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Digital transformation has become a cornerstone of innovation in pharmaceutical research and development (R&D). Pharmaceutical companies now have an imperative to embrace transformation, including mid-sized and small-sized companies despite resource limitations that do not allow economies of scale compared with larger organizations. This article describes the journey undertaken by Chiesi to develop an efficient framework to drive digital transformation along its R&D value chain with the objective of building and refreshing a clear roadmap and relevant priorities, together with identifying and enabling new digital capabilities and skills within R&D, defining tools and processes that will guide Chiesi activities in the space up to mid-long term. This work has led so far to five main achievements, which align with the steps in the framework: a strategically aligned roadmap with key focus areas for digital transformation and a dedicated team to lead the effort; a common language for data across the R&D value chain; an internal mindset that's open to innovation and participation in key external networks and consortia; a set of quick-win use cases for the new framework; and a defined set of Key Performance Indicators (KPIs) and monitoring tools for digital transformation. The work presented here demonstrates that R&D digital transformation should represent an ongoing process to enable cross-functional collaboration and integration within complex corporate environments that face an ever-growing volume of diverse data, to efficiently support business needs, and to ensure a positive impact on patient care.
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AIMS AND OBJECTIVES: To summarise the evidence published to date regarding nursing core competence in stoma care of any type of ostomy throughout the patient's ostomy surgery candidate care pathway from preoperative to follow-up. BACKGROUND: Nurses should play a key role in all ostomy patient care pathways to help them to adapt to the new physics and psychological conditions from the preoperative phases to the prevention of tardive stomal complications. DESIGN: Scoping review. METHODS: This scoping review was conducted following the methodological framework proposed by Arskey and O'Malley, following the Preferred Reporting Item for Systematic Review and Meta-analysis for Scoping Review. PRISMA-ScR Checklist is included in the manuscript. The following databases were queried: PubMed, EMBASE and CINAHL, from August to October 2022. RESULTS: The search strategy in the consulted databases identified 3144 studies. Different types of ostomies were found and investigated: tracheostomy, gastrostomy, jejunostomy, ileostomy, colostomy and urostomy. The results of the included studies helped address the objective that allowed the ostomatherapy skills to be broken down into the different periods of the care pathway. CONCLUSION: Caring for an ostomy patient requires advanced skills and a trusting relationship. The skills outlined in this research suggest how essential the stoma care nurse specialist is in these patients' care.
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Enfermeiros Especialistas , Estomia , Humanos , Colostomia , Procedimentos Clínicos , IleostomiaRESUMO
Vesicle biogenesis, trafficking and signaling via Endoplasmic reticulum-Golgi network support essential developmental processes and their disruption lead to neurodevelopmental disorders and neurodegeneration. We report that de novo missense variants in ARF3, encoding a small GTPase regulating Golgi dynamics, cause a developmental disease in humans impairing nervous system and skeletal formation. Microcephaly-associated ARF3 variants affect residues within the guanine nucleotide binding pocket and variably perturb protein stability and GTP/GDP binding. Functional analysis demonstrates variably disruptive consequences of ARF3 variants on Golgi morphology, vesicles assembly and trafficking. Disease modeling in zebrafish validates further the dominant behavior of the mutants and their differential impact on brain and body plan formation, recapitulating the variable disease expression. In-depth in vivo analyses traces back impaired neural precursors' proliferation and planar cell polarity-dependent cell movements as the earliest detectable effects. Our findings document a key role of ARF3 in Golgi function and demonstrate its pleiotropic impact on development.
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Transtornos do Neurodesenvolvimento , Peixe-Zebra , Humanos , Animais , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Fatores de Ribosilação do ADP/metabolismo , Complexo de Golgi/metabolismo , Retículo Endoplasmático/metabolismo , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/metabolismoRESUMO
This Editorial analyzes the manuscripts accepted, after a careful peer-reviewed process, for the special issue "IoT Sensing Systems for Traffic Monitoring and for Automated and Connected Vehicles" of the Sensors MDPI journal.[...].
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BACKGROUND & AIMS: Homozygous individuals with alpha-1-antitrypsin deficiency (AATD) type PiZ have an increased risk of chronic liver disease and hepatocellular carcinoma (HCC). It is noteworthy that HCCs are composed by hepatocytes without accumulation of AAT, but the reason for this remains unclear. The aim of this study was to determine liver pathology in PiZ mice, focusing the attention on the distribution of AAT globules in normal liver, regenerative foci and neoplastic nodules. METHODS: Liver of 79 PiZ mice and 18 wild type (Wt) was histologically analysed for steatosis, clear cell foci, hyperplasia and neoplasia. The expression of human-AAT transgene and murine AAT, in non-neoplastic liver and in hyperplastic/neoplastic nodules was tested by qPCR and qRT-PCR. RT-PCR was used to study expression of hepatic markers: albumin, α-foetoprotein, transthyretin, AAT, glucose-6-phospate, tyrosine aminotransferase. RESULTS: Liver pathology was seen more frequently in PiZ (47/79) than in Wt (5/18) and its development was age related. In older PiZ mice (18-24 m), livers showed malignant tumours (HCC and angiosarcoma) (17/50), hyperplastic nodules (28/50), non-specific changes (33/50), whereas only 9/50 were normal. Both human-AATZ DNA and mRNA showed no differences between tumours/nodules and normal liver, while murine-AAT mRNA was reduced in tumours/nodules. CONCLUSION: Accumulation of AAT is associated with an increased risk of liver nodules. The presence of globule-devoid hepatocytes and the reduced expression of murine-AAT mRNA in hyperplastic and neoplastic nodules suggest that these hepatic lesions in AATD could originate from proliferating dedifferentiated cells, lacking AAT storage and becoming capable of AFP re-expression.
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Biomarcadores/sangue , Modelos Animais de Doenças , Fígado/patologia , Deficiência de alfa 1-Antitripsina/patologia , Animais , Primers do DNA/genética , Glucose-6-Fosfato/sangue , Técnicas Histológicas , Imuno-Histoquímica , Camundongos , Pré-Albumina/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Albumina Sérica , Estatísticas não Paramétricas , Tirosina Transaminase/sangue , alfa 1-Antitripsina/sangue , alfa-Fetoproteínas/metabolismoRESUMO
GE23077 is a novel RNA polymerase inhibitor that is isolated from the fermentation broth of an Actinomadura sp. It is a cyclic heptapeptide complex made up of four factors, differing in the structure of acyl group connected to the side chain of an alpha,beta-diaminopropanoic acid moiety and in the configuration of the stereocenter of an alpha-amino-malonic acid residue. Although GE23077 shows strong inhibitory activity on both Rifampicin-sensitive and -resistant polymerases, it exhibits poor antimicrobial activity. The most reasonable explanation for this property has been based on the lack of penetration of the molecule across the bacterial membrane, owing to its strong hydrophilic character. To improve penetration, several parts of the molecule were accordingly modified with the aim of altering the physico-chemical properties of GE23077. The current SAR study has identified moieties important for RNA polymerase activity.