes

Background Rare variants ingenecodingregions likely have agreater impactondisease-relatedphenotypes than common variants through disruption of their encoded protein. We searched for rare variants associated with onset of ESKD in individuals with type 1 diabetes at advanced kidney disease stage. Methods Gene-basedexome array analyses of15,449genes infivelarge incidence cohortsof individualswith type 1diabetes andproteinuriawere analyzedfor survival time toESKD, testing the top gene in a sixth cohort (n52372/1115 events all cohorts) and replicating in two retrospective case-control studies (n51072 cases, 752 controls). Deep resequencing of the top associated gene in five cohorts confirmed the findings. We performed immunohistochemistry and gene expression experiments in human control and diseased cells, and in mouse ischemia reperfusion and aristolochic acid nephropathy models. Results Protein coding variants in the hydroxysteroid 17- b dehydrogenase 14 gene (HSD17B14), predicted to affect protein structure, had a net protective effect against development of ESKD at exome-wide significance (n54196; P value53.331027). The HSD17B14 gene and encoded enzyme were robustly expressed in healthy human kidney, maximally in proximal tubular cells. Paradoxically, gene and protein expression were attenuated in human diabetic proximal tubules and in mouse kidney injury models. Expressed HSD17B14 gene and protein levels remained low without recovery after 21 days in a murine ischemic reperfusion injury model. Decreased gene expression was found in other CKD-associated renal pathologies. Conclusions HSD17B14 gene ismechanistically involved in diabetic kidney disease. The encoded sex steroid enzyme is a druggable target, potentially opening a new avenue for therapeutic development.Peer reviewe

Exploring the Genetic Basis of Variation in Gene Predictions with a Synthetic Association Study

Identifying DNA polymorphisms that affect molecular processes like transcription, splicing, or translation typically requires genotyping and experimentally characterizing tissue from large numbers of individuals, which remains expensive and time consuming. Here we introduce an alternative strategy: a “synthetic association study” in which we computationally predict molecular phenotypes on artificial genomes containing randomly sampled combinations of polymorphic alleles, and perform a classical association study to identify genotypes underlying variation in these computationally predicted annotations. We applied this method to characterize the effects on gene structure of 32,792 single-nucleotide polymorphisms between two strains of the antibiotic producing fungus Penicilium chrysogenum. Although these SNPs represent only 0.1 percent of the nucleotides in the genome, they collectively altered 1.8 percent of predicted gene models between these strains. To determine which SNPs or combinations of SNPs were responsible for this variation, we predicted protein-coding genes in 500 intermediate genomes, each identical except for randomly chosen alleles at each SNP position. Of 30,468 gene models in the genome, 557 varied across these 500 genomes. 226 of these polymorphic gene models (40%) were perfectly correlated with individual SNPs, all of which were within or immediately proximal to the affected gene. The genetic architectures of the other 321 were more complex, with several examples of SNP epistasis that would have been difficult to predict a priori. We expect that many of the SNPs that affect computational gene structure reflect a biologically unrealistic sensitivity of the gene prediction algorithm to sequence changes, and we propose that genome annotation algorithms could be improved by minimizing their sensitivity to natural polymorphisms. However, many of the SNPs we identified are likely to affect transcript structure in vivo, and the synthetic association study approach can be easily generalized to any computed genome annotation to uncover relationships between genotype and important molecular phenotypes