Anti-Tac(Fv)-PE40, a single chain antibody Pseudomonas fusion protein directed at interleukin 2 receptor bearing cells

Anti-Tac(Fv)-PE40 is a chimeric single chain immunotoxin in which anti-Tac variable heavy and light chains held together by a peptide linker are attached to PE40, a truncated form of Pseudomonas exotoxin. This molecule was shown to be extremely cytotoxic for interleukin 2 (IL2) receptor bearing cells in tissue culture (Chaudhary, V. K., Queen, C., Junghans, R. P., Waldmann, T. A., FitzGerald, D. J., and Pastan, I. (1989) Nature 339, 394-397). Here we describe various forms of anti-Tac(Fv)-PE40 protein in which the order of the variable domains of anti-Tac has been switched and also three different types of peptide linkers have been used. All these proteins were purified to near homogeneity and were found to have similar cytotoxic activities against various human cells expressing the p55 subunit of the IL2 receptor. Anti-Tac(Fv)-PE40 was also found to have a very potent suppressive activity against phytohemagglutinin-activated human lymphoblasts and in a human mixed lymphocyte reaction. Anti-Tac(Fv)-PE40 appeared in the blood rapidly in mice after intraperitoneal administration and could be detected in the blood for up to 8 h. Anti-Tac(Fv)-PE40 warrants evaluation as an anti-tumor and immunosuppressive agent in humans

The use of commitment techniques to support weight loss maintenance in obese adolescents

Objectives: Obesity is a rising problem in adolescents related to unhealthy behaviours. Commitment devises are one type of behavioural intervention that may help people change their behaviours. The current pilot trial tests whether commitment devices delivered via text message help adolescents maintain their recent weight loss. Methods: During a 12-week pilot trial adolescents who attended a weight loss camp were randomly assigned to either received text messages that contained only information, i.e., advice, about weight loss management (n=13) or asked for them to commit to following the same advise (n=14). Results: The BMI of the adolescents in the commitment group did not change. In contrast, the BMI of adolescents in the information group increased. A linear regression revealed that group was a significant predictor of BMI change. A logistic regression revealed that adolescents in the information group were nearly eight times more likely to regain weight than those in the commitment group. Conclusions: This is the first study with adolescents to show weight maintenance using a commitment device. The results suggest that commitment devices can help adolescents maintain their recent weight loss

Measuring perceived exercise capability and investigating its relationship with childhood obesity: a feasibility study.

BACKGROUND/OBJECTIVES: According to the COM-B ('Capability', 'Opportunity', 'Motivation' and 'Behaviour') model of behaviour, three factors are essential for behaviour to occur: capability, opportunity and motivation. Obese children are less likely to feel capable of exercising. The implementation of a new methodological approach to investigate the relationship between perceived exercise capability (PEC) and childhood obesity was conducted, which involved creating a new instrument, and demonstrating how it can be used to measure obesity intervention outcomes. SUBJECTS/METHODS: A questionnaire aiming to measure perceived exercise capability, opportunity and motivation was systematically constructed using the COM-B model and administered to 71 obese children (aged 9-17 years (12.24±0.2.01), body mass index (BMI) standard deviation scores (SDS) 2.80±0.660) at a weight-management camp in northern England. Scale validity and reliability was assessed. Relationships between PEC, as measured by the questionnaire, and BMI SDS were investigated for the children at the weight-management camp, and for 45 Spanish schoolchildren (aged 9-13 years, (10.52±1.23), BMI SDS 0.80±0.99). A pilot study, demonstrating how the questionnaire can be used to measure the effectiveness of an intervention aiming to bring about improved PEC for weight-management camp attendees, was conducted. No participants withdrew from these studies. RESULTS: The questionnaire domain (exercise capability, opportunity and motivation) composite scales were found to have adequate internal consistency (a=0.712-0.796) and construct validity (χ(2)/degrees of freedom=1.55, root mean square error of approximation=0.072, comparative fit index=0.92). Linear regression revealed that low PEC was associated with higher baseline BMI SDS for both UK (b=-0.289, P=0.010) and Spanish (b=-0.446, P=0.047) participants. Pilot study findings provide preliminary evidence for PEC improvements through intervention being achievable, and measurable using the questionnaire. CONCLUSIONS: Evidence is presented for reliability and validity of the questionnaire, and for feasibility of its use in the context of a childhood obesity intervention. Future research could investigate the link between PEC and childhood obesity further

Ideographic Modeling and Data Visualization of Sleep, Affect, and Psychotic Symptoms: A Case Example

Background: 1. Psychotic disorders are heterogeneous. 2. Current diagnostic categorizations are unable to capture individuals’ unique symptom experiences. 3. Newly-developed ideographic analyses and data visualization tools may be useful in assessing individuals’ symptom experiences and stimulating data informed care.https://knowledgeconnection.mainehealth.org/lambrew-retreat-2021/1019/thumbnail.jp

2-[3-(Methyl­diphenyl­silyl)prop­yl]isoindoline-1,3-dione

In the title compound, C24H23NO2Si, the dihedral angle between the planes of the phenyl rings attached to the Si atom is 80.78 (10)°. In the crystal, the mol­ecules form sheets lying perpendicular to [101] via C—H⋯O inter­actions. These sheets are stacked and linked in a three-dimensional framework by additional C—H⋯O inter­actions in the [10] direction

Extensive cardiac infiltration in acute T-cell lymphoblastic leukemia:occult extra-medullary relapse and remission after salvage chemotherapy

none5noneBaritussio, Anna; Gately, Amy; Pawade, Joya; Marks, David I.; Bucciarelli-Ducci, ChiaraBaritussio, Anna; Gately, Amy; Pawade, Joya; Marks, David I.; Bucciarelli-Ducci, Chiar

The characteristics of cognitive neuroscience tests in a schizophrenia cognition clinical trial: Psychometric properties and correlations with standard measures.

In comparison to batteries of standard neuropsychological tests, cognitive neuroscience tests may offer a more specific assessment of discrete neurobiological processes that may be aberrant in schizophrenia. However, more information regarding psychometric properties and correlations with standard neuropsychological tests and functional measures is warranted to establish their validity as treatment outcome measures. The N-back and AX-Continuous Performance Task (AX-CPT) are two promising cognitive neuroscience tests designed to measure specific components of working memory and contextual processing respectively. In the current study, we report the psychometric properties of multiple outcome measures from these two tests as well as their correlations with standard neuropsychological measures and functional capacity measures. The results suggest that while the AX-CPT and N-back display favorable psychometric properties, they do not exhibit greater sensitivity or specificity with functional measures than standard neurocognitive tests

2-{[(4-Methoxy­phen­yl)dimethyl­silyl]meth­yl}isoindoline-1,3-dione

In the course of our studies of silicon-containing anti­cancer compounds, the title compound, C18H19NO3Si, was synthesized. The mol­ecular geometry including bond distances and angles involving the Si atoms are typical. Torsion angles associated with the isoindoline ring and the silyl group [C—N—Cmethyl­ene—Si = 90.5 (2) and −93.1 (2)°] indicate that there is no inter­action between the O and Si atoms despite silicon’s high affinity for oxygen

Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds

Several genes have recently been identified as risk factors for schizophrenia (SZ) by genome-wide association studies (GWAS), including ZNF804A which is thought to function in transcriptional regulation. However, the downstream pathophysiological changes that these genes confer remain to be elucidated. In 143 subjects (68 clinical high risk, first episode or chronic cases; 75 controls), we examined the association between 21 genetic markers previously identified by SZ GWAS or associated with putative intermediate phenotypes of SZ against three event-related potential (ERP) measures: mismatch negativity (MMN), amplitude of P300 during an auditory oddball task, and P300 amplitude during an auditory novelty oddball task. Controlling for age and sex, significant genetic association surpassing Bonferroni correction was detected between ZNF804A marker rs1344706 and P300 amplitude elicited by novel sounds (beta=4.38, P=1.03 × 10−4), which is thought to index orienting of attention to unexpected, salient stimuli. Subsequent analyses revealed that the association was driven by the control subjects (beta=6.35, P=9.08 × 10−5), and that the risk allele was correlated with higher novel P300b amplitude, in contrast to the significantly lower amplitude observed in cases compared to controls. Novel P300b amplitude was significantly correlated with a neurocognitive measure of auditory attention under interference conditions, suggesting a relationship between novel P300b amplitude and higher-order attentional processes. Our results suggest pleiotropic effects of ZNF804A on risk for SZ and neural mechanisms that are indexed by the novel P300b ERP component

Heritability of neuropsychological measures in Schizophrenia and non-psychiatric populations: a systematic review and meta-analysis

Schizophrenia is characterized by neuropsychological deficits across many cognitive domains. Cognitive phenotypes with high heritability and genetic overlap with schizophrenia liability can help elucidate the mechanisms leading from genes to psychopathology. We performed a meta-analysis of 170 published twin and family heritability studies of >800 000 nonpsychiatric and schizophrenia subjects to accurately estimate heritability across many neuropsychological tests and cognitive domains. The proportion of total variance of each phenotype due to additive genetic effects (A), shared environment (C), and unshared environment and error (E), was calculated by averaging A, C, and E estimates across studies and weighting by sample size. Heritability ranged across phenotypes, likely due to differences in genetic and environmental effects, with the highest heritability for General Cognitive Ability (32%– 67%), Verbal Ability (43%–72%), Visuospatial Ability (20%–80%), and Attention/Processing Speed (28%–74%), while the lowest heritability was observed for Executive Function (20%–40%). These results confirm that many cognitive phenotypes are under strong genetic influences. Heritability estimates were comparable in nonpsychiatric and schizophrenia samples, suggesting that environmental factors and illness-related moderators (eg, medication) do not substantially decrease heritability in schizophrenia samples, and that genetic studies in schizophrenia samples are informative for elucidating the genetic basis of cognitive deficits. Substantial genetic overlap between cognitive phenotypes and schizophrenia liability (average rg = −.58) in twin studies supports partially shared genetic etiology. It will be important to conduct comparative studies in well-powered samples to determine whether the same or different genes and genetic variants influence cognition in schizophrenia patients and the general population