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- Palica, Katarzyna, 1992-, et al.
(author)
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Metallo-β-Lactamase Inhibitor Phosphonamidate Monoesters
- 2022
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In: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 7:5, s. 4550-4562
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Journal article (peer-reviewed)abstract
- Being the second leading cause of death and the leading cause of disability-adjusted life years worldwide, infectious diseases remain─contrary to earlier predictions─a major consideration for the public health of the 21st century. Resistance development of microbes to antimicrobial drugs constitutes a large part of this devastating problem. The most widely spread mechanism of bacterial resistance operates through the degradation of existing β-lactam antibiotics. Inhibition of metallo-β-lactamases is expected to allow the continued use of existing antibiotics, whose applicability is becoming ever more limited. Herein, we describe the synthesis, the metallo-β-lactamase inhibition activity, the cytotoxicity studies, and the NMR spectroscopic determination of the protein binding site of phosphonamidate monoesters. The expression of single- and double-labeled NDM-1 and its backbone NMR assignment are also disclosed, providing helpful information for future development of NDM-1 inhibitors. We show phosphonamidates to have the potential to become a new generation of antibiotic therapeutics to combat metallo-β-lactamase-resistant bacteria.
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| 2. |
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| 3. |
- Andersson, Ulf, 1985-, et al.
(author)
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Clinical Reasoning among Registered Nurses in Emergency Medical Services : A Case Study
- 2022
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In: Journal of Cognitive Engineering and Decision Making. - : Sage Publications. - 1555-3434 .- 2169-5032. ; 16:3, s. 123-156
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Journal article (peer-reviewed)abstract
- In emergency medical services (EMS), the clinical reasoning (CR) of registered nurses (RNs) working in ambulance care plays an important role in providing care and treatment that is timely, accurate, appropriate and safe. However, limited existing knowledge about how CR is formed and influenced by the EMS mission hinders the development of service provision and decision support tools for RNs that would further enhance patient safety. To explore the nature of CR and influencing factors in this context, an inductive case study examined 34 observed patient-RN encounters in an EMS setting focusing on ambulance care. The results reveal a fragmented CR approach involving several parallel decision-making processes grounded in and led by patients' narratives. The findings indicate that RNs are not always aware of their own CR and associated influences until they actively reflect on the process, and additional research is needed to clarify this complex phenomenon.
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| 4. |
- Andersson, Ulf, 1985-, et al.
(author)
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Organizational factors influencing clinical reasoning in a Swedish emergency medical service organization: An explorative qualitative case study
- 2023
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In: Paramedicine. - : Sage Publications. - 2753-6386 .- 2753-6386.
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Journal article (peer-reviewed)abstract
- IntroductionClinical reasoning (CR) among healthcare professionals working in emergency medical services (EMS) who focus on ambulance care is a vital part of ensuring timely and safe patient care. The EMS environment continually fluctuates, so clinicians constantly need to adapt to new situations. Organizational support is described as important for CR, but overall, research on organizational influences for CR in an EMS context is lacking. An increased understanding of these influencing factors can assist in the development of EMS by strengthening CR among clinicians. Therefore, the purpose of this study was to investigate the organizational factors influencing EMS clinicians’ CR.MethodsUsing a qualitative single case study design, an EMS organization in southwestern Sweden was explored. Data were collected from participant observations of patient encounters, individual and group interviews with clinicians and organizational representatives, and organizational document audits. Data were analyzed using qualitative content analysis and triangulation of data sources.ResultsThe results revealed several organizational influencing factors. Collaboration and information sharing internally and externally were emphasized as essential components influencing CR. Additionally, the structure for the clinicians’ ‘room for action’ appeared confused and created uncertainties for CR related to decision mandates.ConclusionThe conclusion is that organizational factors do play an important role in clinicians’ CR. Moreover, the EMS community needs to develop suitable forums for discussing and developing these influencing factors across organizational hierarchies. Finally, clarification is needed on clinicians’ ‘room for action’ within their own organization but also with possible collaborators.
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| 5. |
- Andersson, Ulf, 1985-, et al.
(author)
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Situation awareness in Sweden’s emergency medical services : a goal-directed task analysis
- 2023
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In: Discover Health Systems. - 2731-7501. ; 2
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Journal article (peer-reviewed)abstract
- Situation awareness is knowing what is going on in the situation. Clinicians working in the emergency medical services (EMS) encounter numerous situations in various conditions, and to be able to provide efficient and patient safe care they need to understand what is going on and possible projections of the current situation. The design of this study encompassed a Goal-Directed Task analysis where situation awareness information requirements were mapped in relation to goals related to various aspects of the EMS mission. A group of 30 EMS subject matter experts were recruited and answered a web-based survey in three rounds related to what they though themselves or a colleague might need to achieve situation awareness related to the specific goals of various situations. The answers were analysed using content analysis and descriptive statistics. Answers reached consensus at a predetermined level of 75%. Those who reached consensus were entered into the final goal-directed task analysis protocol. The findings presented that EMS clinicians must rely on their own, or their colleagues prior experience or knowledge to achieve situation awareness. This suggests that individual expertise plays a crucial role in developing situation awareness. There also seems to be limited support for situation awareness from organizational guidelines. Furthermore, achieving situation awareness also involves collaborative efforts from the individuals involved in the situation. These findings could add to the foundation for further investigation in this area which could contribute to the development of strategies and tools to enhance situation awareness among EMS clinicians, ultimately improving patient care and safety.
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| 6. |
- Palica, Katarzyna, 1992-, et al.
(author)
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α-Aminophosphonate inhibitors of metallo-β-lactamases NDM-1 and VIM-2
- 2023
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In: RSC Medicinal Chemistry. - : Royal Society of Chemistry. - 2632-8682. ; 14:11, s. 2277-2300
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Journal article (peer-reviewed)abstract
- The upswing of antibiotic resistance is an escalating threat to human health. Resistance mediated by bacterial metallo-β-lactamases is of particular concern as these enzymes degrade β-lactams, our most frequently prescribed class of antibiotics. Inhibition of metallo-β-lactamases could allow the continued use of existing β-lactam antibiotics, such as penicillins, cephalosporins and carbapenems, whose applicability is becoming ever more limited. The design, synthesis, and NDM-1, VIM-2, and GIM-1 inhibitory activities (IC50 4.1–506 μM) of a series of novel non-cytotoxic α-aminophosphonate-based inhibitor candidates are presented herein. We disclose the solution NMR spectroscopic and computational investigation of their NDM-1 and VIM-2 binding sites and binding modes. Whereas the binding modes of the inhibitors are similar, VIM-2 showed a somewhat higher conformational flexibility, and complexed a larger number of inhibitor candidates in more varying binding modes than NDM-1. Phosphonate-type inhibitors may be potential candidates for development into therapeutics to combat metallo-β-lactamase resistant bacteria.
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| 8. |
- Andersson, Hanna, et al.
(author)
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Trauma-informed support after a complicated childbirth - An early intervention to reduce symptoms of post-traumatic stress, fear of childbirth and mental illness
- 2024
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In: Sexual & Reproductive HealthCare. - : ELSEVIER IRELAND LTD. - 1877-5756 .- 1877-5764. ; 41
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Journal article (peer-reviewed)abstract
- Objective: Women who experience obstetric interventions and complications during childbirth have an increased risk of developing postnatal post-traumatic stress and mental illness. This study aimed to test the effect of a trauma-informed support programme based on psychological first aid (PFA) to reduce the mothers ' symptoms of stress, fear of childbirth (FOC), anxiety and depression after a complicated childbirth. Methods: The study population consisted of women >= 18 years old who had undergone a complicated childbirth (i.e. acute or emergency caesarean section, vacuum extraction, child in need of neonatal care, manual placenta removal, obstetric anal sphincter injury, shoulder dystocia or major haemorrhage ( >1000 ml)). A total of 101 women participated in the study, of whom 43 received the intervention. Demographic questions and three self-assessment instruments measuring stress symptoms, FOC, anxiety and depression were answered one to three months after birth. Results: The women in the intervention group scored significantly lower on the stress symptom scale, with a halved median score compared to the control group. There was no significant difference between the groups regarding FOC, depression and anxiety. Conclusion: Our results indicate that this PFA-based support programme might reduce post-traumatic stress symptoms in women who have gone through a complicated childbirth. With further studies in a larger population, this support programme has the potential to contribute to improved maternal care optimizing postnatal mental health.
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| 9. |
- Ansari, Daniel, et al.
(author)
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Surveillance after surgery for pancreatic cancer : a global scoping review of guidelines and a nordic survey of contemporary practice
- 2024
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In: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708.
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Research review (peer-reviewed)abstract
- Objectives: Most patients with pancreatic cancer who have undergone surgical resection eventually develop disease recurrence. This study aimed to investigate whether there is evidence to support routine surveillance after pancreatic cancer surgery, with a secondary aim of analyzing the implementation of surveillance strategies in the Nordic countries.Materials and Methods: A scoping review was conducted to identify clinical practice guidelines globally and research studies relating to surveillance after pancreatic cancer resection. This was followed by a survey among 20 pancreatic units from four Nordic countries to assess their current practice of follow-up for operated patients.Results: Altogether 16 clinical practice guidelines and 17 research studies were included. The guidelines provided inconsistent recommendations regarding postoperative surveillance of pancreatic cancer. The clinical research data were mainly based on retrospective cohort studies with low level of evidence and lead-time bias was not addressed. Active surveillance was recommended in Sweden and Denmark, but not in Norway beyond the post-operative/adjuvant period. Finland had no national recommendations for surveillance. The Nordic survey revealed a wide variation in reported practice among the different units. About 75% (15 of 20 units) performed routine postoperative surveillance. Routine CA 19-9 testing was used by 80% and routine CT by 67% as part of surveillance. About 73% of centers continued follow-up until 5 years postoperatively.Conclusion: Evidence for routine long-term (i.e. 5 years) surveillance after pancreatic cancer surgery remains limited. Most pancreatic units in the Nordic countries conduct regular follow-up, but protocols vary.
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| 10. |
- Lundin, Samuel B, 1970, et al.
(author)
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A novel precision-serology assay for SARS-CoV-2 infection based on linear B-cell epitopes of Spike protein
- 2023
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In: Frontiers in Immunology. - 1664-3224. ; 14
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Journal article (peer-reviewed)abstract
- IntroductionThe COVID-19 pandemic illustrates the need for serology diagnostics with improved accuracy. While conventional serology based on recognition of entire proteins or subunits thereof has made significant contribution to the antibody assessment space, it often suffers from sub-optimal specificity. Epitope-based, high-precision, serology assays hold potential to capture the high specificity and diversity of the immune system, hence circumventing the cross-reactivity with closely related microbial antigens. MethodsWe herein report mapping of linear IgG and IgA antibody epitopes of the SARS-CoV-2 Spike (S) protein in samples from SARS-CoV-2 exposed individuals along with certified SARS-CoV-2 verification plasma samples using peptide arrays. ResultsWe identified 21 distinct linear epitopes. Importantly, we showed that pre-pandemic serum samples contain IgG antibodies reacting to the majority of protein S epitopes, most likely as a result of prior infection with seasonal coronaviruses. Only 4 of the identified SARS-CoV-2 protein S linear epitopes were specific for SARS-CoV-2 infection. These epitopes are located at positions 278-298 and 550-586, just proximal and distal to the RBD, as well as at position 1134-1156 in the HR2 subdomain and at 1248-1271 in the C-terminal subdomain of protein S. To substantiate the applicability of our findings, we tested three of the high-accuracy protein S epitopes in a Luminex assay, using a certified validation plasma sample set from SARS-CoV-2 infected individuals. The Luminex results were well aligned with the peptide array results, and correlated very well with in-house and commercial immune assays for RBD, S1 and S1/S2 domains of protein S. ConclusionWe present a comprehensive mapping of linear B-cell epitopes of SARS-CoV-2 protein S, that identifies peptides suitable for a precision serology assay devoid of cross-reactivity. These results have implications for development of highly specific serology test for exposure to SARS-CoV-2 and other members of the coronaviridae family, as well as for rapid development of serology tests for future emerging pandemic threats.
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