Diminished differentiation of rewards in individuals at clinical high-risk for psychosis.

Reward processing is impaired in people with schizophrenia, which may begin in the clinical high-risk (CHR) for psychosis period. The Monetary Incentive Delay (MID) task has been important in understanding the neural correlates of reward processing deficits in various psychiatric disorders. Previous research has found that CHR individuals have an imprecise mental representation of rewards, which leads to a diminished differentiation between rewards, though this has not been observed behaviorally. A total of 19 CHR individuals and 20 controls were given a novel variant of the MID task, designed to examine how modulating reward context may impact responses to reward cues, a process often referred to as "adaptive coding." Both groups appeared to update their behavior in response to the rewards available in this adaptive task. However, when compared to controls who showed a more graded decrease in response time to increasing reward contexts, CHR individuals appeared to have a sharp decrease in response time in the low reward context that is nearly stable across higher reward contexts. This is largely driven by the exponential component of the response time distribution, which is often interpreted to be more cognitively or effortfully influenced. Response times are related to negative symptoms, but not positive symptoms, disorganized symptoms, or estimated intelligence. Although an adaptive coding effect was not observed, these results provide novel insight into the reward processing mechanisms and volitional processes in the CHR population, as this was the first study to observe the diminished differentiation of rewards behaviorally.

Testing whether implicit emotion regulation mediates the association between discrimination and symptoms of psychopathology in late childhood: An RDoC perspective.

Discrimination has been associated with adverse mental health outcomes, though it is unclear how early in life this association becomes apparent. Implicit emotion regulation, developing during childhood, is a foundational skill tied to a range of outcomes. Implicit emotion regulation has yet to be tested as an associated process for mental illness symptoms that can often emerge during this sensitive developmental period. Youth aged 9-11 were recruited for the Adolescent Brain Cognitive Development (ABCD) study. Associations between psychotic-like experiences, depressive symptoms, and total discrimination (due to race, ethnicity, nationality, weight, or sexual minority status) were tested, as well as associations with implicit emotion regulation measures (emotional updating working memory and inhibitory control). Analyses examined whether associations with symptoms were mediated by implicit emotion regulation. Discrimination related to decreased implicit emotion regulation performance, and increased endorsement of depressive symptoms and psychotic-like experiences. Emotional updating working memory performance partially mediated the association between discrimination and psychotic-like experiences, while emotional inhibitory control did not. Discrimination and implicit emotion regulation could serve as putative transdiagnostic markers of vulnerability. Results support the utility of using multiple units of analysis to improve understanding of complex emerging neurocognitive functions and developmentally sensitive periods.

The utility of an RDoC motor domain to understand psychomotor symptoms in depression.

Despite the clinical impact of motor symptoms such as agitation or retardation on the course of depression, these symptoms are poorly understood. Novel developments in the field of instrumentation and mobile devices allow for dimensional and continuous recording of motor behavior in various settings, particularly outside the laboratory. Likewise, the use of novel assessments enables to combine multimodal neuroimaging with behavioral measures in order to investigate the neural correlates of motor dysfunction in depression. The research domain criteria (RDoC) framework will soon include a motor domain that will provide a framework for studying motor dysfunction in mood disorders. In addition, new studies within this framework will allow investigators to study motor symptoms across different stages of depression as well as other psychiatric diagnoses. Finally, the introduction of the RDoC motor domain will help test how motor symptoms integrate with the original five RDoC domains (negative valence, positive valence, cognitive, social processes, and arousal/regulation).

Enhancement of bulk second-harmonic generation from silicon nitride films by material composition.

We present a comprehensive tensorial characterization of second-harmonic generation from silicon nitride films with varying compositions. The samples were fabricated using plasma-enhanced chemical vapor deposition, and the material composition was varied by the reactive gas mixture in the process. We found a six-fold enhancement between the lowest and highest second-order susceptibility, with the highest value of approximately 5 pm/V from the most silicon-rich sample. Moreover, the optical losses were found to be sufficiently small (below 6 dB/cm) for applications. The tensorial results show that all samples retain in-plane isotropy independent of the silicon content, highlighting the controllability of the fabrication process.

Reactivity to uncertain threat as a familial vulnerability factor for alcohol use disorder.

BACKGROUND: When sober, problematic drinkers display exaggerated reactivity to threats that are uncertain (U-threat). Since this aversive affective state can be alleviated via acute alcohol intoxication, it has been posited that individuals who exhibit heightened reactivity to U-threat at baseline are motivated to use alcohol as a means of avoidance-based coping, setting the stage for excessive drinking. To date, however, no study has attempted to characterize the dispositional nature of exaggerated reactivity to U-threat and test whether it is a vulnerability factor or exclusively a disease marker of problematic alcohol use. METHOD: The current investigation utilized a family study design to address these gaps by examining whether (1) reactivity to U-threat is associated with risk for problematic alcohol use, defined by family history of alcohol use disorder (AUD) and (2) reactivity to U-threat is correlated amongst adult biological siblings. A total of 157 families, and 458 individuals, participated in the study and two biological siblings completed a threat-of-shock task designed to probe reactivity to U-threat and predictable threat (P-threat). Startle potentiation was collected as an index of aversive responding. RESULTS: Within biological siblings, startle potentiation to U-threat [intraclass correlation (ICC) = 0.35] and P-threat (ICC = 0.63) was significantly correlated. In addition, independent of an individuals' own AUD status, startle potentiation to U-threat, but not P-threat, was positively associated with risk for AUD (i.e. AUD family history). CONCLUSION: This suggests that heightened reactivity to U-threat may be a familial vulnerability factor for problematic drinking and a novel prevention target for AUD.

Molecular epidemiology of Crimean-Congo haemorrhagic fever virus in India.

Crimean-Congo haemorrhagic fever (CCHF) is an emerging zoonotic disease in India which is prevalent in neighbouring countries. CCHF virus (CCHFV) is a widespread tick-borne virus which is endemic in Africa, Asia, Eastern Europe and the Middle East. In the present study, samples of clinically suspected human cases from different areas of northern-western India were tested for the presence of CCHFV by RT-PCR through amplification of nucleocapsid (N) gene of CCHFV. Positive samples were sequenced to reveal the prevailing CCHFV genotype(s) and phylogenetic relatedness. A phylogenetic tree revealed the emergence of diverse strains in the study region showing maximum identity with the Pakistan, Afghanistan and Iran strains, which was different from earlier reported Indian strains. Our findings reveal for the first time the emergence of the Asia 1 group in India; while earlier reported CCHFV strains belong to the Asia 2 group.

Orbitofrontal cortex volume and brain reward response in obesity.

BACKGROUND/OBJECTIVES: What drives overconsumption of food is poorly understood. Alterations in brain structure and function could contribute to increased food seeking. Recently, brain orbitofrontal cortex (OFC) volume has been implicated in dysregulated eating but little is known how brain structure relates to function. SUBJECTS/METHODS: We examined obese (n=18, age=28.7±8.3 years) and healthy control women (n=24, age=27.4±6.3 years) using a multimodal brain imaging approach. We applied magnetic resonance and diffusion tensor imaging to study brain gray and white matter volume as well as white matter (WM) integrity, and tested whether orbitofrontal cortex volume predicts brain reward circuitry activation in a taste reinforcement-learning paradigm that has been associated with dopamine function. RESULTS: Obese individuals displayed lower gray and associated white matter volumes (P<0.05 family-wise error (FWE)- small volume corrected) compared with controls in the orbitofrontal cortex, striatum and insula. White matter integrity was reduced in obese individuals in fiber tracts including the external capsule, corona radiata, sagittal stratum, and the uncinate, inferior fronto-occipital, and inferior longitudinal fasciculi. Gray matter volume of the gyrus rectus at the medial edge of the orbitofrontal cortex predicted functional taste reward-learning response in frontal cortex, insula, basal ganglia, amygdala, hypothalamus and anterior cingulate cortex in control but not obese individuals. CONCLUSIONS: This study indicates a strong association between medial orbitofrontal cortex volume and taste reinforcement-learning activation in the brain in control but not in obese women. Lower brain volumes in the orbitofrontal cortex and other brain regions associated with taste reward function as well as lower integrity of connecting pathways in obesity (OB) may support a more widespread disruption of reward pathways. The medial orbitofrontal cortex is an important structure in the termination of food intake and disturbances in this and related structures could contribute to overconsumption of food in obesity.

Updating the research domain criteria: the utility of a motor dimension.

Within the NIMH Research Domain Criteria (RDoC) framework, dimensions of behavior are investigated across diagnoses with the goal of developing a better understanding of their underlying neural substrates. Currently, this framework includes five domains: cognitive, social, arousal/regulatory, negative, and positive valence systems. We argue that the inclusion of a motor systems domain is sorely needed as well. Independent of medication, distinct areas of motor dysfunction (e.g. motor planning/inhibition/learning/coordination, involuntary movements) commonly appear across a number of mental disorders (e.g. schizophrenia, bipolar disorder, autism, attention deficit hyperactivity disorder, Alzheimer's disease, depression) as well as neurological disorders accompanied by significant psychological symptoms (e.g. Parkinson's disease). In addition, motor systems are amenable to study across multiple levels of analysis from the cellular molecular level focusing on cytoarchitechtonics and neurotransmitter systems, to networks and circuits measured using neuroimaging, and finally at the level of overt behavioral performance. Critically, the neural systems associated with motor performance have been relatively well defined, and different circuits have been linked to distinct aspects of motor behavior. As such, they may also be differentially associated with symptoms and motor dysfunction across diagnoses, and be uniquely informative about underlying etiology. Importantly, motor signs can change across stages of illness; they are also often present in the prodromal phases of disease and closely linked with course, suggesting that these behaviors represent a core feature reflective of pathogenic processes. The inclusion of a motor domain would allow researchers to better understand psychopathology more broadly, and may also reveal important contributions to disease processes across diagnoses.

Influence of calcium depletion on iron-binding properties of milk.

We investigated the effects of calcium depletion on the binding of iron in milk. A weakly acidic cation-exchange resin was used to remove 3 different levels (18-22, 50-55, and 68-72%) of calcium from milk. Five levels of iron (5, 10, 15, 20, and 25 mM) were added to each of these calcium-depleted milks (CDM) and the resultant milks were analyzed for particle size, microstructure, and the distribution of protein and minerals between the colloidal and soluble phases. The depletion of calcium affected the distribution of protein and minerals in normal milk. Iron added to normal milk and low-CDM (~20% calcium depletion) bound mainly to the colloidal phase (material sedimented at 100,000 × g for 1 h at 20 °C), with little effect on the integrity of the casein micelles. Depletion of ~70% of the calcium from milk resulted in almost complete disintegration of the casein micelles, as indicated by all the protein remaining in the soluble phase upon ultracentrifugation. Addition of up to ~20 mM iron to high CDM resulted in the formation of small fibrous structures that remained in the soluble phase of milk. It appeared that the iron bound to soluble (nonsedimentable) caseins in high-CDM. We observed a decrease in the aqueous phosphorus content of all milks upon iron addition, irrespective of their calcium content. We considered the interaction between aqueous phosphorus and added iron to be responsible for the high iron-binding capacity of the proteins in milk. The soluble protein-iron complexes formed in high-CDM (~70% calcium depletion) could be used as an effective iron fortificant for a range of food products because of their good solubility characteristics.

Thermotropic dynamic processes in multiphase polymer systems by (cryo-)AFM.

The structural (volume and enthalpy) relaxation of polymers during physical aging has a great relevance in materials science and engineering as it significantly changes the long-term material performance. In this article, we propose a methodological approach of (cryo-)atomic force microscopy (AFM) monitoring of macromolecular rearrangements which accompany structural relaxation within bulk of the polymer during physical aging. In contrast to conventional spectroscopic, scattering and thermal analysis techniques, high resolution topographical/phase imaging of the bulk cross-section over a large period of time and within a wide range of temperatures (-120 °C to +20 °C) yields unique information about the evolution of the polymer ultrastructure as a function of time and temperature in situ.

Spectrum of imaging findings on MDCT enterography in patients with small bowel tuberculosis.

Abdominal tuberculosis (TB) is the sixth most common extrapulmonary site of involvement. The sites of involvement in abdominal tuberculosis, in descending order of frequency, are lymph nodes, genitourinary tract, peritoneal cavity, and gastrointestinal tract. The radiological armamentarium for evaluating tuberculosis of the small bowel (SBTB) includes barium studies (small bowel follow-through, SBFT), CT (multidetector CT, CT enterography, and CT enteroclysis), ultrasound (sonoenteroclysis), and magnetic resonance imaging (MRI; enterography and enteroclysis). In this review, we illustrate the abnormalities at MDCT enterography in 20 consecutive patients with SB TB and also describe extraluminal findings in these patients. MDCT enterography allows non-invasive good-quality assessment of well-distended bowel loops and the adjacent soft tissues. It displays the thickness and enhancement of the entire bowel wall in all three planes and allows examination of all bowel loops, especially the ileal loops, which are mostly superimposed. The terminal ileum and ileocaecal junction are the most common sites of small bowel involvement in intestinal TB. The most common abnormality is short-segment strictures with symmetrical concentric mural thickening and homogeneous mural enhancement. Other findings include lymphadenopathy, ascites, enteroliths, peritoneal thickening, and enhancement. In conclusion, MDCT enterography is a comprehensive technique for the evaluation of SB TB.

Association of plasma proteins at multiple stages of glycation and antioxidant status with erythrocyte oxidative stress in patients with type 2 diabetes.

This study examines the individual stages of plasma protein glycation, antioxidant status and their association with erythrocyte oxidative stress in patients with type 2 diabetes mellitus (T2DM). Study was carried out on blood from 70 patients with T2DM and 40 healthy age- and gender-matched volunteers. Biomarkers of plasma protein glycation (fructosamine, protein carbonyls, advanced glycation end products [AGEs], amyloid), antioxidant status (thiols, total antioxidant capacity and erythrocyte oxidative parameters), osmotic fragility, lipid peroxidation (LPO), reduced glutathione (GSH) and catalase were determined. Plasma glycation markers were higher in T2DM patients than in healthy volunteers: fructosamine 578 vs. 525 micromol/mL; carbonyl 21.23 vs. 18.84 nmol/mg protein (P < or = 0.01); AGEs 213.94 vs. 178.27 AU/mg protein (P < or = 0. 05); and amyloid 0.53 vs. 0.40 A530 nm (P < 0.01). Plasma antioxidant status was significantly reduced in patients with diabetes compared to the healthy volunteers, with lower plasma protein thiols (1.16 vs. 1.36 nmol/mg protein; P < 0.01) and total antioxidant capacity (26 vs. 34 micromol; P < 0.01). Erythrocytes from the patient group were found to show greater oxidative damage, with elevated numbers of fragile cells and increased LPO, and reduced GSH level. Among the glycation markers, positive correlations were evident between fructosamine and amyloid (r = 0.350, P < 0.001) and AGEs and amyloid (r = 0.070). Plasma glycation markers showed negative correlation with plasma antioxidant status while positive correlation was demonstrated between erythrocytes fragility and AGEs and amyloid. Erythrocyte LPO levels correlated positively with amyloid. These data suggest that increased levels of multiple plasma protein glycation products in T2DM patients play a key role in reduced plasma antioxidant status and amplified erythrocyte oxidative damage.

Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse.

BACKGROUND: Bone marrow-derived endothelial progenitor cells (EPCs) are critical for metastatic progression. This study explores the effect of tetrathiomolybdate (TM), an anti-angiogenic copper chelator, on EPCs in patients at high risk for breast cancer recurrence. PATIENTS AND METHODS: This phase 2 study enrolled breast cancer patients with stage 3 and stage 4 without evidence of disease (NED), and stage 2 if triple-negative. TM 100 mg orally was administered to maintain ceruloplasmin <17 mg/dl for 2 years or until relapse. The primary end point was change in EPCs. RESULTS: Forty patients (28 stage 2/3, 12 stage 4 NED) were enrolled. Seventy-five percent patients achieved the copper depletion target by 1 month. Ninety-one percent of triple-negative patients copper-depleted compared with 41% luminal subtypes. In copper-depleted patients only, there was a significant reduction in EPCs/ml by 27 (P = 0.04). Six patients relapsed while on study, of which only one patient had EPCs maintained below baseline. The 10-month relapse-free survival was 85.0% (95% CI 74.6%-96.8%). Only grade 3/4 toxicity was hematologic: neutropenia (3.1% of cycles), febrile neutropenia (0.2%), and anemia (0.2%). CONCLUSIONS: TM is safe and appears to maintain EPCs below baseline in copper-depleted patients. TM may promote tumor dormancy and ultimately prevent relapse.

Effect of glottal dynamics in the production of shouted speech.

In this paper characteristics of speech produced at different loudness levels are analyzed in terms of changes in the glottal excitation. Four loudness levels are considered in this study, namely, soft, normal, loud, and shout. The distinct changes in the excitation of the shout signal are analyzed using electroglottograph signals. The open and closed phases of the glottal vibration are distinctly different for shout signals, in comparison with those for normal speech. It is generally difficult to derive the glottal pulse information from the speech signal due to limitations in inverse filtering. Hence, the effects of changes in the excitation are examined by analyzing the speech signal using methods that can capture the temporal variations of the spectral features. In particular, the recently proposed methods of zero-frequency filtering and zero-time liftering are used in this analysis. It is shown that the closed phase behavior of the excitation at different loudness levels can be seen in the temporal variation of spectral energy in the low frequency (LF) (<400 Hz) region. The ratio of the LF to high frequency energy clearly discriminates the speech produced at different loudness levels. These distinctions in the excitation features are also observed in different vowel contexts and across several speakers.

Dermatoglyphic asymmetries and fronto-striatal dysfunction in young adults reporting non-clinical psychosis.

OBJECTIVE: Growing evidence indicates that non-clinical psychotic-like experiences occur in otherwise healthy individuals, suggesting that psychosis may occur on a continuum. However, little is known about how the diathesis for formal psychosis maps on to individuals at the non-clinical side of this continuum. Our current understanding of the pathophysiology of schizophrenia implicates certain key factors such as early developmental abnormalities and fronto-striatal dysfunction. To date, no studies have examined these core factors in the context of non-clinical psychosis. METHOD: A total of 221 young adults were assessed for distressing attenuated positive symptoms (DAPS), dermatoglyphic asymmetries (a marker of early developmental insult), and procedural memory (a proxy for fronto-striatal function). RESULTS: Participants reporting DAPS (n = 16; 7.2%) and no-DAPS (n = 205; 92.7%) were split into two groups. The DAPS group showed significantly elevated depression, elevated dermatoglyphic asymmetries, and a pattern of procedural learning consistent with other studies with formally psychotic patients. CONCLUSION: The results indicate that the non-clinical side of the psychosis continuum also shares key vulnerability factors implicated in schizophrenia, suggesting that both early developmental disruption and abnormalities in fronto-striatal function are core aspects underlying the disorder.

The first dominant co-circulation of both dengue and chikungunya viruses during the post-monsoon period of 2010 in Delhi, India.

Independent outbreaks of dengue virus (DENV) infection and sporadic cases of chikungunya virus (CHIKV) have been recorded in the metropolitan city of Delhi on several occasions in the past. However, during a recent 2010 arboviral outbreak in Delhi many cases turned negative for DENV. This prompted us to use duplex reverse transcriptase-polymerase chain reaction (D-RT-PCR) to establish the aetiology of dengue/chikungunya through sequencing of CprM and E1 genes of dengue and chikungunya viruses. Interestingly, for the first time, both DENV and CHIKV co-circulated simultaneously and in equally dominant proportion during the post-monsoon period of 2010. DENV-1 genotype III and the East Central South African genotype of CHIKV were associated with post-monsoon spread of these viruses.

Regression equations for spirometry in children aged 6 to 17 years in Delhi region.

BACKGROUND: Most of the studies carried out in India to develop regression equations for spirometry in children are now several years-to-decades old and had used equipment and measurement protocols that have since changed. Prediction equations using the current standardisation protocols for spirometry are not available. The lung health of the population may have changed too. OBJECTIVE: To develop regression equations for spirometry for children aged 6 to 17 years of north Indian origin in Delhi region. METHODS: School children of north Indian origin, as determined by mother tongue and parentage, aged 6 to 17 years were screened by a health questionnaire and physical examination and those found "normal" underwent spirometry according to the standardised procedure recommended by the American Thoracic Society/European Respiratory Society (ATS/ERS) task force in 2005. Pearson's correlation analysis was carried out to identify the predictor variables for spirometric parameters. Prediction equations were developed using the multiple linear regression procedure. The independent variables were entered in sequence of height, age and weight. R2, adjusted R2 and R2 change, standard errors of the estimate (SEE), and estimates of regression coefficients were obtained and the goodness of fit was examined. RESULTS: Data was obtained in 365 boys and 305 girls. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) peak expiratory flow rate (PEFR), forced expiratory flow rate at 50% and 75% exhalation of vial capacity (F50 and F75) and mean forced expiratory flow rate over the middle 50% of the vital capacity (F25-75) showed moderate to strong correlations with age, height and weight in both boys and girls. In both genders, the equations explained very high variability of FVC, FEV1 and PEFR as shown by the R2 values. The explained variability for flow rates was lesser, with that for F75 being the least. CONCLUSIONS: Regression equations for spirometry variables for children of north Indian origin in Delhi region have been developed. These represent the first such effort from India after the publication of the ATS/ERS task force 2005 guidelines on standardisation of spirometry.

The Critical Roles of Early Development, Stress, and Environment in the Course of Psychosis.

Psychotic disorders are highly debilitating with poor prognoses and courses of chronic illness. In recent decades, conceptual models have shaped understanding, informed treatment, and guided research questions. However, these models have classically focused on the adolescent and early adulthood stages immediately preceding onset while conceptualizing early infancy through all of childhood as a unitary premorbid period. In addition, models have paid limited attention to differential effects of types of stress; contextual factors such as local, regional, and country-level characteristics or sociocultural contexts; and the timing of the stressor or environmental risk. This review discusses emerging research suggesting that (a) considering effects specific to neurodevelopmental stages prior to adolescence is highly informative, (b) understanding specific stressors and levels of environmental exposures (i.e., systemic or contextual features) is necessary, and (c) exploring the dynamic interplay between development, levels and types of stressors, and environments can shed new light, informing a specified neurodevelopmental and multifaceted diathesis-stress model.

Mechanism unravelling for highly efficient and selective 99TcO4 - sequestration utilising crown ether based solvent system from nuclear liquid waste: experimental and computational investigations.

Selective and efficient separation of pertechnetate (TcO4 -) from nuclear waste is desirable for the safe and secure management of radioactive waste. Here, we have projected dibenzo-18-crown-6 ether (DB18C6) in a highly polar nitrobenzene medium for enhancing the removal efficiency of 99Tc from reprocessing plant low level waste (LLW). An effort was made to determine the stoichiometry of metal-ligand complex by slope ratio method, revealing that one ligand (DB18C6) binds with one TcO4 - moiety. Optimum ligand concentration for 99Tc extraction was evaluated. Relevant interference of the anions was studied systematically. The effect of solution pH was analysed on the extraction efficiency of 99Tc. A kinetic study was carried out for maximum extraction of metal ions. A quantitative stripping study was also achieved for metal ions with a suitable stripping solution. After evaluation of all essential parameters, selectivity and feasibility studies were finally carried out with actual low level reprocessing plant waste to demonstrate a laboratory scale process for effective separation of TcO4 - ions. Density functional theory (DFT) calculations were carried out to understand the nature of the complexation of TcO4 - ion with DB18C6 in different solvents systems and to elucidate the key aspect behind ionic selectivity and enhanced the 99Tc extraction efficiency of DB18C6 in the studied diluent systems. The ΔE and ΔG values for different modeled complexation reactions were evaluated systematically. From the calculated free energy of complexation of TcO4 - with DB18C6, it was observed that the consideration of explicit solvent plays a vital role in predicting the experimental selectivity.