Optically pure heterobimetallic helicates from self-assembly and click strategies

Single diastereomer, diamagnetic, octahedral Fe(II) tris chelate complexes are synthesised that contain three pendant pyridine proligands pre-organised for coordination to a second metal. They bind Cu(I) and Ag(I) with coordination geometry depending on the identity of the metal and the detail of the ligand structure, but for example homohelical (ΔFe,ΔCu) configured systems with unusual trigonal planar Cu cations are formed exclusively in solution as shown by VT-NMR and supported by DFT calculations. Similar heterobimetallic tris(triazole) complexes are synthesised via clean CuAAC reactions at a tris(alkynyl) complex, although here the configurations of the two metals differ (ΔFe,ΛCu), leading to the first optically pure heterohelicates. A second series of Fe complexes perform less well in either strategy as a result of lack of preorganisation

Schizophrenia and the progression of emotional expression in relation to others

Gaining an improved understanding of people diagnosed with schizophrenia has the potential to influence priorities for therapy. Psychosis is commonly understood through the perspective of the medical model. However, the experience of social context surrounding psychosis is not well understood. In this research project we used a phenomenological methodology with a longitudinal design to interview 7 participants across a 12-month period to understand the social experiences surrounding psychosis. Eleven themes were explicated and divided into two phases of the illness experience: (a) transition into emotional shutdown included the experiences of not being acknowledged, relational confusion, not being expressive, detachment, reliving the past, and having no sense of direction; and (b) recovery from emotional shutdown included the experiences of being acknowledged, expression, resolution, independence, and a sense of direction. The experiential themes provide clinicians with new insights to better assess vulnerability, and have the potential to inform goals for therapy

Lanthanide Complexes that Respond to Changes in Cyanide Concentration in Water

Cyanide ions are shown to interact with lanthanide complexes of phenacylDO3A derivatives in aqueous solution, giving rise to changes in the luminescence and NMR spectra. These changes are the consequence of cyanohydrin formation, which is favored by the coordination of the phenacyl carbonyl group to the lanthanide center. These complexes display minimal affinity for fluoride and can detect cyanide at concentrations less than 1 μm. By contrast, lanthanide complexes with DOTAM derivatives display no affinity for cyanide in water, but respond to changes in fluoride concentration

Lanthanide appended rotaxanes respond to changing chloride concentration

Lanthanide appended rotaxanes have been prepared by the CuAAC ‘click’ reaction between an azide appended rotaxane and lanthanide complexes of propargyl DO3A. The resulting complexes are luminescent, and exhibit chloride responsive luminescence behavior consistent with the existence of two independent halide binding pockets, one in the rotaxane cavity and one on the ninth (axial) coordination site of the lanthanide. Strong halide binding to europium gives rise to changes in the relative intensity of the hypersensitive ΔJ = 2 transition compared to the rest of the europium emission spectrum, combined with quenching of the overall intensity of emission as a consequence of non-radiative quenching by the bound halide. The weaker interaction with the rotaxane pocket mediates a subsequent recovery of intensity of the europium centered luminescence despite the considerable separation between the lanthanide and the rotaxane binding pocket

Asymmetric triplex metallohelices with high and selective activity against cancer cells

Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and ​p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 ​p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli. At a glanc

Insiders, Outsiders, and the Struggle for Consecration in Cultural Fields: A Core-Periphery Perspective

Building on recent research emphasizing how legitimacy depends on consensus among audiences about candidates’ characteristics and activities, we examine the relationship between cultural producers’ (candidates) position in the social structure and the consecration of their creative work by relevant audiences. We argue that the outcome of this process of evaluation in any cultural field, whether in art or science, is a function of (1) candidates’ embeddedness within the field, and (2) the type of audience—that is, peers versus critics—evaluating candidates’ work. Specifically, we hypothesize that peers are more likely to favor candidates who are highly embedded in the field, whereas critics will not show such favoritism. We find support for these hypotheses in the context of the Hollywood motion picture industry

Systemic pro-inflammatory cytokine status following therapeutic hypothermia in a piglet hypoxia-ischemia model

BACKGROUND: Inflammatory cytokines are implicated in the pathogenesis of perinatal hypoxia-ischemia (HI). The influence of hypothermia (HT) on cytokines after HI is unclear. Our aim was to assess in a piglet asphyxia model, under normothermic (NT) and HT conditions: (i) the evolution of serum cytokines over 48 h and (ii) cerebrospinal fluid (CSF) cytokine levels at 48 h; (iii) serum pro/anti-inflammatory cytokine profile over 48 h and (iv) relation between brain injury measured by magnetic resonance spectroscopy (MRS) and brain TUNEL positive cells with serum cytokines, serum pro/anti-inflammatory cytokines and CSF cytokines. METHODS: Newborn piglets were randomized to NT (n = 5) or HT (n = 6) lasting 2-26 h after HI. Serum samples were obtained 4-6 h before, during and at 6-12 h intervals after HI; CSF was obtained at 48 h. Concentrations of interleukin (IL)-1beta, -4, -6, -8, -10 and TNF-alpha were measured and pro/anti-inflammatory status compared between groups. White matter and thalamic voxel lactate/N-acetyl aspartate (Lac/NAA) (a measure of both oxidative metabolism and neuronal loss) were acquired at baseline, after HI and at 24 and 36 h. RESULTS: Lac/NAA was reduced at 36 h with HT compared to NT (p = 0.013 basal ganglia and p = 0.033 white matter). HT showed lower serum TNF-alpha from baseline to 12 h (p < 0.05). Time-matched (acquired within 5 h of each other) serum cytokine and MRS showed correlations between Lac/NAA and serum IL-1beta and IL-10 (all p < 0.01). The pro/anti-inflammatory ratios IL-1beta/IL-10, IL-6/IL-10, IL-4/IL-10 and IL-8/IL-10 were similar in NT and HT groups until 36 h (24 h for IL-6/IL-10); after this, 36 h pro/anti-inflammatory cytokine ratios in the serum were higher in HT compared to NT (p < 0.05), indicating a pro-inflammatory cytokine surge after rewarming in the HT group. In the CSF at 48 h, IL-8 was lower in the HT group (p < 0.05). At 48 h, CSF TNF-alpha correlated with Lac/NAA (p = 0.02) and CSF IL-8 correlated with white matter TUNEL positive cell death (p = 0.04). CONCLUSIONS: Following cerebral HI, there was a systemic pro-inflammatory surge after rewarming in the HT group, which is counterintuitive to the putative neuroprotective effects of HT. While serum cytokines were variable, elevations in CSF inflammatory cytokines at 48 h were associated with MRS Lac/NAA and white matter cell death

Bone mass of female dance students prior to professional dance training: A cross-sectional study

Article Authors Metrics Comments Related Content Abstract Introduction Methods Results Discussion Conclusions Acknowledgments References Reader Comments (0) Media Coverage (0) Figures Abstract Background Professional dancers are at risk of developing low bone mineral density (BMD). However, whether low BMD phenotypes already exist in pre-vocational dance students is relatively unknown. Aim To cross-sectionally assess bone mass parameters in female dance students selected for professional dance training (first year vocational dance students) in relation to aged- and sex-matched controls. Methods 34 female selected for professional dance training (10.9yrs ±0.7) and 30 controls (11.1yrs ±0.5) were examined. Anthropometry, pubertal development (Tanner) and dietary data (3-day food diary) were recorded. BMD and bone mineral content (BMC) at forearm, femur neck (FN) and lumbar spine (LS) were assessed using Dual-Energy X-Ray Absorptiometry. Volumetric densities were estimated by calculating bone mineral apparent density (BMAD). Results Dancers were mainly at Tanner pubertal stage I (vs. stage IV in controls, p<0.001), and demonstrated significantly lower body weight (p<0.001) and height (p<0.01) than controls. Calorie intake was not different between groups, but calcium intake was significantly greater in dancers (p<0.05). Dancers revealed a significantly lower BMC and BMD values at all anatomical sites (p<0.001), and significantly lower BMAD values at the LS and FN (p<0.001). When adjusted for covariates (body weight, height, pubertal development and calcium intake), dance students continued to display a significantly lower BMD and BMAD at the FN (p<0.05; p<0.001) at the forearm (p<0.01). Conclusion Before undergoing professional dance training, first year vocational dance students demonstrated inferior bone mass compared to controls. Longitudinal models are required to assess how bone health-status changes with time throughout professional training

Modelling Blood Flow and Metabolism in the Preclinical Neonatal Brain during and Following Hypoxic-Ischaemia

Hypoxia-ischaemia (HI) is a major cause of neonatal brain injury, often leading to long-term damage or death. In order to improve understanding and test new treatments, piglets are used as preclinical models for human neonates. We have extended an earlier computational model of piglet cerebral physiology for application to multimodal experimental data recorded during episodes of induced HI. The data include monitoring with near-infrared spectroscopy (NIRS) and magnetic resonance spectroscopy (MRS), and the model simulates the circulatory and metabolic processes that give rise to the measured signals. Model extensions include simulation of the carotid arterial occlusion used to induce HI, inclusion of cytoplasmic pH, and loss of metabolic function due to cell death. Model behaviour is compared to data from two piglets, one of which recovered following HI while the other did not. Behaviourally-important model parameters are identified via sensitivity analysis, and these are optimised to simulate the experimental data. For the non-recovering piglet, we investigate several state changes that might explain why some MRS and NIRS signals do not return to their baseline values following the HI insult. We discover that the model can explain this failure better when we include, among other factors such as mitochondrial uncoupling and poor cerebral blood flow restoration, the death of around 40% of the brain tissue. Copyright

The assessment, serial evaluation, and subsequent sequelae of acute kidney injury (ASSESS-AKI) study: design and methods

<p>Abstract</p> <p>Background</p> <p>The incidence of acute kidney injury (AKI) has been increasing over time and is associated with a high risk of short-term death. Previous studies on hospital-acquired AKI have important methodological limitations, especially their retrospective study designs and limited ability to control for potential confounding factors.</p> <p>Methods</p> <p>The Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study was established to examine how a hospitalized episode of AKI independently affects the risk of chronic kidney disease development and progression, cardiovascular events, death, and other important patient-centered outcomes. This prospective study will enroll a cohort of 1100 adult participants with a broad range of AKI and matched hospitalized participants without AKI at three Clinical Research Centers, as well as 100 children undergoing cardiac surgery at three Clinical Research Centers. Participants will be followed for up to four years, and will undergo serial evaluation during the index hospitalization, at three months post-hospitalization, and at annual clinic visits, with telephone interviews occurring during the intervening six-month intervals. Biospecimens will be collected at each visit, along with information on lifestyle behaviors, quality of life and functional status, cognitive function, receipt of therapies, interim renal and cardiovascular events, electrocardiography and urinalysis.</p> <p>Conclusions</p> <p>ASSESS-AKI will characterize the short-term and long-term natural history of AKI, evaluate the incremental utility of novel blood and urine biomarkers to refine the diagnosis and prognosis of AKI, and identify a subset of high-risk patients who could be targeted for future clinical trials to improve outcomes after AKI.</p