Search

Regulatory T cells (Treg) play a prominent role in utero tolerating non-inherited maternal antigens and in regulating immune responses against pathogens at birth. This study investigates Treg immunity in newborns in West Africa, where sepsis remains a major public health problem. Treg phenotypes on neonates subgroups with early-onset sepsis (EOS), presumed sepsis, and healthy newborn with and without prenatal risk factors were evaluated. Treg phenotypes varied according to prenatal conditions, with increase in Treg frequency and Foxp3 expression in healthy newborns with prenatal risk factors compared to those with none risk. Compared to healthy newborns with prenatal risk factors, EOS neonates had a significantly reduced frequency of Treg and Foxp3 expression. In the Treg pool, higher frequency of activated Treg was observed in EOS neonates, suggesting an in-utero activation upstream of the sepsis onset. Their migration to the infection site may explain the reduced frequency of circulating Integrin α4β1+ Treg suggestive of homing to the endothelial tissue. EOS neonates show increases expression of CTLA-4, PD-1 and CD39 on Treg, which negatively regulate the activation of effector T cells (Teff) corroborating by the lower frequency of Teff in EOS neonates. The higher frequency of CD39+ Treg and the lower frequency of integrinα4β1+ Treg in EOS non-survivor suggests that Treg exhaustement and endothelial homing are associated with outcome severity. Neonates developing EOS are born with an altered Treg phenotypic profile. Treg expression of CTLA-4, PD-1, CD39, and integrinα4β1 cell markers can be considered as early warning or diagnostic markers of EOS.

Introduction Self-contained sanitation systems such as septic tanks, latrines, and public toilets store faecal sludge, which must be regularly evacuated. If this sludge is not regularly collected, transported, and treated in a wastewater treatment plant, it can cause serious harm to the environment and public health. Purpose This study aimed to show that the biosolids resulting from the treatment of septage collected in Kinshasa in the Democratic Republic of the Congo are uncontaminated and contain nutrients and properties that make them a resource to be valorized. Methods The present study was carried out in Kinshasa between January and March 2022. Samples of fresh faecal sludge were taken at Ndolo/auto service, a site where tanker trucks dump sludge from all over the city into a stream that flows into the Congo River. Pathogen levels were detected by counting bacteria. Helminth eggs were identified following the US Environmental Protection Agency's "Rule 503" recommendations for Class A and B biosolids. Total nitrogen was determined by the Kjeldahl method, while phosphorus and potassium were determined spectrometrically. Statistical analyses were performed using Excel 2021 and SPSS v.21 software. Results The results obtained showed values

Abstract A new sensitive method to determine polonium-210 (210Po) and lead-210 (210Pb) in a diversity of environmental samples was developed. For fresh and marine waters, Po was pre-concentrated using a titanium (III) hydroxide (Ti(OH)3) co-precipitation. Solid environmental samples were digested with nitric acid (HNO3) and hydrogen peroxide (H2O2). The alpha thin layer source was prepared using CuS micro-precipitation and 210Po was measured by alpha spectrometry. Lead-210 was left to decay for up to a year and indirectly measured via its progeny, 210Po. The chemical recoveries for 210Po and 210Pb were high, 90% and 97%, respectively, for a large variety of samples and a very low minimum detectable activity (MDA) was obtained. The method was validated using standardized solutions and certified reference materials.

Firefighters can be exposed to complex mixtures of airborne substances, including hazardous substances released during structural fires. This study employed silicone wristbands (SWBs) as passive samplers to investigate potential exposure to polycyclic aromatic hydrocarbons (PAHs) and flame retardants (FRs). SWBs were deployed at different areas of four fire stations, in four truck cabins, and at an office control location; they were also donned outside the jackets of 18 firefighters who responded to fire calls. Overall, office areas had significantly lower PAHs than fire station areas. Vehicle bays and truck cabins had significantly higher concentrations of low molecular weight (LMW) PAHs than sleeping and living room areas. For organophosphate ester flame retardants (OPFRs), tri-n-butyl phosphate (TnBP) and tris(1-chloro-2-propyl) phosphate (TCPP) were detected in all the samples; 2-ethylhexyl diphenyl phosphate (EHDPP) was more frequently detected in the fire station areas. Triphenyl phosphate (TPP) concentrations were highest in the truck cabin and office areas, and tris(1,3-dichloro-2-propyl)phosphate (TDCPP) was highest in truck cabins. Thirteen of 16 PAHs and nine of 36 OPFRs were detected in all the SWBs worn by firefighters, and tris (2-butoxyethyl) phosphate (TBEP) was the predominant OPFR. Levels of LMW PAHs were significantly lower when firefighters did not enter the fire. LMW PAHs, HMW (high molecular weight) PAHs, and EHDPP were significantly elevated when heavy smoke was reported. This work highlights the potential for occupational exposure to PAHs and flame retardants in some fire station areas; moreover, factors that may influence exposure during fire suppression. Whilst firefighters’ occupational exposure to PAHs is likely related to fire suppression and exposure to contaminated gear and trucks, exposure to OPFRs may be more related to their presence in truck interiors and electronics.

Several models have been developed to predict the effects of folic acid fortification programs on prevention of neural tube defects (NTDs), but each relies on different assumptions and data inputs. We identified and reviewed 7 models that predict the effects of folic acid intake or status on NTD risk. We applied 4 of these models [the original and a modified version of the Lives Saved Tool (LiST) and models developed by Arth et al. and Wald et al.] to predict the effect of folic acid fortification of wheat flour on reduction of NTDs using national survey data from Cameroon. The estimated percentage of NTDs averted due to fortified wheat flour (5.0 μg folic acid/g flour) varied by predictive model, with a 21-31% reduction in LiST to 83% in Arth's model, and 15% in Wald's model. As the simulated fortification level was increased from 1.0 to 7.0 μg folic acid/g flour, the pattern of change in estimated numbers of NTDs averted differed due to different model assumptions: the number of NTDs averted increased and then reached a plateau in the modified LiST model (as would be expected in real-world conditions), increased sharply in Arth's model, and increased continuously in Wald's model. This wide variation in predicted effects, and implausible results in some cases, undermines the models' utility for users of model outputs. Concurrent collection of dietary and biomarker data, including plasma and RBC folate concentrations, and NTD outcomes, is necessary to validate these models and monitor change in folic acid intake, folate-related biomarkers, and reduced NTD risk due to fortification. In the meantime, models based on erythrocyte folate concentration are recommended, based on biological plausibility and consistency with empirical evidence. Where erythrocyte folate data are unavailable, sensitivity analyses (using several models) could be conducted to examine the range of possible outcomes.

Animal psychophysics can generate rich behavioral datasets, often comprised of many 1000s of trials for an individual subject. Gradient-boosted models are a promising machine learning approach for analyzing such data, partly due to the tools that allow users to gain insight into how the model makes predictions. We trained ferrets to report a target word's presence, timing, and lateralization within a stream of consecutively presented non-target words. To assess the animals' ability to generalize across pitch, we manipulated the fundamental frequency (F0) of the speech stimuli across trials, and to assess the contribution of pitch to streaming, we roved the F0 from word token to token. We then implemented gradient-boosted regression and decision trees on the trial outcome and reaction time data to understand the behavioral factors behind the ferrets' decision-making. We visualized model contributions by implementing SHAPs feature importance and partial dependency plots. While ferrets could accurately perform the task across all pitch-shifted conditions, our models reveal subtle effects of shifting F0 on performance, with within-trial pitch shifting elevating false alarms and extending reaction times. Our models identified a subset of non-target words that animals commonly false alarmed to. Follow-up analysis demonstrated that the spectrotemporal similarity of target and non-target words rather than similarity in duration or amplitude waveform was the strongest predictor of the likelihood of false alarming. Finally, we compared the results with those obtained with traditional mixed effects models, revealing equivalent or better performance for the gradient-boosted models over these approaches.

Introduction Sickle cell disease is a hereditary condition primarily identified in tropical areas. It is marked by significant anemia, vaso-occlusive seizures, and a heightened vulnerability to both viral and bacterial infections. Additionally, sickle cell disease is distinguished by the depletion of mineral elements during crises. Purpose The purpose of this investigation was to identify the mineral composition of ten plants, namely Alchornea cordifolia, Alternanthera bettzickiana, Annona senegalensis, Cyttaranthus congolensis, Dissotis brazzae, Justicia secunda, Harungana madagascariensis, Hura crepitans, Hypoxis angustifolia, and Vigna unguiculata, traditionally utilized by practitioners in the management of sickle cell disease. Methods In this study, the biological material consists of the leaves, bark, and seeds of ten plant species. These plants were collected in Kwilu, and the mineral composition was assessed through fluorescence spectrometric analysis. The detection and quantification of the mineral elements were done by X-ray fluorescence spectrometric method with an XEPOS fluorescence spectrometer. The analysis of the results was carried out through Excel. R Studio and SPSS software packages were used for the statistical analyses. Results The study identified a total of twenty-three mineral elements in each of these plants, including Potassium (K), Phosphorus (P), Calcium (Ca), Sodium (Na), Magnesium (Mg), Sulphur (S), Chlorine (Cl), as well as trace elements like Aluminum (Al), Silicon (Si), Vanadium (V), Chromium (Cr), Manganese (Mn), Iron (Fe), Nickel (Ni), Copper (Cu), Zinc (Zn), Selenium (Se), Bromine (Br), Molybdenum (Mo), Tin (Sn), Iodine (I), Barium (Ba), and Lead (Pb). Notably, Iron, Zinc, Selenium, Copper, Calcium, Magnesium, and Manganese were found to be mineral elements associated with sickle cell disease. Potassium and Calcium exhibited higher concentrations, while Lead, Tin, Bromine, Copper, and Nickel were present in trace amounts. Conclusion The results obtained confirm that these plants contain some mineral elements such as Fe, Zn, Mg, and Se that are useful for sickle-cell patients.

Abstract Algal bioindicators, such as diatoms, often show subdued responses to eutrophication in Arctic lakes because climate‐related changes (e.g., ice cover) tend to be the overriding factors influencing assemblage composition. Here, we examined how sub‐Arctic ponds historically receiving high nutrient inputs from nesting seabirds have responded to recent climate change. We present diatom data obtained from 12 sediment cores in seaduck‐affected ponds located on islands through Hudson Strait, Canada. All study cores show consistently elevated values of sedimentary ẟ15N, an established proxy for tracking marine‐derived nutrients, indicating seabirds have been present on these islands for at least the duration of the sediment records (~100 to 400 years). We document diverse epiphytic diatom assemblages to the base of all sediment cores, which is in marked contrast to seabird‐free Arctic ponds—these oligotrophic sites typically record epilithic diatom flora prior to recent warming. Diatoms are likely responding indirectly to seabird nutrients via habitat as nutrients promote the growth of mosses supporting epiphytic diatom communities. This masks the typical diatom response to increased warming in the Arctic, which also results in habitat changes and the growth of mosses around the pond edges. Changes in sedimentary chlorophyll a were not consistently synchronous with large changes in ẟ15N values, suggesting that primary production in ponds is not responding linearly to changes in seabird‐derived nitrogen. Across all ponds, we recorded shifts in diatom epiphytic assemblages (e.g., increases in % relative abundance of many Nitzschia species) that often align with increases in chlorophyll a. The changes in diatoms and chlorophyll a, although variable, are most likely driven by climate change as they are generally consistent with longer ice‐free conditions and growing seasons. Together, our results show that to effectively use diatoms in animal population reconstructions across the sub‐Arctic and Arctic, a strong understanding of eutrophication and climate change, based on supplementary proxies, is also required.

The lakes around Yellowknife (Northwest Territories, Canada) have been impacted by multiple environmental stressors throughout the 20th and early 21st centuries. Here, we have synthesized diatom assemblage data from ten lake sediment cores from the Yellowknife area and used a landscape-scale paleolimnological approach to investigate the cumulative impacts of past gold mining activities, urbanization, and climate warming on aquatic biota. Our investigations indicated that diatom species turnover (measured using detrended canonical correspondence analysis) was highest at lakes closer to the city and mines, as these sites were more severely impacted by land-use changes (e.g., sewage disposal, run-off from waste disposal sites) and roaster stack emission from the gold mines. Diatom assemblage shifts indicative of climate-induced changes to lake thermal properties were also observed across the gradient of human activities. The inclusion of remote sites was useful to disentangle the effects of climate-mediated changes from impacts related to mining and urbanization. This investigation suggests that the diatom assemblages of the lakes around Yellowknife have changed markedly over the last ∼80 years and there are no signs of biological recovery since the cessation of mining activities around the turn of the 21st century. The biota of the subarctic lakes around Yellowknife are now strongly influenced by climate-mediated changes to lake thermal properties and the urban lakes are also influenced by the legacies of past land-use changes.

This study consists of biogenic synthesis of Ag-MnO nanocomposite whose aqueous extract from Cyttaranthus congolensis was used as a reducer and stabilizer. The characterization of these particles by visible UV spectroscopy made it possible to identify the band linked to the surface plasmon resonance located around 380 nm. X-ray Diffraction and Fluorescence made it possible to determine the presence of particles of formula Ag 0.21 Mn 0.28 O having crystallized in a Monoclinic system (a= 5.8517 , b = 3.4674 , c = 5.4838 and β = 107.663°). A spherical morphology was determined by Scanning Electron Microscopy (SEM). The haemolytic activity carried out on human blood made it possible to conclude that Ag-MnO nanocomposites are not toxic to human blood. Moreover, these particles showed good antibacterial activity against gram-positive and gram-negative strains of bacteria. Promising results on anthelminthic activity of Ag-MnO nanocomposites against several pathogenic helmints were reported in this study. Besides antibacterial and antihelmintic activities, Ag-MnO nanocomposites also exhibited good anti-inflammatory and antioxidant activity.

Parkinson’s disease (PD) has a long, heterogeneous, pre-diagnostic phase, during which pathology insidiously accumulates. Increasing evidence suggests that environmental and lifestyle factors in early life contribute to disease risk and progression. Thanks to the extensive study of this pre-diagnostic phase, the first prevention trials of PD are being designed. However, the highly heterogenous evolution of the disease across the life course is not yet sufficiently taken into account. This could hamper clinical trial success in the advent of biological disease definitions. In an interdisciplinary patient–clinician study group, we discussed how an approach that incorporates the lifetime evolution of PD may benefit the design of disease-modifying trials by impacting population, target and outcome selection. We argue that the timepoint of exposure to risk and protective factors plays a critical role in PD subtypes, influencing population selection. In addition, recent developments in differential disease mechanisms, aided by biological disease definitions, could impact optimal treatment targets. Finally, multimodal biomarker panels using this lifetime approach will likely be most sensitive as progression markers for more personalized trials. We believe that the lifetime evolution of PD should be considered in the design of clinical trials, and that such initiatives could benefit from more patient–clinician partnerships.

Abstract Background Parkinson’s disease (PD) is a neurodegenerative disease, for which no disease-modifying therapies exist. Preclinical and clinical evidence suggest that hypoxia-based therapy might have short- and long-term benefits in PD. We present the contours of the first study to assess the safety, feasibility and physiological and symptomatic impact of hypoxia-based therapy in individuals with PD. Methods/Design In 20 individuals with PD, we will investigate the safety, tolerability and short-term symptomatic efficacy of continuous and intermittent hypoxia using individual, double-blind, randomized placebo-controlled N-of-1 trials. This design allows for dose finding and for including more individualized outcomes, as each individual serves as its own control. A wide range of exploratory outcomes is deployed, including the Movement Disorders Society Unified Parkinson’s Disease Rating scale (MDS-UPDRS) part III, Timed Up & Go Test, Mini Balance Evaluation Systems (MiniBES) test and wrist accelerometry. Also, self-reported impression of overall symptoms, motor and non-motor symptoms and urge to take dopaminergic medication will be assessed on a 10-point Likert scale. As part of a hypothesis-generating part of the study, we also deploy several exploratory outcomes to probe possible underlying mechanisms of action, including cortisol, erythropoietin and platelet-derived growth factor β. Efficacy will be assessed primarily by a Bayesian analysis. Discussion This evaluation of hypoxia therapy could provide insight in novel pathways that may be pursued for PD treatment. This trial also serves as a proof of concept for deploying an N-of-1 design and for including individualized outcomes in PD research, as a basis for personalized treatment approaches. Trial registration ClinicalTrials.gov Identifier: NCT05214287 (registered January 28, 2022).

Background: Respiratory dysfunction is an important contributor to morbidity and mortality in advanced Parkinson's disease (PD), but it is unclear what parameters are sensitive to diagnose and monitor respiratory dysfunction across disease phases. Objectives: We aimed to characterize respiratory dysfunction in mild to moderate PD. Methods: In 20 individuals without cardiopulmonary comorbidity, pulmonary and inspiratory muscle function testing were performed ON‐medication. Subsequently, the acute ventilatory response to hypoxia (HVR) was assessed by gradually decreasing FIO2 from 0.209 (room air) to 0.127, which was compared to eight age‐ and sex‐matched healthy controls under arterial blood gas monitoring. Lastly, on different days, the same 20 individuals with PD underwent six blinded exposures to 45‐min normobaric hypoxia at FiO2 0.163 and 0.127 or placebo OFF‐medication to assess breathing responses. Results: At rest, individuals with greatest PD severity had a lower tidal volume (pairwise comparisons: 0.59 vs. 0.74, P = 0.038–0.050) and tended to have a higher breathing frequency (17.7 vs. 14.4, P = 0.076), despite normal pulmonary function. A 45‐min exposure to hypoxia induced a significantly lower acute HVR in individuals with PD compared to controls (−0.0489 vs. 0.133 L.min/%, P = 0.0038). Acute HVR was reduced regardless of disease severity. Subacute HVR in individuals with milder disease tended to be higher compared to those with more advanced disease (P = 0.079). Conclusions: Respiratory dysfunction is present in individuals with PD, including those with relatively mild disease severity, and is characterized by altered breathing patterns at rest, as well as a lower HVR, despite normal pulmonary and inspiratory muscle function testing. [ABSTRACT FROM AUTHOR]

Sedentary behavior (SB) may affect arterial stiffness, preceding the development of cardiovascular disease. We investigated the association of objectively measured SB with arterial stiffness. We also investigated factors that affected this association. We recruited adult volunteers and measured SB with thigh‐worn accelerometery for 24 hrs/day for eight consecutive days. Central (carotid‐femoral pulse wave velocity, cfPWV, gold standard) and local carotid arterial stiffness (stiffness index Beta and pressure‐strain elasticity EP) were measured with ultrasound. Linear regression was used and adjusted for demographics, cardiometabolic factors, and moderate‐to‐vigorous physical activity (MVPA) volume. Effect modification was studied with interaction terms. Participants (N = 664, 64 (standard deviation: 11, range: 23–89) years, 397 (59.8%) male) demonstrated 9.1 (1.6) hrs/day of SB, and arterial stiffness was 8.6 (3.0) m/s for cfPWV, 6.4 (2.9) for Beta, and 87 (43) kPa for EP. SB was not associated with cfPWV (β = 0.04 95% CI (−0.11, 0.18), p = 0.60). The association of SB with local arterial stiffness was modified by systolic blood pressure (SBP) and MVPA volume. Stratified analyses revealed positive associations of SB with Beta (β = 0.29 (0.05, 0.53), p = 0.016) and EP (β = 4.83 (1.39, 8.27), p = 0.006) in participants with SBP > 134 mmHg or > 103 min/day of MVPA (β = 0.23 (0.03, 0.42), p = 0.024 and β = 3.55 (0.82, 6.29), p = 0.011, respectively). We found no association of objectively measured SB with central arterial stiffness. However, SB was positively associated with local carotid stiffness in participants with higher SBP or MVPA levels. In certain subgroups, SB may affect carotid arterial stiffening, reinforcing the relation between SB and cardiovascular disease. [ABSTRACT FROM AUTHOR]