Directed mechanisms for apical dendrite development during neuronal polarization.

The development of the dendrite and the axon during neuronal polarization underlies the directed flow of information in the brain. Seminal studies on axon development have dominated the mechanistic analysis of neuronal polarization. These studies, many originating from examinations in cultured hippocampal and cortical neurons in vitro, have established a prevalent view that axon formation precedes and is necessary for neuronal polarization. There is also in vivo evidence supporting this view. Nevertheless, the establishment of bipolar polarity, the leading edge, and apical dendrite development in pyramidal neurons in vivo occur when axon formation is prevented. Furthermore, recent mounting evidence suggest that directed mechanisms might mediate bipolar polarity/leading process and subsequent apical dendrite development. In the presence of spatially directed extracellular cues in the developing brain, these events may operate independently of axon forming events. In this perspective we summarize evidence in support of these evolving views in neuronal polarization and highlight recent findings on dedicated mechanisms acting in apical dendrite development.

Effectiveness of Shared Decision-making for Diabetes Prevention: 12-Month Results from the Prediabetes Informed Decision and Education (PRIDE) Trial.

IMPORTANCE: Intensive lifestyle change (e.g., the Diabetes Prevention Program) and metformin reduce type 2 diabetes risk among patients with prediabetes. However, real-world uptake remains low. Shared decision-making (SDM) may increase awareness and help patients select and follow through with informed options for diabetes prevention that are aligned with their preferences. OBJECTIVE: To test the effectiveness of a prediabetes SDM intervention. DESIGN: Cluster randomized controlled trial. SETTING: Twenty primary care clinics within a large regional health system. PARTICIPANTS: Overweight/obese adults with prediabetes (BMI ≥ 24 kg/m2 and HbA1c 5.7-6.4%) were enrolled from 10 SDM intervention clinics. Propensity score matching was used to identify control patients from 10 usual care clinics. INTERVENTION: Intervention clinic patients were invited to participate in a face-to-face SDM visit with a pharmacist who used a decision aid (DA) to describe prediabetes and four possible options for diabetes prevention: DPP, DPP ± metformin, metformin only, or usual care. MAIN OUTCOMES AND MEASURES: Primary endpoint was uptake of DPP (≥ 9 sessions), metformin, or both strategies at 4 months. Secondary endpoint was weight change (lbs.) at 12 months. RESULTS: Uptake of DPP and/or metformin was higher among SDM participants (n = 351) than controls receiving usual care (n = 1028; 38% vs. 2%, p < .001). At 12-month follow-up, adjusted weight loss (lbs.) was greater among SDM participants than controls (- 5.3 vs. - 0.2, p < .001). LIMITATIONS: Absence of DPP supplier participation data for matched patients in usual care clinics. CONCLUSIONS AND RELEVANCE: A prediabetes SDM intervention led by pharmacists increased patient engagement in evidence-based options for diabetes prevention and was associated with significantly greater uptake of DPP and/or metformin at 4 months and weight loss at 12 months. Prediabetes SDM may be a promising approach to enhance prevention efforts among patients at increased risk. TRIAL REGISTRATION: This study was registered at clinicaltrails.gov (NCT02384109)).

Targeted exome sequencing defines novel and rare variants in complex blood group serology cases for a red blood cell reference laboratory setting.

BACKGROUND: We previously demonstrated that targeted exome sequencing accurately defined blood group genotypes for reference panel samples characterized by serology and single-nucleotide polymorphism (SNP) genotyping. Here we investigate the application of this approach to resolve problematic serology and SNP-typing cases. STUDY DESIGN AND METHODS: The TruSight One sequencing panel and MiSeq platform was used for sequencing. CLC Genomics Workbench software was used for data analysis of the blood group genes implicated in the serology and SNP-typing problem. Sequence variants were compared to public databases listing blood group alleles. The effect of predicted amino acid changes on protein function for novel alleles was assessed using SIFT and PolyPhen-2. RESULTS: Among 29 unresolved samples, sequencing defined SNPs in blood group genes consistent with serologic observation: 22 samples exhibited SNPs associated with varied but known blood group alleles and one sample exhibited a chimeric RH genotype. Three samples showed novel variants in the CROM, LAN, and RH systems, respectively, predicting respective amino acid changes with possible deleterious impact. Two samples harbored rare variants in the RH and FY systems, respectively, not previously associated with a blood group allele or phenotype. A final sample comprised a rare variant within the KLF1 transcription factor gene that may modulate DNA-binding activity. CONCLUSION: Targeted exome sequencing resolved complex serology problems and defined both novel blood group alleles (CD55:c.203G>A, ABCB6:c.1118_1124delCGGATCG, ABCB6:c.1656-1G>A, and RHD:c.452G>A) and rare variants on blood group alleles associated with altered phenotypes. This study illustrates the utility of exome sequencing, in conjunction with serology, as an alternative approach to resolve complex cases.

Evaluation of targeted exome sequencing for 28 protein-based blood group systems, including the homologous gene systems, for blood group genotyping.

BACKGROUND: Blood group single nucleotide polymorphism genotyping probes for a limited range of polymorphisms. This study investigated whether massively parallel sequencing (also known as next-generation sequencing), with a targeted exome strategy, provides an extended blood group genotype and the extent to which massively parallel sequencing correctly genotypes in homologous gene systems, such as RH and MNS. STUDY DESIGN AND METHODS: Donor samples (n = 28) that were extensively phenotyped and genotyped using single nucleotide polymorphism typing, were analyzed using the TruSight One Sequencing Panel and MiSeq platform. Genes for 28 protein-based blood group systems, GATA1, and KLF1 were analyzed. Copy number variation analysis was used to characterize complex structural variants in the GYPC and RH systems. RESULTS: The average sequencing depth per target region was 66.2 ± 39.8. Each sample harbored on average 43 ± 9 variants, of which 10 ± 3 were used for genotyping. For the 28 samples, massively parallel sequencing variant sequences correctly matched expected sequences based on single nucleotide polymorphism genotyping data. Copy number variation analysis defined the Rh C/c alleles and complex RHD hybrids. Hybrid RHD*D-CE-D variants were correctly identified, but copy number variation analysis did not confidently distinguish between D and CE exon deletion versus rearrangement. CONCLUSION: The targeted exome sequencing strategy employed extended the range of blood group genotypes detected compared with single nucleotide polymorphism typing. This single-test format included detection of complex MNS hybrid cases and, with copy number variation analysis, defined RH hybrid genes along with the RHCE*C allele hitherto difficult to resolve by variant detection. The approach is economical compared with whole-genome sequencing and is suitable for a red blood cell reference laboratory setting.

Interprofessional collaboration from nurses and physicians ­ A triangulation of quantitative and qualitative data / Interprofessionelle Zusammenarbeit Pflegefachpersonen und Ärzteschaft. Eine Triangulation quantitativer und qualitativer Daten

Background: Interprofessional collaboration between nurses and physicians is a recurrent challenge in daily clinical practice. To ameliorate the situation, quantitative or qualitative studies are conducted. However, the results of these studies have often been limited by the methods chosen. Aim: To describe the synthesis of interprofessional collaboration from the nursing perspective by triangulating quantitative and qualitative data. Method: Data triangulation was performed as a sub-project of the interprofessional Sinergia DRG Research program. Initially, quantitative and qualitative data were analyzed separately in a mixed methods design. By means of triangulation a "meta-matrix" resulted in a four-step process. Results: The "meta-matrix" displays all relevant quantitative and qualitative results as well as their interrelations on one page. Relevance, influencing factors as well as consequences of interprofessional collaboration for patients, relatives and systems become visible. Conclusion: For the first time, the interprofessional collaboration from the nursing perspective at five Swiss hospitals is shown in a "meta-matrix". The consequences of insufficient collaboration between nurses and physicians are considerable. This is why it's necessary to invest in interprofessional concepts. In the "meta-matrix" the factors which influence the interprofessional collaboration positively or negatively are visible.

Framework for Evaluating the Impact of Advanced Practice Nursing Roles.

PURPOSE: To address the gap in evidence-based information required to support the development of advanced practice nursing (APN) roles in Switzerland, stakeholders identified the need for guidance to generate strategic evaluation data. This article describes an evaluation framework developed to inform decisions about the effective utilization of APN roles across the country. APPROACH: A participatory approach was used by an international group of stakeholders. Published literature and an evidenced-based framework for introducing APN roles were analyzed and applied to define the purpose, target audiences, and essential elements of the evaluation framework. Through subsequent meetings and review by an expert panel, the framework was developed and refined. FINDINGS: A framework to evaluate different types of APN roles as they evolve to meet dynamic population health, practice setting, and health system needs was created. It includes a matrix of key concepts to guide evaluations across three stages of APN role development: introduction, implementation, and long-term sustainability. For each stage, evaluation objectives and questions examining APN role structures, processes, and outcomes from different perspectives (e.g., patients, providers, managers, policy-makers) were identified. CONCLUSIONS: A practical, robust framework based on well-established evaluation concepts and current understanding of APN roles can be used to conduct systematic evaluations. CLINICAL RELEVANCE: The evaluation framework is sufficiently generic to allow application in developed countries globally, both for evaluation as well as research purposes.

Complexity of nursing care in acute care hospital patients: results of a pilot study with a newly developed questionnaire.

AIM: The aim of this pilot study was to develop an instrument for measuring complexity of nursing care in hospitalised acute care patients as well as to examine its comprehensibility, its feasibility, the effort required for data collection, and its inter-rater reliability as well as its face validity. METHODS: This pilot study was designed as a descriptive, explorative cross-sectional survey with multiple measurements of the patient-related complexity of nursing care and a supplemental qualitative questionnaire conducted on six units of a Swiss university hospital. The instrument to assess complexity of nursing care was developed on the framework of Perrow and encompasses on three subscales a total of 15 items with a 5-point Likert scale. ETHICAL CONSIDERATIONS: The study was reviewed and approved by the Cantonal Ethics Committee. RESULTS: In total, 866 assessments of complexity of nursing care were carried out on 234 patients. The variability of the results of the six units, from three different specialties, suggests that the sampling was suitable for capturing a wide spectrum of complexity. The results of the three subscales are consistent and the discussion of them with the participating units shows that they are also plausible. The verification of the inter-rater reliability has satisfactory to high intersubjective correlation of the values. There were also a few suggestions for improving comprehensibility as well as on how to support user application. The time expenditure for the assessment between 2 to 5 minutes per patient was accurately. CONCLUSION: With the newly developed questionnaire to measure the complexity of nursing care in acute care hospitals it seems to be possible to assess and to quantify the complexity of nursing care in various acute care hospital settings. Based on the findings and the feedback of the participating users, the questionnaire needs to be improved for large-scale application.

Moral distress in nurses at an acute care hospital in Switzerland: results of a pilot study.

BACKGROUND: In the context of new reimbursement systems like diagnosis-related groups, moral distress is becoming a growing problem for healthcare providers. Moral distress can trigger emotional and physical reactions in nurses and can cause them to withdraw emotionally from patients or can cause them to change their work place. OBJECTIVE: The aim of this pilot study was to develop an instrument to measure moral distress among acute care nurses in the German-speaking context, to test its applicability, and to obtain initial indications of the instrument's validity. METHOD: The study was designed in 2011 as a cross-sectional pilot survey. Conducted on eight units of one university hospital in German-speaking Switzerland, 294 registered nurses were asked to fill out a web-based questionnaire on moral distress. ETHICAL CONSIDERATIONS: The study proposal was approved by the cantonal ethics committee. All participating nurses provided informed consent and were assured of data confidentiality. RESULTS: The survey had a response rate of 55%. The results show the prevalence of statements on the questionnaire indicating situations with the potential to trigger moral distress. The entire range of answers was used in the responses. Most participants found the questionnaire comprehensible, while some criticized the phraseology of certain statements. Many more found the registration process prior to online access to be too time consuming. Nurses confirmed that the results reflect their subjective assessment of their situation and their experience of moral distress. CONCLUSION: The newly developed moral distress questionnaire appears to produce face validity and is sufficiently applicable for use in our study. The results indicate that moral distress appears to be a relevant phenomenon also in Swiss hospitals and that nurses were experiencing it prior to the introduction of Swiss diagnosis-related groups.

[Monitoring of nursing service context factors: first descriptive results of a cross-sectional Swiss study prior the introduction of SwissDRG]. / Monitoring von Pflegekontextfaktoren - Erste deskriptive Studienresultate einer Querschnittserhebung der schweizerischen DRG Begleitforschung Pflege vor Einführung der SwissDRG.

BACKGROUND: The adoption of DRG-based payment systems has narrowed hospitals' financial margins, necessitating streamlining and process optimization. The experience of other countries shows that this restructuring can influence context factors essential to the delivery of nursing care. As a result, nursing care quality and patient safety may be impacted. AIM: The Sinergia Project aims to develop a monitoring model and related instruments to continuously monitor the impact of DRG-based reimbursement on central nursing service context factors. METHOD: The descriptive, quantitative results were collected within the framework of a study with a mixed methods design by means of an online survey in which nurses from five hospitals participated. RESULTS: The results show that the nursing service context factors examined (nursing care complexity, quality of the work environment, management, moral distress and job satisfaction), have relevance in all practice areas as regards practice setting and nursing care delivery. Patterns can be recognized that are consistent with those found in the literature and which could be an indication of the relationships between the context factors above, as was hypothesized in the model. CONCLUSIONS: The study has provided the participating hospitals with useful data upon which to base discussions on ensuring quality of nursing care and practice development, in addition to information important to the further development of the model and the instruments employed.

Drug driving: a secondary analysis of factors associated with driving under the influence of cannabis in Jamaica.

OBJECTIVES: To determine cannabis use patterns, the predictive sociodemographic correlates of driving under the influence of cannabis (DUIC) and the association between risk perception and cannabis dependence among vehicle drivers in Jamaica. DESIGN: Secondary data analysis. SETTING: Used the Jamaica National Drug Prevalence Survey 2016 dataset. PARTICIPANTS: 1060 vehicle drivers extracted from the population sample of 4623. PRIMARY AND SECONDARY OUTCOME MEASURES: Analysis used Pearson's χ2 test and logistic regression. ORs and 95% CIs were recorded. A p<0.05 was considered statistically significant. RESULTS: More than 10% of Jamaican drivers admitted to DUIC in the past year. Approximately 43.3% of drivers who currently use cannabis reported DUIC only. Evidently, 86.8% of drivers who DUIC were heavy cannabis users. Approximately 30% of drivers with moderate to high-risk perception of smoking cannabis sometimes or often were dependent on cannabis. Notwithstanding, drivers with no to low-risk perception of smoking cannabis sometimes or often were significantly likelier to be dependent (p<0.001 and p<0.001, respectively). Logistic regression highlighted male drivers (OR 4.14, 95% CI 1.59 to 14.20, p=0.009) that were 34 years and under (OR 2.97, 95% CI 1.71 to 5.29, p<0.001) and were the head of the household (OR 2.22, 95% CI 1.10 to 4.75, p=0.031) and operated a machine as part of their job (OR 1.87, 95% CI 1.09 to 3.24, p=0.023) were more likely to DUIC, while those who were married (OR 0.42, 95% CI 0.22 to 0.74, p=0.004) and had achieved a tertiary-level education (OR 0.26, 95% CI 0.06 to 0.76, p=0.031) were less likely. CONCLUSIONS: Two in five Jamaican drivers, who currently smoke cannabis, drive under its influence, with over 85% engaging in heavy use. Public health implications necessitate policy-makers consider mobile roadside drug testing and amending drug-driving laws to meet international standards.

The SATB1-MIR22-GBA axis mediates glucocerebroside accumulation inducing a cellular senescence-like phenotype in dopaminergic neurons.

Idiopathic Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which is associated with neuroinflammation and reactive gliosis. The underlying cause of PD and the concurrent neuroinflammation are not well understood. In this study, we utilize human and murine neuronal lines, stem cell-derived dopaminergic neurons, and mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, and GBA, are components of a single gene regulatory pathway. Our findings indicate that dysregulation of this pathway leads to the upregulation of glucocerebrosides (GluCer), which triggers a cellular senescence-like phenotype in dopaminergic neurons. Specifically, we discovered that downregulation of the transcriptional repressor SATB1 results in the derepression of the microRNA miR-22-3p, leading to decreased GBA expression and subsequent accumulation of GluCer. Furthermore, our results demonstrate that an increase in GluCer alone is sufficient to impair lysosomal and mitochondrial function, thereby inducing cellular senescence. Dysregulation of the SATB1-MIR22-GBA pathway, observed in both PD patients and normal aging, leads to lysosomal and mitochondrial dysfunction due to the GluCer accumulation, ultimately resulting in a cellular senescence-like phenotype in dopaminergic neurons. Therefore, our study highlights a novel pathway involving three genetic risk factors for PD and provides a potential mechanism for the senescence-induced neuroinflammation and reactive gliosis observed in both PD and normal aging.

TCF4 Mutations Disrupt Synaptic Function Through Dysregulation of RIMBP2 in Patient-Derived Cortical Neurons.

BACKGROUND: Genetic variation in the TCF4 (transcription factor 4) gene is associated with risk for a variety of developmental and psychiatric conditions, which includes a syndromic form of autism spectrum disorder called Pitt-Hopkins syndrome (PTHS). TCF4 encodes an activity-dependent transcription factor that is highly expressed during cortical development and in animal models has been shown to regulate various aspects of neuronal development and function. However, our understanding of how disease-causing mutations in TCF4 confer pathophysiology in a human context is lacking. METHODS: To model PTHS, we differentiated human cortical neurons from human induced pluripotent stem cells that were derived from patients with PTHS and neurotypical individuals. To identify pathophysiology and disease mechanisms, we assayed cortical neurons with whole-cell electrophysiology, Ca2+ imaging, multielectrode arrays, immunocytochemistry, and RNA sequencing. RESULTS: Cortical neurons derived from patients with TCF4 mutations showed deficits in spontaneous synaptic transmission, network excitability, and homeostatic plasticity. Transcriptomic analysis indicated that these phenotypes resulted in part from altered expression of genes involved in presynaptic neurotransmission and identified the presynaptic binding protein RIMBP2 as the most differentially expressed gene in PTHS neurons. Remarkably, TCF4-dependent deficits in spontaneous synaptic transmission and network excitability were rescued by increasing RIMBP2 expression in presynaptic neurons. CONCLUSIONS: Taken together, these results identify TCF4 as a critical transcriptional regulator of human synaptic development and plasticity and specifically identifies dysregulation of presynaptic function as an early pathophysiology in PTHS.

Locus of control, depression and quality of life among persons with sickle cell disease in Jamaica.

This study explored how locus of control (LOC), depression and quality of life (QOL) interplay in patients with sickle cell disease. One hundred and forty-three sickle cell clinic patients with consecutive clinic consultations completed the Multidimensional Health Locus of Control and Short Factor 36 (SF-36) scales as well as the Beck Depression Inventory. Participants in this study had higher scores on the "chance", "other people" and "internal" domains of LOC than persons with a number of other chronic illnesses in a previous study. Hierarchical regression analyses showed that high scores on the "internal" domain of LOC were associated with better QOL and fewer symptoms of depression. Depressive symptoms were greater in persons with high scores on the "other people" LOC domain and in younger persons. These findings would suggest that it is possible that interventions which enhance internal LOC and discourage "other people" orientations might improve QOL and ameliorate depression among persons with sickle cell disease.

The SATB1-MIR22-GBA axis mediates glucocerebroside accumulation inducing a cellular senescence-like phenotype in dopaminergic neurons.

Idiopathic Parkinson's Disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which is associated with neuroinflammation and reactive gliosis. The underlying cause of PD and the concurrent neuroinflammation are not well understood. In this study, we utilized human and murine neuronal lines, stem cell-derived dopaminergic neurons, and mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, and GBA, are components of a single gene regulatory pathway. Our findings indicate that dysregulation of this pathway leads to the upregulation of glucocerebrosides (GluCer), which triggers a cellular senescence-like phenotype in dopaminergic neurons. Specifically, we discovered that downregulation of the transcriptional repressor SATB1 results in the derepression of the microRNA miR-22-3p, leading to decreased GBA expression and subsequent accumulation of GluCer. Furthermore, our results demonstrate that an increase in GluCer alone is sufficient to impair lysosomal and mitochondrial function, thereby inducing cellular senescence dependent on S100A9 and stress factors. Dysregulation of the SATB1-MIR22-GBA pathway, observed in both PD patients and normal aging, leads to lysosomal and mitochondrial dysfunction due to the GluCer accumulation, ultimately resulting in a cellular senescence-like phenotype in dopaminergic neurons. Therefore, our study highlights a novel pathway involving three genetic risk factors for PD and provides a potential mechanism for the senescence-induced neuroinflammation and reactive gliosis observed in both PD and normal aging.

TCF4 mutations disrupt synaptic function through dysregulation of RIMBP2 in patient-derived cortical neurons.

Genetic variation in the transcription factor 4 ( TCF4) gene is associated with risk for a variety of developmental and psychiatric conditions, which includes a syndromic form of ASD called Pitt Hopkins Syndrome (PTHS). TCF4 encodes an activity-dependent transcription factor that is highly expressed during cortical development and in animal models is shown to regulate various aspects of neuronal development and function. However, our understanding of how disease-causing mutations in TCF4 confer pathophysiology in a human context is lacking. Here we show that cortical neurons derived from patients with TCF4 mutations have deficits in spontaneous synaptic transmission, network excitability and homeostatic plasticity. Transcriptomic analysis indicates these phenotypes result from altered expression of genes involved in presynaptic neurotransmission and identifies the presynaptic binding protein, RIMBP2 as the most differentially expressed gene in PTHS neurons. Remarkably, TCF4-dependent deficits in spontaneous synaptic transmission and network excitability were rescued by increasing RIMBP2 expression in presynaptic neurons. Together, these results identify TCF4 as a critical transcriptional regulator of human synaptic development and plasticity and specifically identifies dysregulation of presynaptic function as an early pathophysiology in PTHS.

Protein interaction studies in human induced neurons indicate convergent biology underlying autism spectrum disorders.

Autism spectrum disorders (ASDs) have been linked to genes with enriched expression in the brain, but it is unclear how these genes converge into cell-type-specific networks. We built a protein-protein interaction network for 13 ASD-associated genes in human excitatory neurons derived from induced pluripotent stem cells (iPSCs). The network contains newly reported interactions and is enriched for genetic and transcriptional perturbations observed in individuals with ASDs. We leveraged the network data to show that the ASD-linked brain-specific isoform of ANK2 is important for its interactions with synaptic proteins and to characterize a PTEN-AKAP8L interaction that influences neuronal growth. The IGF2BP1-3 complex emerged as a convergent point in the network that may regulate a transcriptional circuit of ASD-associated genes. Our findings showcase cell-type-specific interactomes as a framework to complement genetic and transcriptomic data and illustrate how both individual and convergent interactions can lead to biological insights into ASDs.

Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia.

Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.

Evaluation of a clinical leadership programme for nurse leaders.

AIM: This is an evaluation study of the impact of the adapted RCN Clinical Leadership Programme on the development of leadership competencies of nurse leaders in Switzerland. BACKGROUND: Transformational leadership competencies are essential for delivering high-quality care within health-care organizations. However, many countries have identified a lack of leadership skills in nurse leaders. Consequently, the development of leadership competencies is a major objective for health-care centres. METHODS: This article describes the quantitative results of a mixed methods study. A one-group pre-test-post-test quasi-experimental design was used. A convenience sample of 14 ward leaders were assessed three times using the Leadership Practices Inventory (LPI). Descriptive and inferential data analysis techniques were employed. RESULTS: In total 420 observer-assessment questionnaires and 42 self-assessment questionnaires were distributed. Our main finding was that nurse leaders following the programme, demonstrated significant improvement in two subscales of the LPI -'inspiring a shared vision' and 'challenging the process'. CONCLUSION: This study showed improvement in two leadership practices of nurse leaders following a programme that has been adapted to Swiss health care. IMPLICATIONS FOR NURSING MANAGEMENT: Findings concur with others studies that suggest that investments in educational programs to facilitate leadership skills in nurse leaders are justified.

Semaphorin3A/PlexinA3 association with the Scribble scaffold for cGMP increase is required for apical dendrite development.

The development of the apical dendrite from the leading process of the bipolar pyramidal neuron might be directed by spatially organized extrinsic cues acting on localized intrinsic determinants. The extracellular cues regulating apical dendrite polarization remain elusive. We show that leading process and apical dendrite development are directed by class III Semaphorins and mediated by a localized cGMP-synthesizing complex. The scaffolding protein Scribble that associates with the cGMP-synthesizing enzyme soluble guanylate cyclase (sGC) also associates with the Semaphorin3A (Sema3A) co-receptor PlexinA3. Deletion or knockdown of PlexinA3 and Sema3A or disruption of PlexinA3-Scribble association prevents Sema3A-mediated cGMP increase and causes defects in apical dendrite development. These manipulations also impair bipolar polarity and leading process establishment. Local cGMP elevation or sGC expression rescues the effects of PlexinA3 knockdown or PlexinA3-Scribble complex disruption. During neuronal polarization, leading process and apical dendrite development are directed by a scaffold that links Semaphorin cue to cGMP increase.