Day Care General Anaesthesia for a Child with Bardet-Biedl Syndrome

Bardet-Biedl syndrome is a very rare autosomal-recessive disorder with pan-systemic effects. The perioperative period may be hazardous for patients with this disorder. We describe the presenting features and management of a child who was scheduled for elective ambulatory general anesthesia and discuss the relevant points for the busy anesthesiologist

Occupational Performance Goals of Mothers of Adolescents with and Mothers of Adolescents without Disabilities

Background/Purpose: Mothering is a life-long role that requires significant time and energy (Donovan, VanLeit, Crowe, & Keefe, 2005). The amount and nature of time spent caring for adolescents with and without disabilities may vary (Crowe & Michael, 2010). This qualitative study describes the differences between the occupational performance goals of mothers of adolescents with disabilities and mothers of adolescents without disabilities. Methods: A sample of 20 mothers of adolescents with disabilities and 20 mothers of adolescents without disabilities was recruited. Adolescents had to be between 13 and 19 years of age and identified by the mother as having a disability or no disability. The Canadian Occupational Performance Measure (Law et al., 2005) was used to gather narrative information from the mothers in a semi-structured interview format. The data was then qualitatively analyzed and compared. Results: Using grounded theory and thematic coding, the data was organized into six themes describing the mothers occupational performance goals. Five of the six themes were shared between both groups, with minor differences in the nature of the identified occupations. However, only mothers of adolescents with disabilities identified goals concerning supporting their adolescents. Conclusions: The findings highlight the difference in the nature of occupational performance goals between mothers of adolescents with disabilities and mothers of adolescents without disabilities. While similarities exist between the two groups, it is important to understand the different demands of mothering adolescents with disabilities to better support them in their daily occupations.\u2

Proline residues within spacer peptide p1 are important for human immunodeficiency virus type 1 infectivity, protein processing, and genomic RNA dimer stability

The full-length human immunodeficiency virus type 1 (HIV-1) mRNA encodes two precursor polyproteins, Gag and GagProPol. An infrequent ribosomal frameshifting event allows these proteins to be synthesized from the same mRNA in a predetermined ratio of 20 Gag proteins for each GagProPol. The RNA frameshift signal consists of a slippery sequence and a hairpin stem-loop whose thermodynamic stability has been shown in in vitro translation systems to be critical to frameshifting efficiency. In this study we examined the frameshift region of HIV-1, investigating the effects of altering stem-loop stability in the context of the complete viral genome and assessing the role of the Gag spacer peptide p1 and the GagProPol transframe (TF) protein that are encoded in this region. By creating a series of frameshift region mutants that systematically altered the stability of the frameshift stem-loop and the protein sequences of the p1 spacer peptide and TF protein, we have demonstrated the importance of stem-loop thermodynamic stability in frameshifting efficiency and viral infectivity. Multiple changes to the amino acid sequence of p1 resulted in altered protein processing, reduced genomic RNA dimer stability, and abolished viral infectivity. The role of the two highly conserved proline residues in p1 (position 7 and 13) was also investigated. Replacement of the two proline residues by leucines resulted in mutants with altered protein processing and reduced genomic RNA dimer stability that were also noninfectious. The unique ability of proline to confer conformational constraints on a peptide suggests that the correct folding of p1 may be important for viral function.<br /

Palliative Care of the Infant and Child in the Paediatric Intensive Care Unit

In this chapter we discuss the delivery of palliative care in the paediatric intensive care unit environment. Illustrated by challenging cases, we describe the role of intensive care in symptom management for the child with terminal or life-limiting illness. We detail the importance of a multidisciplinary team and their roles in the provision of individualised care for the child and their family. The importance of family-centred care and advance care planning is expanded upon. In addition, we explore end of life issues that are particular to children in intensive care such as withdrawal of life-sustaining therapies and organ donation. Finally, we discuss how to ensure the delivery of high-quality palliative care in the paediatric intensive care environment

Qualitative assessment of South African healthcare worker perspectives on an instrument-free rapid CD4 test

Background: Accurate measurement of CD4 cell counts remains an important tenet of clinical care for people living with HIV. We assessed an instrument-free point-of-care CD4 test (VISITECT® CD4) based on a lateral flow principle, which gives visual results after 40 min. The test involves five steps and categorises CD4 counts as above or below 350 cells/μL. As one component of a performance evaluation of the test, this qualitative study explored the views of healthcare workers in a large women and children’s hospital on the acceptability and feasibility of the test. Methods: Perspectives on the VISITECT® CD4 test were elicited through in-depth interviews with eight healthcare workers involved in the performance evaluation at an antenatal care facility in Johannesburg, South Africa. Audio recordings were transcribed in full and analysed thematically. Results: Healthcare providers recognised the on-going relevance of CD4 testing. All eight perceived the VISITECT® CD4 test to be predominantly user-friendly, although some felt that the need for precision and optimal concentration in performing test procedures made it more challenging to use. The greatest strength of the test was perceived to be its quick turn-around of results. There were mixed views on the semi-quantitative nature of the test results and how best to integrate this test into existing health services. Participants believed that patients in this setting would likely accept the test, given their general familiarity with other point-of-care tests. Conclusions: Overall, the VISITECT® CD4 test was acceptable to healthcare workers and those interviewed were supportive of scale-up and implementation in other antenatal care settings. Both health workers and patients will need to be oriented to the semi-quantitative nature of the test and how to interpret the results of test

Feasibility of antiretroviral treatment monitoring in the era of decentralized HIV care: a systematic review

Background: Regular monitoring of HIV patients who are receiving antiretroviral therapy (ART) is required to ensure patient benefits and the long-term effectiveness and sustainability of ART programs. Prompted by WHO recommendations for expansion and decentralization of HIV treatment and care in low and middle income countries, we conducted a systematic review to assess the feasibility of treatment monitoring in these settings. Methods: A comprehensive search strategy was developed using a combination of MeSH and free text terms relevant to HIV treatment and care, health service delivery, health service accessibility, decentralization and other relevant terms. Five electronic databases and two conference websites were searched to identify relevant studies conducted in LMICs, published in English between Jan 2006 and Dec 2015. Outcomes of interest included the proportion of patients who received treatment monitoring and health system factors related to monitoring of patients on ART under decentralized HIV service delivery models. Results: From 5363 records retrieved, twenty studies were included in the review; all but one was conducted in subSaharan African countries. The majority of studies (15/20) had relatively short follow-up duration (≤24 months), and only two studies were specifically designed to assess treatment monitoring practices. The most frequently studied follow-up period was 12 months and a wide range of treatment monitoring coverage was observed. The reported proportions of patients on ART who received CD4 monitoring ranged from very low (6%; N = 2145) to very high (95%; N = 488). The median uptake of viral load monitoring was 86% with studies in program settings reporting coverage as low as 14%. Overall, the longer the follow-up period, the lower the proportion of patients who received regular monitoring tests; and programs in rural areas reported low coverage of laboratory monitoring. Moreover, uptake in the context of research had significantly better where monitoring was done by dedicated research staff. In the absence of point of care (POC) testing, the limited capacity for blood sample transportation between clinic and laboratory and poor quality of nursing staff were identified as a major barrier for treatment monitoring practice. Conclusions: There is a paucity of data on the uptake of treatment monitoring, particularly with longer-term followup. Wide variation in access to both virological and immunological regular monitoring was observed, with some clinics in well-resourced settings supported by external donors achieving high coverage. The feasibility of treatment monitoring, particularly in decentralized settings of HIV treatment and care may thus be of concern and requires further study. Significant investment in POC diagnostic technologies and, improving the quality of and training for nursing staff is required to ensure effective scale up of ART programs towards the targets of 90-90-90 by the year 2020

Decreased NK Cell FcRγ in HIV-1 Infected Individuals Receiving Combination Antiretroviral Therapy: a Cross Sectional Study

Background: FcRc is an immunoreceptor tyrosine-based activation motif (ITAM)-signalling protein essential for immunoreceptor signaling and monocyte, macrophage and NK cell function. Previous study from our laboratory showed that FcRc is down-regulated in HIV-infected macrophages in vitro. FcRc expression in immune cells present in HIV-infected individuals is unknown. Methodology/Principal Findings: We compared FcRc expression in peripheral blood mononuclear cells isolated from HIV-1-infected individuals receiving combination antiretroviral therapy and healthy, HIV-1-uninfected individuals. FcRc mRNA and protein levels were measured using quantitative real-time PCR and immunoblotting, respectively. CD56 + CD94 + lymphocytes isolated from blood of HIV-1 infected individuals had reduced FcRc protein expression compared to HIVuninfected individuals (decrease = 76.8%, n = 18 and n = 12 respectively, p = 0.0036). In a second group of patients, highly purified NK cells had reduced FcRc protein expression compared to uninfected controls (decrease = 50.2%, n = 9 and n = 8 respectively, p = 0.021). Decreased FcRc expression in CD56+CD94+ lymphocytes was associated with reduced mRNA (51.7%, p = 0.021) but this was not observed for the smaller group of patients analysed for NK cell expression (p = 0.36). Conclusion/Significance: These data suggest biochemical defects in ITAM-dependent signalling within NK cells in HIVinfecte

Acceptability and feasibility of point-of-care CD4 testing on HIV continuum of care in low and middle income countries: a systematic review

Background: CD4 testing is, and will remain an important part of HIV treatment and care in low and middle income countries (LMICs). We report the findings of a systematic review assessing acceptability and feasibility of POC CD4 testing in field settings. Methods: Electronic databases were searched for studies published in English between 2005 and 2015 that describe POC CD4 platforms. Studies conducted in LMICs and under field conditions outside a laboratory environment were eligible. Qualitative and descriptive data analysis was used to present the findings. Results: Twelve studies were included, 11 of which were conducted in sub-Saharan countries and used one POC CD4 test (The Alere Pima CD4). Patients reported positively regarding the implementation of POC CD4 testing at primary health care and community level with ≥90 % of patients accepting the test across various study settings. Health service providers expressed preference toward POC CD4 testing as it is easy-to-use, efficient and satisfied patients\u27 needs to a greater extent as compared to conventional methods. However, operational challenges including preference toward venous blood rather than finger-prick sampling, frequent device failures and operator errors, quality of training for test operators and supervisors, and increased staff workload were also identified. Conclusions: POC CD4 testing seems acceptable and feasible in LIMCs under field conditions. Further studies using different POC CD4 tests available on the market are required to provide critical data to support countries in selection and implementation of appropriate POC CD4 technologies

Assessment of metabolic and mitochondrial dynamics in CD4+ and CD8+ T cells in virologically suppressed HIV-positive individuals on combination antiretroviral therapy

Metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and mitochondrial biogenesis in subpopulations of CD4+ and CD8+ T cells from 18 virologically-suppressed HIV-positive individuals on combination antiretroviral therapy (cART; median CD4+ cell count: 728 cells/μl) and 13 HIV seronegative controls. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production were also analysed in total CD4+ and CD8+ T cells. Among HIV+/cART individuals, expression of glucose transporter (Glut1) and mitochondrial density were highest within central memory and naïve CD4+ T cells, and lowest among effector memory and transitional memory T cells, with similar trends in HIV-negative controls. Compared to HIV-negative controls, there was a trend towards higher percentage of circulating CD4+Glut1+ T cells in HIV+/cART participants. There were no significant differences in mitochondrial dynamics between subject groups. Glut1 expression was positively correlated with mitochondrial density and MMP in total CD4+ T cells, while MMP was also positively correlated with ROS production in both CD4+ and CD8+ T cells. Our study characterizes specific metabolic features of CD4+ and CD8+ T cells in HIV-negative and HIV+/cART individuals and will invite future studies to explore the immunometabolic consequences of HIV infection

HIV-1 Selection by Epidermal Dendritic Cells during Transmission across Human Skin

Macrophage tropic HIV-1 is predominant during the initial viremia after person to person transmission of HIV-1 (Zhu, T., H. Mo, N. Wang, D.S. Nam, Y. Cao, R.A. Koup, and D.D. Ho. 1993. Science. 261:1179–1181.), and this selection may occur during virus entry and carriage to the lymphoid tissue. Human skin explants were used to model HIV-1 selection that may occur at the skin or mucosal surface. Macrophage tropic, but not T cell line tropic strains of HIV-1 applied to the abraded epidermis were recovered from the cells emigrating from the skin explants. Dermis and epidermis were separated by dispase digestion after virus exposure to determine the site of viral selection within the skin. Uptake and transmission to T cells of all HIV-1 isolates was found with the dermal emigrant cells, but only macrophage tropic virus was transferred by emigrants from the epidermis exposed to HIV-1, indicating selection only within the epidermis. CD3+, CD4+ T cells were found in both the dermal and epidermal emigrant cells. After cell sorting to exclude contaminating T cells, macrophage tropic HIV-1 was found in both the dermal emigrant dendritic cells and in dendritic cells sorted from the epidermal emigrants. These observations suggest that selective infection of the immature epidermal dendritic cells represents the cellular mechanism that limits the initial viremia to HIV-1 that can use the CCR5 coreceptor