Effects of altered sialic acid biosynthesis on N-linked glycan branching and cell surface interactions

GNE myopathy is a rare muscle disorder associated with aging and is related to sporadic inclusion body myositis (sIBM), the most common acquired muscle disease of aging. While the cause of sIBM is unknown, GNE myopathy is associated with mutations in UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE). GNE harbors two enzymatic activities required for biosynthesis of sialic acid in mammalian cells. Mutations to both GNE domains are linked to GNE myopathy. However, correlation between mutation-associated reductions in sialic acid production and disease severity is imperfect. To investigate other potential effects of GNE mutations, we compared sialic acid production in cell lines expressing wild-type or mutant forms of GNE. Although we did not detect any differences attributable to disease-associated mutations, lectin binding and mass spectrometry analysis revealed that GNE deficiency is associated with unanticipated effects on the structure of cell-surface glycans. In addition to exhibiting low levels of sialylation, GNE-deficient cells produced distinct N-linked glycan structures with increased branching and extended poly-N-acetyllactosamine (polyLacNAc). GNE deficiency may affect levels of UDP-GlcNAc, a key metabolite in the nutrient-sensing hexosamine biosynthetic pathway, but this modest effect did not fully account for the change in N-linked glycan structure. Further, GNE deficiency and glucose supplementation acted independently and additively to increase N-linked glycan branching. Notably, N-linked glycans produced by GNE-deficient cells displayed enhanced binding to galectin-1, indicating that changes in GNE activity can alter affinity of cell-surface glycoproteins for the galectin lattice. These findings suggest an unanticipated mechanism by which GNE activity might affect signaling through cell-surface receptors

Vitamins C and E and the risks of preeclampsia and perinatal complications

Copyright © 2006 Massachusetts Medical Society.Background: Supplementation with antioxidant vitamins has been proposed to reduce the risk of preeclampsia and perinatal complications, but the effects of this intervention are uncertain. Methods: We conducted a multicenter, randomized trial of nulliparous women between 14 and 22 weeks of gestation. Women were assigned to daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or placebo (microcrystalline cellulose) until delivery. Primary outcomes were the risks of maternal preeclampsia, death or serious outcomes in the infants (on the basis of definitions used by the Australian and New Zealand Neonatal Network), and delivering an infant whose birth weight was below the 10th percentile for gestational age. Results: Of the 1877 women enrolled in the study, 935 were randomly assigned to the vitamin group and 942 to the placebo group. Baseline characteristics of the two groups were similar. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia (6.0 percent and 5.0 percent, respectively; relative risk, 1.20; 95 percent confidence interval, 0.82 to 1.75), death or serious outcomes in the infant (9.5 percent and 12.1 percent; relative risk, 0.79; 95 percent confidence interval, 0.61 to 1.02), or having an infant with a birth weight below the 10th percentile for gestational age (8.7 percent and 9.9 percent; relative risk, 0.87; 95 percent confidence interval, 0.66 to 1.16). Conclusions: Supplementation with vitamins C and E during pregnancy does not reduce the risk of preeclampsia in nulliparous women, the risk of intrauterine growth restriction, or the risk of death or other serious outcomes in their infants. (Controlledtrials.com number, ISRCTN00416244 [controlled-trials.com] .)Alice R. Rumbold, Caroline A. Crowther, Ross R. Haslam, Gustaaf A. Dekker and Jeffrey S. Robinso

A Clinical and Biological Guide for Understanding Chemotherapy-Induced Alopecia and its Prevention

Chemotherapy-induced alopecia (CIA) is the most visibly distressing side effect of commonly administered chemotherapeutic agents. As psychological health has huge relevance on lifestyle, diet and self-esteem, it is important for clinicians to fully appreciate the psychological burden that CIA can place on patients. Here, for the first time, we provide a comprehensive review encompassing the molecular characteristics of the human hair follicle (HF), how different anticancer agents damage the HF to cause CIA, subsequent HF pathophysiology and we assess known and emerging prevention modalities that have aimed to reduce or prevent CIA. We argue that, at present, scalp cooling is the only safe and FDA-cleared modality available, and we highlight the extensive available clinical and experimental (biological) evidence for its efficacy. The likelihood of a patient that uses scalp cooling during chemotherapy maintaining enough hair to not require a wig is approximately 50%. This is despite different types of chemotherapy regimens, patient-specific differences and possible lack of staff experience in effectively delivering scalp cooling. The increased use of scalp cooling and an understanding of how to deliver it most effectively to patients has enormous potential to ease the psychological burden of CIA, until other, more efficacious, equally safe treatments become available

Mindfulness-based interventions for people diagnosed with a current episode of an anxiety or depressive disorder: a meta-analysis of randomised controlled trials

Objective Mindfulness-based interventions (MBIs) can reduce risk of depressive relapse for people with a history of recurrent depression who are currently well. However, the cognitive, affective and motivational features of depression and anxiety might render MBIs ineffective for people experiencing current symptoms. This paper presents a meta-analysis of randomised controlled trials (RCTs) of MBIs where participants met diagnostic criteria for a current episode of an anxiety or depressive disorder. Method Post-intervention between-group Hedges g effect sizes were calculated using a random effects model. Moderator analyses of primary diagnosis, intervention type and control condition were conducted and publication bias was assessed. Results Twelve studies met inclusion criteria (n = 578). There were significant post-intervention between-group benefits of MBIs relative to control conditions on primary symptom severity (Hedges g = −0.59, 95% CI = −0.12 to −1.06). Effects were demonstrated for depressive symptom severity (Hedges g = −0.73, 95% CI = −0.09 to −1.36), but not for anxiety symptom severity (Hedges g = −0.55, 95% CI = 0.09 to −1.18), for RCTs with an inactive control (Hedges g = −1.03, 95% CI = −0.40 to −1.66), but not where there was an active control (Hedges g = 0.03, 95% CI = 0.54 to −0.48) and effects were found for MBCT (Hedges g = −0.39, 95% CI = −0.15 to −0.63) but not for MBSR (Hedges g = −0.75, 95% CI = 0.31 to −1.81). Conclusions This is the first meta-analysis of RCTs of MBIs where all studies included only participants who were diagnosed with a current episode of a depressive or anxiety disorder. Effects of MBIs on primary symptom severity were found for people with a current depressive disorder and it is recommended that MBIs might be considered as an intervention for this population

A Social Identity Approach to Sport Psychology: Principles, Practice, and Prospects.

Drawing on social identity theory and self-categorization theory, we outline an approach to sport psychology that understands groups not simply as features of sporting contexts but rather as elements that can be, and often are, incorporated into a person's sense of self and, through this, become powerful determinants of their sport-related behavior. The underpinnings of this social identity approach are outlined, and four key lessons for sport that are indicative of the analytical and practical power of the approach are presented. These suggest that social identity is the basis for sports group (1) behavior, (2) formation and development, (3) support and stress appraisal, and (4) leadership. Building on recent developments within sport science, we outline an agenda for future research by identifying a range of topics to which the social identity approach could fruitfully contribute

The effect of high tibial osteotomy on the results of total knee arthroplasty: a matched case control study

BACKGROUND: We performed a matched case control study to assess the effect of prior high tibia valgus producing osteotomy on results and complications of total knee arthroplasty (TKA). METHODS: From 1996 until 2003 356 patients underwent all cemented primary total knee replacement in our institution. Twelve patients with a history of 14 HTO were identified and matched to a control group of 12 patients with 14 primary TKA without previous HTO. The match was made for gender, age, date of surgery, body mass index, aetiology and type of prosthesis. Clinical and radiographic outcome were evaluated after a median duration of follow-up of 3.7 years (minimum, 2.3 years). The SPSS program was used for statistical analyses. RESULTS: The index group had more perioperative blood loss and exposure difficulties with one tibial tuberosity osteotomy and three patients with lateral retinacular releases. No such procedures were needed in the control group. Mid-term HSS, KSS and WOMAC scores were less favourable for the index group, but these differences were not significant. The tibial slope of patients with prior HTO was significantly decreased after this procedure. The tibial posterior inclination angle was corrected during knee replacement but posterior inclination was significantly less compared to the control group. No deep infection or knee component loosening were seen in the group with prior HTO. CONCLUSION: We conclude that TKA after HTO seems to be technically more demanding than a primary knee arthroplasty, but clinical outcome was almost identical to a matched group that had no HTO previously

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Protocol for stage 1 of the GaP study (Genetic testing acceptability for Paget's disease of bone): an interview study about genetic testing and preventive treatment: would relatives of people with Paget's disease want testing and treatment if they were available?

BACKGROUND: Paget's disease of bone (PDB) is characterised by focal increases in bone turnover, affecting one or more bones throughout the skeleton. This disrupts normal bone architecture and causes pain, deformity, deafness, osteoarthritis, and fractures. Genetic factors are recognised to play a role in PDB and it is now possible to carry out genetic tests for research. In view of this, it is timely to investigate the clinical potential for a programme of genetic testing and preventative treatment for people who have a family history of PDB, to prevent or delay the development of PDB. Evidence from non-genetic conditions, that have effective treatments, demonstrates that patients' beliefs may affect the acceptability and uptake of treatment. Two groups of beliefs (illness and treatment representations) are likely to be influential. Illness representations describe how people see their illness, as outlined in Leventhal's Self-Regulation Model. Treatment representations describe how people perceive potential treatment for their disease. People offered a programme of genetic testing and treatment will develop their own treatment representations based on what is offered, but the beliefs rather than the objective programme of treatment are likely to determine their willingness to participate. The Theory of Planned Behaviour is a theoretical model that predicts behaviours from people's beliefs about the consequences, social pressures and perceived control over the behaviour, including uptake of treatment. METHODS/DESIGN: This study aims to examine the acceptability of genetic testing, followed by preventative treatment, to relatives of people with PDB. We aim to interview people with Paget's disease, and their families, from the UK. Our research questions are: 1. What do individuals with Paget's disease think would influence the involvement of their relatives in a programme of genetic testing and preventative treatment? 2. What do relatives of Paget's disease sufferers think would influence them in accepting an offer of a programme of genetic testing and preventative treatment? DISCUSSION: Our research will be informed by relevant psychological theory: primarily the Self-Regulation Model and the Theory of Planned Behaviour. The results of these interviews will inform the development of a separate questionnaire-based study to explore these research questions in greater detail

Bystander responses to a violent incident in an immersive virtual environment

Under what conditions will a bystander intervene to try to stop a violent attack by one person on another? It is generally believed that the greater the size of the crowd of bystanders, the less the chance that any of them will intervene. A complementary model is that social identity is critical as an explanatory variable. For example, when the bystander shares common social identity with the victim the probability of intervention is enhanced, other things being equal. However, it is generally not possible to study such hypotheses experimentally for practical and ethical reasons. Here we show that an experiment that depicts a violent incident at life-size in immersive virtual reality lends support to the social identity explanation. 40 male supporters of Arsenal Football Club in England were recruited for a two-factor between-groups experiment: the victim was either an Arsenal supporter or not (in-group/out-group), and looked towards the participant for help or not during the confrontation. The response variables were the numbers of verbal and physical interventions by the participant during the violent argument. The number of physical interventions had a significantly greater mean in the ingroup condition compared to the out-group. The more that participants perceived that the Victim was looking to them for help the greater the number of interventions in the in-group but not in the out-group. These results are supported by standard statistical analysis of variance, with more detailed findings obtained by a symbolic regression procedure based on genetic programming. Verbal interventions made during their experience, and analysis of post-experiment interview data suggest that in-group members were more prone to confrontational intervention compared to the out-group who were more prone to make statements to try to diffuse the situation

Social identity, social networks and recovery capital in emerging adulthood: a pilot study

Background It has been argued that recovery from substance dependence relies on a change in identity, with past research focused on ‘personal identity’. This study assessed support for a social identity model of recovery in emerging adults through examining associations between social identity, social networks, recovery capital, and quality of life. Methods Twenty participants aged 18–21 in residential treatment for substance misuse were recruited from four specialist youth drug treatment services - three detoxification facilities and one psychosocial rehabilitation facility in Victoria, Australia. Participants completed a detailed social network interview exploring the substance use of groups in their social networks and measures of quality of life, recovery capital, and social identity. Results Lower group substance use was associated with higher recovery capital, stronger identification with non-using groups, and greater importance of non-using groups in the social network. Additionally, greater identification with and importance of non-using groups were associated with better environmental quality of life, whereas greater importance conferred on using groups was associated with reduced environmental quality of life. Conclusions Support was found for the role of social identity processes in reported recovery capital and quality of life. Future research in larger, longitudinal samples is required to improve understanding of social identity processes during treatment and early recovery and its relationship to recovery stability. Keywords Social network Social identity Emerging adult Substance use Treatment Recovery Quality of lif