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2.
Front Neurosci ; 18: 1394478, 2024.
Article in English | MEDLINE | ID: mdl-38903599

ABSTRACT

VPS13A disease and Huntington's disease (HD) are two basal ganglia disorders that may be difficult to distinguish clinically because they have similar symptoms, neuropathological features, and cellular dysfunctions with selective degeneration of the medium spiny neurons of the striatum. However, their etiology is different. VPS13A disease is caused by a mutation in the VPS13A gene leading to a lack of protein in the cells, while HD is due to an expansion of CAG repeat in the huntingtin (Htt) gene, leading to aberrant accumulation of mutant Htt. Considering the similarities of both diseases regarding the selective degeneration of striatal medium spiny neurons, the involvement of VPS13A in the molecular mechanisms of HD pathophysiology cannot be discarded. We analyzed the VPS13A distribution in the striatum, cortex, hippocampus, and cerebellum of a transgenic mouse model of HD. We also quantified the VPS13A levels in the human cortex and putamen nucleus; and compared data on mutant Htt-induced changes in VPS13A expression from differential expression datasets. We found that VPS13A brain distribution or expression was unaltered in most situations with a decrease in the putamen of HD patients and small mRNA changes in the striatum and cerebellum of HD mice. We concluded that the selective susceptibility of the striatum in VPS13A disease and HD may be a consequence of disturbances in different cellular processes with convergent molecular mechanisms already to be elucidated.

3.
J Water Health ; 22(5): 797-810, 2024 May.
Article in English | MEDLINE | ID: mdl-38822460

ABSTRACT

Municipal water supply through truck-to-cistern systems is common in northern Canada. Household satisfaction and concerns about water services likely impact user preferences and practices. This case study explores household perspectives and challenges with regard to domestic access to water in a decentralized truck-to-cistern system. A case study was conducted in the Northern Village of Kangiqsualujjuaq, Nunavik (Quebec, Canada). A paper-based questionnaire was completed by 65 households (one quarter of the population). Many households (37%) reported not drinking tap water from the truck-to-cistern system. Chlorine taste was a frequently reported concern, with those households being significantly less likely to drink water directly from the tap (p = 0.002). Similarly, households that reported a water shortage in the previous week (i.e., no water from the tap at least once) (33%) were more likely to express dissatisfaction with delivered water quantity (rs = 0.395, p = 0.004). Interestingly, 77% of households preferred using alternative drinking water sources for drinking purposes, such as public tap at the water treatment plant, natural sources or bottled water. The study underscores the importance of considering household perspectives to mitigate the risks associated with service disruptions and the use of alternative sources for drinking purposes.


Subject(s)
Drinking Water , Water Supply , Drinking Water/analysis , Humans , Quebec , Family Characteristics , Surveys and Questionnaires , Female , Male , Motor Vehicles , Middle Aged , Adult
4.
J Environ Manage ; 362: 121378, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38838533

ABSTRACT

Source and raw water quality may deteriorate due to rainfall and river flow events that occur in watersheds. The effects on raw water quality are normally detected in drinking water treatment plants (DWTPs) with a time-lag after these events in the watersheds. Early warning systems (EWSs) in DWTPs require models with high accuracy in order to anticipate changes in raw water quality parameters. Ensemble machine learning (EML) techniques have recently been used for water quality modeling to improve accuracy and decrease variance in the outcomes. We used three decision-tree-based EML models (random forest [RF], gradient boosting [GB], and eXtreme Gradient Boosting [XGB]) to predict two critical parameters for DWTPs, raw water Turbidity and UV absorbance (UV254), using rainfall and river flow time series as predictors. When modeling raw water turbidity, the three EML models (rRF-Tu2=0.87, rGB-Tu2=0.80 and rXGB-Tu2=0.81) showed very good performance metrics. For raw water UV254, the three models (rRF-UV2=0.89, rGB-UV2=0.85 and rXGB-UV2=0.88) again showed very good performance metrics. Results from this study suggest that EML approaches could be used in EWSs to anticipate changes in the quality parameters of raw water and enhance decision-making in DWTPs.


Subject(s)
Machine Learning , Water Quality , Water Purification/methods , Models, Theoretical , Rivers
5.
J Environ Manage ; 365: 121505, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38908156

ABSTRACT

Selecting the optimal monitoring points in a water distribution network is challenging due to the complex spatiotemporal variability of water quality degradation. The lack of a standardized methodology for monitoring point selection forces operators to rely on general recommendations, historical data and professional experience, which can mask water quality problems and increase the risk to consumers. This study proposes a new methodology to optimize the selection of monitoring points in distribution networks. The method considers the spatiotemporal degradation of water quality, the definition of representative zones and two selection criteria: global representativeness and potential health risk. Representative zones were determined for each node of the network based on hydraulic paths and their water quality spatial variability. Part of the distribution network in Quebec City, Canada was used as the case study, in which four water quality parameters were investigated: free chlorine residual (FRC), heterotrophic plate counts (HPC), trihalomethanes (THMs) and haloacetic acids (HAAs). Seasonal variabilities (summer and winter) were also analyzed. The results obtained for the two criteria and for both seasons were compared, and methodological and practical recommendations were established for dynamic monitoring programs that respond to the needs of operators.


Subject(s)
Environmental Monitoring , Water Quality , Environmental Monitoring/methods , Quebec , Water Supply , Humans
6.
Can J Microbiol ; 70(7): 262-274, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38700083

ABSTRACT

Cryptosporidium and Giardia are protozoan parasites responsible for gastrointestinal illnesses in humans and in animal species. The main way these parasites are transmitted is by ingestion of their (oo)cysts in drinking water. Monitoring (oo)cysts in water sources is beneficial to evaluate the quality of raw water supplying treatment plants. Currently, the only standardized protocol to enumerate these parasites from water samples is United States Environmental Protection Agency (USEPA) Method 1623.1. With this method, we monitored three major water sources in Quebec over a year to assess temporal and geographical variations of these parasite (oo)cysts. These three water sources have independent watersheds despite being in the same region. We found a general pattern for Giardia, with high concentrations of cysts during cold and transition periods, and significantly lower concentrations during the warm period. Cryptosporidium's concentration was more variable throughout the year. Statistical correlations (Pearson's correlation coefficients) were established between the concentration of each parasite and various environmental parameters. The three study sites each showed unique factors correlating with the presence of both protozoa, supporting the idea that each water source must be seen as a unique entity with its own particular characteristics and therefore, must be monitored independently. Although some environmental parameters could be interesting proxies to the parasitic load, no parameter was strongly correlated throughout the whole sampling year and none of the parameters could be used as a single proxy for all three studies sources.


Subject(s)
Cryptosporidium , Giardia , Cryptosporidium/isolation & purification , Quebec , Giardia/isolation & purification , Environmental Monitoring/methods , Drinking Water/parasitology , Seasons , Water Supply , Humans
7.
J Affect Disord ; 354: 574-588, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38490587

ABSTRACT

BACKGROUND: Chronic stress is an important risk factor for the development of major depressive disorder (MDD). Recent studies have shown microbiome dysbiosis as one of the pathogenic mechanisms associated with MDD. Thus, it is important to find novel non-pharmacological therapeutic strategies that can modulate gut microbiota and brain activity. One such strategy is photobiomodulation (PBM), which involves the non-invasive use of light. OBJECTIVE/HYPOTHESIS: Brain-gut PBM could have a synergistic beneficial effect on the alterations induced by chronic stress. METHODS: We employed the chronic unpredictable mild stress (CUMS) protocol to induce a depressive-like state in mice. Subsequently, we administered brain-gut PBM for 6 min per day over a period of 3 weeks. Following PBM treatment, we examined behavioral, structural, molecular, and cellular alterations induced by CUMS. RESULTS: We observed that the CUMS protocol induces profound behavioral alterations and an increase of sirtuin1 (Sirt1) levels in the hippocampus. We then combined the stress protocol with PBM and found that tissue-combined PBM was able to rescue cognitive alterations induced by CUMS. This rescue was accompanied by a restoration of hippocampal Sirt1 levels, prevention of spine density loss in the CA1 of the hippocampus, and the modulation of the gut microbiome. PBM was also effective in reducing neuroinflammation and modulating the morphology of Iba1-positive microglia. LIMITATIONS: The molecular mechanisms behind the beneficial effects of tissue-combined PBM are not fully understood. CONCLUSIONS: Our results suggest that non-invasive photobiomodulation of both the brain and the gut microbiome could be beneficial in the context of stress-induced MDD.


Subject(s)
Depressive Disorder, Major , Low-Level Light Therapy , Mice , Animals , Depression/psychology , Sirtuin 1/metabolism , Neuroinflammatory Diseases , Brain/metabolism , Hippocampus/metabolism , Cognition , Stress, Psychological/therapy , Stress, Psychological/drug therapy , Disease Models, Animal
8.
Cell Mol Life Sci ; 80(12): 367, 2023 Nov 21.
Article in English | MEDLINE | ID: mdl-37987826

ABSTRACT

BACKGROUND: Huntington's Disease (HD) is a disorder that affects body movements. Altered glutamatergic innervation of the striatum is a major hallmark of the disease. Approximately 30% of those glutamatergic inputs come from thalamic nuclei. Foxp2 is a transcription factor involved in cell differentiation and reported low in patients with HD. However, the role of the Foxp2 in the thalamus in HD remains unexplored. METHODS: We used two different mouse models of HD, the R6/1 and the HdhQ111 mice, to demonstrate a consistent thalamic Foxp2 reduction in the context of HD. We used in vivo electrophysiological recordings, microdialysis in behaving mice and rabies virus-based monosynaptic tracing to study thalamo-striatal and thalamo-cortical synaptic connectivity in R6/1 mice. Micro-structural synaptic plasticity was also evaluated in the striatum and cortex of R6/1 mice. We over-expressed Foxp2 in the thalamus of R6/1 mice or reduced Foxp2 in the thalamus of wild type mice to evaluate its role in sensory and motor skills deficiencies, as well as thalamo-striatal and thalamo-cortical connectivity in such mouse models. RESULTS: Here, we demonstrate in a HD mouse model a clear and early thalamo-striatal aberrant connectivity associated with a reduction of thalamic Foxp2 levels. Recovering thalamic Foxp2 levels in the mouse rescued motor coordination and sensory skills concomitant with an amelioration of neuropathological features and with a repair of the structural and functional connectivity through a restoration of neurotransmitter release. In addition, reduction of thalamic Foxp2 levels in wild type mice induced HD-like phenotypes. CONCLUSIONS: In conclusion, we show that a novel identified thalamic Foxp2 dysregulation alters basal ganglia circuits implicated in the pathophysiology of HD.


Subject(s)
Huntington Disease , Motor Disorders , Humans , Animals , Mice , Thalamus , Corpus Striatum , Movement , Disease Models, Animal , Repressor Proteins , Forkhead Transcription Factors/genetics
9.
Neurobiol Dis ; 187: 106292, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37714309

ABSTRACT

Chorea-acanthocytosis (ChAc) is an inherited neurodegenerative movement disorder caused by VPS13A gene mutations leading to the absence of protein expression. The striatum is the most affected brain region in ChAc patients. However, the study of the VPS13A function in the brain has been poorly addressed. Here we generated a VPS13A knockdown (KD) model and aimed to elucidate the contribution of VPS13A to synaptic plasticity and neuronal communication in the corticostriatal circuit. First, we infected primary cortical neurons with miR30-shRNA against VPS13A and analyzed its effects on neuronal plasticity. VPS13A-KD neurons showed a higher degree of branching than controls, accompanied by decreased BDNF and PSD-95 levels, indicative of synaptic alterations. We then injected AAV-KD bilaterally in the frontal cortex and two different regions of the striatum of mice and analyzed the effects of VPS13A-KD on animal behavior and synaptic plasticity. VPS13A-KD mice showed modification of the locomotor behavior pattern, with increased exploratory behavior and hyperlocomotion. Corticostriatal dysfunction in VPS13A-KD mice was evidenced by impaired striatal long-term depression (LTD) after stimulation of cortical afferents, which was partially recovered by BDNF administration. VPS13A-KD did not lead to neuronal loss in the cortex or the striatum but induced a decrease in the neuronal release of CX3CL1 and triggered a microglial reaction, especially in the striatum. Notably, CX3CL1 administration partially restored the impaired corticostriatal LTD in VPS13A-KD mice. Our results unveil the involvement of VPS13A in neuronal connectivity modifying BDNF and CX3CL1 release. Moreover, the involvement of VPS13A in synaptic plasticity and motor behavior provides key information to further understand not only ChAc pathophysiology but also other neurological disorders.

10.
Front Psychol ; 14: 1172460, 2023.
Article in English | MEDLINE | ID: mdl-37168422

ABSTRACT

The school represents the optimal setting for promoting the physical, emotional, and social health of children, especially during the first years of life. Understanding the pedagogical actions of teachers to address health education is an important first step in promoting healthy behaviors in children. We inhere analyzed the pedagogical action patterns in the preschool teaching of healthy habits from a holistic health perspective. We used photography as a strategy for data collection and applied a Chi-square automatic interaction detection (CHAID) classification tree, a data mining procedure, to generate a pattern model. We found that the school space and the learning playfulness strategies for the development of executive functions, classified according to the exercise, symbolic, assembly, rules (ESAR) model, were the main factors that influence the pedagogical actions fostering healthy habits. By contrast, the school and the pedagogical resources of the classroom are factors with a much smaller impact on working with healthy habits. This pedagogical action pattern is flexible, since teachers conduct a multiplicity of pedagogical actions through different strategies, in different school spaces, at any time. In conclusion, our results unmask the interdependent relationships between the different factors that determine the teacher's actions at the preschool. It also contributes to the understanding of the teacher's practices in fostering healthy habits in a healthy learning environment.

11.
PLoS One ; 18(5): e0285213, 2023.
Article in English | MEDLINE | ID: mdl-37141278

ABSTRACT

Well-being in children with a complex medical condition (CMC) impacts the way they view and communicate with their immediate environment as well as their development, and it is thus necessary to inquire about the contextual issues and different needs that a CMC carries. This pilot study aimed to identify factors of pediatric well-being from the experience of hospitalization and convalescence of youth with CMC and their caregivers, in a cross-sectional analysis using a selective methodology complemented by an indirect observational methodology. We analyzed the quality of life and well-being of youth with CMC using a validated KINDLR questionnaire. We collected 35 surveys: 11 from youth with CMC and 24 from caregivers from Spain. We focused the analysis on sociodemographics, well-being perceptions, and coping strategies variables. The results show that children aged between 3 and 6 years and their caregivers scored physical well-being the lowest out of all dimensions of well-being, and they scored family well-being the highest. Moreover, youth between the ages of 7 and 17 years and their caregivers scored school-related well-being the lowest. Coping strategies to deal with stressful situations differ between children and caregivers. While children mainly engage in social withdrawal, caregivers engage in cognitive restructuring and expressing emotions. However, we did not find a relationship between coping strategies and well-being perceptions. These results highlight the need to facilitate communication spaces with both families and health professionals where the voice of children is considered.


Subject(s)
Convalescence , Quality of Life , Child , Humans , Adolescent , Child, Preschool , Pilot Projects , Cross-Sectional Studies , Caregivers/psychology , Adaptation, Psychological , Hospitalization
12.
Implement Sci Commun ; 4(1): 38, 2023 Apr 06.
Article in English | MEDLINE | ID: mdl-37024984

ABSTRACT

BACKGROUND: Point-of-care medical information systems (POCMIS) can provide an efficient and effective means of strengthening health systems globally through their encouragement of continued medical education. Using the Consolidated Framework for Implementation Research (CFIR) as a guide, this research provides suggestions for improved implementation of POCMIS in low- and middle-income countries informed by an intervention implemented across public and military hospitals in Lima, Peru. METHODS: Analysis is based on qualitative interviews conducted with 12 Peruvian surgeons across eight public hospitals and one military hospital who received an intervention that provided free access to UpToDate and introduced Google Translate. The post-intervention interviews were transcribed, translated, and analyzed for themes overlapping with CFIR constructs to expose barriers to implementation and suggestions for improved implementation of future interventions. RESULTS: Barriers included a lack of seniority buy-in and engaged leadership, an overabundance of personal preferences for multiple POCMIS, and a culture of assumption that inhibited open communication regarding access to and use of POCMIS. Suggestions for improved implementation focused on the adaptation of the intervention. Namely, surgeons discussed regionally-specific adaptations as well as adaptations specific to their surgical specialty including visual, rather than written, representation of the information available via POCMIS. CONCLUSIONS: Results indicate necessary adaptations for implementing interventions including POCMIS in LMICs, mimicking much of the implementation science literature on intervention adaptation. In addition to explicit suggestions provided by surgeons, we also suggest actionable steps to adapt to barriers identified in our data. Rapid assessment procedures (RAP) are one established methodological technique useful for assessing organization culture prior to implementation, allowing for necessary cultural adaptations. Dynamic adaption process (DAP) is another useful and established method that breaks implementation into four phases allowing for adaptations based on the initial assessment of the intervention site.

13.
J Neurosci ; 43(18): 3379-3390, 2023 05 03.
Article in English | MEDLINE | ID: mdl-37001992

ABSTRACT

Early and progressive cortico-striatal circuit alterations have been widely characterized in Huntington's disease (HD) patients. Cortical premotor area, M2 cortex in rodents, is the most affected cortical input to the striatum from early stages in patients and is associated to the motor learning deficits present in HD mice. Yet, M2 cortex sends additional long-range axon collaterals to diverse output brain regions beyond basal ganglia. Here, we aimed to elucidate the contribution of M2 cortex projections to HD pathophysiology in mice. Using fMRI, M2 cortex showed most prominent functional connectivity alterations with the superior colliculus (SC) in symptomatic R6/1 HD male mice. Structural alterations were also detected by tractography, although diffusion weighted imaging measurements suggested preserved SC structure and similar electrophysiological responses were obtained in the SC on optogenetic stimulation of M2 cortical axons. Male and female HD mice showed behavioral alterations linked to SC function, including decreased defensive behavioral responses toward unexpected stimuli, such as a moving robo-beetle, and decreased locomotion on an unexpected flash of light. Additionally, GCamp6f fluorescence recordings with fiber photometry showed that M2 cortex activity was engaged by the presence of a randomly moving robo-bettle, an effect absent in HD male mice. Moreover, acute chemogenetic M2 cortex inhibition in WT mice shift behavioral responses toward an HD phenotype. Collectively, our findings highlight the involvement of M2 cortex activity in visual stimuli-induced behavioral responses, which are deeply altered in the R6/1 HD mouse model.SIGNIFICANCE STATEMENT Understanding brain circuit alterations in brain disorders is critical for developing circuit-based therapeutic interventions. The cortico-striatal circuit is the most prominently disturbed in Huntington's disease (HD); and particularly, M2 cortex has a prominent role. However, the same M2 cortical neurons send additional projections to several brain regions beyond striatum. We characterized new structural and functional circuitry alterations of M2 cortex in HD mouse models and found that M2 cortex projection to the superior colliculus (SC) was deeply impaired. Moreover, we describe differential responses to unexpected sensory stimulus in HD mouse models, which relies on SC function. Our data highlight the involvement of M2 cortex in SC-dependent sensory processing and its alterations in HD pathophysiology.


Subject(s)
Huntington Disease , Mice , Male , Female , Animals , Superior Colliculi , Neurons/physiology , Corpus Striatum , Axons , Disease Models, Animal , Mice, Transgenic
14.
J Environ Manage ; 337: 117734, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-36996548

ABSTRACT

Drinking water may undergo spatiotemporal changes in quality as it leaves the treatment plant and enters the distribution system. This variability means that not all consumers receive water of the same quality. Monitoring water quality in distribution networks makes it possible to verify the compliance of current regulations and reduce consumption risks associated with water quality degradation. An inaccurate interpretation of the spatiotemporal variability of water quality affects the selection of monitoring locations and the sampling frequency, which may conceal problems with the water quality and increase consumers' risk. This paper presents a chronological and critical review of the literature on the evolution, benefits and limitations of methodologies for the optimization of water quality degradation monitoring in water distribution systems supplied by surface sources. This review compares the different methodologies and examines the types of approaches, optimization objectives, variables, and types of spatial and temporal analysis, as well as the main advantages and limitations. A cost-benefit analysis was conducted to assess applicability in different-sized municipalities (small, medium and large). Future research recommendations for optimal water quality monitoring in distribution networks are also provided.


Subject(s)
Drinking Water , Water Quality , Water Supply , Environmental Monitoring/methods , Seasons
15.
J Am Coll Surg ; 236(3): 484-494, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36729680

ABSTRACT

BACKGROUND: Investing in continued medical education strengthens surgical systems. This study assessed the effectiveness of an evidence-based practice (EBP) tutorial and access to UpToDate (UTD) to improve EBP and understand how and why providers practice using evidence. STUDY DESIGN: This is a mixed-methods, implementation study at 9 public hospitals in Peru consisting of a didactic session for surgeons on EBP and Google Translate and support of applications for UTD access. Change in clinical knowledge scores (CKS), access and use of UTD, and impact of language pre-and postintervention were measured. Qualitative interviews uncovered reasons for these changes. RESULTS: Intervention participants had lower CKS at follow-up compared with baseline (odds ratio [OR] of higher score 0.41 [0.18,0.98]; p = 0.044), and this effect was modified (p = 0.003) to the extent that the reverse was true for control participants (OR 2.30 [1.13,4.71]; p = 0.022). Participants with 1 to 20 years of experience had significantly improved CKS compared with students/residents (1 to 10 years: OR 4.5 [1.1,18]; 11 to 20 years: OR 4.9 [1.4,17]); there was no evidence of a different CKS between providers with >20 years of experience compared with students/residents (OR 1.3 [0.5,3.7]). Administrative disconnect, usability, motivation, education, time, resources, and age influenced point-of-care medical information systems impact on knowledge and EBP. Participants reporting low English proficiency translated medical literature mostly used Google Translate. Those with low/no English reading proficiency had higher odds of reporting a negative impact on research than those with working (p = 0.007) or professional (p < 0.001) proficiency. CONCLUSIONS: Providing education on EBP, free UTD access, and translation solutions did not correlate with increased CKS due to complex barriers to using point-of-care medical information systems.


Subject(s)
Point-of-Care Systems , Surgeons , Humans , Evidence-Based Practice , Students , Research Design
16.
J Hazard Mater ; 446: 130633, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36610346

ABSTRACT

Monitoring emerging disinfection byproducts (DBPs) is challenging for many small water distribution networks (SWDNs), and machine learning-based predictive modeling could be an alternative solution. In this study, eleven machine learning techniques, including three multivariate linear regression-based, three regression tree-based, three neural networks-based, and two advanced non-parametric regression techniques, are used to develop models for predicting three emerging DBPs (dichloroacetonitrile, chloropicrin, and trichloropropanone) in SWDNs. Predictors of the models include commonly-measured water quality parameters and two conventional DBP groups. Sampling data of 141 cases were collected from eleven SWDNs in Canada, in which 70 % were randomly selected for model training and the rest were used for validation. The modeling process was reiterated 1000 times for each model. The results show that models developed using advanced regression techniques, including support vector regression and Gaussian process regression, exhibited the best prediction performance. Support vector regression models showed the highest prediction accuracy (R2 =0.94) and stability for predicting dichloroacetonitrile and trichloropropanone, and Gaussian process regression models are optimal for predicting chloropicrin (R2 =0.92). The difference is likely due to the much lower concentrations of chloropicrin than dichloroacetonitrile and trichloropropanone. Advanced non-parametric regression techniques, characterized by a probabilistic nature, were identified as most suitable for developing the predictive models, followed by neural network-based (e.g., generalized regression neural network), regression tree-based (e.g., random forest), and multivariate linear regression-based techniques. This study identifies promising machine learning techniques among many commonly-used alternatives for monitoring emerging DBPs in SWDNs under data constraints.

17.
Brain Behav Immun ; 109: 144-161, 2023 03.
Article in English | MEDLINE | ID: mdl-36702234

ABSTRACT

In the last two decades, microglia have emerged as key contributors to disease progression in many neurological disorders, not only by exerting their classical immunological functions but also as extremely dynamic cells with the ability to modulate synaptic and neural activity. This dynamic behavior, together with their heterogeneous roles and response to diverse perturbations in the brain parenchyma has raised the idea that microglia activation is more diverse than anticipated and that understanding the molecular mechanisms underlying microglial states is essential to unravel their role in health and disease from development to aging. The Ikzf1 (a.k.a. Ikaros) gene plays crucial roles in modulating the function and maturation of circulating monocytes and lymphocytes, but whether it regulates microglial functions and states is unknown. Using genetic tools, here we describe that Ikzf1 is specifically expressed in the adult microglia in brain regions such as cortex and hippocampus. By characterizing the Ikzf1 deficient mice, we observed that these mice displayed spatial learning deficits, impaired hippocampal CA3-CA1 long-term potentiation, and decreased spine density in pyramidal neurons of the CA1, which correlates with an increased expression of synaptic markers within microglia. Additionally, these Ikzf1 deficient microglia exhibited a severe abnormal morphology in the hippocampus, which is accompanied by astrogliosis, an aberrant composition of the inflammasome, and an altered expression of disease-associated microglia molecules. Interestingly, the lack of Ikzf1 induced changes on histone 3 acetylation and methylation levels in the hippocampus. Since the lack of Ikzf1 in mice appears to induce the internalization of synaptic markers within microglia, and severe gliosis we then analyzed hippocampal Ikzf1 levels in several models of neurological disorders. Ikzf1 levels were increased in the hippocampus of these neurological models, as well as in postmortem hippocampal samples from Alzheimer's disease patients. Finally, over-expressing Ikzf1 in cultured microglia made these cells hyporeactive upon treatment with lipopolysaccharide, and less phagocytic compared to control microglia. Altogether, these results suggest that altered Ikzf1 levels in the adult hippocampus are sufficient to induce synaptic plasticity and memory deficits via altering microglial state and function.


Subject(s)
Hippocampus , Microglia , Mice , Animals , Microglia/metabolism , Hippocampus/metabolism , Neuronal Plasticity/physiology , Long-Term Potentiation/physiology , Inflammation/metabolism
18.
Sci Total Environ ; 866: 161085, 2023 Mar 25.
Article in English | MEDLINE | ID: mdl-36586684

ABSTRACT

Heavy rainfall events can lead to the runoff of large amounts of dissolved and particulate matter into surface water sources that may represents challenges for drinking water treatment, such as membrane fouling, increases in chemical demands, and formation of various disinfection by products (DBPs) after disinfection, such as trihalomethanes (THM) and haloacetic acids (HAA). In this study, a framework is defined for analyzing water quality data in relation to climatic variables (rainfalls). The effects of 22 different rain events were assessed on an organic matter proxy (UV absorbance), and on different key water quality parameters for the coagulation step in a drinking water treatment plant. Extended impacts of rewetting events after long term dry period on source water quality were identified, with significant increases in raw water UV 254 nm that last almost 3 weeks. A significant effect on filtered water quality was also noticed and the potential impacts on finished waters quality was confirmed by HAA modelling results. Future studies could focus on the monitoring and modelling of other regulated DBPs such as THM as well as simulations of different scenarios of climate change to estimate the variability of DBPs and its precursors such as organic matter.

19.
Int J Hyg Environ Health ; 247: 114060, 2023 01.
Article in English | MEDLINE | ID: mdl-36413873

ABSTRACT

INTRODUCTION: More than 50 million people living in the Arctic nations remain without access to safely managed drinking water services. Remote northern communities, where large numbers of Indigenous peoples live, are disproportionally affected. Recent research has documented water and health-related problems among Indigenous communities, including poor water quality and insufficient quantities of water. OBJECTIVE: The objective of this scoping review is to examine the extent of available water security evidence as well as identify research gaps and intervention priorities to improve access to domestic water in the Arctic and Subarctic regions of the eight Arctic nations (Canada, the Kingdom of Denmark (Greenland), Finland, Iceland, Norway, Sweden, Russia, and the United States (Alaska)). METHODS: An extensive literature review was conducted to retrieve relevant documentation. Arctic & Antarctic Regions, Compendex, Geobase, Georef, MEDLINE and Web of Science databases were searched to identify records for inclusion. The initial searches yielded a total of 1356 records. Two independent reviewers systematically screened identified records using selection criteria. Descriptive analyses were used to summarize evidence of included studies. RESULTS: A total of 55 studies, mostly conducted in Canada and the United States, were included and classified by four predetermined major dimensions: 1) Water accessibility and availability; 2) Water quality assessment; 3) Water supply and health; 4) Preferences and risk perceptions. CONCLUSIONS: This scoping review used a global approach to provide researchers and stakeholders with a summary of the evidence available regarding water security and domestic access in the Arctic. Culturally appropriate health-based interventions are necessary to ensure inclusive water services and achieve the Sustainable Development Goals (SDG) targets for universal access to water.


Subject(s)
Water Quality , Water Supply , Humans , Alaska , Antarctic Regions , Canada
20.
J Environ Manage ; 325(Pt B): 116537, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36334449

ABSTRACT

Due to rapid population growth, urbanization, water contamination, and climate change, global water resources are under increasing pressure. Water utilities apply drinking water management strategies (DWMS) to ensure that water is safe for drinking. However, in recent years, due to increased inclination towards climate change, environmental emissions, and sustainable development goals; the environmental and economic performance of DWMSs is getting attention. An integrated framework combining life cycle thinking and water quality assessment techniques was developed in this study to evaluate the DWMSs' performance in terms of water quality, environment, and economics. Six DWMSs were assessed using the integrated framework as a case study. The environmental impacts in terms of human health, ecosystem, and resource use ranged from 1.46E-06 to 4.01E-06 DALY, 9.35E-10 to 3.80E-09 species.yr, and 0.0025-0.0071 USD-$, respectively. Pollution water index (PWI) and cost-benefit analysis (CBA) were used as decision-making techniques to assess the overall performance and suitability of DWMSs under given settings. The DWMSs with surface water as a source or ones providing relatively more degree of treatment have a relatively high PWI score (i.e., ≈0.31), reflective of high environmental impacts and water pollution compared to other alternatives. The CBA scores of selected alternatives ranged between 0.22 and 1.0. Furthermore, it was identified that DWMSs applied on relatively bigger water distribution systems can outweigh their costs (i.e., environmental and economic impacts). The proposed framework and approaches are flexible as they can incorporate different criteria in evaluating the performance and applicability of DWMSs.


Subject(s)
Drinking Water , Ecosystem , Humans , Environment , Water Resources , Water Supply
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