Traumatic brain injury (TBI) is the leading cause of death and disability in young adults in the developed world. The accuracy of early outcome-prediction remains poor even when all known prognostic ...factors are considered, suggesting important currently unidentified variables. In addition, whilst survival and neurological outcomes have improved markedly with the utilisation of therapies that optimise physiology, no treatments specifically modulate the underlying pathophysiology. The immunological response to TBI represents both a potential contributor to outcome heterogeneity and a therapeutically tractable component of the acute disease process. Furthermore, chronic inflammation has been linked with neurodegeneration, and may mark a bridge between acute brain injury and the subsequent neurodegenerative process seen in a proportion of patients following TBI. Given the complexity of the immune response and its varying functions ranging from repair of injury to bystander damage of healthy tissue, attempts at immunomodulatory intervention must necessarily be highly targeted towards the maladaptive facets of the inflammatory process. In this review we aim to provide an integrated description of the immunological processes triggered by TBI in both humans and animal models, in particular considering the interplay between the innate immune system, danger-associated molecular patterns and loss of self-tolerance leading to adaptive autoimmunity.
•Significant unexplained heterogeneity in outcome after TBI suggests important undiscovered factors.•Activation of both the innate and adaptive immune systems are seen following TBI.•Persistent immune activation can be seen years after injury.•Attempts at immunomodulation must be precisely targeted to avoid compromising beneficial effects.
Diet quality is significantly impacted by social and environmental factors. People experiencing socio-economic disadvantage face inequitable barriers to accessing nutritious foods and health ...services, resulting in significant health disparities. This study aimed to explore the barriers faced by organisations that provide food support to people experiencing disadvantage as well as to identify potential strategies to enhance this support for improved well-being of clients.
Semi-structured interviews using an exploratory approach and inductive thematic analysis.
Australia.
Individuals from organisations involved in the provision of food support for people experiencing disadvantage aged ≥16 years.
Two major themes were identified from thirteen interviews. 'Dignity and respect for clients' serves as a guiding principle for food-related services across all organisations, while 'food' was a point of connection and a potential gateway to additional support pathways. Five additional subthemes included 'food as a platform to reduce social isolation, foster connection and promote participation', challenges with 'servicing clients with diverse experiences and needs', 'dependence on staff and volunteers with varying knowledge and skillsets', ensuring 'adequate access to services, resources and facilities' and 'necessity of community collaboration'.
This study highlights the unique position of organisations involved in food support to identify client-specific needs and implement broader holistic health support. Future interventions should prioritise dignity, respect and social connection in design. Organisations require an adequately trained, sustainable workforce, with shared or enhanced services, resources and facilities, and greater community coordination with other services to maximise effectiveness.
Neurological update: COVID-19 Ren, A. L.; Digby, R. J.; Needham, E. J.
Journal of neurology,
11/2021, Letnik:
268, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Coronavirus Disease 2019 is predominantly a disorder of the respiratory system, but neurological complications have been recognised since early in the pandemic. The major pathophysiological processes ...leading to neurological damage in COVID-19 are cerebrovascular disease, immunologically mediated neurological disorders and the detrimental effects of critical illness on the nervous system. It is still unclear whether direct invasion of the nervous system by the Severe Acute Respiratory Syndrome Coronavirus 2 occurs; given the vast numbers of people infected at this point, this uncertainty suggests that nervous system infection is unlikely to represent a significant issue if it occurs at all. In this review, we explore what has been learnt about the neurological complications of COVID-19 over the course of the pandemic, and by which mechanisms these complications most commonly occur.
Carbohydrates, proteins and lipids are essential nutrients to all animals; however, closely related species, populations, and individuals can display dramatic variation in diet. Here we explore the ...variation in macronutrient tolerance in Drosophila melanogaster using the Drosophila genetic reference panel, a collection of ~200 strains derived from a single natural population. Our study demonstrates that D. melanogaster, often considered a "dietary generalist", displays marked genetic variation in survival on different diets, notably on high-sugar diet. Our genetic analysis and functional validation identify several regulators of macronutrient tolerance, including CG10960/GLUT8, Pkn and Eip75B. We also demonstrate a role for the JNK pathway in sugar tolerance and de novo lipogenesis. Finally, we report a role for tailless, a conserved orphan nuclear hormone receptor, in regulating sugar metabolism via insulin-like peptide secretion and sugar-responsive CCHamide-2 expression. Our study provides support for the use of nutrigenomics in the development of personalized nutrition.
The inflammatory response to acute brain injuries is a key contributor to subsequent outcome. The study of local central nervous system inflammatory responses is hindered by raised intracranial ...pressure precluding cerebrospinal fluid sampling by lumbar puncture. External ventricular drains are sited in some acute brain injury patients to divert cerebrospinal fluid and thus reduce intracranial pressure, and represent a potential route to safely gather large volumes of cerebrospinal fluid for immunological studies. In this manuscript we show that mononuclear cells can be isolated from cerebrospinal fluid collected from external ventricular drains, and that the large volumes of cerebrospinal fluid available yield sufficient mononuclear cells to allow cryopreservation. Prolonged storage of cerebrospinal fluid in the external ventricular drain collection bag can alter the phenotype of cells recovered, but the predicted effect of this can be estimated for a given flow cytometry panel by assessing the changes in peripheral blood mononuclear cells exposed to the same conditions. The described method will allow clinical studies of acute brain injuries to investigate the immunological processes occurring within the central nervous system compartment, rather than relying on changes in the peripheral circulation.
2,3,7,8-Tetrachlorodibenzo-
p-dioxin (TCDD or dioxin), is commonly considered the most toxic man-made substance. We have previously shown that high serum concentrations of TCDD in parents from ...Seveso, Italy, were linked to their having a relative increase in the number of female births after the parents exposure to a release of dioxin in 1976. We have continued the study to determine whether the parents' sex and/or age at exposure affected the sex ratio of their children.
We measured the TCDD concentrations in serum samples from potentially exposed parents collected in 1976 and 1977, and investigated the sex ratio of their offspring.
Serum samples were collected from 239 men and 296 women. 346 girls and 328 boys were born to potentially exposed parents between 1977 and 1996, showing an increased probability of female births (lower sex ratio) with increasing TCDD concentrations in the serum samples from the fathers (p=0·008). This effect starts at concentrations less than 20 ng per kg bodyweight. Fathers exposed when they were younger than 19 years of age sired significantly more girls than boys (sex ratio 0·38 95% Cl 0·30–0·47).
Exposure of men to TCDD is linked to a lowered male/female sex ratio in their offspring, which may persist for years after exposure. The median concentration of dioxin in fathers in this study is similar to doses that induce epididymal impairments in rats and is about 20 times the estimated average concentration of TCDD currently found in human beings in industrialised countries. These observations could have important public-health implications.
We report population-based concentrations, stratified by age, sex, and racial/ethnic groups, of dialkyl phosphate (DAP) metabolites of multiple organophosphorus pesticides. We measured ...dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP), and diethyldithiophosphate (DEDTP) concentrations in 1,949 urine samples collected in U.S. residents 6-59 years of age during 1999 and 2000 as a part of the ongoing National Health and Nutrition Examination Survey (NHANES). We detected each DAP metabolite in more than 50% of the samples, with DEP being detected most frequently (71%) at a limit of detection of 0.2 μg/L. The geometric means for the metabolites detected in more than 60% of the samples were 1.85 μg/L for DMTP and 1.04 μg/L for DEP. The 95th percentiles for each metabolite were DMP, 13 μg/L; DMTP, 46 μg/L; DMDTP, 19 μg/L; DETP, 2.2 μg/L; and DEDTP, 0.87 μg/L. We determined the molar sums of the dimethyl-containing and diethyl-containing metabolites; their geometric mean concentrations were 49.4 and 10.5 nmol/L, respectively, and their 95th percentiles were 583 and 108 nmol/L, respectively. These data are also presented as creatinine-adjusted concentrations. Multivariate analyses showed concentrations of DAPs in children 6-11 years of age that were consistently significantly higher than in adults and often higher than in adolescents. Although the concentrations between sexes and among racial/ethnic groups varied, no significant differences were observed. These data will be important in evaluating the impact of organophosphorus pesticide exposure in the U.S. population and the effectiveness of regulatory actions.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Degradation of aquatic ecosystems from nutrient pollution is a global issue, and quantifying nutrient removal in coastal ecosystems is a topic of interest for coastal managers worldwide. Analysing ...relationships between natural nitrogen removal processes, such as denitrification, and environmental variables from an ecological (rather than biogeochemical) perspective may help to identify and predict biogeochemically important habitat patches (hot spots). However, in situ measurements of denitrification that are coupled with ecosystem variables are rare. In this study, we analysed a dataset encompassing 18 estuaries, broad environmental gradients, and two methods of measuring denitrification (denitrification enzyme activity (DEA) and in situ N
2
flux quantification) to better understand natural estuarine nitrogen removal processes and to rationalise methods. Generally poor relationships between denitrification measures and environmental variables suggest strong context dependency, with different activation or limiting reactants affecting denitrification rates differentially in space and time. This research illustrates how biogeochemically important habitat patches may develop and demonstrates that single-method studies have the potential to miss hot spots or hot moments of nitrogen removal. A two-method approach that integrates both long-term (DEA) and short-term (in situ N
2
flux) conditions is more likely to lead to the identification of biogeochemically important habitat patches. A better understanding of natural nitrogen removal processes in estuaries will clarify assimilative capacity questions and feed into eutrophication mitigation management efforts in these highly valued freshwater–coastal interface areas.
Most of the variation in outcome following severe traumatic brain injury (TBI) remains unexplained by currently recognized prognostic factors. Neuroinflammation may account for some of this ...difference. We hypothesized that TBI generated variable autoantibody responses between individuals that would contribute to outcome. We developed a custom protein microarray to detect autoantibodies to both CNS and systemic Ags in serum from the acute-phase (the first 7 d), late (6-12 mo), and long-term (6-13 y) intervals after TBI in human patients. We identified two distinct patterns of immune response to TBI. The first was a broad response to the majority of Ags tested, predominantly IgM mediated in the acute phase, then IgG dominant at late and long-term time points. The second was responses to specific Ags, most frequently myelin-associated glycopeptide (MAG), which persisted for several months post-TBI but then subsequently resolved. Exploratory analyses suggested that patients with a greater acute IgM response experienced worse outcomes than predicted from current known risk factors, suggesting a direct or indirect role in worsening outcome. Furthermore, late persistence of anti-MAG IgM autoantibodies correlated with raised serum neurofilament light concentrations at these time points, suggesting an association with ongoing neurodegeneration over the first year postinjury. Our results show that autoantibody production occurs in some individuals following TBI, can persist for many years, and is associated with worse patient outcome. The complexity of responses means that conventional approaches based on measuring responses to single antigenic targets may be misleading.
We describe a sensitive and specific method for measuring cotinine in serum by HPLC coupled to an atmospheric pressure chemical ionization tandem mass spectrometer. This method can analyze 100 ...samples/day on a routine basis, and its limit of detection of 50 ng/L makes it applicable to the analysis of samples from nonsmokers potentially exposed to environmental tobacco smoke. Analytical accuracy has been demonstrated from the analysis of NIST cotinine standards and from comparative analyses by both the current method and gas chromatography/high-resolution mass spectrometry. Precision has been examined through the repetitive analysis of a series of bench and blind QC materials. This method has been applied to the analysis of cotinine in serum samples collected as part of the Third National Health and Nutrition Examination Survey (NHANES III).
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