CD8 lymphocytes do not impact SIV reservoir establishment under ART.

Persistence of the human immunodeficiency virus type-1 (HIV-1) latent reservoir in infected individuals remains a problem despite fully suppressive antiretroviral therapy (ART). While reservoir formation begins during acute infection, the mechanisms responsible for its establishment remain unclear. CD8 T cells are important during the initial control of viral replication.

Designing rare disease care pathways in the Republic of Ireland: a co-operative model.

Background: Rare diseases (RDs) are often complex, serious, chronic and multi-systemic conditions, associated with physical, sensory and intellectual disability. Patients require follow-up management from multiple medical specialists and health and social care professionals involving a high level of integrated care, service coordination and specified care pathways.

Methods And Objectives: This pilot study aimed to explore the best approach for developing national RD care pathways in the Irish healthcare system in the context of a lack of agreed methodology.

CD8 lymphocyte depletion enhances the latency reversal activity of the SMAC mimetic AZD5582 in ART-suppressed SIV-infected rhesus macaques.

Inducing latency reversal to reveal infected cells to the host immune system represents a potential strategy to cure HIV infection. In separate studies, we have previously shown that CD8 T cells may contribute to the maintenance of viral latency and identified a novel SMAC mimetic/IAP inhibitor (AZD5582) capable of reversing HIV/SIV latency by activating the non-canonical (nc) NF-κB pathway. Here, we use AZD5582 in combination with antibody-mediated depletion of CD8α cells to further evaluate the role of CD8 T cells in viral latency maintenance.

Combination of CD8β Depletion and Interleukin-15 Superagonist N-803 Induces Virus Reactivation in Simian-Human Immunodeficiency Virus-Infected, Long-Term ART-Treated Rhesus Macaques.

The "shock and kill" strategy predicates that virus reactivation in latently infected cells is required to eliminate the human immunodeficiency virus (HIV) reservoir. In a recent study, we showed robust and persistent induction of plasma viremia in antiretroviral therapy (ART)-treated simian immunodeficiency virus-infected rhesus macaques (RMs) undergoing CD8α depletion and treated with the interleukin-15 (IL-15) superagonist N-803 (J. B.

Virologic and Immunologic Features of Simian Immunodeficiency Virus Control Post-ART Interruption in Rhesus Macaques.

Antiretroviral therapy (ART) cannot eradicate human immunodeficiency virus (HIV) and a rapid rebound of virus replication follows analytical treatment interruption (ATI) in the vast majority of HIV-infected individuals. Sustained control of HIV replication without ART has been documented in a subset of individuals, defined as posttreatment controllers (PTCs). The key determinants of post-ART viral control remain largely unclear.

Author Correction: Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8 cells.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8 cells.

Human immunodeficiency virus (HIV) persists indefinitely in individuals with HIV who receive antiretroviral therapy (ART) owing to a reservoir of latently infected cells that contain replication-competent virus. Here, to better understand the mechanisms responsible for latency persistence and reversal, we used the interleukin-15 superagonist N-803 in conjunction with the depletion of CD8 lymphocytes in ART-treated macaques infected with simian immunodeficiency virus (SIV). Although N-803 alone did not reactivate virus production, its administration after the depletion of CD8 lymphocytes in conjunction with ART treatment induced robust and persistent reactivation of the virus in vivo.

Bone Marrow-Derived CD4 T Cells Are Depleted in Simian Immunodeficiency Virus-Infected Macaques and Contribute to the Size of the Replication-Competent Reservoir.

The bone marrow (BM) is the key anatomic site for hematopoiesis and plays a significant role in the homeostasis of mature T cells. However, very little is known on the phenotype of BM-derived CD4 T cells, their fate during simian immunodeficiency virus (SIV) infection, and their contribution to viral persistence during antiretroviral therapy (ART). In this study, we characterized the immunologic and virologic status of BM-derived CD4 T cells in rhesus macaques prior to SIV infection, during the early chronic phase of infection, and during ART.

Antibody-Mediated CD4 Depletion Induces Homeostatic CD4 T Cell Proliferation without Detectable Virus Reactivation in Antiretroviral Therapy-Treated Simian Immunodeficiency Virus-Infected Macaques.

A major barrier to human immunodeficiency virus (HIV) eradication is the long-term persistence of latently infected CD4 T cells harboring integrated replication-competent virus. It has been proposed that the homeostatic proliferation of these cells drives long-term reservoir persistence in the absence of virus reactivation, thus avoiding cell death due to either virus-mediated cytopathicity or immune effector mechanisms. Here, we conducted an experimental depletion of CD4 T cells in eight antiretroviral therapy (ART)-treated, simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) to determine whether the homeostatically driven CD4 T-cell proliferation that follows CD4 T-cell depletion results in reactivation of latent virus and/or expansion of the virus reservoir.

Impact of cholinesterase inhibitors or memantine on survival in adults with Down syndrome and dementia: clinical cohort study.

Background: There is little evidence to guide pharmacological treatment in adults with Down syndrome and Alzheimer's disease. Aims To investigate the effect of cholinesterase inhibitors or memantine on survival and function in adults with Down syndrome and Alzheimer's disease.

Method: This was a naturalistic longitudinal follow-up of a clinical cohort of 310 people with Down syndrome diagnosed with Alzheimer's disease collected from specialist community services in England.

Mechanisms of CD8 T cell-mediated suppression of HIV/SIV replication.

In this article, we summarize the role of CD8 T cells during natural and antiretroviral therapy (ART)-treated HIV and SIV infections, discuss the mechanisms responsible for their suppressive activity, and review the rationale for CD8 T cell-based HIV cure strategies. Evidence suggests that CD8 T cells are involved in the control of virus replication during HIV and SIV infections. During early HIV infection, the cytolytic activity of CD8 T cells is responsible for control of viremia.

Predictors of Age of Diagnosis and Survival of Alzheimer's Disease in Down Syndrome.

Background: People with Down syndrome (DS) are an ultra-high risk population for Alzheimer's disease (AD). Understanding the factors associated with age of onset and survival in this population could highlight factors associated with modulation of the amyloid cascade.

Objective: This study aimed to establish the typical age at diagnosis and survival associated with AD in DS and the risk factors associated with these.

The application of differential ratings of perceived exertion to Australian Football League matches.

Objectives: To investigate the application of differential ratings of perceived exertion for the examination of internal load during Australian Football League (AFL) matches.

Design: Single cohort, observational study.

Methods: Using the centiMax rating of perceived exertion (RPE) scale, 26 professional AFL players provided ratings for match exertion (RPE-M), along with differential ratings for breathlessness (RPE-B), leg exertion (RPE-L), and technical demand (RPE-T) following 129 matches (5.

Meeting the health care needs of school-age children with intellectual disability.

Intellectual disability (ID) is common and is known to affect 1-3% of the population. There is a lack of medical epidemiological data in Ireland for this group. Such data is necessary in providing the evidence base to plan for rehabilitation services, provide ongoing health care and consider prevention strategies.

Further case of microdeletion of 8q24 with phenotype overlapping Langer-Giedion without TRPS1 deletion.

Langer-Giedion syndrome results from a microdeletion at 8q24.1 encompassing the EXT1 and the adjacent TRPS1 gene. We report on a boy with an oligo array-cgh characterized small microdeletion involving EXT1 alone but with some features of Langer-Giedion syndrome suggesting a functional disturbance of TRPS1.

Measles outbreak in Dublin, 2000.

Background: An outbreak of measles occurred in Ireland between December 1999 and July 2000. The majority of cases were in north Dublin, the catchment area of The Children's University Hospital (TCUH).

Methods: Details of all of the 111 children attending the hospital with a diagnosis of measles between December 1999 and July 2000 were prospectively entered into a database.

Assessment and diagnosis of depression in people with intellectual disability.

Background: Despite widespread acceptance that depression can occur in adults with intellectual disability (ID), the difficulties encountered in its assessment and diagnosis have hampered the individual clinician, and meant that questions of prevalence, treatment choice and outcome remain problematic.

Method: The present paper reviews the progress in this field since three reviews, all published in the mid-1990s, recommended further attention to three interlinked issues: diagnostic criteria, the symptoms of depression in this group and the lack of rating scales.

Results: Despite a further 11 published papers and other studies in progress, the method of diagnosis for people with severe and profound ID remains debatable, with some authors advocating adherence to standard criteria, others suggesting adding criteria to the standard ones and yet others believing that substitute criteria are called for.

Behavioural training for nurses in mental handicap: an application of the EDY course.

The role of the nurse in the care of mentally handicapped people is increasingly one of teaching and training using behavioural methods, as witnessed, for example, by the new RNMS syllabus. Methods of providing suitable training to equip staff for this changing role are discussed and it is concluded that an economic and effective method may be through locally organized in-service training. One particular in-service course--the education of the developmentally young course for mental handicap practitioners--is described and its applications in two health authorities in the UK are discussed.