56 research outputs found
Designing effective waste management practices in developing economies: the case of Suriname.
Local authorities are responsible for the exponential increase of waste, estimated to be about 9 billion tonnes annually. However, developing economies face enormous waste management challenges compared to developed economies, suggesting the lack of effective waste management approaches in most developing economies, including the small island developing states (SIDS). This study explores waste management practices and behavior in Suriname in support of the government's ongoing efforts in developing a framework to integrate sustainable development goals into its national policies and strategies. The current research adopts a two-stage data collection method involving observation and semi-structured interviews. 15 key informants were purposively recruited and interviewed using the semi-structured interview method to understand the current perceptions and behavior towards waste production and management in Suriname. The results show that Suriname lacks a structured and formal waste management system like many other developing countries. Open dumping and uncontrolled incineration are the dominant waste treatment methods in the country. The semi-structured interviews show that many factors, such as the lack of government commitment, ineffective policies and regulations, lack of investment and infrastructure, and citizens' social-economic status, contribute to Suriname's current unsustainable waste management practices. Although the country faces many challenges, people, especially in villages, have positive attitudes towards the environment, enhancing their engagement in managing waste if the right schemes and facilities are installed. The study argued that the government should improve their participation and commitment to waste management, especially through installing, implementing and enforcing effective waste management policies and strategies. The study further demonstrates the need for collaborations between the government and other institutions, especially NGOs and private firms, to improve waste management investment and efforts. Using the ontology perspective, key findings are synthesized to highlight the practical and theoretical implications of the study. Limitations and future research are discussed
Compensatory Evolution of pbp Mutations Restores the Fitness Cost Imposed by β-Lactam Resistance in Streptococcus pneumoniae
The prevalence of antibiotic resistance genes in pathogenic bacteria is a major challenge to treating many infectious diseases. The spread of these genes is driven by the strong selection imposed by the use of antibacterial drugs. However, in the absence of drug selection, antibiotic resistance genes impose a fitness cost, which can be ameliorated by compensatory mutations. In Streptococcus pneumoniae, β-lactam resistance is caused by mutations in three penicillin-binding proteins, PBP1a, PBP2x, and PBP2b, all of which are implicated in cell wall synthesis and the cell division cycle. We found that the fitness cost and cell division defects conferred by pbp2b mutations (as determined by fitness competitive assays in vitro and in vivo and fluorescence microscopy) were fully compensated by the acquisition of pbp2x and pbp1a mutations, apparently by means of an increased stability and a consequent mislocalization of these protein mutants. Thus, these compensatory combinations of pbp mutant alleles resulted in an increase in the level and spectrum of β-lactam resistance. This report describes a direct correlation between antibiotic resistance increase and fitness cost compensation, both caused by the same gene mutations acquired by horizontal transfer. The clinical origin of the pbp mutations suggests that this intergenic compensatory process is involved in the persistence of β-lactam resistance among circulating strains. We propose that this compensatory mechanism is relevant for β-lactam resistance evolution in Streptococcus pneumoniae
Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for imaging of unstable atherosclerotic plaques
Molecular imaging of matrix metalloproteinases (MMPs) may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9) with high selectivity and inhibitory potency. Inhibitory potencies of several halogenated analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl monohydroxamates) were in the nanomolar range for MMP2/9. The analogue with highest inhibitory potency and selectivity was radiolabelled with [I-123], resulting in moderate radiochemical yield, and high radiochemical purity. Biodistribution studies in mice, revealed stabilization in blood 1 hour after intravenous bolus injection. Intravenous infusion of the radioligand and subsequent autoradiography of excised aortas showed tracer uptake in atheroprone mice. Distribution of the radioligand showed co-localization with MMP2/9 immunohistochemical staining. In conclusion, we have developed a novel selective radiolabeled MMP2/9 inhibitor, suitable for single photon emission computed tomography (SPECT) imaging that effectively targets atherosclerotic lesions in mice
ε/ζ systems: their role in resistance, virulence, and their potential for antibiotic development
Cell death in bacteria can be triggered by activation of self-inflicted molecular mechanisms. Pathogenic bacteria often make use of suicide mechanisms in which the death of individual cells benefits survival of the population. Important elements for programmed cell death in bacteria are proteinaceous toxin–antitoxin systems. While the toxin generally resides dormant in the bacterial cytosol in complex with its antitoxin, conditions such as impaired de novo synthesis of the antitoxin or nutritional stress lead to antitoxin degradation and toxin activation. A widespread toxin–antitoxin family consists of the ε/ζ systems, which are distributed over plasmids and chromosomes of various pathogenic bacteria. In its inactive state, the bacteriotoxic ζ toxin protein is inhibited by its cognate antitoxin ε. Upon degradation of ε, the ζ toxin is released allowing this enzyme to poison bacterial cell wall synthesis, which eventually triggers autolysis. ε/ζ systems ensure stable plasmid inheritance by inducing death in plasmid-deprived offspring cells. In contrast, chromosomally encoded ε/ζ systems were reported to contribute to virulence of pathogenic bacteria, possibly by inducing autolysis in individual cells under stressful conditions. The capability of toxin–antitoxin systems to kill bacteria has made them potential targets for new therapeutic compounds. Toxin activation could be hijacked to induce suicide of bacteria. Likewise, the unique mechanism of ζ toxins could serve as template for new drugs. Contrarily, inhibition of virulence-associated ζ toxins might attenuate infections. Here we provide an overview of ε/ζ toxin–antitoxin family and its potential role in the development of new therapeutic approaches in microbial defense
Review of methods used by chiropractors to determine the site for applying manipulation
Background: With the development of increasing evidence for the use of manipulation in the management of musculoskeletal conditions, there is growing interest in identifying the appropriate indications for care. Recently, attempts have been made to develop clinical prediction rules, however the validity of these clinical prediction rules remains unclear and their impact on care delivery has yet to be established. The current study was designed to evaluate the literature on the validity and reliability of the more common methods used by doctors of chiropractic to inform the choice of the site at which to apply spinal manipulation. Methods: Structured searches were conducted in Medline, PubMed, CINAHL and ICL, supported by hand searches of archives, to identify studies of the diagnostic reliability and validity of common methods used to identify the site of treatment application. To be included, studies were to present original data from studies of human subjects and be designed to address the region or location of care delivery. Only English language manuscripts from peer-reviewed journals were included. The quality of evidence was ranked using QUADAS for validity and QAREL for reliability, as appropriate. Data were extracted and synthesized, and were evaluated in terms of strength of evidence and the degree to which the evidence was favourable for clinical use of the method under investigation. Results: A total of 2594 titles were screened from which 201 articles met all inclusion criteria. The spectrum of manuscript quality was quite broad, as was the degree to which the evidence favoured clinical application of the diagnostic methods reviewed. The most convincing favourable evidence was for methods which confirmed or provoked pain at a specific spinal segmental level or region. There was also high quality evidence supporting the use, with limitations, of static and motion palpation, and measures of leg length inequality. Evidence of mixed quality supported the use, with limitations, of postural evaluation. The evidence was unclear on the applicability of measures of stiffness and the use of spinal x-rays. The evidence was of mixed quality, but unfavourable for the use of manual muscle testing, skin conductance, surface electromyography and skin temperature measurement. Conclusions: A considerable range of methods is in use for determining where in the spine to administer spinal manipulation. The currently published evidence falls across a spectrum ranging from strongly favourable to strongly unfavourable in regard to using these methods. In general, the stronger and more favourable evidence is for those procedures which take a direct measure of the presumptive site of care– methods involving pain provocation upon palpation or localized tissue examination. Procedures which involve some indirect assessment for identifying the manipulable lesion of the spine–such as skin conductance or thermography–tend not to be supported by the available evidence.https://doi.org/10.1186/2045-709X-21-3
Classification of Caesarean Section and Normal Vaginal Deliveries Using Foetal Heart Rate Signals and Advanced Machine Learning Algorithms
ABSTRACT – Background: Visual inspection of Cardiotocography traces by obstetricians and midwives is the gold standard for monitoring the wellbeing of the foetus during antenatal care. However, inter- and intra-observer variability is high with only a 30% positive predictive value for the classification of pathological outcomes. This has a significant negative impact on the perinatal foetus and often results in cardio-pulmonary arrest, brain and vital organ damage, cerebral palsy, hearing, visual and cognitive defects and in severe cases, death. This paper shows that using machine learning and foetal heart rate signals provides direct information about the foetal state and helps to filter the subjective opinions of medical practitioners when used as a decision support tool. The primary aim is to provide a proof-of-concept that demonstrates how machine learning can be used to objectively determine when medical intervention, such as caesarean section, is required and help avoid preventable perinatal deaths. Methodology: This is evidenced using an open dataset that comprises 506 controls (normal virginal deliveries) and 46 cases (caesarean due to pH ≤7.05 and pathological risk). Several machine-learning algorithms are trained, and validated, using binary classifier performance measures. Results: The findings show that deep learning classification achieves Sensitivity = 94%, Specificity = 91%, Area under the Curve = 99%, F-Score = 100%, and Mean Square Error = 1%. Conclusions: The results demonstrate that machine learning significantly improves the efficiency for the detection of caesarean section and normal vaginal deliveries using foetal heart rate signals compared with obstetrician and midwife predictions and systems reported in previous studies
Development of a potent series of MMP-2 and MMP-9 selective inhibitors. MMP-2 and MMP-9 visualization in unstables plaques using PET and SPECT is approaching
Risk of preterm birth with routine first-trimester combined screening for pre-eclampsia.
OBJECTIVES: Preterm birth (PTB) is a major public health problem worldwide. It can occur spontaneously or be medically indicated for obstetric complications, such as pre-eclampsia (PE) or fetal growth restriction. The main objective of the study was to investigate the implication of uteroplacental dysfunction in the first trimester in subsequent PTB. METHODS: This retrospective cohort study on singleton pregnancies was conducted between March 2018 and December 2020. A total of 11,437 women underwent first-trimester screening for preterm PE using the Fetal Medicine Foundation algorithm, which includes maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and pregnancy-associated plasma protein (PAPP-A). Women with a risk of ≥1 in 50 for preterm PE were classified as high-risk and offered prophylactic aspirin 150mg and serial ultrasound assessments. The following outcomes at delivery were collected: PTB, iatrogenic PTB (iPTB) and spontaneous PTB (sPTB). RESULTS: 475 (4.2%) women had preterm births with 308 (64.8%) sPTB and 167 (35.2%) iPTB. Patients with PTB had a higher body mass index, were more likely to be Black or Asian and have a history of previous PTB. They also had higher MAP (87.70 vs 86.00, p<0.0001), higher UtA-PI MoM (0.99 vs 0.92, p<0.0001), lower PAPPA MoM (0.89 vs 1.08, p<0.0001). In women at high risk of PE, the odds ratio (OR) for iPTB was 6.0 (95% CI 4.29-8.43, p<0.0001) and for sPTB was 2.0 (95% CI 1.46-2.86, p<0.0001). A prediction model for PTB developed from this cohort performed as well as an existing first-trimester prediction model. CONCLUSIONS: Increased first-trimester risk for uteroplacental dysfunction was associated with both iatrogenic and spontaneous PTB, implying a shared aetiological pathway. The same factors used to predict PE risk show acceptable discrimination to predict PTB before 33 weeks. Women at high risk of uteroplacental dysfunction may warrant additional monitoring and management for an increased risk of spontaneous PTB. This article is protected by copyright. All rights reserved
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