A new hazard assessment workflow to assess soil contamination from large and artisanal scale gold mining.

Gold mining activities are undertaken both at large and artisanal scale, often resulting in serious 'collateral' environmental issues, including environmental pollution and hazard to human and ecosystem health. Furthermore, some of these activities are poorly regulated, which can produce long-lasting damage to the environment and local livelihoods. The aim of this study was to identify a new workflow model to discriminate anthropogenic versus geogenic enrichment in soils of gold mining regions. The Kedougou region (Senegal, West Africa) was used as a case study. Ninety-four soil samples (76 topsoils and 18 bottom soils) were collected over an area of 6,742 km2 and analysed for 53 chemical elements. Robust spatial mapping, compositional and geostatistical models were employed to evaluate sources and elemental footprint associated with geology and mining activities. Multivariate approaches highlighted anomalies in arsenic (As) and mercury (Hg) distribution in several areas. However, further interpretation with enrichment factor (EFs) and index of geoaccumulation (IGeo) emphasised high contamination levels in areas approximately coinciding with the ones where artisanal and small scale mining (ASGM) activities occur, and robust compositional contamination index (RCCI) isolated potentially harmful elements (PHE) contamination levels in very specific areas of the Kedougou mining region. The study underlined the importance of complementary approaches to identify anomalies and, more significantly, contamination by hazardous material. In particular, the analyses helped to identify discrete areas that would require to be surveyed in more detail to allow a comprehensive and thorough risk assessment, to investigate potential impacts to both human and ecosystem health.

Peri-Operative Risk Factors Associated with Post-Operative Cognitive Dysfunction (POCD): An Umbrella Review of Meta-Analyses of Observational Studies.

This umbrella review aimed to systematically identify the peri-operative risk factors associated with post-operative cognitive dysfunction (POCD) using meta-analyses of observational studies. To date, no review has synthesised nor assessed the strength of the available evidence examining risk factors for POCD. Database searches from journal inception to December 2022 consisted of systematic reviews with meta-analyses that included observational studies examining pre-, intra- and post-operative risk factors for POCD. A total of 330 papers were initially screened. Eleven meta-analyses were included in this umbrella review, which consisted of 73 risk factors in a total population of 67,622 participants. Most pertained to pre-operative risk factors (74%) that were predominantly examined using prospective designs and in cardiac-related surgeries (71%). Overall, 31 of the 73 factors (42%) were associated with a higher risk of POCD. However, there was no convincing (class I) or highly suggestive (class II) evidence for associations between risk factors and POCD, and suggestive evidence (class III) was limited to two risk factors (pre-operative age and pre-operative diabetes). Given that the overall strength of the evidence is limited, further large-scale studies that examine risk factors across various surgery types are recommended.

Intravenous tranexamic acid and thromboembolic events in hip fracture surgery: A systematic review and meta-analysis.

BACKGROUND: Osteoporotic hip fractures are a major health problem in developed countries. Surgical management is the mainstay of treatment for these injuries, and historically presents an increased risk of thromboembolism, blood loss and blood transfusion. Despite the demonstrated safety of tranexamic acid (TXA) in elective hip arthroplasty, there is uncertainty regarding the risk of thromboembolism with the administration of TXA during hip fracture surgery. This study aims to address the following questions regarding patients undergoing traumatic hip fracture surgery: 1. Does intravenous TXA increase the risk of thromboembolic events? 2. Does intravenous TXA reduce peri-operative blood loss? 3. Does intravenous TXA increase the risk of non-thromboembolic complications or post-operative mortality? METHODS: A literature search of Ovid MEDLINE, Embase, PubMed, the Cochrane Register of Controlled Trials and CINAHL was conducted, assessing results from database inception until the 11th May, 2021. We included randomised controlled trials that investigated perioperative administration of intravenous TXA in patients undergoing hip fracture surgery, compared to a control cohort. We excluded articles published in a language other than English, evaluated elective hip arthroplasty, or did not report thromboembolic events. Included trials were analysed using RevMan v5.3. RESULTS: Sixteen articles encompassing 1491 patients met inclusion criteria. The risk difference of thromboembolic events in the TXA group was 0.02 (95%C.I. -0.01-0.04; p=0.17). TXA reduced post-operative transfusion rates by 42% (range: 28-54%, p<0.0001). The mean haemoglobin was higher in the TXA group on post-operative day one (0.77g/dL, p<0.0001), day two (0.56g/dL, p<0.0001) and day three (0.42g/dL, p<0.0001). There was no statistically significant difference in non-thromboembolic complications or post-operative mortality across the two cohorts. DISCUSSION: There is no conclusive evidence from the current published literature that peri-operative intravenous TXA administration increases the risk of thromboembolic events after hip fracture surgery. This meta-analysis reinforces that TXA is effective in reducing post-operative transfusions and haemoglobin decline after hip fracture surgery. This study found that TXA did not increase non-thromboembolic complications or post-operative mortality. Further large-scale studies evaluating thromboembolic complications as a primary outcome are required to definitively establish the safety of TXA in hip fracture surgery. LEVEL OF EVIDENCE: I; meta-analysis of randomised controlled trials.

Circumventing glass vial and diluent effects on solution stability of small molecule analytes during analytical method development and validation.

Solution stability of analytes plays an important part in qualitative analysis, especially in conducting accurate, quantitative analyses. Sample diluents and glass vials as sample containers for HPLC analyses can play a critical role and should be evaluated during chromatographic method development. We have encountered several instances during pharmaceutical development where the glass vial/diluent combination has negatively impacted method performance. One case encompasses adsorption of piperazine, a secondary amine, to non-silanized glass vials, resulting in recovery failures during analytical method transfer. Two further cases describe the propensity for peracetylated C-aryl glucosides being subject chemical transformations relating to sample diluent. The first reports transesterification with methanol-based diluents and the second describes hydrolysis with acetonitrile/water diluents mediated by the mild alkalinity of certain brands of Type I borosilicate vials. A final case explores development of a related substance method, it was found that an impurity was prone to hydrolysis and another impurity with a primary amine tended to be adsorbed on glass vials. Diluents of appropriate pH and buffer strength were strategically selected to neutralize the mild alkalinity of the glass vials as well as to mitigate adsorption of the amine analyte on glass vials. As a result, excellent sample stability and reproducibility were achieved, regardless the quality and brand of Type I glass vials used. Here we present four case studies that demonstrate how the negative impact of Type I glass vials on those susceptible analytes can be effectively eliminated by using appropriate sample diluents, which is essential to ensure accurate analytical data and provide for a smooth method validation and transfer.

Evaluating spatio-temporal soil erosion dynamics in the Winam Gulf catchment, Kenya for enhanced decision making in the land-lake interface.

Soil erosion accelerated by poor agricultural practices, land degradation, deprived infrastructure development and other anthropogenic activities has important implications for nutrient cycling, land and lake productivity, loss of livelihoods and ecosystem services, as well as socioeconomic disruption. Enhanced knowledge of dynamic factors influencing soil erosion is critical for policymakers engaged in land use decision-making. This study presents the first spatio-temporal assessment of soil erosion risk modelling in the Winam Gulf, Kenya using the Revised Universal Soil Loss Equation (RUSLE) within a geospatial framework at a monthly resolution between January 2017 and June 2020. Dynamic rainfall erosivity and land cover management factors were derived from existing datasets to determine their effect on average monthly soil loss by water erosion. By assessing soil erosion rates with enhanced temporal resolution, it is possible to provide greater knowledge regarding months that are particularly susceptible to soil erosion and can better inform future strategies for targeted mitigation measures. Whilst the pseudo monthly average soil loss was calculated (0.80 t ha-1 month-1), the application of this value would lead to misrepresentation of monthly soil loss throughout the year. Our results indicate that the highest erosion rates occur between February and April (average 0.95 t ha-1 month-1). In contrast, between May and August, there is a significantly reduced risk (average 0.72 t ha-1 month-1) due to the low rainfall erosivity and increased vegetation cover as a result of the long rainy season. The mean annual gross soil loss by water erosion in the Winam Gulf catchment amounts to 10.71 Mt year-1, with a mean soil loss rate of 9.63 t ha-1 year-1. These findings highlight the need to consider dynamic factors within the RUSLE model and can prove vital for identifying areas of high erosion risk for future targeted investigation and conservation action.

Assessment of bioaccessibility and health risk of mercury within soil of artisanal gold mine sites, Niger, North-central part of Nigeria.

The occurrence of mercury (Hg) in the environment globally has been linked largely to its use for gold processing. In this research, ore samples, agricultural soil and mine wastes were taken within the vicinity of an artisanal gold mine and processing sites in Niger state, a north-central part of Nigeria to determine Hg contamination in the environment and estimate the potential hazard to health. The values of Hg measured in ore, agricultural soil and mine wastes ranged between 0.03 and 5.9, 0.002 and 5.57 and 0.19 and 20.99 mg/kg, respectively, with the majority of samples observed above the crustal average values of 0.003 mg/kg. All of the samples were 100 times greater than the USEPA residential soil screening level of 0.0023 mg/kg, but were lower than comparable mine sites within the same region. Contamination indices were used to demonstrate the potential exposure to Hg contamination in the study area which ranged from a medium to high level of contamination. Average daily dose and hazard quotient (HQ) were calculated for adults and children in the study area and decreased in the following order: ADDvapour > ADDingestion > ADDdermal > ADDinhalation. The non-carcinogenic health risk index (HI) of Hg calculated for children and adults in the study area was children: 7.42, 2.19, 1.49 and adults: 4.45, 1.26, 1.19, for mine wastes, agricultural soil and ore, respectively. All of these values were higher than a considered safe level (= 1) and therefore showed that Hg posed a serious non-carcinogenic HI for both adults and children exposed to the soil in the study area. The bioaccessible fraction as a measure of ingestion for Hg was generally < 13% across all sample matrices, suggesting a low bioaccessibility. An HQ incorporating bioaccessible data (BHQ) ranged between 0.000005 and 4.06 with a mean value of 0.62. Values for the BHQ were still > 1, threshold limit in some samples and showed that Hg could present a risk to health via ingestion, although further research is required to assess dermal and inhalation bioaccessibility to assess fully the risk to residents. However, the values were lower than the non-carcinogenic health risk index, which is assumed to be overestimated.

Human urinary biomonitoring in Western Kenya for micronutrients and potentially harmful elements.

Spot urinary elemental concentrations are presented for 357 adults from Western Kenya collected between 2016 and 2019 as part of a wider environmental geochemical survey. The aim of this study was to establish population level urinary elemental concentrations in Western Kenya for micronutrients and potentially harmful elements for inference of health status against established thresholds. For elements where thresholds inferring health status were not established in the literature using urine as a non-invasive matrix, this study generated reference values with a 95% confidence interval (RV95s) to contextualise urinary elemental data for this population group. Data are presented with outliers removed based upon creatinine measurements leaving 322 individuals, for sub-categories (e.g. age, gender) and by county public health administrative area. For Western Kenya, reference values with a 95% confidence interval (RV95s) were calculated as follows (µg/L): 717 (I), 89 (Se), 1753 (Zn), 336 (Mo), 24 (Cu), 15.6 (Ni), 22.1 (As), 0.34 (Cd), 0.47 (Sn), 0.46 (Sb), 7.0 (Cs), 13.4 (Ba and 1.9 (Pb). Urinary concentrations at the 25th/75th percentiles were as follows (µg/L): 149/368 (I), 15/42 (Se), 281/845 (Zn), 30/128 (Mo), 6/13 (Cu), 1.7/6.1 (Ni), 2.0/8.2 (As). 0.1/0.3 (Cd), 0.05/0.22 (Sn), 0.04/0.18 (Sb), 1.2/3.6 (Cs), 0.8/4.0 (Ba) and 0.2/0.9 (Pb). Urinary concentrations at a population level inferred excess intake of micronutrients I, Se, Zn and Mo in 38, 6, 57 and 14% of individuals, respectively, versus a bioequivalent (BE) upper threshold limit, whilst rates of deficiency were relatively low at 15, 15, 9 and 18%, respectively. Each of the administrative counties showed a broadly similar range of urinary elemental concentrations, with some exceptions for counties bordering Lake Victoria where food consumption habits may differ significantly to other counties e.g. I, Se, Zn. Corrections for urinary dilution using creatinine, specific gravity and osmolality provided a general reduction in RV95s for I, Mo, Se, As and Sn compared to uncorrected data, with consistency between the three correction methods.

A chemometric model for the quantitative determination of isotopic impurities in d3-methylamine hydrochloride by Fourier-transform infrared spectroscopy.

Deuterated drug molecules are of increasing interest to the pharmaceutical industry due to their capacity to slow metabolism and the potential for improved pharmacokinetics or improved pharmacodynamics they may offer over their non-deuterated counterparts. The desired level of deuteration or isotopic purity is a critical quality attribute for these compounds that can be essential for drug efficacy or patient safety. Deuterated reagents are often used to introduce a deuterated moiety into the drug substance; as such, isotopic impurities in these deuterated input materials need to be tightly controlled. A novel Fourier-transform infrared (FTIR) spectroscopic method was developed and evaluated as a fast and straightforward technique to quantify low-level isotopic impurities in the deuterated reagent d3-methylamine hydrochloride. Using data acquired through LC-MS analysis, the resulting chemometric model was validated according to ICH Q2(R1) guidelines achieving limits of quantitation of 0.31, 0.31, and 0.34 wt% for d0-, d1- and d2-methylamine hydrochloride impurities respectively.

Cystatin M/E Variant Causes Autosomal Dominant Keratosis Follicularis Spinulosa Decalvans by Dysregulating Cathepsins L and V.

Keratosis follicularis spinulosa decalvans (KFSD) is a rare cornification disorder with an X-linked recessive inheritance in most cases. Pathogenic variants causing X-linked KFSD have been described in MBTPS2, the gene for a membrane-bound zinc metalloprotease that is involved in the cleavage of sterol regulatory element binding proteins important for the control of transcription. Few families have been identified with an autosomal dominant inheritance of KFSD. We present two members of an Austrian family with a phenotype of KFSD, a mother and her son. The disease was not observed in her parents, pointing to a dominant inheritance with a de novo mutation in the index patient. Using whole-exome sequencing, we identified a heterozygous missense variant in CST6 in DNA samples from the index patient and her affected son. In line with family history, the variant was not present in samples from her parents. CST6 codes for cystatin M/E, a cysteine protease inhibitor. Patient keratinocytes showed increased expression of cathepsin genes CTSL and CTSV and reduced expression of transglutaminase genes TGM1 and TGM3. A relative gain of active, cleaved transglutaminases was found in patient keratinocytes compared to control cells. The variant found in CST6 is expected to affect protein targeting and results in marked disruption of the balance between cystatin M/E activity and its target proteases and eventually transglutaminases 1 and 3. This disturbance leads to an impairment of terminal epidermal differentiation and proper hair shaft formation seen in KFSD.

Investigating the origin and authenticity of Victoria Cross medals using X-ray fluorescence spectrometry.

The Victoria Cross is the United Kingdom's premier military award for bravery, presented for gallantry during active operations. Since its inception in 1856 just 1358 have been awarded, and, due to their rarity and historic interest, have become highly prized amongst private and public collections. Unresolved, however, is a debate about the source material of the medals. Some authorities adhere to a traditional belief that all medals have been cast from the bronze of guns captured from the Russians at Sebastopol. Furthermore, controversy is attached to the authenticity of some VCs. In this study we used X-ray fluorescence spectrometry data to compare the metal compositions of 100 Victoria Crosses, covering 7% of those ever issued. Using Gaussian mixture modelling we identify that Victoria Crosses fall into four distinct clusters, confirming that the primary split occurred between medals issued prior to and after 1914. Using these data we investigate the potential of X-ray fluorescence to inform the study of medals whose authenticity have been queried, showing some have unusually similar compositions to other VCs. This paper highlights how X-ray fluorescence data in conjunction with clustering approaches can be used to effectively and non-destructively investigate the authenticity and history of Victoria Crosses.

Heavy metals in urban road dusts from Kolkata and Bengaluru, India: implications for human health.

Air pollution and dust pollution are major urban environmental issues, with road dust being a potential source and a pathway for human exposure. The developing megacities of India, where the population may spend a significant portion of their working lives close to the roadside, including consuming street food, have obvious source-pathway-receptor linkages. The aim of this study in Kolkata and Bengaluru, India, was to evaluate the risk to human health from inorganic components of road dust. Samples were collected and analysed from a cross section of urban environments for a wide range of anthropogenic and geogenic elements, some such as antimony showing an increase in response to vehicle activity. Calculated enrichment factors relative to crustal abundance demonstrated significant enrichment in common heavy metals and less commonly reported elements, e.g. molybdenum, antimony, that may be used as contaminant markers. Factor analysis gave multielement signatures associated with geography, vehicle traffic and local industry. The bio-accessibility of road dusts in terms of ingestion was determined using the BARGE method with more than 50% of zinc and lead being available in some cases. A formal human health risk assessment using the US EPA framework showed that lead in Kolkata and chromium in Bengaluru were the elements of most concern amongst chromium, nickel, copper, zinc and lead. However, the only risk combination (hazard index) shown to be significant was lead exposure to children in Kolkata. Ingestion dominated the risk pathways, being significantly greater than dermal and inhalation routes.

Method development for rapid quantification of Rn-222 in surface water and groundwater.

Understanding the risks of a developing unconventional hydrocarbons industry, including shale gas, to the chemical quality of surface water and groundwater involves firstly establishing baseline compositions against which any future changes can be assessed. Contaminants of geogenic origin are of particular interest and radon has been identified as one potential contaminant from shale sources. Robust measurement and monitoring of radon in water at environmental concentrations is essential for ensuring protection of water sources and maintaining public confidence. Traditional techniques for Rn-222 determination in water, such as inference by gamma spectrometry and direct alpha counting, are impractical for direct field measurement, and the relatively short half-life of Rn-222 (~ 3.82 days) means that longer analytical protocols from field to the laboratory may result in greater uncertainty for Rn-222 activity. Therefore, a rapid and low-cost method would be beneficial. We have developed and refined a laboratory procedure for Rn-222 monitoring using liquid scintillation counting (LSC). The accuracy of Rn-222 activities obtained via this procedure was evaluated by the analysis of almost 200 water samples collected from streams and boreholes as part of a detailed baseline investigation in the Vale of Pickering, Yorkshire, one potential location for future shale gas exploration. LSC was preferred for measurement of Rn-222 and had comparable accuracy to gamma spectrometry and direct alpha counting. The methodology provided a rapid, portable and low-maintenance option relative to the two established techniques and is shown to be a favourable choice for the measurement of radon in surface water and groundwater at environmental concentrations.

Iodine status in western Kenya: a community-based cross-sectional survey of urinary and drinking water iodine concentrations.

Spot urinary iodine concentrations (UIC) are presented for 248 individuals from western Kenya with paired drinking water collected between 2016 and 2018. The median UIC was 271 µg L-1, ranging from 9 to 3146 µg L-1, unadjusted for hydration status/dilution. From these data, 12% were potentially iodine deficient (< 100 µg L-1), whilst 44% were considered to have an excess iodine intake (> 300 µg L-1). The application of hydration status/urinary dilution correction methods was evaluated for UICs, using creatinine, osmolality and specific gravity. The use of specific gravity correction for spot urine samples to account for hydration status/urinary dilution presents a practical approach for studies with limited budgets, rather than relying on unadjusted UICs, 24 h sampling, use of significantly large sample size in a cross-sectional study and other reported measures to smooth out the urinary dilution effect. Urinary corrections did influence boundary assessment for deficiency-sufficiency-excess for this group of participants, ranging from 31 to 44% having excess iodine intake, albeit for a study of this size. However, comparison of the correction methods did highlight that 22% of the variation in UICs was due to urinary dilution, highlighting the need for such correction, although creatinine performed poorly, yet specific gravity as a low-cost method was comparable to osmolality corrections as the often stated 'gold standard' metric for urinary concentration. Paired drinking water samples contained a median iodine concentration of 3.2 µg L-1 (0.2-304.1 µg L-1). A weak correlation was observed between UIC and water-I concentrations (R = 0.11).

Source apportionment of micronutrients in the diets of Kilimanjaro,Tanzania and Counties of Western Kenya.

Soil, water and food supply composition data have been combined to primarily estimate micronutrient intakes and subsequent risk of deficiencies in each of the regions studied by generating new data to supplement and update existing food balance sheets. These data capture environmental influences, such as soil chemistry and the drinking water sources to provide spatially resolved crop and drinking water composition data, where combined information is currently limited, to better inform intervention strategies to target micronutrient deficiencies. Approximately 1500 crop samples were analysed, representing 86 food items across 50 sites in Tanzania in 2013 and >230 sites in Western Kenya between 2014 and 2018. Samples were analysed by ICP-MS for 58 elements, with this paper focussing on calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), selenium (Se), iodine (I), zinc (Zn) and molybdenum (Mo). In general, micronutrient supply from food groups was higher from Kilimanjaro,Tanzania than Counties in Western Kenya, albeit from a smaller sample. For both countries leafy vegetable and vegetable food groups consistently contained higher median micronutrient concentrations compared to other plant based food groups. Overall, calculated deficiency rates were <1% for Cu and Mo and close to or >90% for Ca, Zn and I in both countries. For Mg, a slightly lower risk of deficiency was calculated for Tanzania at 0 to 1% across simplified soil classifications and for female/males, compared to 3 to 20% for Kenya. A significant difference was observed for Se, where a 3 to 28% risk of deficiency was calculated for Tanzania compared to 93 to 100% in Kenya. Overall, 11 soil predictor variables, including pH and organic matter accounted for a small proportion of the variance in the elemental concentration of food. Tanzanian drinking water presented several opportunities for delivering greater than 10% of the estimated average requirement (EAR) for micronutrients. For example, 1 to 56% of the EAR for I and up to 10% for Se or 37% for Zn could be contributed via drinking water.

Distinctive phytohormonal and metabolic profiles of Arabidopsis thaliana and Eutrema salsugineum under similar soil drying.

MAIN CONCLUSIONS: Arabidopsis and Eutrema show similar stomatal sensitivity to drying soil. In Arabidopsis, larger metabolic adjustments than in Eutrema occurred, with considerable differences in the phytohormonal responses of the two species. Although plants respond to soil drying via a series of concurrent physiological and molecular events, drought tolerance differs greatly within the plant kingdom. While Eutrema salsugineum (formerly Thellungiella salsuginea) is regarded as more stress tolerant than its close relative Arabidopsis thaliana, their responses to soil water deficit have not previously been directly compared. To ensure a similar rate of soil drying for the two species, daily soil water depletion was controlled to 5-10% of the soil water content. While partial stomatal closure occurred earlier in Arabidopsis (Day 4) than Eutrema (from Day 6 onwards), thereafter both species showed similar stomatal sensitivity to drying soil. However, both targeted and untargeted metabolite analysis revealed greater response to drought in Arabidopsis than Eutrema. Early peaks in foliar phytohormone concentrations and different sugar profiles between species were accompanied by opposing patterns in the bioactive cytokinin profiles. Untargeted analysis showed greater metabolic adjustment in Arabidopsis with more statistically significant changes in both early and severe drought stress. The distinct metabolic responses of each species during early drought, which occurred prior to leaf water status declining, seemed independent of later stomatal closure in response to drought. The two species also showed distinct water usage, with earlier reduction in water consumption in Eutrema (Day 3) than Arabidopsis (Day 6), likely reflecting temporal differences in growth responses. We propose Arabidopsis as a promising model to evaluate the mechanisms responsible for stress-induced growth inhibition under the mild/moderate soil drying that crop plants are typically exposed to.

Intra-household agreement of urinary elemental concentrations in Tanzania and Kenya: potential surrogates in case-control studies.

Element deficiencies and excesses play important roles in non-communicable disease aetiology. When investigating their roles in epidemiologic studies without prospective designs, reverse-causality limits the utility of transient biomarkers in cases. This study aimed to investigate whether surrogate participants may provide viable proxies by assessing concentration correlations within households. We obtained spot urine samples from 245 Tanzanian and Kenyan adults (including 101 household pairs) to investigate intra-household correlations of urinary elements (As, Ba, Ca, Cd, Co, Cs, Cu, Fe, Li, Mn, Mo, Ni, Pb, Rb, S, Se, Sr, Tl, V and Zn) and concentrations (also available for: Bi, Ce, Sb, Sn and U) relative to external population-levels and health-based values. Moderate-strong correlations were observed for As (r = 0.65), Cs (r = 0.67), Li (r = 0.56), Mo (r = 0.57), Se (r = 0.68) and Tl (r = 0.67). Remaining correlations were <0.41. Median Se concentrations in Tanzania (29 µg/L) and Kenya (24 µg/L) were low relative to 5738 Canadians (59 µg/L). Exceedances (of reference 95th percentiles) were observed for: Co, Mn, Mo, Ni and U. Compared to health-based values, exceedances were present for As, Co, Mo and Se but deficiencies were also present for Mo and Se. For well correlated elements, household members in East African settings provide feasible surrogate cases to investigate element deficiencies/excesses in relation to non-communicable diseases.

Post-Operative Cognitive Dysfunction: An exploration of the inflammatory hypothesis and novel therapies.

Post-Operative Cognitive Dysfunction (POCD) is a highly prevalent condition with significant clinical, social and financial impacts for patients and their communities. The underlying pathophysiology is becoming increasingly understood, with the role of neuroinflammation and oxidative stress secondary to surgery and anaesthesia strongly implicated. This review aims to describe the putative mechanisms by which surgery-induced inflammation produces cognitive sequelae, with a focus on identifying potential novel therapies based upon their ability to modify these pathways.

The effect of N-acetylcysteine (NAC) on human cognition - A systematic review.

Oxidative stress, neuroinflammation and neurogenesis are commonly implicated as cognitive modulators across a range of disorders. N-acetylcysteine (NAC) is a glutathione precursor with potent antioxidant, pro-neurogenesis and anti-inflammatory properties and a favourable safety profile. A systematic review of the literature specifically examining the effect of NAC administration on human cognition revealed twelve suitable articles for inclusion: four examining Alzheimer's disease; three examining healthy participants; two examining physical trauma; one examining bipolar disorder, one examining schizophrenia, and one examining ketamine-induced psychosis. Heterogeneity of studies, insufficiently powered studies, infrequency of cognition as a primary outcome, heterogeneous methodologies, formulations, co-administered treatments, administration regimes, and assessment confounded the drawing of firm conclusions. The available data suggested statistically significant cognitive improvements following NAC treatment, though the paucity of NAC-specific research makes it difficult to determine if this effect is meaningful. While NAC may have a positive cognitive effect in a variety of contexts; larger, targeted studies are warranted, specifically evaluating its role in other clinical disorders with cognitive sequelae resulting from oxidative stress and neuroinflammation.

Effect of rate of pyrolysis on the textural properties of naturally-templated porous carbons from alginic acid.

The effect of pyrolysis rate on the properties of alginic acid-derived carbonaceous materials, termed Starbon®, was investigated. Thermal Gravimetry-IR was used to prepare porous carbons up to 800 °C at several rates and highlighted increased CO2 production at higher pyrolysis rates. N2 porosimetry of the resultant carbons shows how pyrolysis rate affects both the mesopore structure and thus surface area and surface energy. Surface capacity of these carbons was analysed by methylene blue dye adsorption. In general, as the rate of pyrolysis increased, the mesopore content and adsorbent capacity decreased. It is considered here that the rapid production of volatiles at these higher rates causes structural collapse of the non-templated pore network. The work here demonstrates that pyrolysis rate is a key variable which needs to be controlled to maximise the textural properties of Starbon® required for adsorption applications.

The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study protocol for a randomised controlled trial.

BACKGROUND: Some degree of cognitive decline after surgery occurs in as many as one quarter of elderly surgical patients, and this decline is associated with increased morbidity and mortality. Cognition may be affected across a range of domains, including memory, psychomotor skills, and executive function. Whilst the exact mechanisms of cognitive change after surgery are not precisely known, oxidative stress and subsequent neuroinflammation have been implicated. N-acetylcysteine (NAC) acts via multiple interrelated mechanisms to influence oxidative homeostasis, neuronal transmission, and inflammation. NAC has been shown to reduce oxidative stress and inflammation in both human and animal models. There is clinical evidence to suggest that NAC may be beneficial in preventing the cognitive decline associated with both acute physiological insults and dementia-related disorders. To date, no trials have examined perioperative NAC as a potential moderator of postoperative cognitive changes in the noncardiac surgery setting. METHODS AND DESIGN: This is a single-centre, randomised, double-blind, placebo-controlled clinical trial, with a between-group, repeated-measures, longitudinal design. The study will recruit 370 noncardiac surgical patients at the University Hospital Geelong, aged 60 years or older. Participants are randomly assigned to receive either NAC or placebo (1:1 ratio), and groups are stratified by age and surgery type. Participants undergo a series of neuropsychological tests prior to surgery, 7 days, 3 months, and 12 months post surgery. It is hypothesised that the perioperative administration of NAC will reduce the degree of postoperative cognitive changes at early and long-term follow-up, as measured by changes on individual measures of the neurocognitive battery, when compared with placebo. Serum samples are taken on the day of surgery and on day 2 post surgery to quantitate any changes in levels of biomarkers of inflammation and oxidative stress. DISCUSSION: The PANACEA trial aims to examine the potential efficacy of perioperative NAC to reduce the severity of postoperative cognitive dysfunction in an elderly, noncardiac surgery population. This is an entirely novel approach to the prevention of postoperative cognitive dysfunction and will have high impact and translatable outcomes if NAC is found to be beneficial. TRIAL REGISTRATION: The PANACEA trial has been registered with the Therapeutic Goods Administration, and the Australian New Zealand Clinical Trials Registry: ACTRN12614000411640 ; registered on 15 April 2014.