Understanding Social Situations (USS): A proof-of-concept social–cognitive intervention targeting theory of mind and attributional bias in individuals with psychosis.

In this proof-of-concept trial, we examined the feasibility and preliminary efficacy of Understanding Social Situations (USS), a new social cognitive intervention that targets higher-level social cognitive skills using methods common to neurocognitive remediation, including drill and practice and hierarchically structured training, which may compensate for the negative effects of cognitive impairment on learning

A randomised controlled trial comparing standard or intensive management of reduced fetal movements after 36 weeks gestation-a feasibility study

BACKGROUND: Women presenting with reduced fetal movements (RFM) in the third trimester are at increased risk of stillbirth or fetal growth restriction. These outcomes after RFM are related to smaller fetal size on ultrasound scan, oligohydramnios and lower human placental lactogen (hPL) in maternal serum. We performed this study to address whether a randomised controlled trial (RCT) of the management of RFM was feasible with regard to: i) maternal recruitment and retention ii) patient acceptability, iii) adherence to protocol. Additionally, we aimed to confirm the prevalence of poor perinatal outcomes defined as: stillbirth, birthweight <10(th) centile, umbilical arterial pH <7.1 or unexpected admission to the neonatal intensive care unit. METHODS: Women with RFM ≥36 weeks gestation were invited to participate in a RCT comparing standard management (ultrasound scan if indicated, induction of labour (IOL) based on consultant decision) with intensive management (ultrasound scan, maternal serum hPL, IOL if either result was abnormal). Anxiety was assessed by state-trait anxiety index (STAI) before and after investigations for RFM. Rates of protocol compliance and IOL for RFM were calculated. Participant views were assessed by questionnaires. RESULTS: 137 women were approached, 120 (88%) participated, 60 in each group, 2 women in the standard group did not complete the study. 20% of participants had a poor perinatal outcome. All women in the intensive group had ultrasound assessment of fetal size and liquor volume vs. 97% in the standard group. 50% of the intensive group had IOL for abnormal scan or low hPL after RFM vs. 26% of controls (p < 0.01). STAI reduced for all women after investigations, but this reduction was greater in the standard group (p = 0.02). Participants had positive views about their involvement in the study. CONCLUSION: An RCT of management of RFM is feasible with a low rate of attrition. Investigations decrease maternal anxiety. Participants in the intensive group were more likely to have IOL for RFM. Further work is required to determine the likely level of intervention in the standard care arm in multiple centres, to develop additional placental biomarkers and to confirm that the composite outcome is valid. TRIAL REGISTRATION: ISRCTN0794430

Design, methods, and participant characteristics of the Impact of Personal Genomics (PGen) Study, a prospective cohort study of direct-to-consumer personal genomic testing customers

Designed in collaboration with 23andMe and Pathway Genomics, the Impact of Personal Genomics (PGen) Study serves as a model for academic-industry partnership and provides a longitudinal dataset for studying psychosocial, behavioral, and health outcomes related to direct-to-consumer personal genomic testing (PGT). Web-based surveys administered at three time points, and linked to individual-level PGT results, provide data on 1,464 PGT customers, of which 71% completed each follow-up survey and 64% completed all three surveys. The cohort includes 15.7% individuals of non-white ethnicity, and encompasses a range of income, education, and health levels. Over 90% of participants agreed to re-contact for future research. Electronic supplementary material The online version of this article (doi:10.1186/s13073-014-0096-0) contains supplementary material, which is available to authorized users

Efficacy of social cognition and interaction training in outpatients with schizophrenia spectrum disorders: randomized controlled trial

Given the relationship between social cognition and functional outcome in schizophrenia, a number of social cognitive interventions have been developed, including Social Cognition Interaction Training (SCIT), a group-based, comprehensive, manualized intervention. In the current trial, we examined SCIT efficacy as well as potential moderators of treatment effects. Fifty-one outpatients were randomized to SCIT or a wait-list-control (WLC), with assessments of social cognition, neurocognition, self-report, symptoms, and functioning conducted at baseline and end of the active phase. Relative to WLC, we did not find significant improvements for SCIT on neurocognition, social cognition, self-report, or symptoms, though there was a trend-level, medium effect favoring the SCIT condition on interpersonal and instrumental role function. Post-hoc analyses indicated that baseline neurocognition did not impact degree of social cognitive or functional change. Shorter duration of illness was significantly associated with better post-training neurocognition and self-esteem and, at trend-level with better symptoms and social functioning. We discuss the importance of outcome measure selection and the need for continued evaluation of potential treatment moderators in order to better match people to existing treatments.Clinical trial registration: Clinicaltrials.gov, Identifier NCT00587561

Disruption of CTCF-YY1-dependent looping of the human papillomavirus genome activates differentiation-induced viral oncogene transcription.

The complex life cycle of oncogenic human papillomavirus (HPV) initiates in undifferentiated basal epithelial keratinocytes where expression of the E6 and E7 oncogenes is restricted. Upon epithelial differentiation, E6/E7 transcription is increased through unknown mechanisms to drive cellular proliferation required to support virus replication. We report that the chromatin-organising CCCTC-binding factor (CTCF) promotes the formation of a chromatin loop in the HPV genome that epigenetically represses viral enhancer activity controlling E6/E7 expression. CTCF-dependent looping is dependent on the expression of the CTCF-associated Yin Yang 1 (YY1) transcription factor and polycomb repressor complex (PRC) recruitment, resulting in trimethylation of histone H3 at lysine 27. We show that viral oncogene up-regulation during cellular differentiation results from YY1 down-regulation, disruption of viral genome looping, and a loss of epigenetic repression of viral enhancer activity. Our data therefore reveal a key role for CTCF-YY1-dependent looping in the HPV life cycle and identify a regulatory mechanism that could be disrupted in HPV carcinogenesis

The Super Eight Galaxies: Properties of a Sample of Very Bright Galaxies at 7 \u3c z \u3c 8

We present the Super Eight galaxies - a set of very luminous, high-redshift (7.1 \u3c z \u3c 8.0) galaxy candidates found in the Brightest of Reionizing Galaxies (BoRG) Survey fields. The original sample includes eight galaxies that are Y-band dropout objects with H-band magnitudes of m H \u3c 25.5. Four of these objects were originally reported in Calvi et al. Combining new Hubble Space Telescope (HST) WFC3/F814W imaging and Spitzer IRAC data with archival imaging from BoRG and other surveys, we explore the properties of these galaxies. Photometric redshift fitting places six of these galaxies in the redshift range of 7.1 \u3c z \u3c 8.0, resulting in three new high-redshift galaxies and confirming three of the four high-redshift galaxy candidates from Calvi et al. We calculate the half-light radii of the Super Eight galaxies using the HST F160W filter and find that the Super Eight sizes are in line with the typical evolution of size with redshift. The Super Eights have a mean mass of log (M ∗/M o) ∼10, which is typical for sources in this luminosity range. Finally, we place our sample on the UV z ∼ 8 luminosity function and find that the Super Eight number density is consistent with other surveys in this magnitude and redshift range

Effects of flavonoids on glycosaminoglycan synthesis: implications for substrate reduction therapy in Sanfilippo disease and other mucopolysaccharidoses

Sanfilippo disease (mucopolysaccharidosis type III, MPS III) is a severe metabolic disorder caused by accumulation of heparan sulfate (HS), one of glycosaminoglycans (GAGs), due to a genetic defect resulting in a deficiency of GAG hydrolysis. This disorder is characterized as the most severe neurological form of MPS, revealing rapid deterioration of brain functions. Among therapeutic approaches for MPS III, one of the most promising appears to be the substrate reduction therapy (SRT). Genistein (5, 7-dihydroxy-3- (4-hydroxyphenyl)-4H-1-benzopyran-4-one) is an isoflavone that has been used in SRT for MPS III. In this report, we tested effects of other flavonoids (apigenin, daidzein, kaempferol and naringenin) on GAG synthesis. Their cytotoxicity and anti-proliferation features were also tested. We found that daidzein and kaempferol inhibited GAG synthesis significantly. Moreover, these compounds were able to reduce lysosomal storage in MPS IIIA fibroblasts. Interestingly, although genistein is believed to inhibit GAG synthesis by blocking the tyrosine kinase activity of the epidermal growth factor receptor, we found that effects of other flavonoids were not due to this mechanism. In fact, combinations of various flavonoids resulted in significantly more effective inhibition of GAG synthesis than the use of any of these compounds alone. These results, together with results published recently by others, suggest that combination of flavonoids can be considered as a method for improvement of efficiency of SRT for MPS III

Differential frequency of NKG2C/KLRC2 deletion in distinct African populations and susceptibility to Trachoma: a new method for imputation of KLRC2 genotypes from SNP genotyping data.

NKG2C is an activating receptor that is preferentially expressed on natural killer (NK) cells. The gene encoding NKG2C (killer cell lectin-like receptor C2, KLRC2) is present at different copy numbers in the genomes of different individuals. Deletion at the NKG2C locus was investigated in a case-control study of 1522 individuals indigenous to East- and West-Africa and the association with the ocular Chlamydia trachomatis infection and its sequelae was explored. The frequency of homozygous KLRC2 deletion was 13.7 % in Gambians and 4.7 % in Tanzanians. A significantly higher frequency of the deletion allele was found in West-Africans from the Gambia and Guinea-Bissau (36.2 % p = 2.105 × 10(-8), 26.8 % p = 0.050; respectively) in comparison to East-African Tanzanians where the frequency of the deletion is comparable to other human populations (20.9 %). We found no evidence for an association between the numbers of KLRC2 gene copies and the clinical manifestations of trachoma (follicular trachoma or conjunctival scarring). A new method for imputation of KLRC2 genotypes from single nucleotide polymorphism (SNP) data in 2621 individuals from the Gambia further confirmed these results. Our data suggest that NKG2C does not play a major role in trachomatous disease. We found that the deletion allele is present at different frequencies in different populations but the reason behind these differences is currently not understood. The new method offers the potential to use SNP arrays from genome wide association studies to study the frequency of KLRC2 deletion in other populations and its association with other diseases

How does gender influence the recognition of cardiovascular risk and adherence to self-care recommendations? : a study in polish primary care

Background: Studies have shown a correlation between gender and an ability to change lifestyle to reduce the risk of disease. However, the results of these studies are ambiguous, especially where a healthy lifestyle is concerned. Additionally, health behaviors are strongly modified by culture and the environment. Psychological factors also substantially affect engagement with disease-related lifestyle interventions. This study aimed to examine whether there are differences between men and women in the frequency of health care behavior for the purpose of reducing cardiovascular risk (CVR), as well as cognitive appraisal of this type of risk. We also aimed to identify the psychological predictors of engaging in recommended behavior for reducing the risk of cardiovascular disease after providing information about this risk in men and women. Methods: A total of 134 consecutive eligible patients in a family practice entered a longitudinal study. At initial consultation, the individual’s CVR and associated health burden was examined, and preventive measures were recommended by the physician. Self-care behavior, cognitive appraisal of risk, and coping styles were then assessed using psychological questionnaires. Six months after the initial data collection, the frequency of subjects’ self-care behavior was examined. Results: We found an increase in health care behavior after providing information regarding the rate of CVR in both sexes; this increase was greater for women than for men. Women followed self-care guidelines more often than men, particularly for preventive measures and dietary advice. Women were more inclined to recognize their CVR as a challenge. Coping style, cognitive appraisal, age, level of health behaviors at baseline and CVR values accounted for 48% of the variance in adherence to self-care guidelines in women and it was 52% in men. In women, total risk of CVD values were most important, while in men, cognitive appraisal of harm/loss was most important. Conclusions: Different predictors of acquisition of health behavior are encountered in men and women. Our results suggest that gender-adjusted motivation models influencing the recognition process need to be considered to optimize compliance in patients with CVR

Consumption of an Anthocyanin-Rich Extract Made From New Zealand Blackcurrants Prior to Exercise May Assist Recovery From Oxidative Stress and Maintains Circulating Neutrophil Function: A Pilot Study

Aim: To evaluate blackcurrant anthocyanin-rich extract (BAE) consumption on time- and dose-dependent plasma anthocyanin bioavailability and conduct a pilot study to explore the potential effect of BAE in promoting recovery from exercise-induced oxidative stress, and maintenance of circulating neutrophil function.Methods: Time- and dose-dependent blackcurrant anthocyanin bioavailability was assessed using LC-MS in 12 participants over 6 h after the ingestion of a placebo or BAE containing 0.8, 1.6, or 3.2 mg/kg total anthocyanins. In a separate pilot intervention exercise trial, 32 participants consumed either a placebo or 0.8, 1.6, or 3.2 mg/kg BAE (8 individuals per group), and then 1 h later performed a 30 min row at 70% VO2max. Blood was collected during the trial for oxidative, antioxidant, inflammatory, and circulating neutrophil status.Results: Consumption of BAE caused a time- and dose-dependent increase in plasma anthocyanins, peaking at 2 h after ingestion of 3.2 mg/kg BAE (217 ± 69 nM). BAE consumed 1 h prior to a 30 min row had no effect on plasma antioxidant status but hastened the recovery from exercise-induced oxidative stress: By 2 h recovery, consumption of 1.6 mg/kg BAE prior to exercise caused a significant (P &lt; 0.05) 34 and 32% decrease in post-exercise plasma oxidative capacity and protein carbonyl levels, respectively, compared to placebo. BAE consumption prior to exercise dose-dependently attenuated a small, yet significant (P &lt; 0.01) transient 13 ± 2% decline in circulating neutrophils observed in the placebo group immediately post-exercise. Furthermore, the timed consumption of either 1.6 or 3.2 mg/kg BAE attenuated a 17 ± 2.4% (P &lt; 0.05) decline in neutrophil phagocytic capability of opsonised FITC-Escherichia coli observed 6 h post-exercise in the placebo group. Similarly, a dose-dependent increase in neutrophil surface expression of complement receptor-3 complex (CR3, critical for effective phagocytosis of opsonised microbes), was observed 6 h post-exercise in both 1.6 and 3.2 mg/kg BAE intervention groups.Conclusions: Consumption of BAE (&gt;1.6 mg/kg) 1 h prior to exercise facilitated recovery from exercise-induced oxidative stress and preserved circulating neutrophil function. This study provides data to underpin a larger study designed to evaluate the efficacy of timed BAE consumption on post-exercise recovery and innate immunity