204 research outputs found
Moral/conventional transgression distinction and psychopathy in conduct disordered adolescent offenders
To date there are no studies examining the ability to make a moral/conventional transgression distinction in adolescent offenders with psychopathic traits. Based on the Psychopathy Checklist: Youth Version, we compared males with high (HP, n = 45), medium (MP, n = 31) and low psychopathy scores (LP, n = 39) on the moral convention distinction task. Under normal rule conditions the psychopathy groups did not differ in their ability to make a moral/conventional distinction. The HP group tended to view both transgression types as more permissible and conventional transgressions as less serious, than the LP group. Under modified rule conditions, the HP group exhibited reduced moral/conventional distinction scores com- pared to the MP group. The findings only partially replicate findings from previous M/C studies in children and adults with psychopathic traits. The work fits with more recent reports suggesting that psychopathy is not strongly associated with marked difficulties in cognitive theory of mind, perspective taking and moral judgements. Future studies should focus on the affective aspects of moral reasoning in offender samples
Asymmetric trehalose analogues to probe disaccharide processing pathways in mycobacteria
The uptake and metabolism of the disaccharide trehalose by Mycobacterium tuberculosis is essential for the virulence of this pathogen. Here we describe the chemoenzymatic synthesis of new azido-functionalised asymmetric trehalose probes that resist degradation by mycobacterial enzymes and are used to probe trehalose processing pathways in mycobacteria
Using integrated absorption to calibrate optical cavity spectrometers
Sensitive absorption techniques using optical cavities (such as CEAS or ICOS) generally need the spectrometer response to be calibrated for quantitative measurements. Most calibrations are based on the instrument response to a known, steady state absorption. Such calibrations often have drawbacks in terms of cost, complexity, or convenience, especially for field measurements. In this paper, we show that the relationship between the integrated absorption and a known amount of absorber provides an alternative calibration strategy that yields a highly linear calibration curve and has a low uncertainty. This method is straightforward to implement and offers a practical alternative to other calibration strategies
Dimeric benzoboroxoles for targeted activity against Mycobacterium tuberculosis
Dimeric benzoboroxoles that are covalently linked by a short scaffold enhance selective anti-tubercular activity. These multimeric benzoboroxole compounds are capable of engaging the specific extracellular Mycobacterium tuberculosis glycans, do not lead to the evolution of resistance and bypass the need to cross the impermeable mycobacterial cell envelope barrier
Imaging of antitubercular dimeric boronic acids at the mycobacterial cell surface by click-probe capture
The relationships between HCAHPS communication and discharge satisfaction items and hospital readmissions
The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey has become a key metric used by organizations and patients to evaluate patient experience. Readmissions also continue to be a metric used to evaluate performance because of the added cost to both healthcare systems and patients. Both measures are also seen in programs such as Value Based Purchasing that have an effect on hospital reimbursements. Previous studies have demonstrated a relationship between patient perceptions and quality of care, and have found patients to be reliable evaluators of their care. While good communication and positive provider relationships have been related to higher satisfaction and higher rates of treatment compliance, past research has been limited to evaluating the relationship between readmissions and satisfaction at an organizational level. This retrospective, cross-sectional study will examine the relationship between communication and discharge HCAHPS questions and readmissions at 30 days, specifically at the patient level. Of the eight HCAHPS questions analyzed, higher scores on questions regarding “nurses listening” and “doctors explaining information” were linked to a decreased risk of readmission, while higher scores regarding “help after discharge” were linked to an increased risk for readmission. These results show the importance that a patient’s severity of illness and hospital procedures have on explaining HCAHPS results. This study’s seemingly paradoxical findings suggest the need to recognize potential trade-offs when reviewing HCAHPS results and using them to drive patient experience initiatives
‘Digital Dancing’ – “Can you see, what I feel” – An exploration of the physical ‘experience’ of dance for Parkinson’s through 3-dimensional motion analysis
This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record. Background
: Parkinson’s is a common, progressive, neurodegenerative movement disorder of the central nervous system. Research has consistently shown that dancing can have a positive impact on the lives of people living with Parkinson’s (PwP).
PwP who dance report that current measurement of the effects fails to appreciate the multifactorial presentation of the condition as well as the biopsychosocial potential of dance holistically.
Aim
: To explore the feasibility of combining measurements of whole-body movement using 3-dimensional motion analysis with the lived experience of dance for PwP, to see if it is possible to ‘see (measure)’ what PwP say they ‘feel (experience)’ when dancing, in a ‘mind/body approach’
Method
: Thirteen PwP and ten Carers took part in three community delivered ‘Parkinson’s Dance Science’ classes followed by focus group reflection. Three PwP wore a 3-dimensional, motion capture suit that recorded whole-body movement throughout the class and were interviewed about their experiences.
Data were analysed using a ‘Convergent Parallel’ mixed methods design, mapping participant’s experiences and reflections over six biomechanical movement variables.
Results
: Quantitative results indicate that it is possible to use 3-dimensional motion capture to measure biomechanical change during and following dance in PwP but the amount and direction of change was different for each participant.
Qualitative results showed PwP felt the methods were feasible and reported a positive immediate and long-term effect of dance in a complete ‘mind/body experience’.
The sample size did not permit further analysis, but areas of development suggest it may not be the change in physical ability that is important, but more the perception of change following dance that is unique to each individual. Thus single measures of the effects of dance for PwP are likely to be insufficient when trying to understand the effect holistically.
Conclusion
: A ‘Convergent Parallel’ mixed methods research design, mapping the experience of dance for PwP (‘what I feel’) and their peers against biomechanical change (‘what you see’) following dance is feasible.
Further research is required to develop the method with a larger sample to truly begin to understand the potential and effects of dance for PwP.NIHRSteve Brown Bursary Scheme – Dance for Parkinson’s Partnership U
Structural and functional determination of homologs of the Mycobacterium tuberculosis N-acetylglucosamine-6-phosphate deacetylase (NagA)
The (Mtb) pathogen encodes an -acetylglucosamine-6-phosphate deacetylase enzyme, NagA (Rv3332), that belongs to the amidohydrolase superfamily. NagA enzymes catalyze the deacetylation of -acetylglucosamine-6-phosphate (GlcNAc6P) to glucosamine-6-phosphate (GlcN6P). NagA is a potential anti-tubercular drug target because it represents the key enzymatic step in the generation of essential amino-sugar precursors required for cell wall biosynthesis and also influences recycling of cell wall peptidoglycan fragments. Here, we report the structural and functional characterization of NagA from (MSNagA) and (MMNagA), close relatives of Using a combination of X-ray crystallography, site-directed mutagenesis, and biochemical and biophysical assays, we show that these mycobacterial NagA enzymes are selective for GlcNAc6P. Site-directed mutagenesis studies revealed crucial roles of conserved residues in the active site that underpin stereo-selective recognition, binding, and catalysis of substrates. Moreover, we report the crystal structure of MSNagA in both ligand-free form and in complex with the GlcNAc6P substrate at 2.6 Å and 2.0 Å resolutions, respectively. The GlcNAc6P-complex structure disclosed the precise mode of GlcNAc6P binding and the structural framework of the active site, including two divalent metals located in the α/β binuclear site. Furthermore, we observed a cysteine residue located on a flexible loop region that occludes the active site. This cysteine is unique to mycobacteria and may represent a unique subsite for targeting mycobacterial NagA enzymes. Our results provide critical insights into the structural and mechanistic properties of mycobacterial NagA enzymes having an essential role in amino-sugar and nucleotide metabolism in mycobacteria
Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages
Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs
Biochemical and phenotypic characterisation of the Mycobacterium smegmatis transporter UspABC
Mycobacterium tuberculosis (Mtb) is an intracellular human pathogen that has evolved to survive in a nutrient limited environment within the host for decades. Accordingly, Mtb has developed strategies to acquire scarce nutrients and the mycobacterial transporter systems provide an important route for the import of key energy sources. However, the physiological role of the Mtb transporters and their substrate preference(s) are poorly characterised. Previous studies have established that the Mtb UspC solute-binding domain recognises amino- and phosphorylated-sugars, indicating that the mycobacterial UspABC transporter plays a key role in the import of peptidoglycan precursors. Herein, we have used a wide array of approaches to investigate the role of UspABC in Mycobacterium smegmatis by analysis of mutant strains that either lack the solute binding domain: ΔuspC or the entire transport complex: ΔuspABC. Analysis of mycobacterial transcripts shows that the uspABC system is functionally expressed in mycobacteria as a contiguous reading frame. Topology mapping confirms an Nin-Cin orientation of the UspAB integral membrane spanning domains. Phenotypic microarray profiling of commercially available sugars suggests, unexpectedly, that the uspC and ΔuspABC mutants had different carbon utilisation profiles and that neither strain utilised glucose-1-phosphate. Furthermore, proteomics analysis showed an alteration in the abundance of proteins involved in sugar and lipid metabolism, crucial for cell envelope synthesis, and we propose that UspABC has an important role in determining the interplay between these pathways
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