The Influence of pH on Zinc Lability and Toxicity to a Tropical Freshwater Microalga.

Increased focus on the development and application of bioavailability-based metal water quality guideline values requires increased understanding of the influence of water chemistry on metal bioavailability and toxicity. Development of empirical models, such as multiple linear regression models, requires the assessment of the influence of individual water quality parameters as toxicity-modifying factors. The present study investigated the effect of pH on the lability and toxicity of zinc (Zn) to a tropical green microalga (Chlorella sp.). Zinc speciation and lability were explored using the Windermere Humic Aqueous Model (WHAM7), ultrafiltration, and diffusive gradients in thin films (DGT). Zinc toxicity increased significantly with increasing pH from 6.7 to 8.3, with 50% growth inhibition effect concentrations decreasing from 185 to 53 µg l-1 across the pH range. Linear relationships between DGT-labile Zn and dissolved Zn did not vary across the tested pH range, nor did the linear relationship between dissolved (<0.45 µm) and ultrafiltered (<3 kDa) Zn. Our findings show that Zn toxicity to this freshwater alga is altered as a function of pH across environmentally realistic pH ranges and that these toxicity changes could not be explained by Zn speciation and lability as measured by DGT and WHAM7. Environ Toxicol Chem 2021;40:2836-2845. © 2021 SETAC

Flecainide overdose – support using an intra-aortic balloon pump

BACKGROUND: Flecainide is an antiarrhythmic agent which is being used increasingly for the management of super-ventricular arrhythmias. Overdose with flecainide is frequently fatal with mortality reported as high as 22% due to arrhythmias, myocardial depression and conduction defects leading to electro-mechanical dissociation and asytole. Supportive measures are often required during the case and previously have included inotropes, extracorporeal membrane oxygenation and cardiopulmonary bypass. CASE PRESENTATION: A 47 year old lady presented to the emergency department with a four hour history of severe central chest pain. Her ECG showed atrial fibrillation and broad QRS complexes with a sine wave appearance. She had a past history of paroxysmal atrial fibrillation and significant psychiatric history. Following thrombolysis for a presumed myocardial infarction she developed cardiogenic shock with severely impaired left ventricular function. An intra-aortic balloon pump was inserted and coronary angiography demonstrated normal coronary arteries. With inotropic support she improved over 48 hours, with both her QRS duration and left ventricular function returning to normal. Biochemical testing following her discharge demonstrated significantly elevated levels of flecainide. CONCLUSION: The use of an intra-aortic balloon pump is a useful supportive measure during the acute phase of flecainide overdose associated with severe myocardial depression

The breadth of primary care: a systematic literature review of its core dimensions

Background: Even though there is general agreement that primary care is the linchpin of effective health care delivery, to date no efforts have been made to systematically review the scientific evidence supporting this supposition. The aim of this study was to examine the breadth of primary care by identifying its core dimensions and to assess the evidence for their interrelations and their relevance to outcomes at (primary) health system level. Methods: A systematic review of the primary care literature was carried out, restricted to English language journals reporting original research or systematic reviews. Studies published between 2003 and July 2008 were searched in MEDLINE, Embase, Cochrane Library, CINAHL, King's Fund Database, IDEAS Database, and EconLit. Results: Eighty-five studies were identified. This review was able to provide insight in the complexity of primary care as a multidimensional system, by identifying ten core dimensions that constitute a primary care system. The structure of a primary care system consists of three dimensions: 1. governance; 2. economic conditions; and 3. workforce development. The primary care process is determined by four dimensions: 4. access; 5. continuity of care; 6. coordination of care; and 7. comprehensiveness of care. The outcome of a primary care system includes three dimensions: 8. quality of care; 9. efficiency care; and 10. equity in health. There is a considerable evidence base showing that primary care contributes through its dimensions to overall health system performance and health. Conclusions: A primary care system can be defined and approached as a multidimensional system contributing to overall health system performance and health

The Interplay between PolyQ and Protein Context Delays Aggregation by Forming a Reservoir of Protofibrils

Polyglutamine (polyQ) diseases are inherited neurodegenerative disorders caused by the expansion of CAG codon repeats, which code for polyQ in the corresponding gene products. These diseases are associated with the presence of amyloid-like protein aggregates, induced by polyQ expansion. It has been suggested that the soluble aggregates rather than the mature fibrillar aggregates are the toxic species, and that the aggregation properties of polyQ can be strongly modulated by the surrounding protein context. To assess the importance of the protein carrier in polyQ aggregation, we have studied the misfolding pathway and the kinetics of aggregation of polyQ of lengths above (Q41) and below (Q22) the pathological threshold fused to the well-characterized protein carrier glutathione S-transferase (GST). This protein, chosen as a model system, is per se able to misfold and aggregate irreversibly, thus mimicking the behaviour of domains of naturally occurring polyQ proteins. We prove that, while it is generally accepted that the aggregation kinetics of polyQ depend on its length and are faster for longer polyQ tracts, the presence of GST alters the polyQ aggregation pathway and reverses this trend. Aggregation occurs through formation of a reservoir of soluble intermediates whose populations and kinetic stabilities increase with polyQ length. Our results provide a new model that explains the toxicity of expanded polyQ proteins, in which the interplay between polyQ regions and other aggregation-prone domains plays a key role in determining the aggregation pathway

Increased searching and handling effort in tall swards lead to a Type IV functional response in small grazing herbivores

Understanding the functional response of species is important in comprehending the species’ population dynamics and the functioning of multi-species assemblages. A Type II functional response, where instantaneous intake rate increases asymptotically with sward biomass, is thought to be common in grazers. However, at tall, dense swards, food intake might decline due to mechanical limitations or if animals selectively forage on the most nutritious parts of a sward, leading to a Type IV functional response, especially for smaller herbivores. We tested the predictions that bite mass, cropping time, swallowing time and searching time increase, and bite rate decreases with increasing grass biomass for different-sized Canada geese (Branta canadensis) foraging on grass swards. Bite mass indeed showed an increasing asymptotic relationship with grass biomass. At high biomass, difficulties in handling long leaves and in locating bites were responsible for increasing cropping, swallowing, and searching times. Constant bite mass and decreasing bite rate caused the intake rate to decrease at high sward biomass after reaching an optimum, leading to a Type IV functional response. Grazer body mass affected maximum bite mass and intake rate, but did not change the shape of the functional response. As grass nutrient contents are usually highest in short swards, this Type IV functional response in geese leads to an intake rate that is maximised in these swards. The lower grass biomass at which intake rate was maximised allows resource partitioning between different-sized grazers. We argue that this Type IV functional response is of more importance than previously thought

CD209 Genetic Polymorphism and Tuberculosis Disease

BACKGROUND: Tuberculosis causes significant morbidity and mortality worldwide, especially in sub-Saharan Africa. DC-SIGN, encoded by CD209, is a receptor capable of binding and internalizing Mycobacterium tuberculosis. Previous studies have reported that the CD209 promoter single nucleotide polymorphism (SNP)-336A/G exerts an effect on CD209 expression and is associated with human susceptibility to dengue, HIV-1 and tuberculosis in humans. The present study investigates the role of the CD209 -336A/G variant in susceptibility to tuberculosis in a large sample of individuals from sub-Saharan Africa. METHODS AND FINDINGS: A total of 2,176 individuals enrolled in tuberculosis case-control studies from four sub-Saharan Africa countries were genotyped for the CD209 -336A/G SNP (rs4804803). Significant overall protection against pulmonary tuberculosis was observed with the -336G allele when the study groups were combined (n = 914 controls vs. 1262 cases, Mantel-Haenszel 2 x 2 chi(2) = 7.47, P = 0.006, odds ratio = 0.86, 95%CI 0.77-0.96). In addition, the patients with -336GG were associated with a decreased risk of cavitory tuberculosis, a severe form of tuberculosis disease (n = 557, Pearson's 2x2 chi(2) = 17.34, P = 0.00003, odds ratio = 0.42, 95%CI 0.27-0.65). This direction of association is opposite to a previously observed result in a smaller study of susceptibility to tuberculosis in a South African Coloured population, but entirely in keeping with the previously observed protective effect of the -336G allele. CONCLUSION: This study finds that the CD209 -336G variant allele is associated with significant protection against tuberculosis in individuals from sub-Saharan Africa and, furthermore, cases with -336GG were significantly less likely to develop tuberculosis-induced lung cavitation. Previous in vitro work demonstrated that the promoter variant -336G allele causes down-regulation of CD209 mRNA expression. Our present work suggests that decreased levels of the DC-SIGN receptor may therefore be protective against both clinical tuberculosis in general and cavitory tuberculosis disease in particular. This is consistent with evidence that Mycobacteria can utilize DC-SIGN binding to suppress the protective pro-inflammatory immune response

Cashew nut allergy: clinical relevance and allergen characterisation

Cashew plant (Anacardium occidentale L.) is the most relevant species of the Anacardium genus. It presents high economic value since it is widely used in human nutrition and in several industrial applications. Cashew nut is a well-appreciated food (belongs to the tree nut group), being widely consumed as snacks and in processed foods by the majority of world's population. However, cashew nut is also classified as a potent allergenic food known to be responsible for triggering severe and systemic immune reactions (e.g. anaphylaxis) in sensitised/allergic individuals that often demand epinephrine treatment and hospitalisation. So far, three groups of allergenic proteins have been identified and characterised in cashew nut: Ana o 1 and Ana o 2 (cupin superfamily) and Ana o 3 (prolamin superfamily), which are all classified as major allergens. The prevalence of cashew nut allergy seems to be rising in industrialised countries with the increasing consumption of this nut. There is still no cure for cashew nut allergy, as well as for other food allergies; thus, the allergic patients are advised to eliminate it from their diets. Accordingly, when carefully choosing processed foods that are commercially available, the allergic consumers have to rely on proper food labelling. In this sense, the control of labelling compliance is much needed, which has prompted the development of proficient analytical methods for allergen analysis. In the recent years, significant research advances in cashew nut allergy have been accomplished, which are highlighted and discussed in this review.This work was supported by FCT/MEC through national funds and co-financed by FEDER, under the Partnership Agreement PT2020 with grant no. UID/QUI/50006/2013–POCI/01/ 0145/FEDER/007265. Joana Costa is grateful to FCT post-doctoral grant (SFRH/BPD/102404/2014) financed by POPH-QREN (subsidised by FSE and MCTES).info:eu-repo/semantics/publishedVersio