The role of graft T-cell size in patients receiving alemtuzumab serotherapy for non-malignant disorders: results of an institutional protocol.

Although graft T cells assist in engraftment, mediate antiviral immune-reconstitution, and cause graft-versus-host disease, graft size is not determined by T-cell content of the graft. The conventional method of graft size determination based on CD34+ cells with alemtuzumab serotherapy is associated with delayed immune reconstitution, contributing to an increased risk of viral infections and graft failure. Alemtuzumab, a long half-life anti-CD52 monoclonal antibody is a robust T-cell depleting serotherapy, and relatively spares memory-effector T cells compared to naïve T cells. We therefore hypothesized that graft size based on T-cell content in patients receiving peripheral blood stem cell graft with alemtuzumab serotherapy would facilitate immune-reconstitution without increasing the risk of graft-versus-host disease. We retrospectively analysed twenty-six consecutive patients with non-malignant disorders grafted using alemtuzumab serotherapy and capping of graft T cells to a maximum of 600 million/kg. The graft T-cell capping protocol resulted in early immune-reconstitution without increasing the risk of severe graft-versus-host disease. Graft T-cell content correlated with CD4+ T-cell reconstitution and acute graft-versus-host disease. The course of CMV viraemia was predictable without recurrence and associated with early T-cell recovery. No patient developed chronic graft-versus-host disease. Overall survival at one year was 100% and disease-free survival was 96% at a median of 899 days (range: 243-1562). Graft size determined by peripheral blood stem cell graft T-cell content in patients receiving alemtuzumab serotherapy for non-malignant disorders is safe and leads to early T-cell immune-reconstitution with excellent survival outcomes.

First episode psychosis: A comparison of caregiving appraisals in parents caring for the same child.

BACKGROUND: The first onset of psychosis can be a traumatic event for diagnosed individuals but can also impact negatively on their families. Little is known about how parents of the same child make sense of the illness. In mothers and fathers caring for the same child with early psychosis, the current study assessed their similarities and differences in key areas of their caregiving role. METHODS: Using a cross-sectional design, parental pairs caring for the same child treated within an early intervention in psychosis service, completed self-report measures on their caregiving experiences, illness beliefs, coping styles and affect. RESULTS: Data from 44 mothers and fathers were analysed. Analyses confirmed that parents reported similar levels of emotional dysfunction and conceptualized the illness in broadly similar ways with regard to what they understood the illness to be, their emotional reactions to the illness, perceived illness consequences and beliefs about treatment. Significant differences were identified in their beliefs about the timeline of the illness and reported approaches to coping. CONCLUSIONS: With exception of beliefs about illness timeline and an expressed preference for use of emotion-based coping, parent caregivers of the same child in early psychosis services are likely to report similar illness beliefs and caregiving reactions. Efforts to ensure staff awareness of the potential areas of divergence in parental caregiving appraisals and exploring the implications of the divergence for the caregiving relationship and patient outcomes are indicated.

MicroRNA biogenesis, gene silencing mechanisms and role in breast, ovarian and prostate cancer.

Micro-ribonucleic acids (miRNAs) are important class of short regulatory RNA molecules involved in regulation of several essential biological processes. In addition to Dicer and Drosha, over the past few years several other gene products are discovered that regulates miRNA biogenesis pathways. Similarly, various models of molecular mechanisms underlying miRNA mediated gene silencing have been uncovered through which miRNA contribute in diverse physiological and pathological processes. Dysregulated miRNA expression has been reported in many cancers manifesting tumor suppressive or oncogenic role. In this review, critical overview of recent findings in miRNA biogenesis, silencing mechanisms and specifically the role of miRNA in breast, ovarian and prostate cancer will be described. Recent advancements in miRNA research summarized in this review will enhance the molecular understanding of miRNA biogenesis and mechanism of action. Also, role of miRNAs in pathogenesis of breast, ovarian and prostate cancer will provide the insights for the use of miRNAs as biomarker or therapeutic agents for the cancers.

Understanding the experience of "burnout" in first-episode psychosis carers.

BACKGROUND: The first onset of psychosis can exert a significant negative impact on the functioning and positive wellbeing of family carers. Carer reports of "burnout" have recently been recorded in early psychosis carers, though the literature is scarce detailing our understanding of how burnout relates to the primary experience of caregiving. The current study investigated reports of burnout and its relationship with beliefs about caregiving and wellbeing in a large group of early psychosis carers who were routinely assessed within an early intervention team. METHODS AND MATERIALS: Using a cross-sectional design, 169 early psychosis carers completed the Maslach Burnout Inventory alongside measures of caregiving experiences, affect and wellbeing. RESULTS: The mean illness length for patients with psychosis was 18 months. Their mean age was 24.4 years and most was male (65%). The majority of carer participants were parental caregivers and living with their relative with psychosis. Across the three key burnout dimensions, 58% of the sample reported high levels of emotional exhaustion; 31% endorsed high levels of depersonalization; and 43% reported low levels personal accomplishment. The most severe level of burnout, reflecting elevated rates across all three dimensions, was observed in 16% of the sample. Carer burnout was positively associated with negative caregiving experiences (i.e. burden), poor affect, and reduced levels of positive wellbeing and perception of being in good health. CONCLUSIONS: Reports by early psychosis carers of exhaustion, feeling inadequate and expressing negativity towards the relative they care for is not uncommon and are closely associated with their overall negative appraisals of caregiving. The results underscore the importance of developing targeted interventions during the early phase, which are designed to reduce the development and entrenchment of burnout responses in carers, but to also mitigate its negative sequelae.

Modifying illness beliefs in recent onset psychosis carers: Evaluating the impact of a cognitively focused brief group intervention in a routine service.

AIMS: At first-episode psychosis (FEP), many patients will be routed within familial networks and supported by informal carers who are predominately close family members such as parents. Carer burden, distress and poorer coping styles are associated with different illness beliefs. The current study sought to examine the impact and acceptability of a 3 session, cognitively informed, group intervention targeting illness beliefs previously linked to distress and poorer caregiving experiences in FEP carers. METHODS: Carers attending a routine FEP service were invited to attend the group intervention and completed a measure of illness beliefs at baseline and post intervention. RESULTS: Data on 68 carers with complete datasets are presented. Carers were predominately females (64.2%). Group attendance was linked to positive improvements in carer baseline beliefs about the negative consequences of the illness for the patient and themselves, attributions of blame about the illness to the patient and themselves and their overall understanding about the illness. Significant improvements in their understanding of the illness timeline and course, and confidence in dealing with difficulties were also identified. CONCLUSIONS: A cognitively informed group approach to targeting the less adaptive illness beliefs reported by FEP carers may offer an effective and acceptable pathway to facilitate their understanding of the illness and adjustment. Further studies using controlled designs are required.

Evolution of Artificial Hearts: An Overview and History.

The heart is a muscular organ which pumps blood through blood vessels to different organs of the body. It is the most significant and vital organ in the human body. Without this organ, life is unimaginable. Doctors and scientists have been trying for a long time to create something similar or equivalent to the heart. The purpose is to develop a temporary machine or pump for a person who has a disease of the heart and their survival without transplant is impossible. These temporary devices can provide enough time for the patient until a donor heart is available. The purpose of this review is to provide an overview and history of how man has developed an artificial heart for survival.