Stigma in youth with Tourette's syndrome: a systematic review and synthesis

Tourette's syndrome (TS) is a childhood onset neurodevelopmental disorder, characterised by tics. To our knowledge, no systematic reviews exist which focus on examining the body of literature on stigma in association with children and adolescents with TS. The aim of the article is to provide a review of the existing research on (1) social stigma in relation to children and adolescents with TS, (2) self-stigma and (3) courtesy stigma in family members of youth with TS. Three electronic databases were searched: PsycINFO, PubMed and Web of Science. Seventeen empirical studies met the inclusion criteria. In relation to social stigma in rating their own beliefs and behavioural intentions, youth who did not have TS showed an unfavourable attitude towards individuals with TS in comparison to typically developing peers. Meanwhile, in their own narratives about their lives, young people with TS themselves described some form of devaluation from others as a response to their disorder. Self-degrading comments were denoted in a number of studies in which the children pointed out stereotypical views that they had adopted about themselves. Finally, as regards courtesy stigma, parents expressed guilt in relation to their children's condition and social alienation as a result of the disorder. Surprisingly, however, there is not one study that focuses primarily on stigma in relation to TS and further studies that examine the subject from the perspective of both the 'stigmatiser' and the recipient of stigma are warranted

An embedding scheme for the Dirac equation

An embedding scheme is developed for the Dirac Hamiltonian H. Dividing space into regions I and II separated by surface S, an expression is derived for the expectation value of H which makes explicit reference to a trial function defined in I alone, with all details of region II replaced by an effective potential acting on S and which is related to the Green function of region II. Stationary solutions provide approximations to the eigenstates of H within I. The Green function for the embedded Hamiltonian is equal to the Green function for the entire system in region I. Application of the method is illustrated for the problem of a hydrogen atom in a spherical cavity and an Au(001)/Ag/Au(001) sandwich structure using basis sets that satisfy kinetic balance.Comment: 16 pages, 5 figure

The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex

Austerity and the lives of people with learning disabilities. A thematic synthesis of current literature

The Financial Crisis of 2008 resulted in many western economies implementing cuts in health and social care. This systematic review provides a holistic picture of the impact of austerity policy on the lives of people with learning disabilities (LD) and the collateral effects on the people who support them. Our review suggests that in the current climate of economic austerity, available funding to support people with LD is no longer aligned to their care needs. Cuts in disability services have adversely affected the well-being both of people with LD and their informal carers. Individuals with LD have lost social support and are experiencing increased social isolation. Heightened demands on family carers’ time have negatively influenced their wider roles, including parental functioning, and labour market participation. Our review provides the foundations for further discourse and research on the effects of austerity on people with LD and their family carers

"I'm not being rude, I'd want somebody normal" Adolescents' perception of their peers with Tourette's syndrome; an exploratory study

Background: Tourette’s syndrome (TS) is a highly stigmatised condition, and typically developing adolescents’ motives and reason for excluding individuals with TS have not been examined. Aims: The aim of the study was to understand how TS is conceptualised by adolescents and explore how individuals with TS are perceived by their typically developing peers. Method: Free text writing and focus groups were used to elicit the views of twenty-two year ten students from a secondary school in South East England. Grounded theory was used to develop an analytical framework. Result: Participants’ understanding about the condition was construed from misconceptions, unfamiliarity and unanswered questions. Adolescents who conceived TS as a disorder beyond the individual’s control perceived their peers as being deprived of agency and strength and as straying from the boundaries of normalcy. People with TS were viewed as individuals deserving pity, and in need of support. Although participants maintained they had feelings of social politeness towards those with TS, they would avoid initiating meaningful social relationships with them due to fear of “social contamination”. Intergroup anxiety would also inhibit a close degree of social contact. Participants that viewed those with TS as responsible for their condition expressed a plenary desire for social distance. However, these behavioural intentions were not limited to adolescents that elicited inferences of responsibility to people with TS, indicating that attributional models of stigmatisation may be of secondary importance in the case of TS. Implications for interventions to improve school belonging among youths with TS are discussed

The GPR55 agonist lysophosphatidylinositol acts as an intracellular messenger and bidirectionally modulates Ca2+-activated large-conductance K+ channels in endothelial cells

Lysophospholipids are known to serve as intra- and extracellular messengers affecting many physiological processes. Lysophosphatidylinositol (LPI), which is produced in endothelial cells, acts as an endogenous agonist of the orphan receptor, G protein-coupled receptor 55 (GPR55). Stimulation of GPR55 by LPI evokes an intracellular Ca2+ rise in several cell types including endothelial cells. In this study, we investigated additional direct, receptor-independent effects of LPI on endothelial large-conductance Ca2+ and voltage-gated potassium (BKCa) channels. Electrophysiological experiments in the inside-out configuration revealed that LPI directly affects the BKCa channel gating properties. This effect of LPI strictly depended on the presence of Ca2+ and was concentration-dependent, reversible, and dual in nature. The modulating effects of LPI on endothelial BKCa channels correlated with their initial open probability (Po): stimulation at low Po (<0.3) and inhibition at high Po levels (>0.3). In the whole-cell configuration, LPI in the pipette facilitated membrane hyperpolarization in response to low (0.1–2 μM) histamine concentrations. In contrast, LPI counteracted membrane hyperpolarization in response to supramaximal cell stimulation with histamine. These results highlight a novel receptor-independent and direct bidirectional modulation of BKCa channels by LPI on endothelial cells. We conclude that LPI via this mechanism serves as an important modulator of endothelial electrical responses to cell stimulation

Activation of store-operated calcium entry in airway smooth muscle cells: insight from a mathematical model

Intracellular dynamics of airway smooth muscle cells (ASMC) mediate ASMC contraction and proliferation, and thus play a key role in airway hyper-responsiveness (AHR) and remodelling in asthma. We evaluate the importance of store-operated entry (SOCE) in these dynamics by constructing a mathematical model of ASMC signaling based on experimental data from lung slices. The model confirms that SOCE is elicited upon sufficient depletion of the sarcoplasmic reticulum (SR), while receptor-operated entry (ROCE) is inhibited in such conditions. It also shows that SOCE can sustain agonist-induced oscillations in the absence of other influx. SOCE up-regulation may thus contribute to AHR by increasing the oscillation frequency that in turn regulates ASMC contraction. The model also provides an explanation for the failure of the SERCA pump blocker CPA to clamp the cytosolic of ASMC in lung slices, by showing that CPA is unable to maintain the SR empty of . This prediction is confirmed by experimental data from mouse lung slices, and strongly suggests that CPA only partially inhibits SERCA in ASMC

The Effect of OPA1 on Mitochondrial Ca2+ Signaling

The dynamin-related GTPase protein OPA1, localized in the intermembrane space and tethered to the inner membrane of mitochondria, participates in the fusion of these organelles. Its mutation is the most prevalent cause of Autosomal Dominant Optic Atrophy. OPA1 controls the diameter of the junctions between the boundary part of the inner membrane and the membrane of cristae and reduces the diffusibility of cytochrome c through these junctions. We postulated that if significant Ca2+ uptake into the matrix occurs from the lumen of the cristae, reduced expression of OPA1 would increase the access of Ca2+ to the transporters in the crista membrane and thus would enhance Ca2+ uptake. In intact H295R adrenocortical and HeLa cells cytosolic Ca2+ signals evoked with K+ and histamine, respectively, were transferred into the mitochondria. The rate and amplitude of mitochondrial [Ca2+] rise (followed with confocal laser scanning microscopy and FRET measurements with fluorescent wide-field microscopy) were increased after knockdown of OPA1, as compared with cells transfected with control RNA or mitofusin1 siRNA. Ca2+ uptake was enhanced despite reduced mitochondrial membrane potential. In permeabilized cells the rate of Ca2+ uptake by depolarized mitochondria was also increased in OPA1-silenced cells. The participation of Na+/Ca2+ and Ca2+/H+ antiporters in this transport process is indicated by pharmacological data. Altogether, our observations reveal the significance of OPA1 in the control of mitochondrial Ca2+ metabolism

Circulating Levels of Adiponectin, Leptin, Fetuin-A and Retinol-Binding Protein in Patients with Tuberculosis: Markers of Metabolism and Inflammation

BACKGROUND: Wasting is known as a prominent feature of tuberculosis (TB). To monitor the disease state, markers of metabolism and inflammation are potentially useful. We thus analyzed two major adipokines, adiponectin and leptin, and two other metabolic markers, fetuin-A and retinol-binding protein 4 (RBP4). METHODS: The plasma levels of these markers were measured using enzyme-linked immunosorbent assays in 84 apparently healthy individuals (=no-symptom group) and 46 patients with active pulmonary TB around the time of treatment, including at the midpoint evaluation (=active-disease group) and compared them with body mass index (BMI), C-reactive protein (CRP), chest radiographs and TB-antigen specific response by interferon-γ release assay (IGRA). RESULTS: In the no-symptom group, adiponectin and leptin showed negative and positive correlation with BMI respectively. In the active-disease group, at the time of diagnosis, leptin, fetuin-A and RBP4 levels were lower than in the no-symptom group [adjusted means 2.01 versus 4.50 ng/ml, P<0.0001; 185.58 versus 252.27 µg/ml, P<0.0001; 23.88 versus 43.79 µg/ml, P<0.0001, respectively]. High adiponectin and low leptin levels were associated with large infiltrates on chest radiographs even after adjustment for BMI and other covariates (P=0.0033 and P=0.0020). During treatment, adiponectin levels increased further and then decreased. Leptin levels remained low. Initial low levels of fetuin-A and RBP4 almost returned to the normal reference range in concert with reduced CRP. CONCLUSIONS: Our data and recent literature suggest that low fat store and underlying inflammation may regulate these metabolic markers in TB in a different way. Decreased leptin, increased adiponectin, or this ratio may be a promising marker for severity of the disease independent of BMI. We should further investigate pathological roles of the balance between these adipokines

Relativistic double-zeta, triple-zeta, and quadruple-zeta basis sets for the lanthanides La–Lu

Relativistic basis sets of double-zeta, triple-zeta, and quadruple-zeta quality have been optimized for the lanthanide elements La-Lu. The basis sets include SCF exponents for the occupied spinors and for the 6p shell, exponents of correlating functions for the valence shells (4f, 5d and 6s) and the outer core shells (4d, 5s and 5p), and diffuse functions, including functions for dipole polarization of the 4f shell. A finite nuclear size was used in all optimizations. The basis sets are illustrated by calculations on YbF. Prescriptions are given for constructing contracted basis sets. The basis sets are available as an internet archive and from the Dirac program web site, http://dirac. chem. sdu. dk. © 2010 The Author(s)