Measurement of resident workload in paediatric intensive care

OBJECTIVE: To measure the workload of residents in a paediatric intensive care unit (PICU) and to compare this value with the possible explanatory variables "nine equivalents of nursing manpower use score" (NEMS), length of stay (LOS), patient age and severity of illness at admission. METHODS: This was a prospective study in a tertiary, interdisciplinary neonatal-paediatric intensive care unit. In 2010 and 2011, residents estimated their workload for each patient they looked after at admission and then twice a day (morning and night shift) (minor workload 0-30 minutes, medium >30-90 minutes, high >90 minutes). The following demographic and illness severity parameters were also collected prospectively: age, LOS, NEMS, Paediatric Index of Mortality (PIM2), and main diagnosis at admission. RESULTS: There were 2,513 admissions to PICU. Independent predictors of residents' workload were LOS (coefficient in multiple regression 8.9, p <0.0001) and NEMS (coefficient 1.4, p <0.0001). R2 of 0.928 indicated a strong overall relationship. Severity of illness at admission and patient age did not explain overall workload for the whole patient stay in PICU. CONCLUSIONS: NEMS, a therapeutic intervention score, and LOS are both independent predictors of clinical workload of residents in PICU. The correlation with LOS means that workload depends mainly on routine procedures (rounds, discussions with parents, administrative tasks) unrelated to the severity of illness. After calibration, LOS or NEMS, two widely used measures, may be used to calculate resident workload

Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors

The serotonergic system and in particular serotonin 1A receptor (5-HT1AR) are implicated in major depressive disorder (MDD). Here we demonstrated that 5-HT1AR is palmitoylated in human and rodent brains, and identified ZDHHC21 as a major palmitoyl acyltransferase, whose depletion reduced palmitoylation and consequently signaling functions of 5-HT1AR. Two rodent models for depression-like behavior show reduced brain ZDHHC21 expression and attenuated 5-HT1AR palmitoylation. Moreover, selective knock-down of ZDHHC21 in the murine forebrain induced depression-like behavior. We also identified the microRNA miR-30e as a negative regulator of Zdhhc21 expression. Through analysis of the post-mortem brain samples in individuals with MDD that died by suicide we find that miR-30e expression is increased, while ZDHHC21 expression, as well as palmitoylation of 5-HT1AR, are reduced within the prefrontal cortex. Our study suggests that downregulation of 5-HT1AR palmitoylation is a mechanism involved in depression, making the restoration of 5-HT1AR palmitoylation a promising clinical strategy for the treatment of MDD

"They accept me, because I was one of them": formative qualitative research supporting the feasibility of peer-led outreach for people who use drugs in Dakar, Senegal.

BACKGROUND: Peer outreach harm reduction initiatives are being developed with and for people who use drugs in Dakar, Senegal. This is in response to growing injecting drug use across the West Africa region and linked emerging epidemics of HIV and hepatitis C. We undertook formative qualitative research to explore the feasibility and potential of peer outreach in this context and in particular how outreach could be linked to fostering community-level processes of change. METHODS: We undertook a total of 44 semi-structured qualitative interviews. Thirty-four interviews were with people who used drugs (comprised of 25 participants who had injected at least once in their life) and included 11 peer educators who delivered "awareness-raising" harm reduction activities. We also interviewed 10 service providers involved in the planning and monitoring of peer outreach initiatives. We used thematic analysis to identify key characteristics of how peer-led outreach is being delivered, beneficiary need, and the nature of the social networks in which the awareness-raising activities operate. RESULTS: Through interviews with peer educators, people who use drugs, and service providers, four main overlapping themes are identified as follows: peer educators as a bridge to responsibilization through awareness-raising activities, awareness-raising activities as an enactment of recovery, awareness raising through social network diffusion, and the contexts and constraints of peer outreach engagement through awareness-raising activities. CONCLUSIONS: The study results suggest that peer education is on a trajectory to develop into a central role for harm reduction interventions in Dakar, Senegal. This research shows how peer education is bound in processes of responsibilization and self-change, which link to varying possibilities for risk reduction or recovery. For peer education to achieve a range of significant goals, broader structural and system changes should be implemented in the region. We caution that without such changes, awareness-raising activities and the role of peer educators may instead become part of state- and agency-sponsored processes of seeking to responsibilize individuals for health and harm reduction

Die Altersvorsorge für Selbständige : die Vielzahl von Möglichkeiten erfordert eine gute Planung

Der Artikel gibt einen ersten Überblick, welche Möglichkeiten Selbständigerwerbende für die Ausgestaltung Ihrer (Alters-)Vorsorge haben

Scaling proprioceptor gene transcription by retrograde NT3 signaling

Cell-type specific intrinsic programs instruct neuronal subpopulations before target-derived factors influence later neuronal maturation. Retrograde neurotrophin signaling controls neuronal survival and maturation of dorsal root ganglion (DRG) sensory neurons, but how these potent signaling pathways intersect with transcriptional programs established at earlier developmental stages remains poorly understood. Here we determine the consequences of genetic alternation of NT3 signaling on genome-wide transcription programs in proprioceptors, an important sensory neuron subpopulation involved in motor reflex behavior. We find that the expression of many proprioceptor-enriched genes is dramatically altered by genetic NT3 elimination, independent of survival-related activities. Combinatorial analysis of gene expression profiles with proprioceptors isolated from mice expressing surplus muscular NT3 identifies an anticorrelated gene set with transcriptional levels scaled in opposite directions. Voluntary running experiments in adult mice further demonstrate the maintenance of transcriptional adjustability of gene

Isolation of genes with enriched expression in proprioceptors.

<p>(a) Affymetrix gene expression profiling data showing probes enriched in TrkC^GFPon proprioceptors and TrkC^GFPoff non-proprioceptors isolated from p0 mice. Diagonal lines indicate cut-off for probes with expression values >5 fold change (outermost dotted lines), >2 fold change (middle dotted lines) and ≤2 fold change (grey squares around central diagonal line). TrkC^GFPon proprioceptor data points with enrichment ≥2 fold are displayed in turquoise and TrkC^GFPoff non-proprioceptors with the same criteria in purple. (b) Venn diagram illustrating the number of probes enriched ≥2 fold in proprioceptors and non-proprioceptors isolated from p0 mice respectively. (c) Analysis of the 25 probes with highest fold changes displayed in detail. Values of two samples of each p0 TrkC^GFPon proprioceptors (left) and TrkC^GFPoff non-proprioceptors (right) are shown. Grey scale values represent row z-score values and log unit average expression values are shown to the right of each probe (scales plotted bottom left). Probe names are displayed to the left of each row. (d–g) Four examples of individual genes with highly enriched expression in proprioceptors (TrkC) when compared to non-proprioceptors (non-TrkC) are displayed. Each panel shows raw Affymetrix expression values to the left (y-scale expression values; ±SEM) and verification by either <i>in situ</i> hybridization on wild-type and <i>TrkC</i> mutant lumbar DRG sections (d–f; scale bar = 50 µm) or immunohistochemistry in ventral spinal cord lamina IX (g; green: Cx36; red: vGlut1; scale bar = 2 µm) to the right.</p

Surplus skeletal muscle NT3 alters proprioceptor gene expression.

<p>(a, b) Analysis of 25 upregulated (a) or downregulated (b) probes in <i>mlc^NT3</i> mice is displayed. Average values of p0 TrkC^on proprioceptors (left; TrkC) and TrkC^off non-proprioceptors (right; non-TrkC) isolated from wild-type and <i>mlc^NT3</i> mice are shown. Grey scale values represent row z-score values and log unit average expression values are shown to the right of each probe (scales plotted top right of each panel). Probe names are displayed to the left of each row. The number of probes regulated in proprioceptors (p≤0.02; regulation ≥1.5 fold) is shown below the plots. (c, d) Detailed expression analysis of two individual genes upregulated (<i>Igf1</i> and <i>Shc4</i>) and two genes downregulated (<i>Tacr3</i> and <i>Myb</i>) in proprioceptors of <i>mlc^NT3</i> mice is shown (Affymetrix analysis: y-scale displays raw expression values; ±SEM).</p

Genes with anticorrelation in NT3 regulation profiles.

<p>(a) Flow diagram to illustrate analysis of gene expression data extracted from proprioceptors and non-proprioceptors of various mouse strains. To isolate genes with anticorrelative expression profile, genes with expression changes in opposing directions in proprioceptors of <i>NT3^−/−Bax^−/−</i> mice and <i>mlc^NT3</i> mice were isolated (purple arrows 1 and 2). (b, c) Detailed expression analysis of three individual genes following anticorrelation scheme 1 (<i>Gas6</i>, <i>Ndst4</i>, and <i>Crim1</i>) and three genes following scheme 2 (<i>Mrg1</i>, <i>Nova1</i>, and <i>P2rx1</i>). Affymetrix analysis: y-scale displays raw expression values; ± SEM.</p

<i>TrkC^GFP</i> BAC line shows enriched expression in proprioceptors.

<p>(a) Immunohistochemisty showing expression overlap between GFP and genes expressed by proprioceptors in p0 L5 DRG of <i>TrkC^GFP</i> BAC transgenic mouse line (top row: Runx3 and Pvalb; bottom row: TrkC and Pvalb; overlay of all three channels shown to the right; scale bar = 60 µm). (b) From left to right: Quantification of percentage of Runx3^on neurons co-expressing the TrkC^GFP allele (86.4% ± SEM), percentage of TrkC^GFPon cells co-expressing Runx3 (97.6% ± SEM; of neurons with Isl1^on nucleus on section), percentage of TrkC^on cells co-expressing TrkC^GFP (49.6% ± SEM) and of percentage of TrkC^GFPon cells co-expressing TrkC (grey bar: 98.5% ± SEM). Data from n = 4 p0 <i>TrkC^GFP</i> mice; total >20 L5 DRG sections. (c) Example of FACS scatterplot (left) and histogram (right) on dissociated lumbar DRG cells isolated from p0 <i>TrkC^GFP</i> mice gated by fluorescence (GFP^off and GFP^on cells are indicated; red-f: red fluorescence; green-f: green fluorescence). Four examples of genes (<i>Runx3</i>, <i>TrkC</i>, <i>Etv1</i>, <i>Pvalb</i>) with known enriched expression in proprioceptors (TrkC^GFPon) when compared to non-proprioceptors (TrkC^GFPoff). Each panel shows Affymetrix expression values to the left (y-scale raw expression values; ± SEM).</p

<i>Gabrg1</i> expression in proprioceptors in rostro-caudal gradient and regulated by NT3.

<p>(a) <i>In situ</i> hybridization experiments demonstrating downregulation of <i>Gabrg1</i> expression in p0 <i>TrkC</i> mutant L5 DRG when compared to wild-type. (b) Affymetrix expression value analysis of <i>Gabrg1</i> in proprioceptors (TrkC) and non-proprioceptors (nonTrkC) of wild-type (left), <i>mlc^NT3</i> (middle) and <i>NT3^−/−Bax^−/−</i> (right) mice (y-scale displays raw expression values; ±SEM). Note selective upregulation of <i>Gabrg1</i> in proprioceptors of <i>mlc^NT3</i> and downregulation in <i>NT3^−/−Bax^−/−</i> mice compared to wild-type values, in absence of gene expression changes in non-proprioceptors. (c–e) <i>In situ</i> hybridization analysis of <i>Gabrg1</i> expression on p0 wild-type DRG, displaying representative images from lumbar levels L1, L3, L5 and L6 (c) and quantification of cell numbers at lumbar (d) and cervical (e) rostro-caudal levels (n = 3 animals; ±SEM). (f) Affymetrix expression value analysis of <i>Gabrg1</i>, <i>TrkC</i>, and <i>Pvalb</i> at L1 and L5 (y-scale displays raw expression values; ±SEM). (g, h) Analysis of <i>Gabrg1</i> expression in adult DRG by <i>in situ</i> hybridization (g: L1 and L5; scale bar = 80 µm), Affymetrix gene expression values (h; n = 3; ±SEM), and quantitative PCR (h; n = 3; ±SEM). In comparison, Affymetrix expression values of <i>TrkC</i> are not significantly different between L1 and L5 adult DRG (h; n = 3; ±SEM).</p