Challenges and support needs of parents and children when a parent is at end of life: A systematic review

Background: Preparing children for the death of a parent is challenging. Parents are often uncertain if and how to communicate and support their children. Many parents feel it is protecting their children by not telling them about the prognosis. Children less prepared for parental death from a terminal illness are more susceptive to later adversities. To facilitate coping and moderate for such adversities, there is a need to gain insight and understand the experience and challenges confronted by families. Aim: This review synthesised evidence on the experiences of parents and children when a parent is at end of life to discern their challenges, support needs and factors that facilitated good practice. Design: Mixed-methods systematic review. Data sources: Four electronic databases (CINAHL, PubMed, PsycINFO and Ovid MEDLINE) using MeSH terms and word searches in October 2018. Studies were not limited by year of publication, language or country. Grey literature searches were also completed on Google Scholar and OpenGrey. Results: In all, 7829 records were identified; 27 qualitative and 0 quantitative studies met the inclusion criteria. Eight descriptive themes were identified, further categorised into two broad themes: (1) barriers and facilitators in sharing the news that a parent is dying and (2) strategies to manage the changing situation. Conclusion: Lack of understanding in relation to the parent’s prognosis, denial and feeling ill-equipped were suggested as barriers for parents to share the news with their children. Engagement with social networks, including extended family relatives and peers, and maintaining routines such as attending school were suggested supportive by parents and children. Findings are limited primarily to White, middle-class two-parent families. A number of areas for future research are identified.</p

Cross-sector, sessional employment of pharmacists in rural hospitals in Australia and New Zealand: a qualitative study exploring pharmacists’ perceptions and experiences

Background: Many rural hospitals in Australia and New Zealand do not have an on-site pharmacist. Sessional employment of a local pharmacist offers a potential solution to address the clinical service needs of non-pharmacist rural hospitals. This study explored sessional service models involving pharmacists and factors (enablers and challenges) impacting on these models, with a view to informing future sessional employment. Methods: A series of semi-structured one-on-one interviews was conducted with rural pharmacists with experience, or intention to practise, in a sessional employment role in Australia and New Zealand. Participants were identified via relevant newsletters, discussion forums and referrals from contacts. Interviews were conducted during August 2012-January 2013 via telephone or Skype™, for approximately 40–55 minutes each, and recorded.Results: Seventeen pharmacists were interviewed: eight with ongoing sessional roles, five with sessional experience, and four working towards sessional employment. Most participants provided sessional hospital services on a weekly basis, mainly focusing on inpatient medication review and consultation. Recognition of the value of pharmacists’ involvement and engagement with other healthcare providers facilitated establishment and continuity of sessional services. Funds pooled from various sources supplemented some pharmacists’ remuneration in the absence of designated government funding. Enhanced employment opportunities, district support and flexibility in services facilitated the continuous operation of the sessional service. Conclusions: There is potential to address clinical pharmacy service needs in rural hospitals by cross-sector employment of pharmacists. The reported sessional model arrangements, factors impacting on sessional employment of pharmacists and learnings shared by the participants should assist development of similar models in other rural communities

HLA-E-restricted SARS-CoV-2-specific T cells from convalescent COVID-19 patients suppress virus replication despite HLA class Ia down-regulation

Pathogen-specific CD8+ T cell responses restricted by the nonpolymorphic nonclassical class Ib molecule human leukocyte antigen E (HLA-E) are rarely reported in viral infections. The natural HLA-E ligand is a signal peptide derived from classical class Ia HLA molecules that interact with the NKG2/CD94 receptors to regulate natural killer cell functions, but pathogen-derived peptides can also be presented by HLA-E. Here, we describe five peptides from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that elicited HLA-E–restricted CD8+ T cell responses in convalescent patients with coronavirus disease 2019. These T cell responses were identified in the blood at frequencies similar to those reported for classical HLA-Ia–restricted anti–SARS-CoV-2 CD8+ T cells. HLA-E peptide–specific CD8+ T cell clones, which expressed diverse T cell receptors, suppressed SARS-CoV-2 replication in Calu-3 human lung epithelial cells. SARS-CoV-2 infection markedly down-regulated classical HLA class I expression in Calu-3 cells and primary reconstituted human airway epithelial cells, whereas HLA-E expression was not affected, enabling T cell recognition. Thus, HLA-E–restricted T cells could contribute to the control of SARS-CoV-2 infection alongside classical T cells

Evolution through segmental duplications and losses : A Super-Reconciliation approach

The classical gene and species tree reconciliation, used to infer the history of gene gain and loss explaining the evolution of gene families, assumes an independent evolution for each family. While this assumption is reasonable for genes that are far apart in the genome, it is not appropriate for genes grouped into syntenic blocks, which are more plausibly the result of a concerted evolution. Here, we introduce the Super-Reconciliation problem which consists in inferring a history of segmental duplication and loss events (involving a set of neighboring genes) leading to a set of present-day syntenies from a single ancestral one. In other words, we extend the traditional Duplication-Loss reconciliation problem of a single gene tree, to a set of trees, accounting for segmental duplications and losses. Existency of a Super-Reconciliation depends on individual gene tree consistency. In addition, ignoring rearrangements implies that existency also depends on gene order consistency. We first show that the problem of reconstructing a most parsimonious Super-Reconciliation, if any, is NP-hard and give an exact exponential-time algorithm to solve it. Alternatively, we show that accounting for rearrangements in the evolutionary model, but still only minimizing segmental duplication and loss events, leads to an exact polynomial-time algorithm. We finally assess time efficiency of the former exponential time algorithm for the Duplication-Loss model on simulated datasets, and give a proof of concept on the opioid receptor genes

Functional Assessment of EnvZ/OmpR Two-Component System in Shewanella oneidensis

EnvZ and OmpR constitute the bacterial two-component signal transduction system known to mediate osmotic stress response in a number of Gram-negative bacteria. In an effort to understand the mechanism through which Shewanella oneidensis senses and responds to environmental osmolarity changes, structure of the ompR-envZ operon was determined with Northern blotting assay and roles of the EnvZ/OmpR two-component system in response to various stresses were investigated with mutational analysis, quantitative reverse transcriptase PCR (qRT-PCR), and phenotype microarrays. Results from the mutational analysis and qRT-PCR suggested that the EnvZ/OmpR system contributed to osmotic stress response of S. oneidensis and very likely engaged a similar strategy employed by E. coli, which involved reciprocal regulation of two major porin coding genes. Additionally, the ompR-envZ system was also found related to cell motility. We further showed that the ompR-envZ dependent regulation of porin genes and motility resided almost completely on ompR and only partially on envZ, indicating additional mechanisms for OmpR phosphorylation. In contrast to E. coli lacking ompR-envZ, however, growth of S. oneidensis did not show a significant dependence on ompR-envZ even under osmotic stress. Further analysis with phenotype microarrays revealed that the S. oneidensis strains lacking a complete ompR-envZ system displayed hypersensitivities to a number of agents, especially in alkaline environment. Taken together, our results suggest that the function of the ompR-envZ system in S. oneidensis, although still connected with osmoregulation, has diverged considerably from that of E. coli. Additional mechanism must exist to support growth of S. oneidensis under osmotic stress

Polydrug Use among IDUs in Tijuana, Mexico: Correlates of Methamphetamine Use and Route of Administration by Gender

Tijuana is situated on the Mexico–USA border adjacent to San Diego, CA, on a major drug trafficking route. Increased methamphetamine trafficking in recent years has created a local consumption market. We examined factors associated with methamphetamine use and routes of administration by gender among injection drug users (IDUs). From 2006–2007, IDUs ≥18 years old in Tijuana were recruited using respondent-driven sampling, interviewed, and tested for HIV, syphilis, and TB. Logistic regression was used to assess associations with methamphetamine use (past 6 months), stratified by gender. Among 1,056 participants, methamphetamine use was more commonly reported among females compared to males (80% vs. 68%, p < 0.01), particularly, methamphetamine smoking (57% vs. 34%; p < 0.01). Among females (N = 158), being aged >35 years (AOR, 0.2; 95% CI, 0.1–0.6) was associated with methamphetamine use. Among males (N = 898), being aged >35 years (AOR, 0.5; 95% CI, 0.3–0.6), homeless (AOR, 1.4 (0.9–2.2)), and ever reporting sex with another male (MSM; AOR, 1.9; 95% CI, 1.4–2.7) were associated with methamphetamine use. Among males, a history of MSM was associated with injection, while sex trade and >2 casual sex partners were associated with multiple routes of administration. HIV was higher among both males and females reporting injection as the only route of methamphetamine administration. Methamphetamine use is highly prevalent among IDUs in Tijuana, especially among females. Routes of administration differed by gender and subgroup which has important implications for tailoring harm reduction interventions and drug abuse treatment

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal coronavirus disease (COVID-19) outcomes is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses, and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to intensive care units (ICU) with fatal COVID-19 outcomes, but not in individuals with non-fatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to ICU with fatal and non-fatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an original antigenic sin type-response

Synaptically-Competent Neurons Derived from Canine Embryonic Stem Cells by Lineage Selection with EGF and Noggin

Pluripotent stem cell lines have been generated in several domestic animal species; however, these lines traditionally show poor self-renewal and differentiation. Using canine embryonic stem cell (cESC) lines previously shown to have sufficient self-renewal capacity and potency, we generated and compared canine neural stem cell (cNSC) lines derived by lineage selection with epidermal growth factor (EGF) or Noggin along the neural default differentiation pathway, or by directed differentiation with retinoic acid (RA)-induced floating sphere assay. Lineage selection produced large populations of SOX2+ neural stem/progenitor cell populations and neuronal derivatives while directed differentiation produced few and improper neuronal derivatives. Primary canine neural lines were generated from fetal tissue and used as a positive control for differentiation and electrophysiology. Differentiation of EGF- and Noggin-directed cNSC lines in N2B27 with low-dose growth factors (BDNF/NT-3 or PDGFαα) produced phenotypes equivalent to primary canine neural cells including 3CB2+ radial progenitors, MOSP+ glia restricted precursors, VIM+/GFAP+ astrocytes, and TUBB3+/MAP2+/NFH+/SYN+ neurons. Conversely, induction with RA and neuronal differentiation produced inadequate putative neurons for further study, even though appropriate neuronal gene expression profiles were observed by RT-PCR (including Nestin, TUBB3, PSD95, STX1A, SYNPR, MAP2). Co-culture of cESC-derived neurons with primary canine fetal cells on canine astrocytes was used to test functional maturity of putative neurons. Canine ESC-derived neurons received functional GABAA- and AMPA-receptor mediated synaptic input, but only when co-cultured with primary neurons. This study presents established neural stem/progenitor cell populations and functional neural derivatives in the dog, providing the proof-of-concept required to translate stem cell transplantation strategies into a clinically relevant animal model