Arvostava haastattelu muutosjohtamisen työkaluna terveydenhuollossa

Tiivistelmä. Tämän kandidaatintutkielman tarkoitus oli kuvailla arvostavan haastattelun menetelmän käyttöä muutosjohtamisessa terveydenhuollon kontekstissa. Aiheen valintaan vaikutti käsitys siitä, että arvostavan haastattelun menetelmä ei ole laajasti tunnettu malli muutosjohtamisen työvälineenä suomalaisessa terveydenhuollon ympäristössä. Aineistona tutkielmassa oli viisi vertaisarvioitua tutkimusartikkelia, jotka olivat julkaistu akateemisissa julkaisuissa vuosien 2007–2016 välillä. Arvostavan haastattelun käyttöä muutosjohtamisessa analysoitiin sisällönanalyysia mukaillen. Arvostavan haastattelun menetelmä oli tehokasta terveydenhuollon ympäristössä muutosjohtamisen apuvälineenä erityisesti työpaikan sosiaaliseen rakenteeseen liittyvien tekijöiden osalta. Näitä olivat vuorovaikutuksen ja yhteistyön lisääntyminen, vaikuttamismahdollisuuksien ja osallisuuden tunteen lisääntyminen sekä sairaanhoitajien työtyytyväisyyden lisääntyminen. Arvostavan haastattelun luonne tasa-arvoa edistävänä ja demokraattisena menetelmänä oli tutkielman aineiston mukaan tärkeää. Arvostavan haastattelun menetelmän käyttämisen edellytyksenä nähtiin erittäin vahva ammatillinen menetelmäosaaminen sekä arvostavan haastattelun taustateorioiden syvä tuntemus. Arvostavan haastattelun menetelmällä edistettiin tieteellisen, näyttöön perustuvan tiedon käyttöä terveydenhuollon ammattilaisten keskuudessa. Arvostavan haastattelun arvioitiin vähentävän liian byrokraattisuuden rakentumisen riskiä, lisäävän tehokkuutta sekä alentavan muutosvastarintaa. Pitkän aikavälin organisaatiokulttuurin muutosten onnistumisen arviointi oli tutkielman aineiston perusteella hankalaa. Johtopäätöksenä voidaan todeta, että arvostavan haastattelun menetelmää kannattaa käyttää terveydenhuollon toimintaympäristössä muutosjohtamisessa erityisesti silloin, kun halutaan vaikuttaa yksikön tai organisaation sosiaaliseen rakenteeseen ja uusien käytäntöjen syntymiseen

A carbohydrate-active enzyme (CAZy) profile links successful metabolic specialization of Prevotella to its abundance in gut microbiota

Gut microbiota participates in diverse metabolic and homeostatic functions related to health and well-being. Its composition varies between individuals, and depends on factors related to host and microbial communities, which need to adapt to utilize various nutrients present in gut environment. We profiled fecal microbiota in 63 healthy adult individuals using metaproteomics, and focused on microbial CAZy (carbohydrate-active) enzymes involved in glycan foraging. We identified two distinct CAZy profiles, one with many Bacteroides-derived CAZy in more than one-third of subjects (n = 25), and it associated with high abundance of Bacteroides in most subjects. In a smaller subset of donors (n = 8) with dietary parameters similar to others, microbiota showed intense expression of Prevotella-derived CAZy including exo-beta-(1,4)-xylanase, xylan-1,4-beta-xylosidase, alpha-L-arabinofuranosidase and several other CAZy belonging to glycosyl hydrolase families involved in digestion of complex plant-derived polysaccharides. This associated invariably with high abundance of Prevotella in gut microbiota, while in subjects with lower abundance of Prevotella, microbiota showed no Prevotella-derived CAZy. Identification of Bacteroides- and Prevotella-derived CAZy in microbiota proteome and their association with differences in microbiota composition are in evidence of individual variation in metabolic specialization of gut microbes affecting their colonizing competence

Agro-biodiversity in national pathways for food system transformation: case of West Africa

The challenges relating to biodiversity loss, food insecurity and climate change show the urgent need to make transition towards sustainable food systems in West Africa. To bring about such a transition worldwide, the United Nations’ Food Systems Summit was held in September 2021. One of the main outcomes of the Summit was the national pathways to sustainable food systems. This review analyses whether and how agro-biodiversity is addressed in the food system transformation pathways submitted by West African countries in the framework of the Summit. The content analysis suggests that agro-biodiversity is not a central topic in the national transformation pathways. In fact, it is completely overlooked in some pathways documents, and rather marginal in others. Some national documents (cf. Burkina Faso, Ghana, Niger, Nigeria) refer to the promotion of the diversity of crops and farm animals as a means of adapting to climate change, improving livelihoods and diversifying diets thus contributing to nutrition security. Moreover, only a few measures and actions dealing with the valorisation of the neglected and underutilised species (NUS) and traditional crop varieties are included in the national transformation pathways (cf. Guinea, Liberia, Niger, Sierra Leone). The conservation, management and restoration of agro-biodiversity and agro-ecosystems are crucial to boost the transition towards nature-positive food systems in the region. Therefore, a paradigm change is needed in policy, research and practice to conserve the natural resource base and contribute to sustainable development by addressing, inter alia, food insecurity and malnutrition, rural poverty and climate change challenges

Brain TSPO-PET predicts later disease progression independent of relapses in multiple sclerosis

Overactivation of microglia is associated with most neurodegenerative diseases. In this study we examined whether PET-measurable innate immune cell activation predicts multiple sclerosis disease progression. Activation of microglia/macrophages was measured using the 18-kDa translocator protein (TSPO)-binding radioligand 11C-PK11195 and PET imaging in 69 patients with multiple sclerosis and 18 age- and sex-matched healthy controls. Radioligand binding was evaluated as the distribution volume ratio from dynamic PET images. Conventional MRI and disability measurements using the Expanded Disability Status Scale were performed for patients at baseline and 4.1 ± 1.9 (mean ± standard deviation) years later. Fifty-one (74%) of the patients were free of relapses during the follow-up period. Patients had increased activation of innate immune cells in the normal-appearing white matter and in the thalamus compared to the healthy control group (P = 0.033 and P = 0.003, respectively, Wilcoxon). Forward-type stepwise logistic regression was used to assess the best variables predicting disease progression. Baseline innate immune cell activation in the normal-appearing white matter was a significant predictor of later progression when the entire multiple sclerosis cohort was assessed [odds ratio (OR) = 4.26; P = 0.048]. In the patient subgroup free of relapses there was an association between macrophage/microglia activation in the perilesional normal-appearing white matter and disease progression (OR = 4.57; P = 0.013). None of the conventional MRI parameters measured at baseline associated with later progression. Our results strongly suggest that innate immune cell activation contributes to the diffuse neural damage leading to multiple sclerosis disease progression independent of relapses

Orphan G protein-coupled receptor GPRC5A modulates integrin β1-mediated epithelial cell adhesion

G-Protein Coupled Receptor (GPCR), Class C, Group 5, Member A (GPRC5A) has been implicated in several malignancies. The underlying mechanisms, however, remain poorly understood. Using a panel of human cell lines, we demonstrate that CRISPR/Cas9-mediated knockout and RNAi-mediated depletion of GPRC5A impairs cell adhesion to integrin substrates: collagens I and IV, fibronectin, as well as to extracellular matrix proteins derived from the Engelbreth-Holm-Swarm (EHS) mouse sarcoma (Matrigel). Consistent with the phenotype, knock-out of GPRC5A correlated with a reduced integrin β1 (ITGB1) protein expression, impaired phosphorylation of the focal adhesion kinase (FAK), and lower activity of small GTPases RhoA and Rac1. Furthermore, we provide the first evidence for a direct interaction between GPRC5A and a receptor tyrosine kinase EphA2, an upstream regulator of FAK, although its contribution to the observed adhesion phenotype is unclear. Our findings reveal an unprecedented role for GPRC5A in regulation of the ITGB1-mediated cell adhesion and it's downstream signaling, thus indicating a potential novel role for GPRC5A in human epithelial cancers.</p

Mast Cells in Human Cutaneous Neurofibromas: Density, Subtypes, and Association with Clinical Features in Neurofibromatosis 1

Background: Cutaneous neurofibromas (cNFs) are hallmarks of neurofibromatosis 1 (NF1) and cause the main disease burden in adults with NF1. Mast cells are a known component of cNFs. However, no comprehensive characterization of mast cells in cNFs is available, and their contributions to cNF growth and symptoms such as itch are not known.Methods: We collected 60 cNFs from ten individuals with NF1, studied their mast cell proteinase content, and compared the mast cell numbers to selected clinical features of the tumors and patients. The tumors were immunolabeled for the mast cell markers CD117, tryptase, and chymase, and the percentage of immunopositive cells was determined using computer-assisted methods.Results: The median proportions of positive cells were 5.5% (range 0.1-14.4) for CD117, 4.0% (1.2-7.0) for tryptase, and 5.0% (1.1-15.9) for chymase. The median densities of cells immunopositive for CD117, tryptase, and chymase were 280, 243, and 250 cells/mm2, respectively. Small tumors, growing tumors, and tumors from patients below the median age of 33 years displayed a high proportion of mast cells. Cells expressing both tryptase and chymase were the predominant mast cell type in cNFs, followed by cells expressing chymase only.Conclusion: The results highlight the abundance of mast cells in cNFs and that their number and subtypes clearly differ from those previously reported in unaffected skin.</p

Effect of homogenised and pasteurised versus native cows' milk on gastrointestinal symptoms, intestinal pressure and postprandial lipid metabolism

Some people experience gastrointestinal symptoms related to cow's milk consumption even if neither lactose intolerance nor cow's milk allergy can be diagnosed. To investigate whether milk homogenization could cause gastrointestinal problems, homogenized and pasteurized milk and native milk were served to eleven volunteers who reported such sensitivity in a random order together with an ingestible pressure measuring capsule. Postprandial lipemia did not differ between the two milk types, but significant differences were found in the postprandial plasma fatty acid composition. No significant difference was found in the amount of gastrointestinal symptoms or in the intestinal pressure after the consumption of native and processed milk. However, the obtained results on pressure in the large intestine (P = 0.068) as well as reported symptoms (P = 0.103) suggest that further studies in this area are needed with a bigger subject group and with longer exposure times to differently processed milk types. (C) 2017 Elsevier Ltd. All rights reserved

Microglial activation, white matter tract damage, and disability in MS

ObjectiveTo investigate the relationship of in vivo microglial activation to clinical and MRI parameters in MS.MethodsPatients with secondary progressive MS (n = 10) or relapsing-remitting MS (n = 10) and age-matched healthy controls (n = 17) were studied. Microglial activation was measured using PET and radioligand [C-11](R)-PK11195. Clinical assessment and structural and quantitative MRI including diffusion tensor imaging (DTI) were performed for comparison.Results[C-11](R)-PK11195 binding was significantly higher in the normal-appearing white matter (NAWM) of patients with secondary progressive vs relapsing MS and healthy controls, in the thalami of patients with secondary progressive MS vs controls, and in the perilesional area among the progressive compared with relapsing patients. Higher binding in the NAWM was associated with higher clinical disability and reduced white matter (WM) structural integrity, as shown by lower fractional anisotropy, higher mean diffusivity, and increased WM lesion load. Increasing age contributed to higher microglial activation in the NAWM among patients with MS but not in healthy controls.ConclusionsPET can be used to quantitate microglial activation, which associates with MS progression. This study demonstrates that increased microglial activity in the NAWM correlates closely with impaired WM structural integrity and thus offers one rational pathologic correlate to diffusion tensor imaging (DTI) parameters

Natalizumab treatment reduces microglial activation in the white matter of the MS brain

ObjectiveTo evaluate whether natalizumab treatment reduces microglial activation in MS.MethodsWe measured microglial activation using the 18-kDa translocator protein (TSPO)-binding radioligand [C-11] PK11195 and PET imaging in 10 patients with MS before and after 1 year treatment with natalizumab. Microglial activation was evaluated as the distribution volume ratio (DVR) of the specifically bound radioligand in brain white and gray matter regions of interest. MRI and disability measurements were performed for comparison. Evaluation was performed identically with 11 age-and sex-matched patients with MS who had no MS therapy.ResultsNatalizumab treatment reduced microglial activation in the normal-appearing white matter (NAWM; baseline DVR vs DVR after 1 year of treatment 1.25 vs 1.22, p = 0.014, Wilcoxon) and at the rim of chronic lesions (baseline DVR vs DVR after 1 year of treatment 1.24 vs 1.18, p = 0.014). In patients with MS with no treatment, there was an increase in microglial activation at the rim of chronic lesions (1.23 vs 1.27, p = 0.045). No alteration was observed in microglial activation in gray matter areas. In the untreated patient group, higher microglial activation at baseline was associated with more rapid disability progression during an average of 4 years of follow-up.ConclusionsTSPO-PET imaging can be used as a tool to assess longitudinal changes in microglial activation in the NAWM and in the perilesional areas in the MS brain in vivo. Natalizumab treatment reduces the diffuse compartmentalized CNS inflammation related to brain resident innate immune cells

Prodromal neuroinflammatory, cholinergic and metabolite dysfunction detected by PET and MRS in the TgF344-AD transgenic rat model of AD: A collaborative multi-modal study

Mouse models of Alzheimer s disease (AD) are valuable but do not fully recapitulate human AD pathology, such as spontaneous Tau fibril accumulation and neuronal loss, necessitating the development of new AD models. The transgenic (TG) TgF344-AD rat has been reported to develop age-dependent AD features including neuronal loss and neurofibrillary tangles, despite only expressing APP and PSEN1 mutations, suggesting an improved modelling of AD hallmarks. Alterations in neuronal networks as well as learning performance and cognition tasks have been reported in this model, but none have combined a longitudinal, multimodal approach across multiple centres, which mimics the approaches commonly taken in clinical studies. We therefore aimed to further characterise the progression of AD-like pathology and cognition in the TgF344-AD rat from young-Adults (6 months (m)) to mid-(12 m) and advanced-stage (18 m, 25 m) of the disease. Methods: TgF344-AD rats and wild-Type (WT) littermates were imaged at 6 m, 12 m and 18 m with [18F]DPA-714 (TSPO, neuroinflammation), [18F]Florbetaben (A) and [18F]ASEM (7-nicotinic acetylcholine receptor) and with magnetic resonance spectroscopy (MRS) and with (S)-[18F]THK5117 (Tau) at 15 and 25 m. Behaviour tests were also performed at 6 m, 12 m and 18 m. Immunohistochemistry (CD11b, GFAP, A, NeuN, NeuroChrom) and Tau (S)-[18F]THK5117 autoradiography, immunohistochemistry and Western blot were also performed. Results: [18F]DPA-714 positron emission tomography (PET) showed an increase in neuroinflammation in TG vs wildtype animals from 12 m in the hippocampus (+11%), and at the advanced-stage AD in the hippocampus (+12%), the thalamus (+11%) and frontal cortex (+14%). This finding coincided with strong increases in brain microgliosis (CD11b) and astrogliosis (GFAP) at these time-points as assessed by immunohistochemistry. In vivo [18F]ASEM PET revealed an age-dependent increase uptake in the striatum and pallidum/nucleus basalis of Meynert in WT only, similar to that observed with this tracer in humans, resulting in TG being significantly lower than WT by 18 m. In vivo [18F]Florbetaben PET scanning detected A accumulation at 18 m, and (S)-[18F]THK5117 PET revealed subsequent Tau accumulation at 25m in hippocampal and cortical regions. A plaques were low but detectable by immunohistochemistry from 6 m, increasing further at 12 and 18 m with Tau-positive neurons adjacent to A plaques at 18 m. NeuroChrom (a pan neuronal marker) immunohistochemistry revealed a loss of neuronal staining at the A plaques locations, while NeuN labelling revealed an age-dependent decrease in hippocampal neuron number in both genotypes. Behavioural assessment using the novel object recognition task revealed that both WT & TgF344-AD animals discriminated the novel from familiar object at 3 m and 6 m of age. However, low levels of exploration observed in both genotypes at later time-points resulted in neither genotype successfully completing the task. Deficits in social interaction were only observed at 3 m in the TgF344-AD animals. By in vivo MRS, we showed a decrease in neuronal marker N-Acetyl-Aspartate in the hippocampus at 18 m (-18% vs age-matched WT, and-31% vs 6 m TG) and increased Taurine in the cortex of TG (+35% vs age-matched WT, and +55% vs 6 m TG). Conclusions: This multi-centre multi-modal study demonstrates, for the first time, alterations in brain metabolites, cholinergic receptors and neuroinflammation in vivo in this model, validated by robust ex vivo approaches. Our data confirm that, unlike mouse models, the TgF344-AD express Tau pathology that can be detected via PET, albeit later than by ex vivo techniques, and is a useful model to assess and longitudinally monitor early neurotransmission dysfunction and neuroinflammation in AD