43 research outputs found

    Crystal structure of Mycobacterium tuberculosis FadB2 implicated in mycobacterial β-oxidation

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    The intracellular pathogen Mycobacterium tuberculosis is the causative agent of tuberculosis, which is a leading cause of mortality worldwide. The survival of M. tuberculosis in host macrophages through long-lasting periods of persistence depends, in part, on breaking down host cell lipids as a carbon source. The critical role of fatty-acid catabolism in this organism is underscored by the extensive redundancy of the genes implicated in β-oxidation (∼100 genes). In a previous study, the enzymology of the M. tuberculosisl-3-hydroxyacyl-CoA dehydrogenase FadB2 was characterized. Here, the crystal structure of this enzyme in a ligand-free form is reported at 2.1 Å resolution. FadB2 crystallized as a dimer with three unique dimer copies per asymmetric unit. The structure of the monomer reveals a dual Rossmann-fold motif in the N-terminal domain, while the helical C-terminal domain mediates dimer formation. Comparison with the CoA- and NAD + -bound human orthologue mitochondrial hydroxyacyl-CoA dehydrogenase shows extensive conservation of the residues that mediate substrate and cofactor binding. Superposition with the multi-catalytic homologue M. tuberculosis FadB, which forms a trifunctional complex with the thiolase FadA, indicates that FadB has developed structural features that prevent its self-association as a dimer. Conversely, FadB2 is unable to substitute for FadB in the tetrameric FadA–FadB complex as it lacks the N-terminal hydratase domain of FadB. Instead, FadB2 may functionally (or physically) associate with the enoyl-CoA hydratase EchA8 and the thiolases FadA2, FadA3, FadA4 or FadA6 as suggested by interrogation of the STRING protein-network database

    Rethinking feasibility analysis for urban development: a multidimensional decision support tool

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    Large-scale urban development projects featured over the past thirty years have shown some critical issues related to the implementation phase. Con-sequently, the current practice seems oriented toward minimal and wide-spread interventions meant as urban catalyst. This planning practice might solve the problem of limited reliability of large developments’ feasibility studies, but it rises an evaluation demand related to the selection of coali-tion of projects within a multidimensional and multi-stakeholders deci-sion-making context. This study aims to propose a framework for the generation of coalitions of elementary actions in the context of urban regeneration processes and for their evaluation using a Multi Criteria Decision Analysis approach. The proposed evaluation framework supports decision makers in exploring dif-ferent combinations of actions in the context of urban interventions taking into account synergies, i.e. positive or negative effects on the overall per-formance of an alternative linked to the joint realization of specific pairs of actions. The proposed evaluation framework has been tested on a pilot case study dealing with urban regeneration processes in the city of Milan (Italy)

    Effects of biofertilizer containing N-fixer, P and K solubilizers and AM fungi on maize growth: A greenhouse trial.

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    An in vitro study was undertaken to evaluate the compatibility of indigenous plant growth promoting rhizobacteria (PGPR) with commonly used inorganic and organic sources of fertilizers in tea plantations. The nitrogenous, phosphatic and potash fertilizers used for this study were urea, rock phosphate and muriate of potash, respectively. The organic sources of fertilizers neem cake, composted coir pith and vermicompost were also used. PGPRs such as nitrogen fixer; Azospirillum lipoferum, Phosphate Solubilizing Bacteria (PSB); Pseudomonas putida, Potassium Solubilizing Bacteria (KSB); Burkholderia cepacia and Pseudomonas putida were used for compatibility study. Results were indicated that PGPRs preferred the coir pith and they proved their higher colony establishment in the formulation except Azospirillum spp. that preferred vermicompost for their establishment. The optimum dose of neem cake powder

    Mental health crises in the emergency department: simulation training for interprofessional collaboration and teamwork attitudes

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    Introduction Emergency departments can often be the first place to which people present when in mental health emergencies, although these departments and staff are not always adequately supported to meet the needs of these patients. This study aimed to evaluate the impact of simulation-based training for mental health crisis in the emergency department on knowledge, confidence and attitudes towards interprofessional collaboration. Methods Healthcare professionals (n = 85) from a range of professions participated in a multicentred simulation-based training activity. Questionnaires evaluating participant knowledge, confidence and interprofessional attitudes were administered pre- and post-activity, and analyses were conducted. Thematic analysis was conducted on free-form participation simulation training evaluation forms. Results Participants reported that the simulation training improved their communication skills, clinical practice, encouraged reflective practice and promoted interprofessional collaboration between emergency department and mental health professionals. Significant improvements were seen in participant knowledge and confidence in providing care to individuals presenting to emergency departments in mental health crises. Attitudes towards interprofessional collaboration in a variety of domains improved because of taking the simulation training. Discussion The pedagogical qualities of the in-situ simulation-based training presented fostered interprofessional collaboration and allowed participants to achieve challenging outcomes. It is suggested that further research should investigate the impact of simulation-based training on mental health related patient care outcomes in the emergency department

    Simulation Training in Psychiatry for Medical Education: A Review

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    Despite recognised benefits of Simulation-Based Education (SBE) in healthcare, specific adaptations required within psychiatry have slowed its adoption. This article aims to discuss conceptual and practical features of SBE in psychiatry that may support or limit its development, so as to encourage clinicians and educators to consider the implementation of SBE in their practice. SBE took off with the aviation industry and has been steadily adopted in clinical education, alongside role play and patient educators, across many medical specialities. Concurrently, healthcare has shifted towards patient-centred approaches and clinical education has recognised the importance of reflective learning and teaching centred on learners' experiences. SBE is particularly well-suited to promoting a holistic approach to care, reflective learning, emotional awareness in interactions and learning, cognitive reframing, and co-construction of knowledge. These features present an opportunity to enhance education throughout the healthcare workforce, and align particularly well to psychiatric education, where interpersonal and relational dimensions are at the core of clinical skills. Additionally, SBE provides a strategic opportunity for people with lived experience of mental disorders to be directly involved in clinical education. However, tenacious controversies have questioned the adequacy of SBE in the psychiatric field, possibly limiting its adoption. The ability of simulated patients (SPs) to portray complex and contradictory cognitive, psychological and emotional states has been questioned. The validity of SBE to develop a genuine empathetic understanding of patients, to facilitate a comprehensive multiaxial diagnostic formulation, or to develop flexible interpersonal skills has been criticised. Finally, SBE's relevance to developing complex psychotherapeutic skills is much debated, while issues such as symptom induction in SPs or patients involvement raise ethical dilemmas. These controversies can be addressed through adequate evidence, robust learning design, and high standards of practice. Well-designed simulated scenarios can promote a positive consideration of mental disorders and complex clinical skills. Shared guidelines and scenario libraries for simulation can be developed, with expert psychiatrists, patients and students involvement, to offer SPs and educators a solid foundation to develop training. Beyond scenario design, the nuances and complexities in mental healthcare are also duly acknowledged during the debriefing phases, providing a crucial opportunity to reflect on complex interpersonal skills or the role of emotions in clinicians' behaviour. Considered recruitment and support of SPs by clinical educators can help to maintain psychological safety and manage ethical issues. The holistic and reflexive nature of SBE aligns to the rich humanistic tradition nurtured within psychiatry and medicine, presenting the opportunity to expand the use of SBE to support a range of clinical skills and workforce competencies required in psychiatry
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