831 research outputs found
Cumulative mutagenesis of the basic residues in the 201-218 region of insulin-like growth factor (IGF)-binding protein-5 results in progressive loss of both IGF-I binding and inhibition of IGF-I biological action
We have reported previously that mutation of two conserved nonbasic amino acids (G203 and Q209) within the highly basic 201–218 region in the C-terminal domain of IGF-binding protein-5 (IGFBP-5) decreases binding to IGFs. This study reveals that cumulative mutagenesis of the 10 basic residues in this region, to create the C-Term series of mutants, ultimately results in a 15-fold decrease in the affinity for IGF-I and a major loss in heparin binding. We examined the ability of mutants to inhibit IGF-mediated survival of MCF-7 cells and were able to demonstrate that this depended not only upon the affinity for IGF-I, but also the kinetics of this interaction, because IGFBP-5 mutants with similar affinity constants (KD) values, but with different association (Ka) and dissociation (Kd) rate values, had markedly different inhibitory properties. In contrast, the affinity for IGF-I provided no predictive value in terms of the ability of these mutants to enhance IGF action when bound to the substratum. Instead, these C-Term mutants appeared to enhance the actions of IGF-I by a combination of increased dissociation of IGF-IGFBP complexes from the substratum, together with dissociation of IGF-I from IGFBP-5 bound to the substratum. These effects of the IGFBPs were dependent upon binding to IGF-I, because a non-IGF binding mutant (N-Term) was unable to inhibit or enhance the actions of IGF-I. These results emphasize the importance of the kinetics of association/dissociation in determining the enhancing or inhibiting effects of IGFBP-5 and demonstrate the ability to generate an IGFBP-5 mutant with exclusively IGF-enhancing activity
“A sustained, productive, constructive relationship with someone who can help”—A qualitative exploration of the experiences of help seekers and support persons using the emergency department during a suicide crisis
For Australians experiencing a suicide crisis, the emergency department (ED) is the recommended point of contact for intervention and to ensure personal safety. However, negative ED experiences can deter individuals from returning, thus impacting future suicide risk. In order to improve the ED environment for individuals in suicidal crisis, an in-depth understanding of this experience is needed. In-depth semi-structured interviews with 17 help seekers and 16 support persons were conducted. A grounded theory approach uncovered a core organising concept—all participants wanted a “a sustained, productive, constructive relationship with someone who can help” during the ED visit—which guided analysis. Thematic analysis resulted in two themes and four subthemes exploring the systemic and interpersonal aspects of the ED visit and the roadblocks and pathways to development of the relationship. Interpersonal factors included aspects of staff interaction and presence of a support person. Systemic factors related to aspects controlled by the physical space and internal policies and procedures and included aspects such as the chaotic environment, long waiting times, and access to staff. Overwhelmingly, there were more roadblocks than pathways reported by participants. Improving the ED environment, increasing staff training and encouraging the presence of support persons may help mitigate some of these roadblocks
Interaction between atypical microorganisms and E. coli in catheter-associated urinary tract biofilms
Most biofilms involved in catheter-associated urinary tract infections (CAUTIs) are polymicrobial, with disease causing
(eg Escherichia coli) and atypical microorganisms (eg Delftia tsuruhatensis) frequently inhabiting the same catheter.
Nevertheless, there is a lack of knowledge about the role of atypical microorganisms. Here, single and dual-species
biofilms consisting of E. coli and atypical bacteria (D. tsuruhatensis and Achromobacter xylosoxidans), were evaluated.
All species were good biofilm producers (Log 5.84–7.25 CFU cm−2 at 192 h) in artificial urine. The ability of atypical
species to form a biofilm appeared to be hampered by the presence of E. coli. Additionally, when E. coli was added to a
pre-formed biofilm of the atypical species, it seemed to take advantage of the first colonizers to accelerate adhesion, even
when added at lower concentrations. The results suggest a greater ability of E. coli to form biofilms in conditions
mimicking the CAUTIs, whatever the pre-existing microbiota and the inoculum concentration.This work was supported by the Portuguese Science Foundation (FCT), DNA mimics Research Project [Ref. PIC/IC/82815/2007] from the FCT and MCTES; PhD Fellowship [SFRH/BD/82663/2011]; and Postdoctoral Fellowship [SFRH/BPD/74480/2010]. The authors would like to thank to M. Fenice M and A. Steinbuchel for kindly providing the Delftia tsuruhatensis BM90 and Achromobacter xylosoxidans B3 species, respectively
Core excitations across the neutron shell gap in ²⁰⁷Tl
The single closed-neutron-shell, one proton-hole nucleus 207Tl was populated in deep-inelastic collisions of a 208Pb beam with a 208Pb target. The yrast and near-yrast level scheme has been established up to high excitation energy, comprising an octupol
A Qualitative Analysis of Motivators to Participation in Suicide-Focused Research from a Community-Based Australian Sample
Suicide prevention strategies internationally appear to be falling short of making a meaningful impact on global suicide deaths. Increasing the rates of general community participation in suicide research may improve knowledge generalisability as it relates to suicidal behaviour and leads to new suicide prevention approaches. This study aims to explore the motivations of a community-based sample to participate in suicide research. A subsample of the Australian general population took part in an online survey which is part of a multilevel suicide prevention trial. The survey concluded with an optional open-text question asking about peoples’ motivations for participating in the study; 532 participants left a response to this question. These responses were qualitatively analysed using Thematic Network Analysis. Motivations to participate in suicide research were represented by four global themes: altruism, solve systemic problems, lived experience, and personal benefit. Of these themes, three were focused on the benefit of others, while only the final theme articulated motivation to participate that was self-focused. The impact of suicide is felt throughout the wider community. This new understanding of the motivations of community-based samples to participate in suicide research should be used to increase participation rates and reach people who would not normally contribute their voice to suicide researc
Suicide among emergency service workers: a retrospective mortality study of national coronial data, 2001–2017
Background. Emergency service workers (ESW) are known to be at increased risk of mental disorders but population-level and longitudinal data regarding their risk of suicide are lacking. Method. Suicide data for 2001–2017 were extracted from the Australian National Coronial Information Service (NCIS) for two occupational groups: ESW (ambulance personnel, firefighters and emergency workers, police officers) and individuals employed in all other occupations. Age-standardised suicide rates were calculated and risk of suicide compared using negative binomial regression modelling. Results. 13 800 suicide cases were identified among employed adults (20–69 years) over the study period. The age-standardised suicide rate across all ESW was 14.3 per 100 000 (95% CI 11.0–17.7) compared to 9.8 per 100 000 (95% CI 9.6–9.9) for other occupations. Significant occupational differences in the method of suicide were identified (p < 0.001). There was no evidence for increased risk of suicide among ESW compared to other occupations once age, gender and year of death were accounted for (RR = 0.99, 95% CI 0.84–1.17; p = 0.95). In contrast, there was a trend for ambulance personnel to be at elevated risk of suicide (RR = 1.41, 95% CI 1.00–2.00, p = 0.053). Conclusion. Whilst age-standardised suicide rates among ESW are higher than other occupations, emergency service work was not independently associated with an increased risk of suicide, with the exception of an observed trend in ambulance personnel. Despite an increased focus on ESW mental health and wellbeing over the last two decades, there was no evidence that rates of suicide among ESW are changing over time
Risk factors for human brucellosis in northern Tanzania
Little is known about the epidemiology of human brucellosis in sub-Saharan Africa. This hampers prevention and control efforts at the individual and population levels. To evaluate risk factors for brucellosis in northern Tanzania, we conducted a study of patients presenting with fever to two hospitals in Moshi, Tanzania. Serum taken at enrollment and at 4–6 week follow-up was tested by Brucella microagglutination test. Among participants with a clinically compatible illness, confirmed brucellosis cases were defined as having a ≥ 4-fold rise in agglutination titer between paired sera or a blood culture positive for Brucella spp., and probable brucellosis cases were defined as having a single reciprocal titer ≥ 160. Controls had reciprocal titers < 20 in paired sera. We collected demographic and clinical information and administered a risk factor questionnaire. Of 562 participants in the analysis, 50 (8.9%) had confirmed or probable brucellosis. Multivariable analysis showed that risk factors for brucellosis included assisting goat or sheep births (Odds ratio [OR] 5.9, 95% confidence interval [CI] 1.4, 24.6) and having contact with cattle (OR 1.2, 95% CI 1.0, 1.4). Consuming boiled or pasteurized dairy products was protective against brucellosis (OR 0.12, 95% CI 0.02, 0.93). No participants received a clinical diagnosis of brucellosis from their healthcare providers. The under-recognition of brucellosis by healthcare workers could be addressed with clinician education and better access to brucellosis diagnostic tests. Interventions focused on protecting livestock keepers, especially those who assist goat or sheep births, are needed
Risk factors for human acute leptospirosis in northern Tanzania
Introduction:
Leptospirosis is a major cause of febrile illness in Africa but little is known about risk factors for human infection. We conducted a cross-sectional study to investigate risk factors for acute leptospirosis and Leptospira seropositivity among patients with fever attending referral hospitals in northern Tanzania.
Methods:
We enrolled patients with fever from two referral hospitals in Moshi, Tanzania, 2012–2014, and performed Leptospira microscopic agglutination testing on acute and convalescent serum. Cases of acute leptospirosis were participants with a four-fold rise in antibody titers, or a single reciprocal titer ≥800. Seropositive participants required a single titer ≥100, and controls had titers <100 in both acute and convalescent samples. We administered a questionnaire to assess risk behaviors over the preceding 30 days. We created cumulative scales of exposure to livestock urine, rodents, and surface water, and calculated odds ratios (OR) for individual behaviors and for cumulative exposure variables.
Results:
We identified 24 acute cases, 252 seropositive participants, and 592 controls. Rice farming (OR 14.6), cleaning cattle waste (OR 4.3), feeding cattle (OR 3.9), farm work (OR 3.3), and an increasing cattle urine exposure score (OR 1.2 per point) were associated with acute leptospirosis.
Conclusions:
In our population, exposure to cattle and rice farming were risk factors for acute leptospirosis. Although further data is needed, these results suggest that cattle may be an important source of human leptospirosis. Further investigation is needed to explore the potential for control of livestock Leptospira infection to reduce human disease
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