Genetics, epigenetics, and neurobiology of childhood-onset depression: an umbrella review.

Depression is a serious and persistent psychiatric disorder that commonly first manifests during childhood. Depression that starts in childhood is increasing in frequency, likely due both to evolutionary trends and to increased recognition of the disorder. In this umbrella review, we systematically searched the extant literature for genetic, epigenetic, and neurobiological factors that contribute to a childhood onset of depression. We searched PubMed, EMBASE, OVID/PsychInfo, and Google Scholar with the following inclusion criteria: (1) systematic review or meta-analysis from a peer-reviewed journal; (2) inclusion of a measure assessing early age of onset of depression; and (3) assessment of neurobiological, genetic, environmental, and epigenetic predictors of early onset depression. Findings from 89 systematic reviews of moderate to high quality suggest that childhood-onset depressive disorders have neurobiological, genetic, environmental, and epigenetic roots consistent with a diathesis-stress theory of depression. This review identified key putative markers that may be targeted for personalized clinical decision-making and provide important insights concerning candidate mechanisms that might underpin the early onset of depression.

Impact of Vision Impairment and Ocular Morbidity and Their Treatment on Quality of Life in Children: A Systematic Review.

TOPIC: This review summarizes existing evidence of the impact of vision impairment and ocular morbidity and their treatment on children's quality of life (QoL). CLINICAL RELEVANCE: Myopia and strabismus are associated with reduced QoL among children. Surgical treatment of strabismus significantly improves affected children's QoL. METHODS: We conducted a systematic review and meta-analysis by screening articles in any language in 9 databases published from inception through August 22, 2022, addressing the impact of vision impairment, ocular morbidity, and their treatment on QoL in children. We reported pooled standardized mean differences (SMDs) using random-effects meta-analysis models. Quality appraisal was performed using Joanna Briggs Institute and National Institutes of Health tools. This study was registered with the International Prospective Register of Systematic Reviews (identifier, CRD42021233323). RESULTS: Our search identified 29 118 articles, 44 studies (0.15%) of which were included for analysis that included 32 318 participants from 14 countries between 2005 and 2022. Seventeen observational and 4 interventional studies concerned vision impairment, whereas 10 observational and 13 interventional studies described strabismus and other ocular morbidities. Twenty-one studies were included in the meta-analysis. The QoL scores did not differ between children with and without vision impairment (SMD, -1.04; 95% confidence interval [CI], -2.11 to 0.03; P = 0.06; 9 studies). Myopic children demonstrated significantly lower QoL scores than those with normal vision (SMD, -0.60; 95% CI, -1.09 to -0.11; P = 0.02; 7 studies). Children with strabismus showed a significantly lower QoL score compared with those without (SMD, -1.19; 95% CI, -1.66 to -0.73; P < 0.001; 7 studies). Strabismus surgery significantly improved QoL in children (SMD, 1.36; 95% CI, 0.48-2.23; P < 0.001; 7 studies). No randomized controlled trials (RCTs) concerning refractive error and QoL were identified. Among all included studies, 35 (79.5%) were scored as low to moderate quality; the remaining met all quality appraisal tools criteria. DISCUSSION: Reduced QoL was identified in children with myopia and strabismus. Surgical correction of strabismus improves the QoL of affected children, which supports insurance coverage of strabismus surgery. Further studies, especially RCTs, investigating the impact of correction of myopia on QoL are needed. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Consensus Paper: Cerebellum and Reward.

Cerebellum is a key-structure for the modulation of motor, cognitive, social and affective functions, contributing to automatic behaviours through interactions with the cerebral cortex, basal ganglia and spinal cord. The predictive mechanisms used by the cerebellum cover not only sensorimotor functions but also reward-related tasks. Cerebellar circuits appear to encode temporal difference error and reward prediction error. From a chemical standpoint, cerebellar catecholamines modulate the rate of cerebellar-based cognitive learning, and mediate cerebellar contributions during complex behaviours. Reward processing and its associated emotions are tuned by the cerebellum which operates as a controller of adaptive homeostatic processes based on interoceptive and exteroceptive inputs. Lobules VI-VII/areas of the vermis are candidate regions for the cortico-subcortical signaling pathways associated with loss aversion and reward sensitivity, together with other nodes of the limbic circuitry. There is growing evidence that the cerebellum works as a hub of regional dysconnectivity across all mood states and that mental disorders involve the cerebellar circuitry, including mood and addiction disorders, and impaired eating behaviors where the cerebellum might be involved in longer time scales of prediction as compared to motor operations. Cerebellar patients exhibit aberrant social behaviour, showing aberrant impulsivity/compulsivity. The cerebellum is a master-piece of reward mechanisms, together with the striatum, ventral tegmental area (VTA) and prefrontal cortex (PFC). Critically, studies on reward processing reinforce our view that a fundamental role of the cerebellum is to construct internal models, perform predictions on the impact of future behaviour and compare what is predicted and what actually occurs.

Aberrant brain network topology in youth with a familial risk for bipolar disorder: a task-based fMRI connectome study.

BACKGROUND: Youth with a family history of bipolar disorder (BD) may be at increased risk for mood disorders and for developing side effects after antidepressant exposure. The neurobiological basis of these risks remains poorly understood. We aimed to identify biomarkers underlying risk by characterizing abnormalities in the brain connectome of symptomatic youth at familial risk for BD. METHODS: Depressed and/or anxious youth (n = 119, age = 14.9 ± 1.6 years) with a family history of BD but no prior antidepressant exposure and typically developing controls (n = 57, age = 14.8 ± 1.7 years) received functional magnetic resonance imaging (fMRI) during an emotional continuous performance task. A generalized psychophysiological interaction (gPPI) analysis was performed to compare their brain connectome patterns, followed by machine learning of topological metrics. RESULTS: High-risk youth showed weaker connectivity patterns that were mainly located in the default mode network (DMN) (network weight = 50.1%) relative to controls, and connectivity patterns derived from the visual network (VN) constituted the largest proportion of aberrant stronger pairs (network weight = 54.9%). Global local efficiency (Elocal , p = .022) and clustering coefficient (Cp , p = .029) and nodal metrics of the right superior frontal gyrus (SFG) (Elocal : p < .001; Cp : p = .001) in the high-risk group were significantly higher than those in healthy subjects, and similar patterns were also found in the left insula (degree: p = .004; betweenness: p = .005; age-by-group interaction, p = .038) and right hippocampus (degree: p = .003; betweenness: p = .003). The case-control classifier achieved a cross-validation accuracy of 78.4%. CONCLUSIONS: Our findings of abnormal connectome organization in the DMN and VN may advance mechanistic understanding of risk for BD. Neuroimaging biomarkers of increased network segregation in the SFG and altered topological centrality in the insula and hippocampus in broader limbic systems may be used to target interventions tailored to mitigate the underlying risk of brain abnormalities in these at-risk youth.

Self-assembly of choline-based surface-active ionic liquids and concentration-dependent enhancement in the enzymatic activity of cellulase in aqueous medium.

The micellization of choline-based anionic surface-active ionic liquids (SAILs) having lauroyl sarcosinate [Sar]-, dodecylsulfate [DS]-, and deoxycholate [Doc]- as counter-ions was investigated in an aqueous medium. Density functional theory (DFT) was employed to investigate the net interactional energy (Enet), extent of non-covalent interactions, and band gap of the choline-based SAILs. The critical micelle concentration (cmc) along with various parameters related to the surface adsorption, counter-ion binding (ß), and polarity of the cores of the micelles were deduced employing surface tension measurements, conductometric titrations and fluorescence spectroscopy, respectively. A dynamic light scattering (DLS) system equipped with zeta-potential measurement set-up and small-angle neutron scattering (SANS) were used to predict the size, zeta-potential, and morphology, respectively, of the formed micelles. Thermodynamic parameters such as standard Gibb's free energy and standard enthalpy change of micellization were calculated using isothermal titration calorimetry (ITC). Upon comparing with sodium salt analogues, it was established that the micellization was predominantly governed by the extent of hydration of [Cho]+, the head groups of the respective anions, and the degree of counter-ion binding (ß). Considering the concentration dependence of the enzyme-SAIL interactions, aqueous solutions of the synthesized SAILs at two different concentrations (below and above the cmc) were utilized as the medium for testing the enzymatic activity of cellulase. The activity of cellulase was found to be ∼7- to ∼13-fold higher compared to that observed in buffers in monomeric solutions of the SAILs and followed the order: [Cho][Sar] > [Cho][DS] > [Cho][Doc]. In the micellar solution, a ∼4- to 5-fold increase in enzymatic activity was observed.

High risk and low prevalence diseases: Cavernous sinus thrombosis.

INTRODUCTION: Cavernous sinus thrombosis (CST) is a serious condition that carries with it a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of CST, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: CST is a potentially deadly thrombophlebitic disease involving the cavernous sinuses. The most common underlying etiology is sinusitis or other facial infection several days prior to development of CST, though other causes include maxillofacial trauma or surgery, thrombophilia, dehydration, or medications. Staphylococcus aureus, streptococcal species, oral anaerobic species, and gram-negative bacilli are the most frequent bacterial etiologies. The most prevalent presenting signs and symptoms are fever, headache, and ocular manifestations (chemosis, periorbital edema, ptosis, ophthalmoplegia, vision changes). Cranial nerve (CN) VI is the most commonly affected CN, resulting in lateral rectus palsy. Other CNs that may be affected include III, IV, and V. The disease may also affect the pulmonary and central nervous systems. Laboratory testing typically reveals elevated inflammatory markers, and blood cultures are positive in up to 70% of cases. Computed tomography of the head and orbits with intravenous contrast delayed phase imaging is recommended in the ED setting, though magnetic resonance venography demonstrates the highest sensitivity. Management includes resuscitation, antibiotics, and anticoagulation with specialist consultation. CONCLUSION: An understanding of CST can assist emergency clinicians in diagnosing and managing this potentially deadly disease.

Future Directions: The Phenomenology of Irritable Mood and Outbursts: Hang Together or Hang Separately1.

Recognition of the importance of irritable mood and outbursts has been increasing over the past several decades. This "Future Directions" aims to develop a set of recommendations for future research emphasizing that irritable mood and outbursts "hang together," but have important distinctions and thus also need to "hang separately." Outbursts that are the outcome of irritable mood may be quite different from outbursts that are the trigger or driving force that make youth and his/her environment miserable. What, then, is the relation between irritable mood and outbursts? As the field currently stands, we not only cannot answer this question, but we may also lack the tools to effectively do so. Here, we will propose recommendations for understanding the phenomenology of irritable mood and outbursts so that more directed and clinically useful assessment tools can be designed. We discuss the transdiagnostic and treatment implications that relate to improvements in measurement. We describe the need to do more than repurpose our current assessment tools, specifically interviews and rating scales, which were designed for different purposes. The future directions of the study and treatment of irritable mood and outbursts will require, among others, using universally accepted nomenclature, supporting the development of tools to measure the characteristics of each irritable mood and outbursts, understanding the effects of question order, informant, development and longitudinal course, and studying the ways in which outbursts and irritable mood respond to treatment.

Comparative evaluation of self-pressurized Air-Q® and Proseal™ LMA® in patients undergoing elective surgery under general anaesthesia: A randomized clinical trial.

Background and Aims: Intra-cuff pressure of Air-Q self-pressurized laryngeal airways (Air-Q SP) balances airway pressure and adapts to patient's pharyngeal and periglottic structures, thus improves oropharyngeal leak pressure (OLP).This study was performed to compare efficacy of Air-Q SP with Proseal laryngeal mask airway (PLMA) in patients undergoing elective surgery. Material and Methods: The study design was prospective, randomized and controlled. Ninety patients were randomly assigned to Air-Q SP or PLMA group. All patients were premedicated and shifted to operation theatre. Monitoring was instituted. After securing IV-line, induction with inj. Morphine + Propofol, relaxation with inj. Vecuronium was done. Supraglottic was inserted according to group allocation. Outcome measures were OLP, fibreoptic view of larynx, success rate, device insertion parameters, haemodynamic and respiratory parameters and post-operative laryngopharyngeal complications. Neostigmine + glycopyrrolate were given, device was extubated. Results: All supraglottic airway devices (SADs) were successfully placed in two attempts. The mean initial OLP, OLP at 10 minutes, and device insertion time were significantly lower in Air-Q SP group. Fiber-optic laryngeal view grading was significantly better with Air-Q SP. No significant difference was observed with respect to rate of successful insertion in first attempt, ease of insertion, and manipulations required. The hemodynamic/respiratory parameters and post-operative sore throat in the two both groups were similar. Conclusions: Proseal LMA has a higher OLP than Air-Q SP but average insertion time was better, and fiber-optic grading of laryngeal view was shorter with Air-Q SP. However, Air-Q SP and Proseal LMA were both effective for lung ventilation.

Water Induced Alterations in Self-Assembly of a Bio-Surfactant in Deep Eutectic Solvent for Enhanced Enzyme Activity.

Deep eutectic solvents (DESs) meet important requirements for green solvent technology, including non-toxicity, biodegradability, sustainability, and affordability. Despite possessing low cohesive energy density than water, DESs have been found to support the self-assembly of amphiphiles. It is very much pertinent to examine the effect of water on self-assembly of surfactants in DESs as the presence of water alters the inherent structure of DES, which is expected to affect the characteristic properties of self-assembly. Following this, we have investigated the self-assembly of amino-acid based surfactant, Sodium N-lauroyl sarcosinate (SLS), in DES-water mixtures (10, 30 and 50 w/w% of water) and explored the catalytic activity of Cytochrome-c (Cyt-c) in the formed colloidal systems. Investigations using surface tension, fluorescence, dynamic light scattering (DLS), and isothermal titration calorimetry (ITC) have shown that DES-water mixtures promote the aggregation of SLS, resulting in the lower critical aggregation concentration (cac ∼1.5-6-fold) of the surfactant as compared to water. The nanoclustering of DES at low water content and it's complete de-structuring at high water content affects the self-assembly in a contrasting manner governed by different set of interactions. Further, Cyt-c dispersed in DES-water colloidal solutions demonstrated 5-fold higher peroxidase activity than that observed in phosphate buffer.

Mixed Aggregates of Surface-Active Ionic Liquids and 14-2-14 Gemini Surfactants in an Aqueous Medium as Fluid Scaffolds for Enzymology of Cytochrome-c.

The aggregation behavior of the surface-active ionic liquid (SAIL), 3-(2-(hexadecyloxy)-2-oxoethyl)-1-methyl-1H-imidazol-3-ium chloride, [C16Emim][Cl], and a gemini surfactant (GS) (14-2-14) in the whole mole fraction range has been investigated in an aqueous medium employing various techniques. Experimentally obtained values of critical aggregation concentration (cac) are in good agreement with the theoretical cac values obtained using Clint's equation. Rubingh's model has been employed to evaluate the extent of synergistic interactions between two components, which has been found to be dependent upon the composition of a mixture of surfactants. The polarity index, hydrodynamic diameter (Dh), zeta potential (ζ-Pot.), and morphology of the aggregates have been found to be dependent upon the extent of hydrophobic as well as dipolar interactions and the degree of counterion binding governed by the content of the GS in mixed aggregates. Thermodynamic parameters evaluated employing isothermal titration calorimetry have revealed the aggregation as an entropy-driven process. Density functional theory calculations provide a detailed account of the SAIL-GS interactions at the molecular level. The reduced density gradient (RDG) along with the calculated isosurfaces asserts that the dominant interactions are noncovalent interactions. Furthermore, the enzymology of cytochrome-c in the aqueous SAIL-GS aggregated systems has been investigated and a two-fold increase in the enzyme activity has been observed in the aggregates formed by the GS as compared to that in buffer.

Largely Entangled Diamondoid Framework with High-Density Urea and Divergent Metal Nodes for Selective Scavenging of CO2 and Molecular Dimension-Mediated Size-Exclusive H-Bond Donor Catalysis.

Pore environment modulation with high-density polarizing groups in metal-organic frameworks (MOFs) can effectively accomplish selective and multicyclic carbon dioxide (CO2) adsorption, whereas the incorporation of task-specific organic sites inside these porous vessels promise to evade self-quenching, solubility, and recyclability issues in hydrogen-bond donating (HBD) catalysis. However, concurrent amalgamation of both these attributes over a single platform is rare but extremely demanding in view of sustainable applications. We designed a robust diamondoid framework CSMCRI-17 (CSMCRI = Central Salt and Marine Chemicals Research Institute) from the mixed-ligand assembly of azo group-containing dicarboxylate ligand, urea-functionalized pyridyl linker, and Zn(II) nodes with specific divergent coordination. Seven-fold interpenetration to the microporous structure largely augments N-rich functionality that facilitates high CO2 uptake in the activated form (17a) with good CO2 selectivity over N2 and CH4 that outperform many reported materials. The framework displays very strong CO2 affinity and no reduction in adsorption capacity over multiple uptake-release cycles. Benefitting from the pore-wall decoration with urea functionality from the pillaring strut, 17a further demonstrates hydrogen-bond-mediated Friedel-Crafts alkylation of indole with ß-nitrostyrene under mild conditions, with multicyclic usability and excellent reactivity toward wide ranges of substituted nucleophiles and electrophiles. Interestingly, interpenetration-generated optimum-sized pores induce poor conversion to sterically encumbered substrate via molecular dimension-mediated size selectivity that is alternatively ascribed from additional control experiments and support the occurrence of HBD reaction within the MOF cavity. The catalytic path is detailed in light of the change of emission intensity of the framework by the electrophile as well as the judicious choice of the substrate, which authenticates the prime role of urea moiety-governed two-point hydrogen bonding.

Self-regulation of the posterior cingulate cortex with real-time fMRI neurofeedback augmented mindfulness training in healthy adolescents: A nonrandomized feasibility study.

Mindfulness training (MT) promotes the development of one's ability to observe and attend to internal and external experiences with objectivity and nonjudgment with evidence to improve psychological well-being. Real-time functional MRI neurofeedback (rtfMRI-nf) is a noninvasive method of modulating activity of a brain region or circuit. The posterior cingulate cortex (PCC) has been hypothesized to be an important hub instantiating a mindful state. This nonrandomized, single-arm study examined the feasibility and tolerability of training typically developing adolescents to self-regulate the posterior cingulate cortex (PCC) using rtfMRI-nf during MT. Thirty-four adolescents (mean age: 15 years; 14 females) completed the neurofeedback augmented mindfulness training task, including Focus-on-Breath (MT), Describe (self-referential thinking), and Rest conditions, across three neurofeedback and two non-neurofeedback runs (Observe, Transfer). Self-report assessments demonstrated the feasibility and tolerability of the task. Neurofeedback runs differed significantly from non-neurofeedback runs for the Focus-on-Breath versus Describe contrast, characterized by decreased activity in the PCC during the Focus-on-Breath condition (z = -2.38 to -6.27). MT neurofeedback neural representation further involved the medial prefrontal cortex, anterior cingulate cortex, dorsolateral prefrontal cortex, posterior insula, hippocampus, and amygdala. State awareness of physical sensations increased following rtfMRI-nf and was maintained at 1-week follow-up (Cohens' d = 0.69). Findings demonstrate feasibility and tolerability of rtfMRI-nf in healthy adolescents, replicates the role of PCC in MT, and demonstrate a potential neuromodulatory mechanism to leverage and streamline the learning of mindfulness practice. ( ClinicalTrials.gov identifier #NCT04053582; August 12, 2019).

Impact of Vision Impairment and Ocular Morbidity and Their Treatment on Depression and Anxiety in Children: A Systematic Review.

TOPIC: This systematic review and meta-analysis summarizes existing evidence to establish whether vision impairment, ocular morbidity, and their treatment are associated with depression and anxiety in children. CLINICAL RELEVANCE: Understanding and quantifying these associations support early detection and management of mental health symptoms in children with vision impairment and ocular morbidity. Additionally, this review provides evidence in favor of insurance coverage for timely strabismus surgery. METHODS: We searched 9 electronic databases from inception through February 18, 2021, including observational and interventional studies assessing whether vision impairment, ocular morbidity, or both and their treatment are associated with depression, anxiety, or both in children. We used narrative synthesis and meta-analysis with the residual maximum likelihood method. A protocol was registered and published on The International Prospective Register of Systematic Reviews (identifier: CRD42021233323). RESULTS: Among 28 992 studies, 28 956 studies (99.9%) were excluded as duplicates or unrelated content. Among 36 remaining studies, 21 studies (58.3%) were observational studies concerning vision impairment, 8 studies (22.2%) were observational studies concerning strabismus, and 7 studies (19.4%) were interventional studies. Vision impaired children demonstrated significantly higher scores of depression (standard mean difference [SMD], 0.57; 95% confidence interval [CI], 0.26-0.89; 11 studies) and anxiety (SMD, 0.62; 95% CI, 0.40-0.83; 14 studies) than normally sighted children. In particular, children with myopia demonstrated higher scores of depression (SMD, 0.58; 95% CI, 0.36-0.81; 6 studies) than normally sighted children. Strabismus surgery significantly improved symptoms of depression (SMD, 0.59; 95% CI, 0.12-1.06; 3 studies) and anxiety (SMD, 0.69; 95% CI, 0.25-1.14; 4 studies) in children. CONCLUSION: Among children, vision impairment is associated with greater symptoms of depression and anxiety. Surgical treatment of strabismus improved these symptoms. Further randomized controlled trials exploring the impact of public health measures for myopia correction on mental health in children are needed. Scaling up access to strabismus surgery could improve the mental health of affected children.

Selective and Multicyclic CO2 Adsorption with Visible Light-Driven Photodegradation of Organic Dyes in a Robust Metal-Organic Framework Embracing Heteroatom-Affixed Pores.

Pore environment modulation with polarizing groups is one of the essential prerequisites for selective carbon dioxide (CO2) adsorption in metal-organic frameworks (MOFs), wherein judicious installation of the photocatalytic feature can promise visible light-triggered degradation of toxic organic dye molecules. However, astute amalgamation of both these attributes over a single MOF is rather rare, yet much anticipated in view of sustainable applications. Pore engineering is effectively harnessed in a Zn(II)-based three-dimensional (3D) MOF, CSMCRI-16 (CSMCRI = Central Salt and Marine Chemicals Research Institute), through mixed-ligand assembly of a N-rich linker (L), 4,4'-oxybis(benzoic acid) (H2oba) ligand, and [Zn2(CO2)4N2] paddle-wheel secondary building units (SBUs). The noninterpenetrated structure contains unbound nitrogen and accessible oxygen atom-decorated porous channels and exhibits admirable stability in diverse organic solvents, open air, and at elevated temperatures. The heteroatom-decorated porous channels facilitated excellent CO2 uptake in the activated MOF (16a) with high selectivity over N2 (CO2/N2: 155.3) at 273 K. The framework further exhibits reasonable CO2 affinity and multicyclic CO2 sorption recurrence without a significant loss in the uptake capacity. Benefitting from the presence of the [Zn2(CO2)4N2] cluster in conjugation with π-conjugated organic ligands, the extended 3D network revealed an optical band gap energy of 2.55 eV, which makes the MOF an efficient photocatalyst toward the degradation of the cationic dyes crystal violet (CV) and methylene blue (MB) in the presence of a simple 40 W visible light lamp without any assistance of external oxidants. The catalyst exhibits multicyclic performance and short reaction time in addition to the fact that catalytic efficiencies (CV: 97.2%, MB: 97.8%) are comparable to those of contemporary materials.

Parenting centers and caregiver mental health: Evidence from a large-scale randomized controlled trial in China.

This study conducts an exploratory analysis of the impacts of a center-based early childhood development intervention on the mental health of caregivers, using data from a cluster-randomized controlled trial of 1664 caregivers (Mage  = 36.87 years old) of 6- to 24-month-old children in 100 villages in rural China. Caregivers and children in 50 villages received individual parenting training, group activities and open play space in village parenting centers. The results show no significant overall change in caregiver-reported mental health symptoms after 1 year of intervention. Subgroup analyses reveal heterogeneous effects by caregiver socioeconomic status and identity (mother vs. grandmother). Findings suggest that early childhood development interventions without targeted mental health components may not provide sufficient support to improve caregiver mental health.

Prefrontal cortex and amygdala anatomy in youth with persistent levels of harsh parenting practices and subclinical anxiety symptoms over time during childhood.

Childhood adversity and anxiety have been associated with increased risk for internalizing disorders later in life and with a range of brain structural abnormalities. However, few studies have examined the link between harsh parenting practices and brain anatomy, outside of severe maltreatment or psychopathology. Moreover, to our knowledge, there has been no research on parenting and subclinical anxiety symptoms which remain persistent over time during childhood (i.e., between 2.5 and 9 years old). Here, we examined data in 94 youth, divided into four cells based on their levels of coercive parenting (high / low) and of anxiety (high / low) between 2.5 and 9 years old. Anatomical images were analyzed using voxel-based morphometry (VBM) and FreeSurfer. Smaller gray matter volumes in the prefrontal cortex regions and in the amygdala were observed in youth with high versus low levels of harsh parenting over time. In addition, we observed significant interaction effects between parenting practices and subclinical anxiety symptoms in rostral anterior cingulate cortical thickness and in amygdala volume. These youth should be followed further in time to identify which youth will or will not go on to develop an anxiety disorder, and to understand factors associated with the development of sustained anxiety psychopathology.

Broad white matter impairment in multiple system atrophy.

Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by the widespread aberrant accumulation of α-synuclein (α-syn). MSA differs from other synucleinopathies such as Parkinson's disease (PD) in that α-syn accumulates primarily in oligodendrocytes, the only source of white matter myelination in the brain. Previous MSA imaging studies have uncovered focal differences in white matter. Here, we sought to build on this work by taking a global perspective on whole brain white matter. In order to do this, in vivo structural imaging and diffusion magnetic resonance imaging were acquired on 26 MSA patients, 26 healthy controls, and 23 PD patients. A refined whole brain approach encompassing the major fiber tracts and the superficial white matter located at the boundary of the cortical mantle was applied. The primary observation was that MSA but not PD patients had whole brain deep and superficial white matter diffusivity abnormalities (p < .001). In addition, in MSA patients, these abnormalities were associated with motor (Unified MSA Rating Scale, Part II) and cognitive functions (Mini-Mental State Examination). The pervasive whole brain abnormalities we observe suggest that there is widespread white matter damage in MSA patients which mirrors the widespread aggregation of α-syn in oligodendrocytes. Importantly, whole brain white matter abnormalities were associated with clinical symptoms, suggesting that white matter impairment may be more central to MSA than previously thought.

Spontaneous Fibrillation of Bovine Serum Albumin at Physiological Temperatures Promoted by Hydrolysis-Prone Ionic Liquids.

This study highlights the role of time-dependent hydrolysis of ionic liquid anion, [BF4]-, of ionic liquid (IL), 1-ethyl-3-methylimidazolium tetrafluoroborate, [C2mim][BF4], which results in ever-changing pH conditions. Such pH changes along with the ionic interactions bring conformational changes in bovine serum albumin (BSA), leading to the formation of amyloid fibers at 37 °C without external control of pH or addition of electrolyte. The fibrillation of BSA occurs spontaneously with the addition of IL; however, the highest growth rate has been observed in aqueous solution of 10% IL (v/v %) among investigated systems. Thioflavin T (ThT) fluorescence emission has been employed to monitor the growth and development of ß-sheet content in amyloid fibrils. The structural alterations in BSA have also been investigated using intrinsic fluorescence measurements. Circular dichroism (CD) measurements confirmed the formation of amyloid fibrils. Transmission electron microscopy (TEM) has been explored to establish the morphologies of BSA fibrils at different intervals of time, whereas atomic force microscopy (AFM) has established the helically twisted nature of grown amyloid fibrils. The docking studies have been utilized to understand the insertion of IL ions in different domains of BSA, which along with decreased pH cause the unfolding and growth of BSA into amyloid fibrils. It is expected that the results obtained from this study would help to understand the impact of IL containing [BF4]- anion on protein stability and aggregation along with providing a new platform to control the formation of amyloid fibrils and other biomaterials driven via ionic interactions and alterations in pH.

Neural changes in youth at high risk for bipolar disorder undergoing family-focused therapy or psychoeducation.

BACKGROUND: Patients with mood disorders may benefit from psychosocial interventions through changes in brain networks underlying emotion processing. In this study, we used functional magnetic resonance imaging (fMRI) to investigate treatment-related changes in emotion processing networks in youth at familial high risk for bipolar disorder (BD). METHODS: Youth, ages 9-17, were randomly assigned to family-focused therapy for high-risk youth (FFT-HR) or an active comparison treatment, Enhanced Care (EC). Before and after these 4-month treatments, participants underwent fMRI while viewing happy, fearful, and calm facial expressions. Twenty youth in FFT-HR and 20 in EC were included in analyses of pre- to post-treatment changes in activation across the whole brain. Significant clusters were assessed for correlation with mood symptom improvement. RESULTS: In the dorsolateral prefrontal cortex (DLPFC), activation increased from pre- to post-treatment in the FFT-HR group and decreased in the EC group. Insula activation decreased in the FFT-HR group and did not change in the EC group. Across both treatments, decreasing activation in the hippocampus and amygdala was correlated with pre- to post-treatment improvement in hypomania, while increasing activation in the DLPFC was correlated with pre- to post-treatment improvement in depression. DISCUSSION: Psychosocial treatment addresses abnormalities in emotion regulation networks in youth at high risk for BD. Increased prefrontal cortex activation suggests enhanced emotion regulation from pre- to post-treatment with FFT-HR. Improvements in family interactions may facilitate the development of prefrontal resources that provide protection against future mood episodes.

Biamphiphilic ionic liquid based aqueous microemulsions as an efficient catalytic medium for cytochrome c.

Considering the remarkable applicability of ionic liquids (ILs) in bio-catalysis involving enzymes, herein, we report new IL based aqueous microemulsions as a catalytic reactor for cytochrome c (Cyt-c). Microemulsions (µEs), comprising water as the polar component, imidazolium (cation) and dioctylsulfosuccinate (AOT) (anion) based biamphiphilic ionic liquid (BAIL) as the surfactant and a hydrophobic ionic liquid (HIL) as the non-polar component have been prepared and characterized. The use of BAIL has promoted the formation of µEs without any co-surfactant, owing to its higher surface activity. The effect of ester- or amide-functionalization of the alkyl chain of the imidazolium cation of BAILs on the phase behavior of µEs has been investigated. The prepared µEs have been characterized via conductivity, dynamic light scattering (DLS), UV-vis absorption and steady-state fluorescence (using external polarity probes) techniques. The prepared µEs have been employed as nano-reactors for exploring the catalytic activity of Cyt-c. The formed BAIL-water nano-interfaces in reverse µEs have exerted a positive effect on the catalytic activity of Cyt-c stored in a water pool of reverse µEs. A five-fold higher rate constant in µEs as compared to buffer establishes µEs as a better catalytic medium. Furthermore, the differing nature of nano-interfaces created by BAILs and water in reverse µEs, depending on the functionalization of the alkyl chain of the cationic part of BAIL, has exerted varying influence on the catalytic activity of Cyt-c. It is expected that the present work will result in providing a versatile platform for the creation of new IL and water based µEs for bio-catalytic applications.