Training for impact: the socio-economic impact of a fit for purpose health workforce on communities.

Across the globe, a "fit for purpose" health professional workforce is needed to meet health needs and challenges while capitalizing on existing resources and strengths of communities. However, the socio-economic impact of educating and deploying a fit for purpose health workforce can be challenging to evaluate. In this paper, we provide a brief overview of six promising strategies and interventions that provide context-relevant health professional education within the health system. The strategies focused on in the paper are:1. Distributed community-engaged learning: Education occurs in or near underserved communities using a variety of educational modalities including distance learning. Communities served provide input into and actively participate in the education process.2. Curriculum aligned with health needs: The health and social needs of targeted communities guide education, research and service programmes.3. Fit for purpose workers: Education and career tracks are designed to meet the needs of the communities served. This includes cadres such as community health workers, accelerated medically trained clinicians and extended generalists.4. Gender and social empowerment: Ensuring a diverse workforce that includes women having equal opportunity in education and are supported in their delivery of health services.5. Interprofessional training: Teaching the knowledge, skills and attitudes for working in effective teams across professions.6. South-south and north-south partnerships: Sharing of best practices and resources within and between countries.In sum, the sharing of resources, the development of a diverse and interprofessional workforce, the advancement of primary care and a strong community focus all contribute to a world where transformational education improves community health and maximizes the social and economic return on investment.

Delirium detection and improved delirium management in older patients hospitalized for hip fracture.

Delirium is a common and potentially devastating problem for older patients following hip fracture. Although early detection is recommended, description and evaluation of standardized approaches are scarce. The aims of this quality improvement project were to: (1) implement a clinical algorithm for improving delirium detection and management and (2) assess the impact of the clinical algorithm on length of stay, discharge disposition and patient satisfaction. The pilot study was implemented on an orthopedic unit to evaluate the effectiveness of a clinical protocol for delirium detection and management to improve outcomes. Outcomes of 33 elderly post-operative hip fracture patients were compared to historical controls from the same unit. Delirium was detected in 18% of patients. Length of stay was reduced by 22% (P < .001), discharge disposition showed a 13% improvement (P = .17) and patient satisfaction scores showed a 15% (P = .15) improvement post-intervention. Implementation of a clinical algorithm to promote early detection and treatment of delirium in post-operative hip fracture patients is feasible and associated with improved outcomes.

Effects of Low Amyloid-ß (Aß) Concentration on Aß1-42 Oligomers Binding and GluN2B Membrane Expression.

Numerous studies have shown that amyloid-ß (Aß) modulate intracellular metabolic cascades and an intracellular Ca2+ homeostasis and a cell surface NMDA receptor expression alteration in Alzheimer's disease (AD). However most of these findings have been obtained by using non-physiological Aß concentrations. The present study deals with the effect of low Aß concentrations on cellular homeostasis. We used nerve growth factor-differentiated PC12 cells and murine cortical neurons sequentially treated with low chronic monomeric or small oligomeric Aß concentrations and high acute oligomeric Aß concentrations to bring out a priming effect of chronic treatment on subsequently high Aß concentrations-elicited cellular response. Both cell types indeed displayed an enhanced capacity to bind oligomeric Aß after monomeric or small oligomeric Aß application. Furthermore, the results show that monomeric Aß1-42 application to the cells induces an increase of the Ca2+-response and of the membrane expression of the extrasynaptic subunit of the NMDA receptor GluN2B in PC12 cells, while the opposite effects were observed in cultured neurons. This suggests a sequential interaction of Aß with the cellular plasma membrane involving monomers or small Aß oligomers which would facilitate the binding of the deleterious high molecular Aß oligomers. This mechanism would explain the slow progression of AD in the human nervous system and the deep gradient of neuronal death observed around the amyloid plaques in the nervous tissue.

Fake medicines: a global threat.

COUNTERFEIT MEDICINES are a growing problem in developing and developed countries. In May, the Medicines and Healthcare products Regulatory Agency (MHRA) announced that £8.6 million of counterfeit and unlicensed medicines, including huge hauls of potentially harmful slimming pills, and controlled drugs such as diazepam and anabolic steroids, had been seized in the UK ( MHRA 2014 ).

The global summit on nurse faculty migration.

As global demand for health care workers burgeons, information is scant regarding the migration of faculty who will train new nurses. With dual roles as clinicians and educators, and corresponding dual sets of professional and legal obligations, nurse faculty may confront unique circumstances in migration that can impact nations' ability to secure an adequate, stable nursing workforce. In a seminal effort to address these concerns, the Honor Society of Nursing, Sigma Theta Tau International, and the International Council of Nurses invited a diverse group of international experts to a summit designed to elucidate forces that drive nurse faculty migration. The primary areas of consideration were the impact on nurse faculty migration of rapid health care workforce scale-up, international trade agreements, and workforce aging. Long-term summit goals included initiating action affecting national, regional, and global supplies of nurse educators and helping to avert catastrophic failure of health care delivery systems caused by an inadequate ability to educate next-generation nurses.

Deficits of psychomotor and mnesic functions across aging in mouse lemur primates.

Owing to a similar cerebral neuro-anatomy, non-human primates are viewed as the most valid models for understanding cognitive deficits. This study evaluated psychomotor and mnesic functions of 41 young to old mouse lemurs (Microcebus murinus). Psychomotor capacities and anxiety-related behaviors decreased abruptly from middle to late adulthood. However, mnesic functions were not affected in the same way with increasing age. While results of the spontaneous alternation task point to a progressive and widespread age-related decline of spatial working memory, both spatial reference and novel object recognition (NOR) memory tasks did not reveal any tendency due to large inter-individual variability in the middle-aged and old animals. Indeed, some of the aged animals performed as well as younger ones, whereas some others had bad performances in the Barnes maze and in the object recognition test. Hierarchical cluster analysis revealed that declarative-like memory was strongly impaired only in 7 out of 25 middle-aged/old animals. These results suggest that this analysis allows to distinguish elder populations of good and bad performers in this non-human primate model and to closely compare this to human aging.

Advancing nursing practice through social media: a global perspective.

Social media has been used globally as a key vehicle for communication. As members of an innovative profession, many nurses have embraced social media and are actively utilizing its potential to enhance practice and improve health. The ubiquity of the Internet provides social media with the potential to improve both access to health information and services and equity in health care. Thus there are a number of successful nurse-led initiatives. However, the open and democratising nature of social media creates a number of potential risks, both individual and organisational. This article considers the use of social media within nursing from a global perspective, including discussion of policy and guidance documents. The impact of social media on both healthcare consumers and nurses is reviewed, followed by discussion of selected risks associated with social media. To help nurses make the most of social media tools and avoid potential pitfalls, the article conclusion suggests implications appropriate for global level practice based on available published guidance.

Clostridium perfringens epsilon toxin targets granule cells in the mouse cerebellum and stimulates glutamate release.

Epsilon toxin (ET) produced by C. perfringens types B and D is a highly potent pore-forming toxin. ET-intoxicated animals express severe neurological disorders that are thought to result from the formation of vasogenic brain edemas and indirect neuronal excitotoxicity. The cerebellum is a predilection site for ET damage. ET has been proposed to bind to glial cells such as astrocytes and oligodendrocytes. However, the possibility that ET binds and attacks the neurons remains an open question. Using specific anti-ET mouse polyclonal antibodies and mouse brain slices preincubated with ET, we found that several brain structures were labeled, the cerebellum being a prominent one. In cerebellar slices, we analyzed the co-staining of ET with specific cell markers, and found that ET binds to the cell body of granule cells, oligodendrocytes, but not astrocytes or nerve endings. Identification of granule cells as neuronal ET targets was confirmed by the observation that ET induced intracellular Ca(2+) rises and glutamate release in primary cultures of granule cells. In cultured cerebellar slices, whole cell patch-clamp recordings of synaptic currents in Purkinje cells revealed that ET greatly stimulates both spontaneous excitatory and inhibitory activities. However, pharmacological dissection of these effects indicated that they were only a result of an increased granule cell firing activity and did not involve a direct action of the toxin on glutamatergic nerve terminals or inhibitory interneurons. Patch-clamp recordings of granule cell somata showed that ET causes a decrease in neuronal membrane resistance associated with pore-opening and depolarization of the neuronal membrane, which subsequently lead to the firing of the neuronal network and stimulation of glutamate release. This work demonstrates that a subset of neurons can be directly targeted by ET, suggesting that part of ET-induced neuronal damage observed in neuronal tissue is due to a direct effect of ET on neurons.

Protein kinase C as a peripheral biomarker for Alzheimer's disease.

Numerous studies have been performed, which assess an important role of protein kinase C (PKC) in the physiopathology of Alzheimer disease (AD). The alteration of PKC activity stimulates amyloid-beta peptides production and protein tau hyperphosphorylation. This recently led to consider PKC as a potential therapeutic target for disease modifying drugs. Moreover PKC alterations were also observed in peripheral cells including blood cells. This short review recalls the main findings on the role of PKC in the disease process and focuses on its use as an AD biomarker in blood cells. Using fluorescent probes specific for PKC, it is possible to detect the conformational changes of the enzyme in living cells. Such probes can be used to detect PKC alterations in red blood cells and thus to distinguish AD patients from healthy controls with unmatched specificity and sensitivity.

Two chromogranin a-derived peptides induce calcium entry in human neutrophils by calmodulin-regulated calcium independent phospholipase A2.

BACKGROUND: Antimicrobial peptides derived from the natural processing of chromogranin A (CgA) are co-secreted with catecholamines upon stimulation of chromaffin cells. Since PMNs play a central role in innate immunity, we examine responses by PMNs following stimulation by two antimicrobial CgA-derived peptides. METHODOLOGY/PRINCIPAL FINDINGS: PMNs were treated with different concentrations of CgA-derived peptides in presence of several drugs. Calcium mobilization was observed by using flow cytometry and calcium imaging experiments. Immunocytochemistry and confocal microscopy have shown the intracellular localization of the peptides. The calmodulin-binding and iPLA2 activating properties of the peptides were shown by Surface Plasmon Resonance and iPLA2 activity assays. Finally, a proteomic analysis of the material released after PMNs treatment with CgA-derived peptides was performed by using HPLC and Nano-LC MS-MS. By using flow cytometry we first observed that after 15 s, in presence of extracellular calcium, Chromofungin (CHR) or Catestatin (CAT) induce a concentration-dependent transient increase of intracellular calcium. In contrast, in absence of extra cellular calcium the peptides are unable to induce calcium depletion from the stores after 10 minutes exposure. Treatment with 2-APB (2-aminoethoxydiphenyl borate), a store operated channels (SOCs) blocker, inhibits completely the calcium entry, as shown by calcium imaging. We also showed that they activate iPLA2 as the two CaM-binding factors (W7 and CMZ) and that the two sequences can be aligned with the two CaM-binding domains reported for iPLA2. We finally analyzed by HPLC and Nano-LC MS-MS the material released by PMNs following stimulation by CHR and CAT. We characterized several factors important for inflammation and innate immunity. CONCLUSIONS/SIGNIFICANCE: For the first time, we demonstrate that CHR and CAT, penetrate into PMNs, inducing extracellular calcium entry by a CaM-regulated iPLA2 pathway. Our study highlights the role of two CgA-derived peptides in the active communication between neuroendocrine and immune systems.

ARF6 regulates the synthesis of fusogenic lipids for calcium-regulated exocytosis in neuroendocrine cells.

An important role for specific lipids in membrane fusion has recently emerged, but regulation of their biosynthesis remains poorly understood. Among fusogenic lipids, phosphatidic acid and phosphoinositol 4,5-bisphosphate (PIP(2)) have been proposed to act at various steps of neurotransmitter and hormone exocytosis. Using real time FRET (fluorescence resonance energy transfer) measurements, we show here that the GTPase ARF6, potentially involved in the synthesis of these lipids, is activated at the exocytotic sites in PC12 cells stimulated for secretion. Depletion of endogenous ARF6 by siRNA dramatically inhibited secretagogue-evoked exocytosis. ARF6-siRNA greatly reduced secretagogue-evoked phospholipase D (PLD) activation and phosphatidic acid formation at the plasma membrane and moderately reduced constitutive levels of PIP(2) present at the plasma membrane in resting cells. Expression of an ARF6 insensitive to short interference RNA (siRNA) fully rescued secretion in ARF6-depleted cells. However, a mutated ARF6 protein specifically impaired in its ability to stimulate PLD had no effect. Finally, we show that the ARF6-siRNA-mediated inhibition of exocytosis could be rescued by an exogenous addition of lysophosphatidylcholine, a lipid that favors negative curvature on the inner leaflet of the plasma membrane. Altogether these data indicate that ARF6 is a critical upstream signaling element in the activation of PLD necessary to produce the fusogenic lipids required for exocytosis.

Panaxadiol glycosides that induce neuronal differentiation in neurosphere stem cells.

Bioassay-guided fractionation, combined with screening based on EGF-responsive neural stem cells (NSCs) differentiation assay, has been used to search for active molecules from Panax notoginseng. Ginsenosides Rg3 (1), Rk1 (2), and Rg5 (3) were identified as potential neurogenic molecules. The degrees of their neurogenic effects were found to be 3 > 2 > 1. The neurogenic effect of 3 represents a biphasic dose- and time-dependent regulation. Transient exposure of NSCs to 8 microM 3 for 24 h followed by 1 microM and 72 h incubation was the optimal procedure for the induction of neurons in NSCs, and compound 3 resulted in an approximately 3-fold increase in neurogenesis at the expense of astrogliogenesis. The neurogenic effect of 3 was completely eliminated by the Ca2+ channel antagonist nifedipine. These findings imply that 3 may be utilized as a pharmacological agent in studying the molecular regulation of neurogenesis of brain stem cells and, subsequently, for treatment of neurodegenerative diseases.