Sustained 24-hour blockade of the renin-angiotensin system: a high dose of a long-acting blocker is as effective as a lower dose combined with an angiotensin-converting enzyme inhibitor.

Whether a higher dose of a long-acting angiotensin II receptor blocker (ARB) can provide as much blockade of the renin-angiotensin system over a 24-hour period as the combination of an angiotensin-converting enzyme inhibitor and a lower dose of ARB has not been formally demonstrated so far. In this randomized double-blind study we investigated renin-angiotensin system blockade obtained with 3 doses of olmesartan medoxomil (20, 40, and 80 mg every day) in 30 normal subjects and compared it with that obtained with lisinopril alone (20 mg every day) or combined with olmesartan medoxomil (20 or 40 mg). Each subject received 2 dose regimens for 1 week according to a crossover design with a 1-week washout period between doses. The primary endpoint was the degree of blockade of the systolic blood pressure response to angiotensin I 24 hours after the last dose after 1 week of administration. At trough, the systolic blood pressure response to exogenous angiotensin I was 58% +/- 19% with 20 mg lisinopril (mean +/- SD), 58% +/- 11% with 20 mg olmesartan medoxomil, 62% +/- 16% with 40 mg olmesartan medoxomil, and 76% +/- 12% with the highest dose of olmesartan medoxomil (80 mg) (P = .016 versus 20 mg lisinopril and P = .0015 versus 20 mg olmesartan medoxomil). With the combinations, blockade was 80% +/- 22% with 20 mg lisinopril plus 20 mg olmesartan medoxomil and 83% +/- 9% with 20 mg lisinopril plus 40 mg olmesartan medoxomil (P = .3 versus 80 mg olmesartan medoxomil alone). These data demonstrate that a higher dose of the long-acting ARB olmesartan medoxomil can produce an almost complete 24-hour blockade of the blood pressure response to exogenous angiotensin in normal subjects. Hence, a higher dose of a long-acting ARB is as effective as a lower dose of the same compound combined with an angiotensin-converting enzyme inhibitor in terms of blockade of the vascular effects of angiotensin.

La chirurgie combinée phacoémulsification/pelage de membrane épirétinienne et oedème maculaire [Combined phacoemulsification/membrane resection and macular edema].

PURPOSE: To evaluate the occurrence of macular edema (ME) after epiretinal membrane resection, managed either with simple vitrectomy or with combined vitrectomy and phacoemulsification. MATERIAL AND METHODS: Two groups of 12 patients had a vitrectomy for epiretinal membrane associated or not to a phacoemulsification. A fundus fluorescein angiography was performed pre and postoperatively and at least 3 months after the surgery. RESULTS: In the group of patients who had a simple vitrectomy, a ME was observed in 50% of the cases preoperatively and in 25% of the cases at the end of follow-up. In 3 cases, preoperative ME was worsened after the surgery. In the group of patients who were treated by a combined vitrectomy and phacoemulsification, a ME was observed in 25% of the cases preoperatively and in 50% of the cases at the end of follow-up. A de novo ME was observed in 3 cases. CONCLUSION: Combined vitrectomy and cataract surgery could allow a rapid recovery of visual acuity but might increase the occurrence of ME.

Chronic delivery of antibody fragments using immunoisolated cell implants as a passive vaccination tool.

BACKGROUND: Monoclonal antibodies and antibody fragments are powerful biotherapeutics for various debilitating diseases. However, high production costs, functional limitations such as inadequate pharmacokinetics and tissue accessibility are the current principal disadvantages for broadening their use in clinic. METHODOLOGY AND PRINCIPAL FINDINGS: We report a novel method for the long-term delivery of antibody fragments. We designed an allogenous immunoisolated implant consisting of polymer encapsulated myoblasts engineered to chronically release scFv antibodies targeted against the N-terminus of the Aβ peptide. Following a 6-month intracerebral therapy we observed a significant reduction of the production and aggregation of the Aβ peptide in the APP23 transgenic mouse model of Alzheimer's disease. In addition, functional assessment showed prevention of behavioral deficits related to anxiety and memory traits. CONCLUSIONS AND SIGNIFICANCE: The chronic local release of antibodies using immunoisolated polymer cell implants represents an alternative passive vaccination strategy in Alzheimer's disease. This novel technique could potentially benefit other diseases presently treated by local and systemic antibody administration.

Loss to follow-up of HIV-infected women after delivery : The Swiss HIV Cohort Study and the Swiss Mother and Child HIV Cohort Study

INTRODUCTION: HIV-infected pregnant women are very likely to engage in HIV medical care to prevent transmission of HIV to their newborn. After delivery, however, childcare and competing commitments might lead to disengagement from HIV care. The aim of this study was to quantify loss to follow-up (LTFU) from HIV care after delivery and to identify risk factors for LTFU. METHODS: We used data on 719 pregnancies within the Swiss HIV Cohort Study from 1996 to 2012 and with information on follow-up visits available. Two LTFU events were defined: no clinical visit for >180 days and no visit for >360 days in the year after delivery. Logistic regression analysis was used to identify risk factors for a LTFU event after delivery. RESULTS: Median maternal age at delivery was 32 years (IQR 28-36), 357 (49%) women were black, 280 (39%) white, 56 (8%) Asian and 4% other ethnicities. One hundred and seven (15%) women reported any history of IDU. The majority (524, 73%) of women received their HIV diagnosis before pregnancy, most of those (413, 79%) had lived with diagnosed HIV longer than three years and two-thirds (342, 65%) were already on antiretroviral therapy (ART) at time of conception. Of the 181 women diagnosed during pregnancy by a screening test, 80 (44%) were diagnosed in the first trimester, 67 (37%) in the second and 34 (19%) in the third trimester. Of 357 (69%) women who had been seen in HIV medical care during three months before conception, 93% achieved an undetectable HIV viral load (VL) at delivery. Of 62 (12%) women with the last medical visit more than six months before conception, only 72% achieved an undetectable VL (p=0.001). Overall, 247 (34%) women were LTFU over 180 days in the year after delivery and 86 (12%) women were LTFU over 360 days with 43 (50%) of those women returning. Being LTFU for 180 days was significantly associated with history of intravenous drug use (aOR 1.73, 95% CI 1.09-2.77, p=0.021) and not achieving an undetectable VL at delivery (aOR 1.79, 95% CI 1.03-3.11, p=0.040) after adjusting for maternal age, ethnicity, time of HIV diagnosis and being on ART at conception. CONCLUSIONS: Women with a history of IDU and women with a detectable VL at delivery were more likely to be LTFU after delivery. This is of concern regarding their own health, as well as risk for sexual partners and subsequent pregnancies. Further strategies should be developed to enhance retention in medical care beyond pregnancy.

Cognitive behavioural skills for practice a model for delivery in the Irish mental health service.

This publication outlines a model of delivery for introductory level Cognitive Behavioural Therapy (CBT) training in the Mental Health Service, HSE South (Carlow, Kilkenny, South Tipperary, Waterford, Wexford). This model has proved useful in guiding the development of four introductory programmes during 2009 and 2010. As a result of this experience, we have amended and updated our programme delivery strategies. We see this process as organic and ever changing, thus these reflections are a snap shot of our current thinking which we have no doubt will evolve as we proceed with future programmes. This booklet will act as a guide for our upcoming programmes in 2010 and 2011 and we believe it may also offer guidance to others who will be involved in the delivery of CBT training within the Irish Mental Health Service.This resource was contributed by The National Documentation Centre on Drug Use.

Public Policy and Ageing in Northern Ireland: Identifying Levers for Change

Public Policy and Ageing in Northern Ireland: Identifying Levers for Change Judith Cross, Policy Officer with the Centre for Ageing Research Development in Ireland (CARDI)��������Introduction Identifying a broad range of key public policy initiatives as they relate to age can facilitate discussion and create new knowledge within and across government to maximise the opportunities afforded by an ageing population. This article looks at how examining the current public policy frameworks in Northern Ireland can present opportunities for those working in this field for the benefit of older people. Good policy formulation needs to be evidence-based, flexible, innovative and look beyond institutional boundaries. Bringing together architects and occupational therapists, for example, has the potential to create better and more effective ways relevant to health, housing, social services and government departments. Traditional assumptions of social policy towards older people have tended to be medically focused with an emphasis on care and dependency. This in turn has consequences for the design and delivery of services for older people. It is important that these assumptions are challenged as changes in thinking and attitudes can lead to a redefinition of ageing, resulting in policies and practices that benefit older people now and in the future. Older people, their voices and experiences, need to be central to these developments. The Centre for Ageing Research and Development in Ireland The Centre for Ageing Research and Development in Ireland (CARDI) (1) is a not for profit organisation developed by leaders from the ageing field across Ireland (North and South) including age sector focused researchers and academics, statutory and voluntary, and is co-chaired by Professor Robert Stout and Professor Davis Coakley. CARDI has been established to provide a mechanism for greater collaboration among age researchers, for wider dissemination of ageing research information and to advance a research agenda relevant to the needs of older people in Ireland, North and South. Operating at a strategic level and in an advisory capacity, CARDI�۪s work focuses on promoting research co-operation across sectors and disciplines and concentrates on influencing the strategic direction of research into older people and ageing in Ireland. It has been strategically positioned around the following four areas: Identifying and establishing ageing research priorities relevant to policy and practice in Ireland, North and South;Promoting greater collaboration and co-operation on ageing research in order to build an ageing research community in Ireland, North and South;Stimulating research in priority areas that can inform policy and practice relating to ageing and older people in Ireland, North and South;Communicating strategic research issues on ageing to raise the profile of ageing research in Ireland, North and South, and its role in informing policy and practice. Context of Ageing in Ireland Ireland �۪s population is ageing. One million people aged 60 and over now live on the island of Ireland. By 2031, it is expected that Northern Ireland�۪s percentage of older people will increase to 28% and the Republic of Ireland�۪s to 23%. The largest increase will be in the older old; the number aged 80+ is expected to triple by the same date. However while life expectancy has increased, it is not clear that life without disability and ill health has increased to the same extent. A growing number of older people may face the combined effects of a decline in physical and mental function, isolation and poverty. Policymakers, service providers and older people alike recognise the need to create a high quality of life for our ageing population. This challenge can be meet by addressing the problems relating to healthy ageing, reducing inequalities in later life and creating services that are shaped by, and appropriate for, older people. Devolution and Structures of Government in Northern Ireland The Agreement (2) reached in the Multi-Party Negotiations in Belfast 1998 established the Northern Ireland Assembly which has full legislative authority for all transferred matters. The majority of social and economic public policy such as; agriculture, arts, education, health, environment and planning is determined by the Northern Ireland Assembly at Stormont. There are 11 Government Departments covering the main areas of responsibility with 108 elected Members of the Legislative Assembly (MLA�۪s). The powers of the Northern Ireland Assembly do not cover ��� reserved�۪ matters or ��� excepted�۪ matters . These are the responsibility of Westminster and include issues such as, tax, social security, policing, justice, defence, immigration and foreign affairs. Northern Ireland has 18 elected Members of Parliament (MP�۪s) to the House of Commons. Public Policy Context in Northern Ireland The economic, social and political consequence of an ageing population is a challenge for policy makers across government. Considering the complex and diverse causal factors that contribute to ageing in Northern Ireland, there are a number of areas of government policy at regional, national and international levels that are likely to impact in this area. International The Madrid International Plan of Action on Ageing (3) and the Research Agenda on Ageing for the 21st Century (4) provide important mechanisms for furthering research into ageing. The United Kingdom has signed up to these. The Madrid International Plan of Action on Ageing commits member states to a systematic review of the Plan of Action through Regional Implementation Strategies. The United Kingdom�۪s Regional Implementation Strategy covers Northern Ireland. National At National level, pension and social security are high on the agenda. The Pensions Act (5) became law in 2007 and links pensions increases with earnings as opposed to prices from 2012. Additional credits for people raising children and caring for older people to boost their pensions were introduced. Some protections are included for those who lost occupational pensions as a result of underfunded schemes being wound up before April 2005. In relation to State Pensions and benefits, this Act will bring changes to state pensions in future. The Act now places the Pension Credit element which is up-rated in line with or above earnings, on a permanent, statutory footing. Regional At regional level there are a number of age related public policy initiatives that have the potential to impact positively on the lives of older people in Northern Ireland. Some are specific to ageing such as the Ageing in an Inclusive Society (6) and others by their nature are cross-cutting such as Lifetime Opportunities: Governments Anti-Poverty Strategy for Northern Ireland (7). The main public policy framework in Northern Ireland is the Programme for Government: Building a Better Future, 2008-2011(PfG) (8) . The PfG, is the overarching high level policy framework for Northern Ireland and provides useful principles for ageing research and public policy in Northern Ireland. The PfG vision is to build a peaceful, fair and prosperous society in Northern Ireland, with respect for the rule of law. A number of Public Service Agreements (PSA) aligned to the PfG confirm key actions that will be taken to support the priorities that the Government aim to achieve over the next three years. For example objective 2 of PSA 7: Making Peoples�۪ Lives Better: Drive a programme across Government to reduce poverty and address inequality and disadvantage, refers to taking forward strategic action to promote social inclusion for older people; and to deliver a strong independent voice for older people. The Office of the First Minister and deputy First Minister (OFMDFM) have recently appointed an Interim Older People�۪s Advocate, Dame Joan Harbison to provide a focus for older peoples issues across Government. Ageing in an Inclusive Society is the cross-departmental strategy for older people in Northern Ireland and was launched in March 2005. It sets out the approach to be taken across Government to promote and support the inclusion of older people. The vision coupled with six strategic objectives form the basis of the action plans accompanying the strategy. The vision is: ���To ensure that age related policies and practices create an enabling environment, which offers everyone the opportunity to make informed choices so that they may pursue healthy, active and positive ageing.�۝ (Ageing in an Inclusive Society, Office of the First Minister and Deputy First Minister, 2005) Action planning and maintaining momentum across government in relation to this strategy has proved to be slower than anticipated. It is proposed to refresh this Strategy in line with Opportunity Age ��� meeting the challenges of ageing in the 21st Century (9). There are a number of policy levers elsewhere which can also be used to promote the positive aspects of an ageing society. The Investing for Health (10) and A Healthier Future:A 20 Year Vision for Health and Well-being in Northern Ireland (11), seek to ensure that the overall vision for health and wellbeing is achievable and provides a useful framework for ageing policy and research in the health area. These health initiatives have the potential to positively impact on the quality of life of older people and provide a useful framework for improving current policy and practice. In addition to public policy initiatives, the anti-discrimination frameworks in terms of employment in Northern Ireland cover age as well as a range of other grounds. Goods facilitates and services are currently excluded from the Employment Equality (age) Regulations (NI) 2006 (12). Supplementing the anti-discrimination measures, Section 75 of the Northern Ireland Act 1998 (13), unique to Northern Ireland, places a statutory obligation on public authorities in fulfilling their functions to promote equality of opportunity across nine grounds, one of which is age(14). This positive duty has the potential to make a real difference to the lives of older people in Northern Ireland. Those affected by policy decisions must be consulted and their interests taken into account. This provides an opportunity for older people and their representatives to participate in public policy-making, right from the start of the process. Policy and Research Interface ���Ageing research is vital as decisions in relation to policy and practice and resource allocation will be made on the best available information�۝. (CARDI�۪s Strategic Plan 2008-2011) As outlined earlier, CARDI has been established to bridge the gap to ensure that research reaches those involved in making policy decisions. CARDI is stimulating the ageing research agenda in Ireland through a specific research fund that has a policy and practice focus. My work is presently focusing on helping to build a greater awareness of the key policy levers and providing opportunities for those within research and policy to develop closer links. The development of this shared understanding by establishing these links between researchers and policy makers is seen as the best predictor for research utilization. It is important to acknowledge and recognise that researchers and policy makers operate in different institutional, political and cultural contexts. Research however needs to ���resonate�۪ with the contextual factors in which policy makers operate. Conclusions Those working within the public policy field recognise all too often that the development of government policies and initiatives in respect of age does not guarantee that they will result in changes in actual provision of services, despite Government recommendations and commitments. The identification of public policy initiatives as they relate to age has the potential to highlight persistent and entrenched difficulties that social policy has previously failed to address. Furthermore, the identification of these difficulties can maximise the opportunities for progressing these across government. A focus on developing effective and meaningful targets to ensure measurable outcomes in public policy for older people can assist in this. Access to sound, credible and up-to-date evidence will be vital in this respect. As well as a commitment to working across departmental boundaries to effect change. Further details: If you would like to discuss this paper or for further information about CARDI please contact: Judith Cross, Policy Officer, Centre for Ageing Research and Development in Ireland CARDI). t: +44 (0) 28 9069 0066; m: +353 (0) 867 904 171; e: judith@cardi.ie ; or visit our website at: www.cardi.ie References 1) Centre for Ageing Research and Development in Ireland (2008) Strategic Plan 2008-2011. Belfast. CARDI 2) The Agreement: Agreement Reached in the Multi-Party Negotiations. Belfast 1998 3) Madrid International Plan of Action on Ageing. http://www.un.org/ageing/ 4) UN Programme on Ageing (2007) Research Agenda on Ageing for the 21st Century: 2007 Update. New York. New York. UN Programme on Ageing and the International Association of Gerontology and Geriatrics. 5) The Pensions Act 2007 Chapter 22 6) Office of the First Minister and deputy First Minister (2005). Ageing in an Inclusive Society. Belfast. OFMDFM Central Anti-Poverty Unit. 7) Office of the First Minister and deputy First Minister (2005). Lifetime Opportunities: Government�۪s Anti-Poverty and Social Inclusion Strategy for Northern Ireland. Belfast. OFMDFM Central Anti-Poverty Unit. 8) Northern Ireland Executive (2008) Building a Better Future: Programme for Government 2008-2011. Belfast. OFMDFM Economic Policy Unit. 9) Department for Work and Pensions, (2005) Opportunity Age: Meeting the Challenges of Ageing in the 21 st Century. London. DWP. 10) Department of Health, Social Services and Public Safety (DHSS&PS) (2002) Investing for Health. Belfast. DHSS&PS. 11) Department of Health, Social Services and Public Safety (DHSS&PS) (2005) A Healthier Future:A 20 Year Vision for Health and Well-being in Northern Ireland Belfast. DHSS&PS. �� 12) The Employment Equality (Age) Regulations (Northern Ireland) 2006 SR2006 No.261 13) The Northern Ireland Act 1998, Part VII, S75 14) The nine grounds covered under S75 of the Northern Ireland Act are: gender, religion, race, sexual orientation, those with dependents, disability, political opinion, marital status and age.

Are We Choosing Health? The Impact of policy on the delivery of health improvement programmes and services

The Audit Commission and Healthcare Commission have jointly published 'Are we choosing health? The impact of policy on the delivery of health improvement programmes and services'. The report assesses the impact government policy has had over the past decade on: narrowing health inequalities; improving sexual and mental health; and reducing smoking, alcohol misuse and obesity.

Health Development Agency Delivery Plan 2003-06

This plan sets out the contribution the Health Development Agency (HDA) aims to make over the next three years to the cross-government objective of improving public health and reducing health inequalities. It reflects clear guidance given to the HDA by the minister for public health following the HDA۪s 2002 accountability review. The result is a smaller number of longer-term programmes fosused on four key delivery priorities: ۢ Underlying determinants of health ۢ The big killers coronary heart disease and cancer ۢ Children and young people ۢ Vulnerable adults

Quality Standards for the Delivery of Specialist Stop Smoking Services in Northern Ireland September 2011

Cigarette smoking is the major cause of preventable ill health in Northern Ireland. It accounts for 2400 premature deaths every year. Fifty percent or one in every two smokers will die prematurely due to their addiction; many will suffer chronic ill health and poor quality of life before their death (DHSSPS, 2007; ASH, 2008). Approximately 340,000 people smoke in Northern Ireland or 24% of the population over 16yrs. The Public Health Agency (PHA) commissions specialist stop smoking services across Northern Ireland. It has enabled the establishment of specialist stop smoking services in a range of settings including GP practices, pharmacies, hospitals and community settings. Tobacco control activities are overseen locally by the PHA's Tobacco Control Groups. The multi-agency groups oversee and advise on tobacco control initiatives.All stop smoking services are required to comply with the requirements of 18 standards. This report highlights the standards.

What is the most relevant standard of success in assisted reproduction?: The cumulated singleton/twin delivery rates per oocyte pick-up: the CUSIDERA and CUTWIDERA.

National and international registries are essential tools for establishing new standards and comparing success rates, but they do not take into account the total pregnancy/delivery rate per oocyte recovery. In Switzerland and Germany, because of legal constraints, a maximum of three two-pronuclear zygotes are allocated for transfer whereas all the supernumerary pronuclear zygotes are immediately cryopreserved, preventing selection of the transferred embryos. We report on a 10 years' experience (1993-2002) of our centre which performs transfers of unselected embryos and cryopreservation at the two-pronuclear zygote stage. As approximately 30% of all deliveries are from cryo cycles, it is essential to take into account the contribution of the cryo transfers, and we propose therefore to evaluate, as a measure of IVF performance, the cumulated delivery rate per oocyte pick-up. This delivery rate is broken down further into the cumulated singleton delivery rate (CUSIDERA) and the cumulated twin delivery rate (CUTWIDERA). The sum (S) of these two rates is a measure of efficacy while the ratio CUTWIDERA/S as a percentage is a measure of safety of IVF treatments. Using these new indexes, the average 10 year efficacy and safety of our IVF programme were 26 and 19%, respectively. Both CUSIDERA and CUTWIDERA can be calculated easily in any clinical situation and yield useful parameters for patient counselling and internal/external benchmarking purposes.

Retinal dysfunction in combined methylmalonic aciduria and homocystinuria (Cblc) disease: a spectrum of disorders.

BACKGROUND: Cobalamin C methylmalonic aciduria with homocystinuria (cblC disease) is a rare hereditary inborn error of cobalamin metabolism, characterised by neurological, haematological and ophthalmological abnormalities. PATIENTS AND METHODS: Three consecutive patients with Cblc disease were examined. Investigations included slit lamp and fundus examination and full-field ERG. RESULTS: A maculopathy associated with both photopic and scotopic abnormal ERG was present in two cases and a salt and pepper retinopathy with abnormal photopic ERG was detected in the third patient. CONCLUSIONS: Despite early treatment and regular metabolic controls, all our patients exhibited both retinal and ERG abnormalities. There was no correlation between funduscopic appearance and the type of photoreceptor dysfunction. A literature review disclosed a retinopathy in 29 / 70 cases with cblC disease, with an abnormal ERG in 8 of the 12 tested cases, most with retinopathy. Retinal dysfunction in cblC disease may be more frequent than previously thought, and can involve cones only or both rods and cones. We recommend a formal ocular examination with full-field ERG in patients with Cblc disease.

Comparative vascular and renal tubular effects of angiotensin II receptor blockers combined with a thiazide diuretic in humans.

OBJECTIVE: The goal of this study was to investigate whether angiotensin II receptor blockers (ARBs) induce a comparable blockade of AT1 receptors in the vasculature and in the kidney when the renin-angiotensin system is activated by a thiazide diuretic. METHOD: Thirty individuals participated in this randomized, controlled, single-blind study. The blood pressure and renal hemodynamic and tubular responses to a 1-h infusion of exogenous angiotensin II (Ang II 3 ng/kg per min) were investigated before and 24 h after a 7-day administration of either irbesartan 300 mg alone or in association with 12.5 or 25 mg hydrochlorothiazide (HCTZ). Irbesartan 300/25 mg was also compared with losartan 100 mg, valsartan 160 mg, and olmesartan 20 mg all in association with 25 mg HCTZ. Each participant received two treatments with a 1-week washout period between treatments. RESULTS: The blood pressure response to Ang II was blocked by more than 90% with irbesartan alone or in association with HCTZ and with olmesartan/HCTZ and by nearly 60% with valsartan/HCTZ and losartan/HCTZ (P < 0.05). In the kidney, Ang II reduced renal plasma flow by 36% at baseline (P < 0.001). Irbesartan +/- HCTZ and olmesartan/HCTZ blocked the renal hemodynamic response to Ang II nearly completely, whereas valsartan/HCTZ and losartan/HCTZ only blunted this effect by 34 and 45%, respectively. At the tubular level, Ang II significantly reduced urinary volume (-84%) and urinary sodium excretion (-65%) (P < 0.01). These tubular effects of Ang II were only partially blunted by the administration of ARBs. CONCLUSION: These data demonstrate that ARBs prescribed at their recommended doses do not block renal tubular AT1 receptors as effectively as vascular receptors do. This observation may account for the need of higher doses of ARB for renal protection. Moreover, our results confirm that there are significant differences between ARBs in their capacity to induce a sustained vascular and tubular blockade of Ang II receptors.

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.

Collagen (NeuraGen®) nerve conduits and stem cells for peripheral nerve gap repair.

Collagen nerve guides are used clinically for peripheral nerve defects, but their use is generally limited to lesions up to 3 cm. In this study we combined collagen conduits with cells as an alternative strategy to support nerve regeneration over longer gaps. In vitro cell adherence to collagen conduits (NeuraGen(®) nerve guides) was assessed by scanning electron microscopy. For in vivo experiments, conduits were seeded with either Schwann cells (SC), SC-like differentiated bone marrow-derived mesenchymal stem cells (dMSC), SC-like differentiated adipose-derived stem cells (dASC) or left empty (control group), conduits were used to bridge a 1cm gap in the rat sciatic nerve and after 2-weeks immunohistochemical analysis was performed to assess axonal regeneration and SC infiltration. The regenerative cells showed good adherence to the collagen walls. Primary SC showed significant improvement in distal stump sprouting. No significant differences in proximal regeneration distances were noticed among experimental groups. dMSC and dASC-loaded conduits showed a diffuse sprouting pattern, while SC-loaded showed an enhanced cone pattern and a typical sprouting along the conduits walls, suggesting an increased affinity for the collagen type I fibrillar structure. NeuraGen(®) guides showed high affinity of regenerative cells and could be used as efficient vehicle for cell delivery. However, surface modifications (e.g. with extracellular matrix molecule peptides) of NeuraGen(®) guides could be used in future tissue-engineering applications to better exploit the cell potential.