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1.
J Infect Dis ; 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38349364

ABSTRACT

BACKGROUND: Cytochrome bd complexes are respiratory oxidases found exclusively in prokaryotes that are important during infection for numerous bacterial pathogens. METHODS: In silico docking was employed to screen approved drugs for their ability to bind to the quinol site of Escherichia coli cytochrome bd-I. Respiratory inhibition was assessed with oxygen electrodes using membranes isolated from E. coli and methicillin-resistant Staphylococcus aureus strains expressing single respiratory oxidases (ie, cytochromes bd, bo', or aa3). Growth/viability assays were used to measure bacteriostatic and bactericidal effects. RESULTS: The steroid drugs ethinylestradiol and quinestrol inhibited E. coli bd-I activity with median inhibitory concentration (IC50) values of 47 ± 28.9 µg/mL (158 ± 97.2 µM) and 0.2 ± 0.04 µg/mL (0.5 ± 0.1 µM), respectively. Quinestrol inhibited growth of an E. coli "bd-I only" strain with an IC50 of 0.06 ± 0.02 µg/mL (0.2 ± 0.07 µM). Growth of an S. aureus "bd only" strain was inhibited by quinestrol with an IC50 of 2.2 ± 0.43 µg/mL (6.0 ± 1.2 µM). Quinestrol exhibited potent bactericidal effects against S. aureus but not E. coli. CONCLUSIONS: Quinestrol inhibits cytochrome bd in E. coli and S. aureus membranes and inhibits the growth of both species, yet is only bactericidal toward S. aureus.

2.
Children (Basel) ; 10(8)2023 Aug 17.
Article in English | MEDLINE | ID: mdl-37628400

ABSTRACT

BACKGROUND: Preschoolers with developmental disabilities are referred to occupational therapy due to their decreased participation in daily life occupations. The purpose of this study was to evaluate the improvement in preschoolers' participation and sensory-motor abilities following an occupational therapy intervention. MATERIALS AND METHODS: A prospective cohort study of 38 preschoolers and their parents was conducted using an interrupted time-series design, including assessments at three time points: base line (upon referral to an occupational therapy assessment), pre-intervention, and post-intervention after 9-12 sessions of occupational therapy interventions. Children were evaluated with the Developmental Test of Visual-Motor Integration, as well as the balance and fine motor precision sub tests of the Bruininks-Oseretsky Test of Motor Proficiency. Parents completed the Children's Participation Questionnaire and the Child Performance Skills Questionnaire. Each intervention session was documented by the therapists using the Documentation of Occupational Therapy Session Intervention form. RESULTS: Significant improvement in children's sensory-motor abilities were found in balance, visual integration, and fine motor precision post-intervention. There were also improvements in the measures of diversity, children's independence, and parental satisfaction. CONCLUSIONS: A short-term occupational therapy intervention applied to preschoolers with developmental disabilities is effective in improving their sensory-motor abilities, as well as in promoting their participation in daily activities.

3.
Aust N Z J Psychiatry ; 57(3): 391-400, 2023 03.
Article in English | MEDLINE | ID: mdl-35642543

ABSTRACT

PURPOSE: This study aimed to explore risk factors for suicide in Aboriginal and non-Aboriginal people following hospital admission for suicidal ideation and self-harm in the Northern Territory, Australia to help clarify opportunities for improved care and intervention for these population groups. METHODS: Individuals with at least one hospital admission involving suicidal ideation and/or self-harm between 1 July 2001 and 31 December 2013 were retrospectively recruited and followed up using linked mortality records to 31 December 2014. Survival analyses stratified by Indigenous status identified socio-demographic and clinical characteristics from index hospital admissions associated with suicide. RESULTS: Just over half of the 4391 cohort members identified as Aboriginal (n = 2304; 52.4%). By 2014, 281 deaths were observed comprising 68 suicides, representing a 2.6% and 2.0% probability of suicide for Aboriginal and non-Aboriginal people, respectively. After adjusting for other characteristics, a higher risk of suicide was associated with male sex (Aboriginal adjusted hazard ratio: 4.14; 95% confidence interval: [1.76, 9.75]; non-Aboriginal adjusted hazard ratio: 5.96; 95% confidence interval: [1.98, 17.88]) and repeat hospital admissions involving self-harm (Aboriginal adjusted hazard ratio: 1.37; 95% confidence interval: [1.21, 1.55]; non-Aboriginal adjusted hazard ratio: 1.29; 95% confidence interval: [1.10, 1.51]). Severe mental disorders were associated with a four times higher risk of suicide (adjusted hazard ratio: 4.23; 95% confidence interval: [1.93, 9.27]) in Aboriginal people only. CONCLUSION: The findings highlight non-clinical risk factors for suicide that suggest the need for comprehensive psychosocial assessment tailored to Aboriginal and non-Aboriginal people hospitalised with suicidal ideation or self-harm. Implementing appropriate management and aftercare within a broader public health framework is needed to support recovery and reduce long-term suicide risk in the community, especially for Aboriginal people and males.


Subject(s)
Self-Injurious Behavior , Suicide , Humans , Male , Suicide/psychology , Suicidal Ideation , Retrospective Studies , Northern Territory , Self-Injurious Behavior/epidemiology , Hospitals
4.
Arch Microbiol ; 204(5): 289, 2022 Apr 30.
Article in English | MEDLINE | ID: mdl-35488016

ABSTRACT

In recent years, much attention has been focused on the biogenesis, engineering and utilisation of outer membrane vesicles (OMVs) in Gram-negative bacteria in a range of environments and niches. While the precise mechanism of biogenesis is unknown, it is focused on the modification of the Gram-negative cell wall to facilitate blebbing at sites of weakness in and around the characteristically thin peptidoglycan layer within the periplasm. Here, we investigate the biogenesis of membrane vesicles (MVs) in the Gram-positive organism Streptomyces albus S4 (Seipke et al. J Bacteriol 193:4270-4271, 2011 and Fazal et al. Antonie Van Leeuwenhoek 113:511-520, 2020). The S. albus S4 strain is an antifungal (candicidin and antimycin) producing organism that was isolated from attine ants (Barke et al. BMC Biol 8:109, 2010). The biogenesis and characterisation of S. albus S4 MVs is demonstrated using the wild-type (WT) and mutant strains ΔantC (no antimycin production) ΔfscC (no candicidin production) and ΔantC ΔfscC (produces neither antimycin nor candicidin). Here, we have shown that the S. albus S4 strain produces MVs and that these are comprised of both specific protein profiles and secondary metabolites, with a clear demonstration of the ability to selectively package one antifungal (candicidin) but not the other (antimycin).


Subject(s)
Ants , Candicidin , Streptomyces , Animals , Antifungal Agents/metabolism , Antifungal Agents/pharmacology , Ants/microbiology , Candicidin/metabolism , Polyenes/metabolism , Polyenes/pharmacology , Streptomyces/genetics , Streptomyces/metabolism
5.
Arch Microbiol ; 204(1): 120, 2022 Jan 06.
Article in English | MEDLINE | ID: mdl-34989857

ABSTRACT

It is well known that loss of aerobic respiration in Gram-negative bacteria can diminish the efficacy of a variety of bactericidal antibiotics, which has lead to subsequent demonstrations that the formation of reactive oxygen species (ROS) and the proton motive force (PMF) can both play a role in antibiotic toxicity. The susceptibility of Gram-negative bacteria to aminoglycoside antibiotics, particularly gentamicin, has previously been linked to both the production of ROS and the rate of antibiotic uptake that is mediated by the PMF, although the relative contributions of ROS and PMF to aminoglycoside toxicity has remained poorly understood. Herein, gentamicin was shown to elicit a very modest increase in ROS levels in an aerobically grown Escherichia coli clinical isolate. The well-characterised uncoupler 2,4-dinitrophenol (DNP) was used to disrupt the PMF, which resulted in a significant decrease in gentamicin lethality towards E. coli. DNP did not significantly alter respiratory oxygen consumption, supporting the hypothesis that this uncoupler does not increase ROS production via elevated respiratory oxidase activity. These observations support the hypothesis that maintenance of PMF rather than induction of ROS production underpins the mechanism for how the respiratory chain potentiates the toxicity of aminoglycosides. This was further supported by the demonstration that the uncoupler DNP elicits a dramatic decrease in gentamicin lethality under anaerobic conditions. Together, these data strongly suggest that maintenance of the PMF is the dominant mechanism for the respiratory chain in potentiating the toxic effects of aminoglycosides.


Subject(s)
Aminoglycosides , Escherichia coli , Aminoglycosides/pharmacology , Anti-Bacterial Agents/pharmacology , Proton-Motive Force , Respiration
6.
PLoS One ; 17(1): e0262406, 2022.
Article in English | MEDLINE | ID: mdl-35015776

ABSTRACT

PURPOSE: We aimed to test the reliability and validity of two brief measures of resilience adopted for the evaluation of a preventative social-emotional curriculum implemented for Aboriginal middle school students from socially disadvantaged remote communities in Australia's Northern Territory. The questionnaires chosen were intended to measure psychological resilience and socio-cultural resilience as complementary dimensions of the capacity to cope in circumstances of significant life stress and risk of self-harm. METHODS: Confirmatory factor analysis (CFA) was conducted to assess construct validity of the 10-item Connor-Davidson Resilience Scale (CD-RISC-10), a measure of psychological resilience, and the 12-item Child and Youth Resilience Measure (CYRM-12), a measure of socio-cultural resilience, with a sample of 520 students. Associations between resilience and psychological distress and emotional and behavioural difficulty were analysed in relation to life stressors to assess criterion validity of the scales. RESULTS: CFA provided support for the validity of the respective constructs. There was good fit for both scales. However, assessment of criterion validity of the scales suggested that the adapted measure of socio-cultural resilience (CYRM-12NT) showed higher reliability and a clearer indication of predictive validity than the measure of psychological resilience (CD-RISC-10). CONCLUSIONS: The CYRM-12NT appears to be a more useful measure of resilience among Aboriginal youth exposed to significant life stress and disadvantage. However, both measures may require further development to enhance their validity and utility among potentially at-risk adolescents in socially, culturally and linguistically diverse remote Aboriginal communities.


Subject(s)
Adaptation, Psychological , Curriculum/standards , Emotions/physiology , Psychological Distress , Resilience, Psychological/physiology , Social Learning/physiology , Students/psychology , Adolescent , Adult , Child , Cultural Diversity , Factor Analysis, Statistical , Female , Humans , Male , Native Hawaiian or Other Pacific Islander , Psychology, Adolescent , Psychometrics , Reproducibility of Results , Social Adjustment , Surveys and Questionnaires , Young Adult
7.
Int J Psychiatry Med ; 57(3): 226-247, 2022 05.
Article in English | MEDLINE | ID: mdl-33910408

ABSTRACT

The current study addresses the need to empirically develop effective mental health interventions for youth from ethnic/racial minority and low-income neighborhoods. Using Stage Model evaluation methods supported by the National Institutes of Health in the US to address underutilization of mental healthcare among racial/ethnic minority youth, this feasibility study demonstrates empirical adaptation of an innovative sport-specific psychological intervention for use in youth from ethnic/racial minority and low-income neighborhoods. An international group of professionals familiar with sport performance and mental health intervention serving the target population experientially examined the adapted intervention protocols in workshops and provided feedback. Survey results indicated the professionals found the intervention components were easy to administer and likely to be safe, enjoyable, engaging and efficacious for youth mental health and sport performance. The protocols were revised based on feedback from these professionals and the intervention was examined in a case trial involving an Asian American youth who evidenced Social Anxiety Disorder. Case study results indicated the intervention could be implemented with integrity, and severity of psychiatric symptoms and factors interfering with sport performance decreased after intervention implementation. The participant's relationships with family, coaches and teammates were also improved.


Subject(s)
Ethnicity , Mental Health , Adolescent , Athletes , Ethnic and Racial Minorities , Feasibility Studies , Humans , Minority Groups/psychology , National Institutes of Health (U.S.) , United States
8.
Microb Biotechnol ; 15(5): 1574-1585, 2022 05.
Article in English | MEDLINE | ID: mdl-34927803

ABSTRACT

The development and advent of mutagenesis tools for solventogenic clostridial species in recent years has allowed for the increased refinement of industrially relevant strains. In this study we have utilised CLEAVE™, a CRISPR/Cas genome editing system developed by Green Biologics Ltd., to engineer a strain of Clostridium saccharoperbutylacetonicum N1-4(HMT) with potentially useful solvents titres and energy metabolism. As one of two enzymes responsible for the conversion of glyceraldehyde-3-phosphate (GAP) to 3-phosphoglyceric acid in glycolysis, it was hypothesised that deletion of gapN would increase ATP and NADH production that could in turn improve solvent production. Herein, whole genome sequencing has been used to evaluate CLEAVE™ and the successful knockout of gapN, demonstrating a clean knockout with no other detectable variations from the wild type sequence. Elevated solvent levels were detected during the first 24 h of batch fermentation, indicating an earlier shift to solventogenesis. A 2.4-fold increase in ATP concentration was observed, and quantitation of NAD(P)H derivatives revealed a more reducing cytoplasm for the gapN strain. These findings expand our understanding of clostridium carbon metabolism and report a new approach to optimising biofuel production.


Subject(s)
Clostridium , Glyceraldehyde-3-Phosphate Dehydrogenases , Adenosine Triphosphate/metabolism , Clostridium/genetics , Clostridium/metabolism , Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism , Solvents/metabolism
9.
Int J Parasitol Drugs Drug Resist ; 17: 204-212, 2021 12.
Article in English | MEDLINE | ID: mdl-34875573

ABSTRACT

Naegleria fowleri is both a pathogenic and a free-living microbial eukaryote, responsible for the development of primary amoebic meningoencephalitis (PAM) in humans. PAM is a rapid, severe and fatal underestimated infectious disease, which has been reported in countries with warmer climates. The major drawbacks with PAM are the lack of effective therapies and delay in diagnosis. The current frontline treatment presents a low rate of recovery (5%) and severe adverse effects. For example, many drug candidates lack efficacy, since they do not effectively cross the blood-brain-barrier. Consequently, more effective drugs are urgently needed. Herein, we report a new in vitro method suitable for medium- and high-throughput drug discovery assays, using the closely related Naegleria gruberi as a model. We have subsequently used this method to screen a library of 1175 Food and Drug Administration-approved drugs. As a result, we present three drugs (camptothecin, pyrimethamine, and terbinafine) that can be repurposed, and are anticipated to readily cross the blood-brain-barrier with activity against Naegleria species in therapeutically achievable concentrations. Successively, we integrated several in vitro assays that resulted in identifying fast-acting and high amoebicidal drugs. In conclusion, we present a new approach for the identification of anti-Naegleria drugs along with three potential drug candidates for further development for the treatment of PAM.


Subject(s)
Amoeba , Naegleria fowleri , Pharmaceutical Preparations , Brain , Drug Repositioning , Humans , United States
10.
Access Microbiol ; 3(4): 000225, 2021.
Article in English | MEDLINE | ID: mdl-34151176

ABSTRACT

When working with anaerobic bacteria it is important to have the capability to perform parallel bioreactor growth experiments that are both controllable and reproducible, although capital and consumables costs for commercially available systems are often prohibitively high. Hence, a three-vessel parallel bioreactor system was designed and constructed that has the capabilities for batch and fed batch processes and can also be set up for continuous culture at a fraction of the cost of commercial systems. This system carries over many of the same functionalities of those systems with a higher price point of entry, including in-line monitoring of temperature, pH, and redox poise. To validate the performance of this system Clostridium saccharoperbutylacetonicum was grown under conditions that promote ABE fermentation, an established industrial process used to produce the solvents acetone, butanol and ethanol. Measurements of cell density, pH, and redox poise all confirmed reproducible culture conditions for these parallel vessels, and solvent quantitation via GCMS verified consistent metabolic activities for the separate cultures. In future, this system will be of interest to researchers that require high performance parallel fermentation platforms but where commercial systems are not accessible.

11.
Front Microbiol ; 12: 557455, 2021.
Article in English | MEDLINE | ID: mdl-33643229

ABSTRACT

Fundamental aspects of outer membrane vesicle (OMV) biogenesis and the engineering of producer strains have been major research foci for many in recent years. The focus of this study was OMV production in a variety of Escherichia coli strains including wild type (WT) (K12 and BW25113), mutants (from the Keio collection) and proprietary [BL21 and BL21 (DE3)] strains. The present study investigated the proteome and prospective mechanism that underpinned the key finding that the dominant protein present in E. coli K-12 WT OMVs was fimbrial protein monomer (FimA) (a polymerizable protein which is the key structural monomer from which Type 1 fimbriae are made). However, mutations in genes involved in fimbriae biosynthesis (ΔfimA, B, C, and F) resulted in the packaging of flagella protein monomer (FliC) (the major structural protein of flagella) into OMVs instead of FimA. Other mutations (ΔfimE, G, H, I, and ΔlrhA-a transcriptional regulator of fimbriation and flagella biosynthesis) lead to the packaging of both FimA and Flagellin into the OMVs. In the majority of instances shown within this research, the production of OMVs is considered in K-12 WT strains where structural appendages including fimbriae or flagella are temporally co-expressed throughout the growth curve as shown previously in the literature. The hypothesis, proposed and supported within the present paper, is that the vesicular packaging of the major FimA is reciprocally regulated with the major FliC in E. coli K-12 OMVs but this is abrogated in a range of mutated, non-WT E. coli strains. We also demonstrate, that a protein of interest (GFP) can be targeted to OMVs in an E. coli K-12 strain by protein fusion with FimA and that this causes normal packaging to be disrupted. The findings and underlying implications for host interactions and use in biotechnology are discussed.

12.
Arch Microbiol ; 203(5): 2541-2550, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33682076

ABSTRACT

The spread of multidrug-resistance in Gram-negative bacterial pathogens presents a major clinical challenge, and new approaches are required to combat these organisms. Nitric oxide (NO) is a well-known antimicrobial that is produced by the immune system in response to infection, and numerous studies have demonstrated that NO is a respiratory inhibitor with both bacteriostatic and bactericidal properties. However, given that loss of aerobic respiratory complexes is known to diminish antibiotic efficacy, it was hypothesised that the potent respiratory inhibitor NO would elicit similar effects. Indeed, the current work demonstrates that pre-exposure to NO-releasers elicits a > tenfold increase in IC50 for gentamicin against pathogenic E. coli (i.e. a huge decrease in lethality). It was therefore hypothesised that hyper-sensitivity to NO may have arisen in bacterial pathogens and that this trait could promote the acquisition of antibiotic-resistance mechanisms through enabling cells to persist in the presence of toxic levels of antibiotic. To test this hypothesis, genomics and microbiological approaches were used to screen a collection of E. coli clinical isolates for antibiotic susceptibility and NO tolerance, although the data did not support a correlation between increased carriage of antibiotic resistance genes and NO tolerance. However, the current work has important implications for how antibiotic susceptibility might be measured in future (i.e. ± NO) and underlines the evolutionary advantage for bacterial pathogens to maintain tolerance to toxic levels of NO.


Subject(s)
Aminoglycosides/pharmacology , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Escherichia coli/drug effects , Nitric Oxide/pharmacology , Biological Evolution , Drug Resistance, Bacterial/drug effects , Drug Resistance, Bacterial/genetics , Escherichia coli/genetics , Escherichia coli/isolation & purification , Escherichia coli Infections/microbiology , Gentamicins/pharmacology , Humans , Microbial Sensitivity Tests
13.
Front Public Health ; 8: 552878, 2020.
Article in English | MEDLINE | ID: mdl-33282808

ABSTRACT

Purpose: Skills for Life (SFL) is a social-emotional curriculum for Indigenous middle school students that was co-developed with educators and community members in a remote community of northern Australia. This preliminary study aimed to test the feasibility of processes and methods of data-gathering, the reliability of youth self-report measures, and to identify the direction of effects for an evaluation of a longer-term pilot of the curriculum. Design/Methodology/Approach: Indigenous Students in years 7-9 of a remote school participated in SFL over 2 years. The Strengths and Difficulties Questionnaire (SDQ), Kessler 6 (K6), and a purpose-designed Connected Self Scale (CSS) were administered to 63 students pre- and post-program. Findings: Only the K6, Prosocial behavior (SDQ), and two CSS subscales showed sufficient internal consistency for analysis. Change was positive but non-significant for SDQ and CSS. There was evidence of a dosage effect: students receiving the intervention over 2 years showed greater reduction in psychological distress than other students. There was no evidence of iatrogenic effects. Conclusions: The feasibility pilot is a critically important phase in the development of evaluation design and cjhoice of evaluation measures for challenging remote settings. This study found that evaluation of SFL with culturally and linguistically distinct Indigenous middle school students using self-report measures is feasible. However, the SDQ may not be suitable for this project. High levels of psychological distress suggest the need to investigate sources of life stress and potential supports for adolescent resilience in this context. This preliminary pilot aimed to trial methods and measures for evaluation of a social-emotional curriculum developed specifically for remote Australian Indigenous students who are at risk of poor psychosocial outcomes. No studies have examined the appropriateness of standardized self-report measures for evaluation of SEL with this student population in remote school settings.


Subject(s)
Schools , Students , Adolescent , Australia , Feasibility Studies , Humans , Reproducibility of Results
14.
Aust N Z J Psychiatry ; 54(9): 874-882, 2020 09.
Article in English | MEDLINE | ID: mdl-32456445

ABSTRACT

OBJECTIVE: To develop guidelines for the culturally responsive psychosocial assessment of Aboriginal and Torres Strait Islander people presenting to hospital with self-harm and suicidal thoughts. METHOD: The Delphi method was used to establish expert consensus. A systematic search and review of relevant research literature, existing guidelines and grey literature was undertaken to develop a 286-item questionnaire. The questionnaire contained best practice statements to guide clinicians undertaking psychosocial assessment of Aboriginal and Torres Strait Islander people presenting to hospital with self-harm and suicidal thoughts. An expert panel comprising 28 individuals with clinical, community-based and lived experience in Aboriginal and Torres Strait Islander mental health and/or suicide prevention were recruited and independently rated the items over three rounds. Statements endorsed as essential or important by 90% or more of the expert panel were then synthesised into recommendations for the best practice guideline document. RESULTS: A total of 226 statements across all relevant areas of clinical practice were endorsed. No statements covering the use of structured assessment tools were endorsed. The endorsed statements informed the development of a set of underlying principles of culturally competent practice and recommendations for processes of effective and appropriate engagement; risks, needs and strengths to be assessed; formulation of psychosocial assessment; and recommendations specific to children and young people. CONCLUSION: The guidelines are based on recommendations endorsed across a range of expertise to address an important gap in the evidence-base for clinically effective and culturally responsive assessment of self-harm and suicidal thoughts by Aboriginal and Torres Strait Islander people in hospital settings. Further work is needed to develop an implementation strategy and evaluate the recommendations in practice.


Subject(s)
Self-Injurious Behavior , Suicidal Ideation , Adolescent , Child , Hospitals , Humans , Mental Health , Native Hawaiian or Other Pacific Islander , Practice Guidelines as Topic , Self-Injurious Behavior/diagnosis
15.
Crisis ; 41(6): 459-468, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32343170

ABSTRACT

Background: Rates of hospital admission for suicide-related thoughts and behaviors (SRTBs) are elevated in the Northern Territory (NT) of Australia, especially by Aboriginal people, but very little is known about emergency department (ED) presentations. Aim: We aimed to profile ED presentations in the NT involving SRTBs by Indigenous status and compare discharge arrangements. Method: Logistic regression analyses were performed on data from electronic patient records of consecutive ED presentations involving SRTBs. Results: During the study period, 167 presentations were observed. Aboriginal patients were more likely to present from remote areas and to report substance misuse and family conflict or violence compared with non-Aboriginal patients. In both groups, males were more likely than females to be admitted as were persons presenting with self-harm compared with those who had suicidal thoughts only. No differences in discharge arrangements were identified by Indigenous status. Limitations: The small scale of the study and use of administrative records points to the need for further research to improve the quality of the evidence. Conclusion: While presentations by high-risk groups are more likely to be admitted for further care, the assessment of psychosocial risks and needs in EDs is vital to informing decisions for aftercare that support recovery in the community for Aboriginal patients and patients discharged from EDs.


Subject(s)
Self-Injurious Behavior , Suicidal Ideation , Emergency Service, Hospital , Female , Hospitalization , Humans , Male , Population Groups
16.
FEBS J ; 287(17): 3827-3840, 2020 09.
Article in English | MEDLINE | ID: mdl-32153092

ABSTRACT

The scsABCD (suppressor of copper sensitivity) locus of Salmonella encodes four proteins that resemble the disulfide folding machinery of other bacteria. Previous work has shown that Salmonella encounters toxic levels of copper during infection and the Scs system provides protection against this copper-mediated toxicity. The current work reports that expression of the soluble periplasmic protein StScsC is induced by copper and that intramacrophage survival in the presence of copper is diminished by the loss of StScsC. Using a combination of genetic and proteomic approaches, the abundance of various cysteine-containing periplasmic proteins was found to be elevated by StScsC in the Salmonella periplasm, implicating StScsC in the disulfide folding of superoxide dismutases and proteins involved in amino acid sensing and import. Co-purification and mass spectrometry approaches confirmed that the arginine-sensing periplasmic protein ArtI associates with StScsC via a disulfide interaction, and purified ArtI was shown to alter the thiol redox state of purified StScsC. This work reports the first demonstration of a redox partner for the Scs system of Salmonella and provides insights into how this bacterial pathogen responds to copper stress during infection.


Subject(s)
ATP-Binding Cassette Transporters/physiology , Bacterial Proteins/physiology , Copper Sulfate/pharmacology , Macrophages/microbiology , Periplasmic Proteins/physiology , Salmonella typhimurium/physiology , ATP-Binding Cassette Transporters/chemistry , ATP-Binding Cassette Transporters/genetics , Amino Acid Sequence , Animals , Arginine/metabolism , Bacterial Load , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Biological Transport , Disulfides/metabolism , Escherichia coli/metabolism , Genes, Bacterial , Gram-Negative Bacteria/genetics , Mice , Models, Molecular , Oxidation-Reduction , Periplasmic Proteins/chemistry , Periplasmic Proteins/genetics , Protein Conformation , Protein Folding , Protein Interaction Mapping , RAW 264.7 Cells , Recombinant Proteins/metabolism , Salmonella Infections, Animal/microbiology , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Sequence Alignment , Sequence Homology, Amino Acid
17.
Article in English | MEDLINE | ID: mdl-31991876

ABSTRACT

Boarding schools can provide quality secondary education for Aboriginal students from remote Aboriginal Australian communities. However, transition into boarding school is commonly challenging for Aboriginal students as they need to negotiate unfamiliar cultural, social and learning environments whilst being separated from family and community support. Accordingly, it is critical for boarding schools to provide programs that enhance the social and emotional skills needed to meet the challenges. This study evaluated a 10-session social and emotional learning (SEL) program for Aboriginal boarders and identified contextual factors influencing its effectiveness. The study combined a pre-post quantitative evaluation using diverse social and emotional wellbeing measures with 28 students between 13-15 years (10 female, 11 male, 7 unidentified) and qualitative post focus groups with 10 students and episodic interviews with four staff delivering the program. Students' social and emotional skills significantly improved. The qualitative findings revealed improvements in students seeking and giving help, working in groups, managing conflict, being assertive and discussing cultural issues. The focus groups and interviews also identified program elements that worked best and that need improvement. Secure relationships with staff delivering the program and participation in single sex groups stood out as critical enablers. The findings lend evidence to the critical importance of collaborative design, provision and evaluation of SEL programs with Aboriginal peoples.


Subject(s)
Child Welfare/psychology , Emotions , Learning , Students/psychology , Adolescent , Female , Humans , Male , Northern Territory , Residence Characteristics , Social Learning
18.
Musculoskelet Sci Pract ; 36: 54-60, 2018 08.
Article in English | MEDLINE | ID: mdl-29738929

ABSTRACT

STUDY DESIGN: Case-control study. BACKGROUND: A large number of student and professional musicians are affected by long term playing related musculoskeletal disorders (PRMSDs) during their career, with prevalence rates above 80%. OBJECTIVE: To investigate if there were differences between musicians with and without prolonged symptoms of upper quarter PRMSDs in the presence of: (1) scapular dyskinesis; (2) cervical motor control and endurance deficits. METHODS: Seventy-two musicians (24 males; 48 females) were matched based on sex, type of instrument and average hours played per week and assigned to one of two groups: A symptomatic group (mean age 23.3 ±â€¯8.2 years) with history of prolonged PRMSDs (constant symptoms lasting more than one week) during the past year; and a control group (mean age 25 ±â€¯10.5 years) with no history of PRMSDs lasting more than one week. Musicians completed a questionnaire and underwent clinical testing for the presence of scapular dyskinesis and cervical motor control and endurance deficits using the following tests: (1) cervical flexor endurance test; (2) scapular dyskinesis test; and (3) craniocervical flexion test. Assessor blinding as to group assignment was ensured. RESULTS: Participants in the symptomatic group presented with a statistically significant higher prevalence of positive scapular dyskinesis (P < .0001; OR = 7.8) and lower scores for the craniocervical flexion test (P < .0001). CONCLUSION: Musicians with prolonged symptoms of PRMSDs presented with higher prevalence of scapular and cervical motor control deficits detected by standard clinical tests when compared to the control group. LEVEL OF EVIDENCE: Therapy, level 4. CLINICALTRIALS. GOV IDENTIFIER: NCT02267395.


Subject(s)
Dystonic Disorders/epidemiology , Musculoskeletal Diseases/epidemiology , Music , Occupational Diseases/epidemiology , Adult , Age Factors , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prevalence , Surveys and Questionnaires , Young Adult
19.
Rural Remote Health ; 16(3): 3852, 2016.
Article in English | MEDLINE | ID: mdl-27534884

ABSTRACT

INTRODUCTION: Early detection of developmental difficulties is universally considered a necessary public health measure, with routine developmental monitoring an important function of primary healthcare services. This study aimed to describe the developmental monitoring practice in two remote Australian Aboriginal primary healthcare services and to identify gaps in the delivery of developmental monitoring services. METHODS: A cross-sectional baseline medical record audit of all resident children aged less than 5 years in two remote Aboriginal health centres in the Northern Territory (NT) in Australia was undertaken between December 2010 and November 2011. RESULTS: A total of 151 medical records were audited, 80 in Community A and 71 in Community B. Developmental checks were more likely among children who attended services more regularly. In Community A, 63 (79%) medical records had some evidence of a developmental check and in Community B there were 42 (59%) medical records with such evidence. However, there was little indication of how assessments were undertaken: only one record noted the use of a formal developmental screening measure. In Community A, 16 (16%) records documented parent report and 20 (20%) documented staff observations, while in Community B, the numbers were 2 (3%) and 11 (19%), respectively. The overall recorded prevalence of developmental difficulties was 21% in Community A and 6% in Community B. CONCLUSIONS: This is the first study to describe the quality of developmental monitoring practice in remote Australian Aboriginal health services. The audit findings suggest the need for a systems-wide approach to the delivery and recording of developmental monitoring services. This will require routine training of remote Aboriginal health workers and remote area nurses in developmental monitoring practice including the use of a culturally appropriate, structured developmental screening measure.


Subject(s)
Child Development , Child Health Services/organization & administration , Health Services, Indigenous/organization & administration , Monitoring, Physiologic/methods , Rural Health Services/organization & administration , Australia , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Infant, Newborn , Male , Native Hawaiian or Other Pacific Islander , Northern Territory
20.
PLoS One ; 11(3): e0149701, 2016.
Article in English | MEDLINE | ID: mdl-26934587

ABSTRACT

There remains limited knowledge of how offshore windfarm developments influence fish assemblages, particularly at a local scale around the turbine structures. Considering the existing levels of anthropogenic pressures on coastal fish populations it is becoming increasingly important for developers and environmental regulators to gain a more comprehensive understanding of the factors influencing fish assemblages. Improving our ability to assess such fish populations in close proximity to structures will assist in increasing this knowledge. In the present study we provide the first trial use of Baited Remote Underwater Stereo-Video systems (stereo BRUVs) for the quantification of motile fauna in close proximity to offshore wind turbines. The study was conducted in the Irish Sea and finds the technique to be a viable means of assessing the motile fauna of such environments. The present study found a mixture of species including bottom dwellers, motile crustaceans and large predatory fish. The majority of taxa observed were found to be immature individuals with few adult individuals recorded. The most abundant species were the angular crab (Goneplax rhomboides) and the small-spotted catshark (Scyliorhinus canicula). Of note in this study was the generally low abundance and diversity of taxa recorded across all samples, we hypothesise that this reflects the generally poor state of the local fauna of the Irish Sea. The faunal assemblages sampled in close proximity to turbines were observed to alter with increasing distance from the structure, species more characteristic of hard bottom environments were in abundance at the turbines (e.g. Homarus gammarus, Cancer pagarus, Scyliorhinus spp.) and those further away more characteristic of soft bottoms (e.g. Norwegian Lobster). This study highlights the need for the environmental impacts of offshore renewables on motile fauna to be assessed using targeted and appropriate tools. Stereo BRUVs provide one of those tools, but like the majority of methods for sampling marine biota, they have limitations. We conclude our paper by providing a discussion of the benefits and limitations of using this BRUV technique for assessing fauna within areas close to offshore windfarms.


Subject(s)
Fishes/growth & development , Fishes/physiology , Animals , Biodiversity , Brachyura/growth & development , Brachyura/physiology , Ecosystem , Environment , Marine Biology , Nephropidae/growth & development , Nephropidae/physiology , Oceans and Seas , Wind
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