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OBJECTIVES: To identify indications for exchange transfusions, assess the use and waste of exchange transfusion products (ie, reconstituted whole blood exchange transfusions), and determine nationwide distribution and prevalence of these transfuions in the Netherlands. STUDY DESIGN: All nine neonatal intensive care units (NICU) and 15 non-NICU hospitals participated in this retrospective, observational, cohort study. We retrieved data on indications for and use of all exchange transfusion products ordered by participating centers over an 11-year period. RESULTS: A total of 574 patients for whom 1,265 products were ordered were included for analyses. Severe ABO (32.6%) and non-ABO (25.2%) immune hemolysis and subsequent hyperbilirubinemia were the most frequent indications. Rare indications were severe leukocytosis in Bordetella pertussis (2.1%) and severe anemia (1.5%). Approximately half of all ordered products remained unused. In 278 of 574 neonates (48.4%), one or more products were not used, of which 229 (82.7%) were due to the resolving of severe hyperbilirubinemia with further intensification of phototherapy. The overall prevalence of neonates who received an exchange transfusion was 14.6:100,000 liveborn neonates. CONCLUSION: A considerable proportion of products remained unused, and annually a limited number of patients are treated with an exchange transfusion in the Netherlands, highlighting the rarity of the procedure in the Netherlands.
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Anal squamous cell carcinoma (ASCC) incidence is increasing globally. International consensus guidelines published in 2024 include HPV and/or cytology testing of anal swabs in those at greatest risk of ASCC. Self-collected anal swabs may be important for increasing screening uptake, but evidence is needed as to their equivalence to clinician-collected swabs. We searched Medline, Embase, Cochrane Library, and CINAHL databases for publications to 13 June 2023. Studies were included if reporting data on HPV testing, cytology testing, or acceptability, for both self- and clinician-collected anal swabs. Risk of bias was assessed using the QUADAS-2 assessment tool. The primary outcome was HPV and cytology sampling adequacy. Secondary outcomes were HPV and cytology results, and acceptability of collection methods. Thirteen papers describing 10 studies were eligible. Sample adequacy was comparable between self- and clinician-collected swabs for HPV testing (meta-adequacy ratio: 1.01 [95% CI 0.97-1.05]) but slightly lower for cytology by self-collection (meta-adequacy ratio: 0.91 [95% CI 0.88-0.95]). There was no significant difference in prevalence (meta-prevalence ratio: 0.83 (95% CI 0.65-1.07) for any HR-HPV, 0.98 (95% CI 0.84-1.14) for any HPV, and 0.68 (95% CI 0.33-1.37) for HPV16), or any cytological abnormality (meta-prevalence ratio 1.01 [95% CI 0.86-1.18]). Only three papers reported acceptability results. Findings indicate self-collection gives equivalent sample adequacy for HPV testing and ~ 10% inferior adequacy for cytological testing. Meta-prevalence was similar for HPV and cytology, but confidence intervals were wide. Larger studies are required to definitively assess use of self-collected swabs in anal cancer screening programs, including acceptability.
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Double-blind, placebo-controlled, randomized controlled trials are the gold standard for clinical trials in nutrition science. For trials of whole diets, dietary counseling are advantageous as they offer clinical translatability although can vary in the fidelity of the intended intervention from participant to participant and across studies. Feeding trials, in which most or all food is provided, offer high precision and can provide proof-of-concept evidence that a dietary intervention is efficacious and can also better evaluate the effect of known quantities of foods and nutrients on physiology. However, they come with additional methodological complexities. Feeding trials also call for a variety of unique methodological considerations, not least of which relate to the design and delivery of diets to participants. This review aims to provide a comprehensive summary of recommendations for design and conduct of feeding trials, encompassing domiciled and non-domiciled feeding trials. Several pertinent aspects of trial design and methodology are discussed, including defining the study population to maximize retention, safety and generalisability of findings, recommendations for design of control interventions and optimising blinding, and specific considerations for clinical populations. A detailed stepwise process for menu design, development, validation and delivery are also presented. These recommendations aim to facilitate methodologic consistency and execution of high quality feeding trials, ultimately facilitating improved understanding of the role of diet in treating disease and the underpinning mechanisms.
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Background: To report on the implementation and outcomes of a virtual ward established for the management of mpox during the 2022 outbreak, we conducted a 2-center, observational, cross-sectional study over a 3-month period. Methods: All patients aged ≥17 years with laboratory polymerase chain reaction-confirmed monkeypox virus managed between 14 May and 15 August 2022, at the Hospital for Tropical Diseases at University College London Hospitals National Health Service (NHS) Foundation Trust and sexual health services at Central North and West London NHS Foundation Trust, were included. Main outcomes included the proportion of patients managed exclusively on the virtual ward, proportion of patients requiring inpatient admission, proportion of patients with human immunodeficiency virus, and duration of lesion reepithelialization. Results: Among confirmed cases (N = 221), 86% (191/221) were managed exclusively on the virtual ward, while 14% (30/221) required admission. Treatment for concomitant sexually transmitted infections was provided to 25% (55/221) of patients, antibiotics for other infective complications to 16% (35/221), and symptomatic relief to 27% (60/221). The median time from onset to complete lesion reepithelialization and de-isolation was 18 days (range, 8-56 days). Eleven percent (24/221) of individuals disengaged from services within 4 days of testing. Conclusions: The virtual ward model facilitated safe and holistic outpatient management of mpox, while minimizing admissions. This approach could serve as a model for future outbreak responses.
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The retinal pigment epithelium (RPE) is an essential component of the retina that plays multiple roles required to support visual function. These include light onset- and circadian rhythm-dependent tasks, such as daily phagocytosis of photoreceptor outer segments. Mitochondria provide energy to the highly specialized and energy-dependent RPE. In this study, we examined the positioning of mitochondria and how this is influenced by the onset of light. We identified a population of mitochondria that are tethered to the basal plasma membrane pre- and post-light onset. Following light onset, mitochondria redistributed apically and interacted with melanosomes and phagosomes. In a choroideremia mouse model that has regions of the RPE with disrupted or lost infolding of the plasma membrane, the positionings of only the non-tethered mitochondria were affected. This provides evidence that the tethering of mitochondria to the plasma membrane plays an important role that is maintained under these disease conditions. Our work shows that there are subpopulations of RPE mitochondria based on their positioning after light onset. It is likely they play distinct roles in the RPE that are needed to fulfil the changing cellular demands throughout the day.
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Membrana Celular , Luz , Mitocôndrias , Epitélio Pigmentado da Retina , Epitélio Pigmentado da Retina/metabolismo , Animais , Mitocôndrias/metabolismo , Camundongos , Membrana Celular/metabolismo , Camundongos Endogâmicos C57BL , Melanossomas/metabolismo , Ritmo Circadiano/fisiologia , Fagossomos/metabolismoRESUMO
OBJECTIVE: Genetic and environmental factors influence pathogenesis and rising incidence of paediatric inflammatory bowel disease (PIBD). The aim was to meta-analyse evidence of diet and environmental factors in PIBD. METHODS: A systematic search was conducted to identify diet and environmental factors with comparable risk outcome measures and had been reported in two or more PIBD studies for inclusion in meta-analyses. Those with ≥2 PIBD risk estimates were combined to provide pooled risk estimates. RESULTS: Of 4763 studies identified, 36 studies were included. PIBD was associated with higher risk with exposure to ≥/=4 antibiotic courses (includes prescriptions/purchases/courses), passive smoking, not being breastfed, sugary drink intake, being a non-Caucasian child living in a high-income country and infection history (odds ratio [OR] range: 2-3.8). Paediatric Crohn's disease (CD) was associated with higher risk with exposure to antibiotics during early childhood, ≥/=4 antibiotic courses, high socioeconomic status (SES), maternal smoking, history of atopic conditions and infection history (OR range: 1.6-4.4). A history of infection was also associated with higher risk of paediatric ulcerative colitis (UC) (OR: 3.73). Having a higher number of siblings (≥2) was associated with lower risk of paediatric CD (OR: 0.6) and paediatric UC (OR: 0.7). Pet exposure was associated with lower risk of paediatric UC (OR: 0.5). CONCLUSION: Several factors associated with PIBD risk were identified that could potentially be used to develop a disease screening tool. Future research is needed to address risk reduction in PIBD.
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BACKGROUND: A sleeve gastrectomy (SG) is a lifelong treatment that improves health and better outcomes are associated with follow-up. However, there is lack of access or high attrition to aftercare. This potentially contributes to sub-optimal dietary intake and a lack of evidence for nutrition interventions. The present study assessed the feasibility and preliminary efficacy of a nutrition intervention to improve diet quality in Australian adults living with a SG. METHODS: Adults (n = 96) post-SG were recruited into a cross-sectional diet quality study, with 68 eligible for randomisation to an intervention or wait-list control group. Over 10 weeks, a Facebook group was used to post daily nutrition education. Feasibility outcomes included participant recruitment, engagement, retention and acceptability. Preliminary efficacy was assessed using change in Australian Recommended Food Score (ARFS). Linear mixed models were used to measure differences in mean outcome between the experimental groups over time. RESULTS: Sixty-eight participants (97% female) aged 48.2 ± 9.8 years, body mass index 33.1 ± 5.8 kg/m2, and mean ± SD ARFS 39 ± 9 points were randomised to the intervention, with 66% retention at 10 weeks. At follow-up, diet quality increased for the intervention group (mean ARFS, 95% confidence interval = 0.2 [-1.5 to 1.9]) and decreased for the control group (mean ARFS, 95% confidence interval= -2.0 [-5.2 to 1.2]) with no between group difference (p = 0.2). Participants (n = 30) rated the intervention positively. CONCLUSIONS: Recruiting and retaining adults post-SG into a nutrition intervention is feasible. Low-cost recruitment attracted strong interest from women to identify greater support to know what to eat following SG. A future fully powered trial to assess intervention efficacy is warranted.
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Gene expression is regulated by changes in chromatin architecture intrinsic to cellular differentiation and as an active response to environmental stimuli. Chromatin dynamics are a major driver of phenotypic diversity, regulation of development, and manifestation of disease. Remarkably, we know little about the evolutionary dynamics of chromatin reorganisation through time, data essential to characterise the impact of environmental stress during the ongoing biodiversity extinction crisis (20th-21st century). Linking the disparate fields of chromatin biology and museum science through their common use of the preservative formaldehyde (a constituent of formalin), we have generated historical chromatin profiles in museum specimens up to 117 years old. Historical chromatin profiles are reproducible, tissue-specific, sex-specific, and environmental condition-dependent in vertebrate specimens. Additionally, we show that over-fixation modulates differential chromatin accessibility to enable semi-quantitative estimates of relative gene expression in vertebrates and a yeast model. Our approach transforms formalin-fixed biological collections into an accurate, comprehensive, and global record of environmental impact on gene expression and phenotype.
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Cromatina , Formaldeído , Fixação de Tecidos , Animais , Cromatina/metabolismo , Cromatina/genética , Fixação de Tecidos/métodos , Feminino , Masculino , Vertebrados/genética , Fixadores/química , MuseusRESUMO
INTRODUCTION: The transition to secondary school involves significant changes in children's social and physical environment, which are often accompanied by changes in dietary habits. However, evidence around how dietary habits change during this life-stage transition is variable. OBJECTIVE: This review aimed to identify, critically appraise, and summarise the wide-ranging evidence on changes in dietary habits across the primary-secondary school transition. METHODS: Four electronic databases (PubMed, Embase, Web of Science, and Scopus) were searched for relevant studies published in English or Spanish from inception to February 2024. Longitudinal studies with a baseline quantitative assessment of dietary habits when children were in their last year or two of primary/elementary school with at least one follow-up assessment of dietary habits when children were in their first or second year of secondary/middle/junior-high school were eligible for inclusion. RESULTS: Seven studies (10 independent samples) were eligible for inclusion, and fourteen different dietary habits outcomes were reported across the seven studies. The frequency of consuming breakfast, fruit, vegetables, and milk decreased across the primary-secondary school transition. Inconsistent results were found regarding changes in the frequency of consumption of sugar-sweetened beverages, fruit juice, snacks, and fast-foods. Many dietary habits were only evaluated in single studies. CONCLUSIONS: There is moderate evidence for a decrease in the frequency of consumption of breakfast, fruit, vegetables, and milk in children across the transition from primary to secondary school. This highlights this timeframe as a valuable period for intervention to promote the continuation of positive dietary habits. More high-quality longitudinal studies using homogeneous methodologies to evaluate changes in dietary habits across the school transition are needed to fully understand the implications of this transition on children's diet and health behaviours.
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Mutations in the epidermal growth factor receptor (EGFR) are common in non-small cell lung cancer (NSCLC), particularly in never-smoker patients. However, these mutations are not always carcinogenic, and have recently been reported in histologically normal lung tissue from patients with and without lung cancer. To investigate the outcome of EGFR mutation in healthy lung stem cells, we grow murine alveolar type II organoids monoclonally in a three-dimensional Matrigel. Our experiments show that the EGFR-L858R mutation induces a change in organoid structure: mutated organoids display more 'budding', in comparison with non-mutant controls, which are nearly spherical. We perform on-lattice computational simulations, which suggest that this can be explained by the concentration of division among a small number of cells on the surface of the mutated organoids. We are currently unable to distinguish the cell-based mechanisms that lead to this spatial heterogeneity in growth, but suggest a number of future experiments which could be used to do so. We suggest that the likelihood of L858R-fuelled tumorigenesis is affected by whether the mutation arises in a spatial environment that allows the development of these surface protrusions. These data may have implications for cancer prevention strategies and for understanding NSCLC progression.
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Recently, there has been an increasing emphasis on single cell profiling for high-throughput screening workflows in drug discovery and life sciences research. However, the biology underpinning these screens is often complex and is insufficiently addressed by singleplex assay screens. Traditional single cell screening technologies have created powerful sets of 'omic data that allow users to bioinformatically infer biological function, but have as of yet not empowered direct functional analysis at the level of each individual cell. Consequently, screening campaigns often require multiple secondary screens leading to laborious, time-consuming and expensive workflows in which attrition points may not be queried until late in the process. We describe a platform that harnesses droplet microfluidics and optical electrowetting-on-dielectric (oEWOD) to perform highly-controlled sequential and multiplexed single cell assays in massively parallelised workflows to enable complex cell profiling during screening. Soluble reagents or objects, such as cells or assay beads, are encapsulated into droplets of media in fluorous oil and are actively filtered based on size and optical features ensuring only desirable droplets (e.g. single cell droplets) are retained for analysis, thereby overcoming the Poisson probability distribution. Droplets are stored in an array on a temperature-controlled chip and the history of individual droplets is logged from the point of filter until completion of the workflow. On chip, droplets are subject to an automated and flexible suite of operations including the merging of sample droplets and the fluorescent acquisition of assay readouts to enable complex sequential assay workflows. To demonstrate the broad utility of the platform, we present examples of single-cell functional workflows for various applications such as antibody discovery, infectious disease, and cell and gene therapy.
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Eletroumectação , Análise de Célula Única , Análise de Célula Única/instrumentação , Eletroumectação/instrumentação , Humanos , Técnicas Analíticas Microfluídicas/instrumentação , Dispositivos Lab-On-A-Chip , Desenho de Equipamento , AutomaçãoRESUMO
Understanding fate and transport processes for per- and poly-fluoroalkyl substances (PFAS) is critical for managing impacted sites. "PFAS Salting Out" in groundwater, defined herein, is an understudied process where PFAS in fresh groundwater mixes with saline groundwater near marine shorelines, which increases sorption of PFAS to aquifer solids. While sorption reduces PFAS mass discharge to marine surface water, the fraction that sorbs to beach sediments may be mobilized under future salinity changes. The objective of this study was to conceptually explore the potential for PFAS Salting Out in sandy beach environments and to perform a preliminary broad-scale characterization of sandy shoreline areas in the continental U.S. While no site-specific PFAS data were collected, our conceptual approach involved developing a multivariate regression model that assessed how tidal amplitude and freshwater submarine groundwater discharge affect the mixing of fresh and saline groundwater in sandy coastal aquifers. We then applied this model to 143 U.S. shoreline areas with sandy beaches (21% of total beaches in the USA), indirectly mapping potential salinity increases in shallow freshwater PFAS plumes as low (<10 ppt), medium (10-20 ppt), or high (>20 ppt) along groundwater flow paths before reaching the ocean. Higher potential salinity increases were observed in West Coast bays and the North Atlantic coastline, due to the combination of moderate to large tides and large fresh groundwater discharge rates, while lower increases occurred along the Gulf of Mexico and the southern Florida Atlantic coast. The salinity increases were used to estimate potential perfluorooctane sulfonic acid (PFOS) sorption in groundwater due to salting out processes. Low-category shorelines may see a 1- to 2.5-fold increase in sorption of PFOS, medium-category a 2.0- to 6.4-fold increase, and high-category a 3.8- to 25-fold increase in PFOS sorption. The analysis presented provides a first critical step in developing a large-scale approach to classify the PFAS Salting Out potential along shorelines and the limitations of the approach adopted highlights important areas for further research.
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Environmental carcinogens increase cancer incidence via both mutagenic and non-mutagenic mechanisms. There are over 500 known or suspected carcinogens classified by the International Agency for Research on Cancer. Sequencing of both cancerous and histologically non-cancerous tissue has been instrumental in improving our understanding of how environmental carcinogens cause cancer. Understanding how and defining which environmental or lifestyle exposures drive cancer will support cancer prevention. Recent research is revisiting the mechanisms of early tumorigenesis, paving the way for an era of molecular cancer prevention. Significance: Recent data have improved our understanding of how carcinogens cause cancer, which may reveal novel opportunities for molecular cancer prevention.
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Neoplasias , Humanos , Neoplasias/genética , Neoplasias/prevenção & controle , Carcinógenos/toxicidade , AnimaisRESUMO
The Myddosome is a key innate immune signalling platform. It forms at the cell surface and contains MyD88 and IRAK proteins which ultimately coordinate the production of pro-inflammatory cytokines. Toll-like receptor 4 (TLR4) signals via the Myddosome when triggered by lipopolysaccharide (LPS) or amyloid-beta (Aß) aggregates but the magnitude and time duration of the response are very different for reasons that are unclear. Here, we followed the formation of Myddosomes in live macrophages using local delivery of TLR4 agonist to the cell surface and visualisation with 3D rapid light sheet imaging. This was complemented by super-resolution imaging of Myddosomes in fixed macrophages to determine the size of the signalling complex at different times after triggering. Myddosomes formed more rapidly after LPS than in response to sonicated Aß 1-42 fibrils (80 vs 372 s). The mean lifetimes of the Myddosomes were also shorter when triggered by LPS compared to sonicated Aß fibrils (170 and 220 s), respectively. In both cases, a range of Myddosome of different sizes (50-500 nm) were formed. In particular, small round Myddosomes around 100 nm in size formed at early time points, then reduced in proportion over time. Collectively, our data suggest that compared to LPS the multivalency of Aß fibrils leads to the formation of larger Myddosomes which form more slowly and, due to their size, take longer to disassemble. This explains why sonicated Aß fibrils results in less efficient triggering of TLR4 signalling and may be a general property of protein aggregates.
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Peptídeos beta-Amiloides , Lipopolissacarídeos , Fator 88 de Diferenciação Mieloide , Receptor 4 Toll-Like , Receptor 4 Toll-Like/metabolismo , Peptídeos beta-Amiloides/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Animais , Camundongos , Cinética , Macrófagos/metabolismo , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Transdução de SinaisRESUMO
Contaminated drinking water from widespread environmental pollutants such as perfluoroalkyl and polyfluoroalkyl substances (PFAS) poses a rising threat to public health. PFAS monitoring in groundwater is limited and fails to consider pesticides found to contain PFAS as a potential contamination source. Given previous findings on the disproportionate exposure of communities of Color to both pesticides and PFAS, we investigated disparities in PFAS-contaminated pesticide applications in California based on community-level sociodemographic characteristics. We utilized statewide pesticide application data from the California Department of Pesticide Regulation and recently reported concentrations of PFAS chemicals detected in eight pesticide products to calculate the areal density of PFAS applied within 1 km of individual community water systems' (CWSs) supply wells. Spatial regression analyses suggest that statewide, CWSs that serve a greater proportion of Latinx and non-Latinx People of Color residents experience a greater areal density of PFAS applied and greater likelihood of PFAS application near their public supply wells. These results highlight agroecosystems as potentially important sources of PFAS in drinking water and identify areas that may be at risk of PFAS contamination and warrant additional PFAS monitoring and remediation.
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BACKGROUND: To investigate relationships among different physical health problems in a large, sociodemographically diverse sample of 9-to-10-year-old children and determine the extent to which perinatal health factors are associated with childhood physical health problems. METHODS: A cross-sectional study was conducted utilizing the Adolescent Brain Cognitive Developmentâ (ABCD) Study (n = 7613, ages 9-to-10-years-old) to determine the associations among multiple physical health factors (e.g., prenatal complications, current physical health problems). Logistic regression models controlling for age, sex, pubertal development, household income, caregiver education, race, and ethnicity evaluated relationships between perinatal factors and childhood physical health problems. RESULTS: There were significant associations between perinatal and current physical health measures. Specifically, those who had experienced perinatal complications were more likely to have medical problems by 9-to-10 years old. Importantly, sleep disturbance co-occurred with several physical health problems across domains and developmental periods. CONCLUSION: Several perinatal health factors were associated with childhood health outcomes, highlighting the importance of understanding and potentially improving physical health in youth. Understanding the clustering of physical health problems in youth is essential to better identify which physical health problems may share underlying mechanisms. IMPACT: Using a multivariable approach, we investigated the associations between various perinatal and current health problems amongst youth. Our study highlights current health problems, such as sleep problems at 9-to-10 years old, that are associated with a cluster of factors occurring across development (e.g., low birth weight, prenatal substance exposure, pregnancy complications, current weight status, lifetime head injury). Perinatal health problems are at large, non-modifiable (in this retrospective context), however, by identifying which are associated with current health problems, we can identify potential targets for intervention and prevention efforts.
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BACKGROUND: People with intellectual disability have diverse needs and experience higher rates of diet-related chronic disease such as type 2 diabetes compared to people without disability. However, they are infrequently included in development and implementation of interventions to address diet-related chronic disease. The present study describes the process to plan, develop and refine the Food and Lifestyle Information Program (FLIP) culinary nutrition intervention for adults with mild-to-moderate intellectual disability. METHODS: The project was initiated by a disability service provider and was guided by the Cook-Ed™ model and inclusive research principles. Initially the disability service provider and academic research team members co-designed pre-program consultation and pilot studies, and draft program resources. Pre-program consultation explored paid disability support worker (n = 10) perceptions of cooking and food skills, nutrition priorities and optimal program format, which guided further program drafting. Program resources and pilot study design were further developed and refined with co-researchers with lived experience of intellectual disability who attended a pre-pilot and then pilot study sessions as remunerated co-facilitators. RESULTS: Key characteristics of the FLIP intervention arising from pre-program consultation included providing cooking task instruction in small steps, enabling participant choice in program activities, promoting an inclusive and social atmosphere, and providing paper-based resources. CONCLUSIONS: FLIP intervention co-design was enabled through ongoing input from the disability service provider and people with lived experience of intellectual disability. Evaluation of FLIP feasibility, acceptability and preliminary effectiveness to improve diet-related health is underway.
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Culinária , Deficiência Intelectual , Humanos , Adulto , Projetos Piloto , Culinária/métodos , Feminino , Masculino , Estilo de Vida , Desenvolvimento de Programas , Dieta/métodos , Pessoa de Meia-Idade , Dieta Saudável/métodosRESUMO
Phosphorus (P) that accumulates in agricultural riparian zones can be released under certain hydrological and biogeochemical conditions, thereby limiting the effectiveness of these zones in reducing P loads from field to stream. The study objective was to explore factors that may be contributing to, or limiting, high soluble reactive phosphorus (SRP) concentrations in the shallow aquifer of an alluvial upland riparian zone located in a continental climate. Field investigations including porewater sampling from six vertical nests, soil sampling, and continuous soil moisture, groundwater table, and redox measurements were conducted over 19 months. Porewater SRP concentrations were generally low in the aquifer considering all sampling times (median = 14.7 µg/L; interquartile range [IQR] = 11.1 µg/L, 287 samples). The overall low SRP may be due to low reducible labile soil P (median = 21.1 µgP/g dw, IQR = 10.9 µgP/g dw, 21 samples). However, high SRP concentrations (>52 µg/L, 95% quartile) did occur intermittently in space and time with no clear spatial or temporal patterns. Analyses indicate that most high concentrations were likely not associated with factors previously reported to influence SRP release in riparian aquifers, including redox conditions, pH, and soil drying and wetting. Further, data indicate that internally released or externally supplied SRP may undergo rapid (re-) sequestration within the aquifer, limiting its vertical or horizontal transport. The study findings highlight the complexity of P behavior in riparian zones and the need for caution when assessing the effectiveness of conservation practices and in interpreting potential impacts of subsurface water quality on stream water quality when monitoring locations are distant from the stream.
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Monitoramento Ambiental , Água Subterrânea , Fósforo , Poluentes Químicos da Água , Fósforo/análise , Água Subterrânea/química , Água Subterrânea/análise , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Hidrologia , Solo/química , Rios/químicaRESUMO
CONTEXT: Diet quality indices (DQIs) assess the level of adherence to dietary recommendations and a specified dietary pattern in populations; however, there is limited evidence regarding the construct criteria and validation methodology of DQIs used in pregnant women. OBJECTIVES: The objectives of this study were to (i) identify and describe characteristics of DQIs that have been validated for use in pregnant women in high-income countries, and (ii) evaluate criteria used to develop DQIs and validation methodologies employed. DATA SOURCES: CINAHL, Embase, Medline, SCOPUS, and Web of Science were systematically searched for eligible articles published between 1980 and November 2022 that focused on DQIs validated for use in pregnant women from high-income countries. DATA EXTRACTION: Characteristics, development criteria, and validation methodologies used in the included articles were extracted by one reviewer and checked by a second reviewer. DATA ANALYSIS: A narrative synthesis and descriptive statistics were used to summarize the review findings. Reporting was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. RESULTS: Six articles with 5 validated DQIs were identified. In total, 3777 participants were included - five articles had pregnant women aged 31-50 years and in their second trimester. Food frequency questionnaires were used as the dietary assessment method in all studies, and 3 DQIs were used to assess dietary intake at 1 time point, using 2 different dietary assessment methods. No indices fulfilled preferred features for the DQI development criteria developed by Burggraf et al (2018). Construct validity was assessed by all DQIs, followed by criterion validity (n = 4) and test-retest reliability (n = 2). CONCLUSION: Limited high-quality validated DQIs for use in pregnant women in high-income countries were identified. Scoring for DQI components were not specific to nutrient requirements for pregnant women. Findings from this review may inform the development of DQIs that evaluate specific dietary requirements and specific food safety considerations applicable to pregnancy. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/u2hrq.
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N-(Benzothiazole-2-yl)pyrrolamide DNA gyrase inhibitors with benzyl or phenethyl substituents attached to position 3 of the benzothiazole ring or to the carboxamide nitrogen atom were prepared and studied for their inhibition of Escherichia coli DNA gyrase by supercoiling assay. Compared to inhibitors bearing the substituents at position 4 of the benzothiazole ring, the inhibition was attenuated by moving the substituent to position 3 and further to the carboxamide nitrogen atom. A co-crystal structure of (Z)-3-benzyl-2-((4,5-dibromo-1H-pyrrole-2-carbonyl)imino)-2,3-dihydrobenzo[d]-thiazole-6-carboxylic acid (I) in complex with E. coli GyrB24 (ATPase subdomain) was solved, revealing the binding mode of this type of inhibitor to the ATP-binding pocket of the E. coli GyrB subunit. The key binding interactions were identified and their contribution to binding was rationalised by quantum theory of atoms in molecules (QTAIM) analysis. Our study shows that the benzyl or phenethyl substituents bound to the benzothiazole core interact with the lipophilic floor of the active site, which consists mainly of residues Gly101, Gly102, Lys103 and Ser108. Compounds with substituents at position 3 of the benzothiazole core were up to two orders of magnitude more effective than compounds with substituents at the carboxamide nitrogen. In addition, the 6-oxalylamino compounds were more potent inhibitors of E. coli DNA gyrase than the corresponding 6-acetamido analogues.