Promoting young people's social and emotional wellbeing in secondary education.

This guidance is for all those who have a responsibility for the social and emotional wellbeing of young people in secondary education. This includes teachers, support staff, governors and professionals with public health as part of their remit working in education (including the independent sector), local authorities, the NHS and the wider public, voluntary and community sectors. It focuses on interventions to support all young people aged 11-19 who attend any education establishment. Social and emotional wellbeing includes being happy, confident and in control, with the ability to solve and cope with problems and have good relationships with other people. The six recommendations cover: strategy, the key principles and conditions, working in partnership with parents, families and young people, the curriculum, and training and professional development. They include: â?¢ Secondary education establishments should have access to the specialist skills, advice and support they require. â?¢ Practitioners should have the knowledge, understanding and skills they need to develop young peopleâ?Ts social and emotional wellbeing. â?¢ Secondary education establishments should provide a safe environment which nurtures and encourages young peopleâ?Ts sense of self-worth, reduces the threat of bullying and violence and promotes positive behaviour. â?¢ Social and emotional skills education should be tailored to the developmental needs of young people.This resource was contributed by The National Documentation Centre on Drug Use.

Responses to exercise in normobaric hypoxia: comparison of elite and recreational ski mountaineers.

PURPOSE: Hypoxia is known to reduce maximal oxygen uptake (VO(2max)) more in trained than in untrained subjects in several lowland sports. Ski mountaineering is practiced mainly at altitude, so elite ski mountaineers spend significantly longer training duration at altitude than their lower-level counterparts. Since acclimatization in hypobaric hypoxia is effective, the authors hypothesized that elite ski mountaineers would exhibit a VO2max decrement in hypoxia similar to that of recreational ski mountaineers. METHODS: Eleven elite (E, Swiss national team) and 12 recreational (R) ski mountaineers completed an incremental treadmill test to exhaustion in normobaric hypoxia (H, 3000 m, F(1)O(2) 14.6% ± 0.1%) and in normoxia (N, 485 m, F(1)O(2) 20.9% ± 0.0%). Pulse oxygen saturation in blood (SpO(2)), VO(2max), minute ventilation, and heart rate were recorded. RESULTS: At rest, hypoxic ventilatory response was higher (P < .05) in E than in R (1.4 ± 1.9 vs 0.3 ± 0.6 L · min⁻¹ · kg⁻¹). At maximal intensity, SpO(2) was significantly lower (P < .01) in E than in R, both in N (91.1% ± 3.3% vs 94.3% ± 2.3%) and in H (76.4% ± 5.4% vs 82.3% ± 3.5%). In both groups, SpO(2) was lower (P < .01) in H. Between N and H, VO(2max) decreased to a greater extent (P < .05) in E than in R (-18% and -12%, P < .01). In E only, the VO(2max) decrement was significantly correlated with the SpO(2) decrement (r = .74, P < .01) but also with VO(2max) measured in N (r = .64, P < .05). CONCLUSION: Despite a probable better acclimatization to altitude, VO(2max) was more reduced in E than in R ski mountaineers, confirming previous results observed in lowlander E athletes.

Renal and hormonal responses to direct renin inhibition with aliskiren in healthy humans.

BACKGROUND: Pharmacological interruption of the renin-angiotensin system focuses on optimization of blockade. As a measure of intrarenal renin activity, we have examined renal plasma flow (RPF) responses in a standardized protocol. Compared with responses with angiotensin-converting enzyme inhibition (rise in RPF approximately 95 mL x min(-1) x 1.73 m(-2)), greater renal vasodilation with angiotensin receptor blockers (approximately 145 mL x min(-1) x 1.73 m(-2)) suggested more effective blockade. We predicted that blockade with the direct oral renin inhibitor aliskiren would produce renal vascular responses exceeding those induced by angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. METHODS AND RESULTS: Twenty healthy normotensive subjects were studied on a low-sodium (10 mmol/d) diet, receiving separate escalating doses of aliskiren. Six additional subjects received captopril 25 mg as a low-sodium comparison and also received aliskiren on a high-sodium (200 mmol/d) diet. RPF was measured by clearance of para-aminohippurate. Aliskiren induced a remarkable dose-related renal vasodilation in low-sodium balance. The RPF response was maximal at the 600-mg dose (197+/-27 mL x min(-1) x 1.73 m(-2)) and exceeded responses to captopril (92+/-20 mL x min(-1) x 1.73 m(-2); P<0.01). Furthermore, significant residual vasodilation was observed 48 hours after each dose (P<0.01). The RPF response on a high-sodium diet was also higher than expected (47+/-17 mL x min(-1) x 1.73 m(-2)). Plasma renin activity and angiotensin levels were reduced in a dose-related manner. As another functional index of the effect of aliskiren, we found significant natriuresis on both diets. CONCLUSIONS: Renal vasodilation in healthy people with the potent renin inhibitor aliskiren exceeded responses seen previously with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. The effects were longer lasting and were associated with significant natriuresis. These results indicate that aliskiren may provide more complete and thus more effective blockade of the renin-angiotensin system.

Cardiorespiratory responses to the 30-15 intermittent ice test

PURPOSE: In this study, the authors compared the cardiorespiratory responses between the 30-15 Intermittent Ice Test (30-15(IIT)) and the 30-15 Intermittent Fitness Test (30-15(IFT)) in semiprofessional hockey players. METHODS: Ten players (age 24 ± 6 y) from a Swiss League B team performed the 30-15(IIT) and 30-15(IFT) in random order (13 ± 4 d between trials). Cardiorespiratory variables were measured with a portable gas analyzer. Ventilatory threshold (VT), respiratory-compensation point (RCP), and maximal speeds were measured for both tests. Peak blood lactate ([La(peak)]) was measured at 1 min postexercise. RESULTS: Compared with 30-15(IFT), 30-15(IIT) peak heart rate (HR(peak); mean ± SD 185 ± 7 vs 189 ± 10 beats/min, P = .02) and peak oxygen consumption (VO(2peak)); 60 ± 7 vs 62.7 ± 4 mL/min/kg, P = .02) were lower, whereas [La(peak)] was higher (10.9 ± 1 vs 8.6 ± 2 mmol/L, P < .01) for the 30-15(IIT). VT and RCP values during the 30-15(IIT) and 30-15(IFT) were similar for %HR(peak) (76.3% ± 5% vs 75.5% ± 3%, P = .53, and 90.6% ± 3% vs. 89.8% ± 3%, P = .45) and % VO(2peak) (62.3% ± 5% vs 64.2% ± 6%, P = .46, and 85.9% ± 5% vs 84.0% ± 7%, P = .33). VO(2peak ))(r = .93, P < .001), HR(peak) (r = .86, P = .001), and final velocities (r = .69, P = .029) were all largely to almost perfectly correlated. CONCLUSIONS: Despite slightly lower maximal cardiorespiratory responses than in the field-running version of the test, the on-ice 30-15(IIT) is of practical interest since it is a specific maximal test with a higher anaerobic component.

PPARs as drug targets to modulate inflammatory responses?

The three peroxisome proliferator-activated receptors (PPARs) isotypes (PPAR alpha, beta/delta and gamma) belong to the nuclear hormone receptor family. During the last decade, they have been identified as anti-inflammatory transcription factors. Part of this regulation antiinflammatory is mediated through negative interference between PPARs and other nuclear factors such as NFkB, AP-1 and C/EBP, which regulate innate as well as adaptative immunity. In addition, the PPARs control the functions of macrophages, B cells and T cells. In this review, we summarise the pathways through which the PPARs control inflammatory responses. We also discuss the potential utilisation of PPAR specific ligands in the treatment of inflammatory diseases, such as inflammatory bowel diseases, atherosclerosis, Parkinson's and Alzheimer's diseases.

The role of interferon-gamma on immune and allergic responses

Allergic diseases have been closely related to Th2 immune responses, which are characterized by high levels of interleukin (IL) IL-4, IL-5, IL-9 and IL-13. These cytokines orchestrate the recruitment and activation of different effector cells, such as eosinophils and mast cells. These cells along with Th2 cytokines are key players on the development of chronic allergic inflammatory disorders, usually characterized by airway hyperresponsiveness, reversible airway obstruction, and airway inflammation. Accumulating evidences have shown that altering cytokine-producing profile of Th2 cells by inducing Th1 responses may be protective against Th2-related diseases such as asthma and allergy. Interferon-gamma (IFN-gamma), the principal Th1 effector cytokine, has shown to be crucial for the resolution of allergic-related immunopathologies. In fact, reduced production of this cytokine has been correlated with severe asthma. In this review, we will discuss the role of IFN-gamma during the generation of immune responses and its influence on allergic inflammation models, emphasizing its biologic properties during the different aspects of allergic responses.

Epithelial cell signaling responses to enterohemorrhagic Escherichia coli infection

Enterohemorrhagic Escherichia coli, including the serotype O157:H7 that is most commonly identified with human disease, cause both sporadic cases and outbreaks of non-bloody diarrhea and hemorrhagic colitis. In about 10% of infected subjects, the hemolytic uremic syndrome (hemolytic anemic, thrombocytopenia, and acute renal failure) develops, likely as a consequence of systemic spread of bacterial-derived toxins variously referred to as Shiga-like toxin, Shiga toxin, and Verotoxin. Increasing evidence points to a complex interplay between bacterial products - for example, adhesins and toxins - and host signal transduction pathways in mediating responses to infection. Identification of critical signaling pathways could result in the development of novel strategies for intervention to both prevent and treat this microbial infection in humans.

Jasmonates and related oxylipins in plant responses to pathogenesis and herbivory.

The vigorous production of oxygenated fatty acids (oxylipins) is a characteristic response to pathogenesis and herbivory, and is often accompanied by the substantial release of small and reactive lipid-fragmentation products. Some oxylipins, most notably those of the jasmonate family, have key roles as potent regulators. Recent advances have been made in understanding oxylipin-regulated signal transduction in response to attack. Much jasmonate signaling takes place via a genetically defined signal network that is linked to the ethylene, auxin, and salicylic acid signal pathways, but a second aspect of jasmonate signaling is emerging. Some jasmonates and several newly discovered cyclopentenone lipids can activate or repress gene expression through the activities of a conserved electrophilic atom group.

Thogoto virus infection induces sustained type I interferon responses that depend on RIG-I-like helicase signaling of conventional dendritic cells.

Type I interferon (IFN-α/β) induction upon viral infection contributes to the early antiviral host defense and ensures survival until the onset of adaptive immunity. Many viral infections lead to an acute, transient IFN expression which peaks a few hours after infection and reverts to initial levels after 24 to 36 h. Robust IFN expression often is conferred by specialized plasmacytoid dendritic cells (pDC) and may depend on positive-feedback amplification via the type I IFN receptor (IFNAR). Here, we show that mice infected with Thogoto virus (THOV), which is an influenza virus-like orthomyxovirus transmitted by ticks, mounted sustained IFN responses that persisted up to 72 h after infection. For this purpose, we used a variant of THOV lacking its IFN-antagonistic protein ML, an elongated version of the matrix (M) protein [THOV(ΔML)]. Of note, large amounts of type I IFN were also found in the serum of mice lacking the IFNAR. Early IFN-α expression seemed to depend on Toll-like receptor (TLR) signaling, whereas prolonged IFN-α responses strictly depended on RIG-I-like helicase (RLH) signaling. Unexpectedly, THOV(ΔML)-infected bone marrow-derived pDC (BM-pDC) produced only moderate IFN levels, whereas myeloid DC (BM-mDC) showed massive IFN induction that was IPS-1-dependent, suggesting that BM-mDC are involved in the massive, sustained IFN production in THOV(ΔML)-infected animals. Thus, our data are compatible with the model that THOV(ΔML) infection is sensed in the acute phase via TLR and RLH systems, whereas at later time points only RLH signaling is responsible for the induction of sustained IFN responses.

Emotional behavior in acute stroke : the Lausanne emotion in stroke study

Résumé : Objectif: Etudier les comportements émotionnels chez les patients ayant souffert d'un accident vasculaire cérébral (AVC) Contexte: Les modifications du comportement émotionnel après un AVC sont actuellement bien reconnues mais ont été très peu étudiées dans la phase aigüe de l'AVC. Méthode: Tous les patients présentant un AVC datant de moins de 24 heures ont été inclus prospectivement. Nous avons validé une échelle (the Emotional Behavior Index (EBI)), comprenant 38 qualificatifs, représentant la tristesse, l'agressivité, la désinhibition, l'adaptation, la passivité, l'indifférence et le déni. Les informations cliniques et radiologiques (CT et IRM) ont été obtenues par le biais de notre Registre des AVC. L'analyse statistique a été faite au moyen de tests uni- et multi-variés Résultats: Des 254 patients inclus, 40% présentaient de la tristesse, 49% de la passivité, 17% de l'agressivité, 53% de l'indifférence, 76% de la désinhibition, 18% un manque d'adaptation et 44% une réaction de déni. Plusieurs interactions statistiquement significatives ont été mises en évidence. En effet, la tristesse semble corréler à des antécédents d'alcoolisme (r = p< 0.037), au sexe féminin (r = p<0.028) et à la nature hémorragique de l'AVC (r = p<0.063). L'agressivité corrèle à des antécédents de troubles dépressifs (r = p<0.046) et à la nature hémorragique de l'AVC (r = p<0.06). Le déni corrèle plutôt au sexe masculin (r = p<0.035) et aux lésions hémorragiques (r = p<0.05). Le comportement émotionnel ne corrèle ni au degré et type d'atteinte neurologique, ni à la localisation de l'AVC mais une association entre Les lésions hémorragiques et un comportement agressif a été mis en évidence (p<0.001) de même qu'avec un manque d'adaptation (r = p<0.015), une certaine indifférence (r = p<0.018) et une réaction de déni (r = p<0.045). Conclusion: L'observation systématique des modifications du comportement émotionnel après un AVC suggère que les altérations émotionnelles sont indépendantes de la thymie et de l'atteinte physique et représentent donc probablement des séquelles à part entière de l'AVC. Abstract: Objective: To study emotional behaviors in an acute stroke population. Background: Alterations in emotional behavior after stroke have been recently recognized, but little attention has been paid to these changes in the very acute phase of stroke. Methods: Adult patients presenting with acute stroke were prospectively recruited and studied. We validated the Emotional Behavior Index (EBI), a 38-item scale designed to evaluate behavioral aspects of sadness, aggressiveness, disinhibition, adaptation, passivity, indifference, and denial. Clinical, historical, and imaging (computed tomography/magnetic resonance imaging) data were obtained on each subject through our Stroke Registry. Statistical analysis was performed with both univariate and multivariate tests. Results: Of the 254 patients, 40% showed sadness, 49% passivity, 17% aggressiveness, 53% indifference, 76% disinhibition, 18% lack of adaptation, and 44% denial reactions. Several significant correlations were identified. Sadness was correlated with a personal history of alcohol abuse (r = P < 0.037), female gender (r = P < 0.028), and hemorrhagic nature of the stroke (r = P < 0.063). Aggressiveness was correlated with a personal history of depression (r = P < 0.046) and hemorrhage (r = P < 0.06). Denial was correlated with male gender (r= P < 0.035) and hemorrhagic lesions (r = P < 0.05). Emotional behavior did not correlate with either neurologic impairment or lesion localization, but there was an association between hemorrhage and aggressive behavior (P < 0.001), lack of adaptation (r = P < 0.015), indifference (r = P < 0.018), and denial (r = P < 0.045). Conclusions: Systematic observations of acute emotional behaviors after stroke suggest that emotional alterations are independent of mood and physical status and should be considered as a separate consequence of stroke.

Impact of Sirtuin 2 knockout on innate immune responses

Purpose/Objective: Histone deacetylases (HDACs) deacetylate histones and transcriptional regulators thereby affecting numerous biological functions. Seven mammalian sirtuins (SIRT1-7) constitute the NAD-dependent class III subfamily of HDACs. Sirtuins are the center of great interest due to their regulatory role in the control of metabolism, ageing and age-related diseases. Up to now, little is known about the influence of sirtuins on immune responses, and nothing about the role of SIRT2. The aim of the study was to analyze the influence of SIRT2 knockout on immune cell development and innate immune responses in vitro and in vivo. Materials and methods: SIRT2 germline knockout were produced on a C57BL/6J background. The cellularity of thymus and spleen was assessed by flow cytometry (n = 3). Bone marrow derived macrophages (BMDMs) and dendritic cells (BMDCs) and splenocytes were stimulated with LPS, Pam3CSK4 lipopeptide, CpG ODN, E. coli, S. aureus, TSST-1, SEB, anti-CD3+ CD28 and concanavalin A (n = 3_8). TNF, IL-2, IL-6, IL-12p40 and IFNc production, SIRT1_7 and CD40 expression, and proliferation were quantified by real time-PCR, ELISA, flow cytometry and H3-thymidine incorporation. Mice (n = 6_16) were challenged with LPS, TNF/D-galactosamine, E. coli and K. pneumonia titrated to cause either mild or severe infections or shock. Blood was collected to quantify cytokines and bacteria. Mortality was checked regularly. Results: SIRT2 is the most expressed sirtuin in macrophages and myeloid DCs. To test whether SIRT2 impacts on innate immune responses, we generated SIRT2 germline knockout mice. SIRT2-/- mice born at the expected Mendelian ratio and develop normally. The proportions and absolute numbers of DN1-4, DP and SP thymocytes, and of T-cells (DN and SP, naı¨ve and memory), B-cells (immature and mature), DCs (cDCs and pDCs) and granulocytes in the spleen are similar in SIRT2+/+ and SIRT2-/- mice. SIRT2+/+ and SIRT2-/- BMDMs, BMDCs and splenocytes produce cytokines (RNA and protein), upregulate CD40, and proliferate to the same extent. SIRT2+/+ and SIRT2-/- mice respond similarly (cytokine blood levels, bacterial counts and mortality) to non-severe and lethal endotoxemia, E. coli peritonitis, K. pneumonia pneumonia and TNF-induced shock. Conclusions: SIRT2 knockout has no dramatic impact on the development of immune cells and on innate immune responses in vitro and in vivo. Considering that SIRT2 may participate to control metabolic homeostasis, we are currently assessing the impact of SIRT2 deficiency on innate immune responses under metabolic stress.

Directory of services to help improve mental health and emotional wellbeing

These five directories list the names, numbers and web addresses (where applicable) of organisations that offer services to help improve mental health and emotional wellbeing. Where possible, additional information has also been provided, such as email addresses and contact details within each Health and Social Care Trust area.

Combined Use of Mycobacterium tuberculosis-Specific CD4 and CD8 T-Cell Responses Is a Powerful Diagnostic Tool of Active Tuberculosis.

Immune-based assays are promising tools to help to formulate diagnosis of active tuberculosis. A multiparameter flow cytometry assay assessing T-cell responses specific to Mycobacterium tuberculosis and the combination of both CD4 and CD8 T-cell responses accurately discriminated between active tuberculosis and latent infection.

Anti-malaria humoral responses in children exposed to Plasmodium falciparum and Schistosoma haematobium

Antibody responses directed against the Plasmodium falciparum antigens, total extract, anti-merozoite surface protein-3 (MSP3b) and glutamate-rich protein (Glurp-R0) were studied in 42 children exposed to both Schistosoma haematobium and P. falciparum infections. The association between levels of the anti-malaria IgG subclasses and IgM with host age, sex, schistosome infection intensity and schistosome specific antibodies was studied before chemotherapeutic treatment of schistosome infections. This showed a significant negative association between schistosome infection intensity and levels of IgG1, IgG3, and IgG4 directed against malaria total extract antigen, and a positive association between levels of anti-schistosome soluble egg antigen IgG2, IgG3, and IgG4 and levels of the same subclasses directed against malaria total extract antigens. The effect of treating schistosome infections with praziquantel on malaria specific responses was also studied. This treatment resulted in increases in significant IgG4 levels against MSP3b and IgM against Glurp R0. Treatment also resulted in a significant decrease in IgG4 levels against Glurp R0. Host age, sex or pre-treatment infection intensity was not associated with the magnitude of change in the two IgG4 responses while males showed a significantly higher increase in levels of IgM. The results suggest cross reactivity between schistosome and malaria antigens in this population.

Therapeutic Blockade of LIGHT Interaction With Herpesvirus Entry Mediator and Lymphotoxin β Receptor Attenuates In Vivo Cytotoxic Allogeneic Responses.

BACKGROUND: Tumor necrosis factor/tumor necrosis factor receptor superfamily members conform a group of molecular interaction pathways of essential relevance during the process of T-cell activation and differentiation toward effector cells and particularly for the maintenance phase of the immune response. Specific blockade of these interacting pathways, such as CD40-CD40L, contributes to modulate the deleterious outcome of allogeneic immune responses. We postulated that antagonizing the interaction of LIGHT expression on activated T cells with its receptors, herpesvirus entry mediator and lymphotoxin β receptor, may decrease T cell-mediated allogeneic responses. METHODS: A flow cytometry competition assay was designed to identify anti-LIGHT monoclonal antibodies capable to prevent the interaction of mouse LIGHT with its receptors expressed on transfected cells. An antibody with the desired specificity was evaluated in a short-term in vivo allogeneic cytotoxic assay and tested for its ability to detect endogenous mouse LIGHT. RESULTS: We provide evidence for the first time that in mice, as previously described in humans, LIGHT protein is rapidly and transiently expressed after T-cell activation, and this expression was stronger on CD8 T cells than on CD4 T cells. Two anti-LIGHT antibodies prevented interactions of mouse LIGHT with its two known receptors, herpesvirus entry mediator and lymphotoxin β receptor. In vivo administration of anti-LIGHT antibody (clone 10F12) ameliorated host antidonor short-term cytotoxic response in wild type B6 mice, although to a lesser extent than that observed in LIGHT-deficient mice. CONCLUSION: The therapeutic targeting of LIGHT may contribute to achieve a better control of cytotoxic responses refractory to current immunosuppressive drugs in transplantation.