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Association of accelerometry-based and self-reported physical activity with cardiovascular risk in South African children
No full textThe burden of non-communicable diseases is increasing, with risk factors emerging early in life. Physical activity reduces cardiovascular risk, but limited evidence exists for children from lower-income countries and mostly relies on self-reported methods that might be inaccurate and biased. We aimed to compare self-reported and accelerometer-measured physical activity in relation to cardiovascular risk markers in children from underserved communities in South Africa. We analysed cross-sectional data from 594 children aged 8 to 13. Physical activity was measured via accelerometry and the Physical Activity Questionnaire for Older Children (PAQ-C). Correlation analyses and linear regression models examined the relationship between accelerometer-measured and self-reported physical activity and their association with cardiovascular risk markers (body mass index, blood pressure, blood lipid profile and glycated haemoglobin). Results show a positive but weak correlation between PAQ-C scores and accelerometer-measured moderate-to-vigorous physical activity (MVPA). MVPA was inversely associated with body mass index, whilst sedentary behaviour correlated positively with lipid levels. PAQ-C scores were inversely associated with systolic blood pressure. The comparison of self-reported and accelerometer-measured physical activity in children from Gqeberha, South Africa, revealed inconsistencies in their correlation and association with cardiovascular risk markers. Accelerometry provided a more accurate cardiovascular risk estimation than PAQ-C, although associations were weak. Further, longitudinal studies should investigate the predictive power of both methodologies. These findings inform researchers and public health practitioners in the choice of method for physical activity appraisal beyond practical considerations, especially when combined with cardiovascular risk and in lower-income settings. Significance: We explore two widely used methods to assess physical activity levels in children. By comparing both methods, we expose inconsistencies in their correlation and association with cardiovascular risk markers. These data can guide researchers and public health practitioners in the use of one method beyond practical considerations. Whilst this work focuses on children from marginalised areas of South Africa, the issues explored are of relevance to other lower-income settings. Open data set: https://doi.org/10.5281/zenodo.721714
Guillain-Barre syndrome associated with hepatitis E virus infection: a case report
Get PDFKEY CLINICAL MESSAGE: Hepatitis E virus (HEV) infection can be manifested with several neurological syndromes including GBS. Therefore, healthcare providers should consider HEV in their differential diagnosis for patients with neurological disorders. ABSTRACT: We report a case of Guillain-Barré syndrome associated with hepatitis E virus infection. The current case-report demonstrates diagnostic challenge to identify GBS case in a limited-resources country like Sudan. However, HEV infection should be highly suspected in patients with neurological manifestation with high liver enzymes
Health economic evaluation of strategies to eliminate gambiense human African trypanosomiasis in the Mandoul disease focus of Chad
Get PDFHuman African trypanosomiasis, caused by the gambiense subspecies of Trypanosoma brucei (gHAT), is a deadly parasitic disease transmitted by tsetse. Partners worldwide have stepped up efforts to eliminate the disease, and the Chadian government has focused on the previously high-prevalence setting of Mandoul. In this study, we evaluate the economic efficiency of the intensified strategy that was put in place in 2014 aimed at interrupting the transmission of gHAT, and we make recommendations on the best way forward based on both epidemiological projections and cost-effectiveness. In our analysis, we use a dynamic transmission model fit to epidemiological data from Mandoul to evaluate the cost-effectiveness of combinations of active screening, improved passive screening (defined as an expansion of the number of health posts capable of screening for gHAT), and vector control activities (the deployment of Tiny Targets to control the tsetse vector). For cost-effectiveness analyses, our primary outcome is disease burden, denominated in disability-adjusted life-years (DALYs), and costs, denominated in 2020 US750/DALY averted) which substantially increased the probability of reaching the 2030 elimination target for gHAT as set by the World Health Organization. Our transmission modelling and economic evaluation suggest that the gains that have been made could be maintained by passive screening. Our analysis speaks to comparative efficiency, and it does not take into account all possible considerations; for instance, any cessation of ongoing active screening should first consider that substantial surveillance activities will be critical to verify the elimination of transmission and to protect against the possible importation of infection from neighbouring endemic foci
IVDR: analysis of the social, economic, and practical consequences of the application of an ordinance of the in vitro diagnostic ordinance in Switzerland
Get PDFIVDR regulation represents a major challenge for diagnostic microbiology laboratories. IVDR complicates a broad range of aspects and poses a risk given the high diversity of pathogens (including rare but highly virulent microbes) and the large variety of samples submitted for analysis. The regular emergence of new pathogens (including Echovirus E-11, Adenovirus 41, Monkeypox virus, Alongshan virus, and Enterovirus D68, as recent examples in Europe in the post SARS-CoV-2 era) is another factor that makes IVDR regulation risky, because its detrimental effect on production of in-house tests will negatively impact knowledge and expertise in the development of new diagnostic tests. Moreover, such regulations negatively impact the availability of diagnostic tests, especially for neglected pathogens, and has a detrimental effect on the overall costs of the tests. The increased regulatory burden of IVDR may thereby pose an important risk for public health. Taken together, it will have a negative impact on the financial balance of diagnostic microbiology laboratories (especially small ones). The already-high standards of quality management of all ISO-accredited and Swissmedic-authorized laboratories render IVDR law of little value, at least in Switzerland, while tremendously increasing the regulatory burden and associated costs. Eventually, patients will need to pay for diagnostic assays outside of the framework of their insurance in order to obtain a proper diagnostic assessment, which may result in social inequity. Thus, based on the risk assessment outlined above, the coordinated commission for clinical microbiology proposes adjusting the IvDO ordinance by (i) introducing an obligation to be ISO 15189 accredited and (ii) not implementing the IvDO 2028 milestone
Parasitic, bacterial, viral, immune-mediated, metabolic and nutritional factors associated with nodding syndrome
Get PDFNodding syndrome is a neglected, disabling and potentially fatal epileptic disorder of unknown aetiology affecting thousands of individuals mostly confined to Eastern sub-Saharan Africa. Previous studies have identified multiple associations-including Onchocerca volvulus, antileiomodin-1 antibodies, vitamin B(6) deficiency and measles virus infection-yet, none is proven causal. We conducted a case-control study of children with early-stage nodding syndrome (symptom onset <1 year). Cases and controls were identified through a household survey in the Greater Mundri area in South Sudan. A wide range of parasitic, bacterial, viral, immune-mediated, metabolic and nutritional risk factors was investigated using conventional and state-of-the-art untargeted assays. Associations were examined by multiple logistic regression analysis, and a hypothetical causal model was constructed using structural equation modelling. Of 607 children with nodding syndrome, 72 with early-stage disease were included as cases and matched to 65 household- and 44 community controls. Mansonella perstans infection (odds ratio 7.04, 95% confidence interval 2.28-21.7), Necator americanus infection (odds ratio 2.33, 95% confidence interval 1.02-5.3), higher antimalarial seroreactivity (odds ratio 1.75, 95% confidence interval 1.20-2.57), higher vitamin E concentration (odds ratio 1.53 per standard deviation increase, 95% confidence interval 1.07-2.19) and lower vitamin B(12) concentration (odds ratio 0.56 per standard deviation increase, 95% confidence interval 0.36-0.87) were associated with higher odds of nodding syndrome. In a structural equation model, we hypothesized that Mansonella perstans infection, higher vitamin E concentration and fewer viral exposures increased the risk of nodding syndrome while lower vitamin B(12) concentration, Necator americanus and malaria infections resulted from having nodding syndrome. We found no evidence that Onchocerca volvulus, antileiomodin-1 antibodies, vitamin B(6) and other factors were associated with nodding syndrome. Our results argue against several previous causal hypotheses including Onchocerca volvulus. Instead, nodding syndrome may be caused by a complex interplay between multiple pathogens and nutrient levels. Further studies need to confirm these associations and determine the direction of effect
Relationship between insecticide resistance profiles in Anopheles gambiae sensu lato and agricultural practices in Côte d'Ivoire
Get PDFBACKGROUND: Insecticide-based malaria vector control is increasingly undermined due to the development of insecticide resistance in mosquitoes. Insecticide resistance may partially be related to the use of pesticides in agriculture, while the level and mechanisms of resistance might differ between agricultural practices. The current study aimed to assess whether phenotypic insecticide resistance and associated molecular resistance mechanisms in Anopheles gambiae sensu lato differ between agricultural practices. METHODS: We collected An. gambiae s.l. larvae in six sites with three different agricultural practices, including rice, vegetable and cocoa cultivation. We then exposed the emerging adult females to discriminating concentrations of bendiocarb (0.1%), deltamethrin (0.05%), DDT (4%) and malathion (5%) using the standard World Health Organization insecticide susceptibility test. To investigate underlying molecular mechanisms of resistance, we used multiplex TaqMan qPCR assays. We determined the frequency of target-site mutations, including Vgsc-L995F/S and Vgsc-N1570Y, and Ace1-G280S. In addition, we measured the expression levels of genes previously associated with insecticide resistance in An. gambiae s.l., including the cytochrome P450-dependent monooxygenases CYP4G16, CYP6M2, CYP6P1, CYP6P3, CYP6P4, CYP6Z1 and CYP9K1, and the glutathione S-transferase GSTe2. RESULTS: The An. gambiae s.l. populations from all six agricultural sites were resistant to bendiocarb, deltamethrin and DDT, while the populations from the two vegetable cultivation sites were additionally resistant to malathion. Most tested mosquitoes carried at least one mutant Vgsc-L995F allele that is associated with pyrethroid and DDT resistance. In the cocoa cultivation sites, we observed the highest 995F frequencies (80-87%), including a majority of homozygous mutants and several in co-occurrence with the Vgsc-N1570Y mutation. We detected the Ace1 mutation most frequently in vegetable-growing sites (51-60%), at a moderate frequency in rice (20-22%) and rarely in cocoa-growing sites (3-4%). In contrast, CYP6M2, CYP6P3, CYP6P4, CYP6Z1 and CYP9K1, previously associated with metabolic insecticide resistance, showed the highest expression levels in the populations from rice-growing sites compared to the susceptible Kisumu reference strain. CONCLUSION: In our study, we observed intriguing associations between the type of agricultural practices and certain insecticide resistance profiles in the malaria vector An. gambiae s.l. which might arise from the use of pesticides deployed for protecting crops
Perioperative Factors Associated With Postoperative Delirium in Patients Undergoing Noncardiac Surgery: An Individual Patient Data Meta-Analysis
Get PDFPostoperative delirium (POD) is a common and serious complication after surgery. Various predisposing factors are associated with POD, but their magnitude and importance using an individual patient data (IPD) meta-analysis have not been assessed.; To identify perioperative factors associated with POD and assess their relative prognostic value among adults undergoing noncardiac surgery.; MEDLINE, EMBASE, and CINAHL from inception to May 2020.; Studies were included that (1) enrolled adult patients undergoing noncardiac surgery, (2) assessed perioperative risk factors for POD, and (3) measured the incidence of delirium (measured using a validated approach). Data were analyzed in 2020.; Individual patient data were pooled from 21 studies and 1-stage meta-analysis was performed using multilevel mixed-effects logistic regression after a multivariable imputation via chained equations model to impute missing data.; The end point of interest was POD diagnosed up to 10 days after a procedure. A wide range of perioperative risk factors was considered as potentially associated with POD.; A total of 192 studies met the eligibility criteria, and IPD were acquired from 21 studies that enrolled 8382 patients. Almost 1 in 5 patients developed POD (18%), and an increased risk of POD was associated with American Society of Anesthesiologists (ASA) status 4 (odds ratio [OR], 2.43; 95% CI, 1.42-4.14), older age (OR for 65-85 years, 2.67; 95% CI, 2.16-3.29; OR for >85 years, 6.24; 95% CI, 4.65-8.37), low body mass index (OR for body mass index 10 mg/dL, 3.56; 95% CI, 2.46-5.17). Completing a college degree or higher was associated with a decreased likelihood of developing POD (OR 0.45; 95% CI, 0.28-0.72).; In this systematic review and meta-analysis of individual patient data, several important factors associated with POD were found that may help identify patients at high risk and may have utility in clinical practice to inform patients and caregivers about the expected risk of developing delirium after surgery. Future studies should explore strategies to reduce delirium after surgery
Making food safer in Palestine: a one health approach to antimicrobial resistance
Get PDFBackground
Foodborne diseases, combined with the growing threat of antimicrobial resistance (AMR), present significant public health challenges, especially in relation to climate change and the risks of zoonotic epidemics. Unsafe food consumption can cause various health issues, ranging from food poisoning to reproductive problems, and can contribute to the emergence of AMR, resulting in severe consequences such as cancer and death. The use of antimicrobials in food production raises safety concerns due to the presence of antibiotic residues, antibiotic-resistant bacteria (ARB), and antibiotic-resistant genes (ARGs) in animals, food products, and the environment.
Foodborne diseases caused by antibiotic-resistant bacteria from animals, such as foodborne urinary tract infections (UTIs), have recently attracted considerable attention. Resistant bacteria from contaminated food can colonize the human gastrointestinal tract, acting as a reservoir for further infections. This hinders infection prevention and control efforts, as well as antimicrobial stewardship programs in communities and hospitals.
The political unrest due to the conflicts and wars, such as in Palestine, have severe consequences for food safety and the spread of AMR. Infrastructure damage, limited resources for food safety programs, increased antibiotic use, hindered access to medical care, and displacement of individuals contribute to compromised food safety and the rise of AMR.
A comprehensive One Health approach is vital to tackle AMR throughout the entire food production process. It considers all relevant factors, from upstream to downstream, and includes an integrated surveillance-response system encompassing human and animal health, the environment, and food production. This holistic approach safeguards antimicrobial efficacy by ensuring food safety, preserving food security, and effectively combating communicable and noncommunicable diseases, benefiting future generations.
Objectives
This PhD thesis utilizes the One Health approach to examine zoonotic bacteria and AMR in the food production chain, particularly in conflict-affected regions. It aims to identify integrated One Health studies on Middle Eastern foodborne illnesses, assess food safety for an operational strategy in Palestine, and evaluate the benefits of implementing an integrated surveillance system for foodborne pathogens and AMR.
Methods
This PhD project tries to find a critical methodology to foster food safety by better understanding the zoonotic foodborne illnesses transmission and their resistance to antimicrobials in socio-ecological systems like in Palestine. The research conducted a systematic review and meta-analysis of scientific literature from 2010 to 2021 to assess the implementation of the One Health approach in the Middle East, with a particular emphasis on Salmonella and Campylobacter strains. Stakeholder perspectives were gathered through multi-stakeholder discussion groups, facilitating communication and identifying diverse viewpoints on the food production monitoring system in Palestine. Additionally, a semi-structured observation design was employed to evaluate hygiene practices in broiler farms, slaughterhouses, and meat stores, pinpointing potential transmission routes and contamination sources. The project also investigated the knowledge, attitudes, and practices of workers in the broiler production industry, to explore the relationship between their attitudes, practices, and hygiene knowledge regarding zoonotic diseases. Furthermore, a One Health integrated surveillance system for Campylobacter and Salmonella, including antimicrobial resistance analysis, was piloted in the central West Bank, Palestine, involving the collection and analysis of samples from various sources. This comprehensive approach provides valuable insights into the complex dynamics of food safety and antimicrobial resistance in Palestine's socio-ecological context.
Results
In the Middle East, a total of 41 studies were analyzed to determine the prevalence rates of non-typhoid Salmonella (NTS) and Campylobacter. The findings revealed that NTS had a prevalence of 9% among humans and 13% among food-producing animals, while Campylobacter had prevalence rates of 22% in humans and 30% in animals. The most common NTS serovars were Salmonella Enteritidis and Salmonella Typhimurium, and the predominant species of Campylobacter were Campylobacter jejuni and Campylobacter coli. Notably, both NTS and Campylobacter showed high resistance to multiple antibiotics, including erythromycin, amoxicillin, tetracycline, and more. However, the implementation of the One Health approach in the Middle East was limited, and data reporting varied across countries.
In Palestine, several challenges were observed in the food production chain, such as the scarcity of public slaughterhouses, inadequate coordination between authorities, and discrepancies in law enforcement. Hygiene practices also varied, with public slaughterhouses and meat markets demonstrating better hygiene compared to large-scale farms. While participants expressed awareness of zoonotic disease transmission and emphasized the importance of hygiene standards, there were conflicting findings between observations and survey results regarding actual hygiene practices.
In a cross-sectional study conducted in Palestine using integrated One Health surveillance, the positivity rate for C. jejuni in chicken manure samples was 24%, while S. enterica had a positivity rate of 6%. The dominant serotypes of both C. jejuni and S. enterica were found in chicken manure, chicken meat sold in markets, and the feces of asymptomatic farm workers, indicating genetic similarities across different sources. Strain turnover was observed in C. jejuni between 2021 and 2022. In 2021, C. jejuni isolates exhibited identical drug resistance gene patterns, including resistance to aminoglycosides, macrolides, quinolones, and tetracycline. In 2022, a different resistance gene pattern emerged, involving beta-lactamase and quinolone resistance genes. Among the Salmonella isolates collected, most belonged to S. enterica serotype Muenchen and showed multidrug resistance, facilitated by the pESI megaplasmid carrying resistance genes to multiple antibiotics, including aminoglycosides, fluoroquinolones, sulfonamides, tetracycline, and trimethoprim.
Conclusion
To effectively implement a One Health strategy in Palestine, the establishment of a technical committee is crucial. This committee would focus on food safety, zoonotic diseases, and AMR, promoting coordination, communication, and partnerships. Proposed measures include developing an integrated quality control system for food production, implementing product certification for broiler meat, and improving slaughterhouse capacity. Veterinary inspections, careful monitoring of antimicrobial use, and sharing of AMR data would further strengthen the food safety system.
Furthermore, implementing an integrated surveillance system and adopting a transdisciplinary approach are key to addressing AMR and enhancing the food safety system in Palestine. Sharing responsibilities and resources among relevant authorities is vital for successful AMR mitigation. The establishment of the Palestinian Integrated Program for Antimicrobial Resistance Surveillance (PIPARS) would lead to financial savings and a comprehensive approach. Employing efficient testing methods like whole genome sequencing enables early identification and timely response to AMR threats, serving as an essential tool for the One Health integrated surveillance system
Metabolism and metabolic effects of the alternative sweeteners erythritol and xylitol
Get PDFObesity has reached dramatic proportions worldwide. It represents a significant health and economic burden as it is linked to an increased risk of non-communicable diseases (NCDs), such as cardiovascular diseases, cancer, type 2 diabetes mellitus (T2DM), and chronic respiratory diseases. Obesity is a complex condition caused by a combination of different factors. An unhealthy diet - especially high sugar consumption - is an important determinant of obesity. Therefore, the World Health Organization (WHO) recommends reducing the consumption of added sugars to less than 10% of total energy intake as an effective and low-cost measure to prevent as well as to treat obesity.
Consequently, low-caloric sweeteners (LCS) have garnered widespread interest as sugar substitutes to reduce added sugar intake without cutting on the sweet taste. There are many different LCS. Although they can be grouped by common properties (sweet taste, caloric content), each molecule is metabolized differently and has its own characteristics. Therefore, extrapolating the effects of one sweetener to other sweeteners, even within the same group, is not appropriate. Studies on each parameter of interest for each sweetener are warranted before drawing general conclusions.
This thesis focused on assessing the potential of the low-caloric bulk sweeteners erythritol and xylitol as sugar and artificial low-caloric sweeteners substitutes. Among all aspects necessary to describe their full potential as substitutes, this work aimed to deepen the topics of absorption and metabolism, and to assess specific metabolic effects. These aims were pursued in three clinical trials.
In the first trial, we determined the absorption of different concentrations of erythritol and xylitol and their potential metabolization into erythronate. For this purpose, we conducted a study in 17 healthy volunteers who received intragastric solutions of different concentrations of erythritol or xylitol. We assessed plasma concentrations of erythritol, xylitol, and erythronate at fixed time intervals after administration. We found a dose-dependent and saturable absorption of erythritol, and very low absorption of xylitol. We demonstrated a dose-dependent metabolization of erythritol into erythronate, and no metabolization of xylitol into erythronate.
In the second trial, we investigated whether a chronic intake of erythritol and xylitol impacts glucose absorption in humans with obesity, based on previous findings observed in rat models. Participants with obesity were randomized to consume either 36 g erythritol, 24 g xylitol, or no substance (control group) daily for five to seven weeks. Before and after the intervention we assessed intestinal glucose absorption during an oral glucose tolerance test by means of 3-Ortho-methyl-glucose concentrations in plasma. We found that a chronic intake of the natural sweeteners erythritol and xylitol does not affect intestinal glucose absorption in humans with obesity.
In the third trial, we assessed the impact of a chronic intake of erythritol and xylitol on vascular function, abdominal fat and blood lipids, glucose tolerance, uric acid, hepatic enzymes, creatinine, gastrointestinal tolerance, and dietary patterns in humans with obesity. Participants were randomized to consume either 36 g erythritol, 24 g xylitol, or no substance (control group) daily for five weeks. The parameters mentioned above were assessed before and after the intervention. We found that the chronic intake of erythritol and xylitol did not affect vascular function and had no impact on abdominal fat, glucose tolerance, uric acid, hepatic enzymes, and creatinine. Gastrointestinal tolerance was good, except for a few diarrhea-related symptoms. Participants of all groups reduced their consumption of sweetened beverages and sweets compared to pre-intervention. These results suggest that erythritol and xylitol have no negative effects regarding the parameters assessed, even when consumed by participants with obesity, who are particularly at risk of cardiovascular diseases, hepatic steatosis, and type 2 diabetes mellitus.
In summary, these findings support the view that erythritol and xylitol are sweeteners that do not induce the negative effects observed in association with a high sugar consumption. Therefore, both sweeteners can be helpful in reducing sugar consumption and thus contribute to combating overweight, obesity, T2DM, and other associated NCDs
The role of loop extrusion in the dynamics of chromosome folding
Get PDFIn mammalian genomes, physical interactions between chromosomal loci and notably between enhancers and promoters, enable control of gene expression across large genomic distances. However, it remains unknown how frequent and stable contacts between chromosomal sequences are over the course of the cell cycle and how they depend on the underlying dynamics of chromosome folding and on the loop extrusion activity of cohesin.
To address these questions, we engineered mouse embryonic stem cells (mESCs) to carry tens of random integrations of bacterial operator arrays that can be visualized using live cell fluorescence microscopy. By imaging these in the context of auxin-inducible degron systems for factors such as CCCTC-binding factor (CTCF) and RAD21, a subunit of the cohesin complex, we observed that on a global scale cohesin serves to constrain chromosome motion, while the loss of CTCF does not impact global chromosome dynamics.
However, by imaging two distinguishable chromosomal locations separated by 150 kb in cis within a topologically associating domain (TAD), we discovered that their interactions are transient events occurring frequently during the course of a cell cycle and that these interactions become substantially more frequent and longer (∼16 minutes) in the presence of convergent CTCF sites. By contrast, cohesin depletion results in shorter and less frequent cis-contacts. These observations thereby indicate a role for cohesin and CTCF in the suppression of variability in chromosome folding across time. Comparison of the experimental results to physical models of chromosome dynamics additionally suggests that individual CTCF anchored, cohesin-mediated loops last around 10 minutes. These measurements therefore indicate that long-range transcriptional regulation might rely on transient physical proximity, and show that cohesin and CTCF stabilize otherwise highly dynamic chromosome structures to facilitate selected subsets of chromosomal interactions.
In a complimentary approach, we further investigated what function of cohesin leads to this effect: its role in sister-chromatid cohesion or in loop extrusion. We therefore employed a single-particle tracking (SPT) approach following individual RAD21 molecules bound to DNA at the same time as the motion of DNA loci. We found that cohesin motion on DNA is characterized by a more sub-diffusive behavior than that of DNA itself. Furthermore, by simultaneously depleting regulators of cohesin in loop extrusion (NIPBL) or sister-chromatid cohesion (Sororin), we showed that both functions contribute to imposing constraints on the dynamics of chromosomes