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

Robotic Lepidoptery: Structural Characterization of (mostly) Unexpected Palladium Complexes Obtained from High-Throughput Catalyst Screening

In the course of a high-throughput search for optimal combinations of bidentate ligands with Pd(II) carboxylates to generate oxidation catalysts, we obtained and crystallographically characterized a number of crystalline products. While some combinations afforded the anticipated (L-L)Pd(OC(O)R)_2 structures (L-L = bipyridine, tmeda; R = CH_3, CF_3), many gave unusual oligometallic complexes resulting from reactions such as C−H activation (L-L = sparteine), P−C bond cleavage (L-L = 1,2-bis(diphenylphosphino)ethane, and C−C bond formation between solvent (acetone) and ligand (L-L = 1,4-bis(2,6-diisopropylphenyl)-1,4-diaza-1,3-butadiene). These findings illustrate potential pitfalls of screening procedures based on assuming uniform, in situ catalyst self-assembly

Quantitative sensory testing in children with sickle cell disease: additional insights and future possibilities.

Quantitative sensory testing (QST) is used in a variety of pain disorders to characterize pain and predict prognosis and response to specific therapies. In this study, we aimed to confirm results in the literature documenting altered QST thresholds in sickle cell disease (SCD) and assess the test-retest reliability of results over time. Fifty-seven SCD and 60 control subjects aged 8-20 years underwent heat and cold detection and pain threshold testing using a Medoc TSAII. Participants were tested at baseline and 3 months; SCD subjects were additionally tested at 6 months. An important facet of our study was the development and use of a novel QST modelling approach, allowing us to model all data together across modalities. We have not demonstrated significant differences in thermal thresholds between subjects with SCD and controls. Thermal thresholds were consistent over a 3- to 6-month period. Subjects on whom hydroxycarbamide (HC) was initiated shortly before or after baseline testing (new HC users) exhibited progressive decreases in thermal sensitivity from baseline to 6 months, suggesting that thermal testing may be sensitive to effective therapy to prevent vasoocclusive pain. These findings inform the use of QST as an endpoint in the evaluation of preventative pain therapies

Low cancer suspicion following experience of a cancer 'warning sign'

© 2015 The Authors. Published by Elsevier Ltd. Aim Lower socioeconomic status (SES) is associated with a higher risk of late-stage cancer diagnosis. A number of explanations have been advanced for this, but one which has attracted recent attention is lower patient knowledge of cancer warning signs, leading to delay in help-seeking. However, although there is psychometric evidence of SES differences in knowledge of cancer symptoms, no studies have examined differences in 'cancer suspicion' among people who are actually experiencing a classic warning sign. Methods A 'health survey' was mailed to 9771 adults (≥50 years, no cancer diagnosis) with a symptom list including 10 cancer 'warning signs'. Respondents were asked if they had experienced any of the symptoms in the past 3 months, and if so, were asked 'what do you think caused it?' Any mention of cancer was scored as 'cancer suspicion'. SES was indexed by education. Results Nearly half the respondents (1732/3756) had experienced a 'warning sign', but only 63/1732 (3.6%) mentioned cancer as a possible cause. Lower education was associated with lower likelihood of cancer suspicion: 2.6% of respondents with school-only education versus 7.3% with university education suspected cancer as a possible cause. In multivariable analysis, low education was the only demographic variable independently associated with lower cancer suspicion (odds ratio (OR) = 0.34, confidence interval (CI): 0.20-0.59). Conclusion Levels of cancer suspicion were low overall in this community sample, and even lower in people from less educated backgrounds. This may hinder early symptomatic presentation and contribute to inequalities in stage at diagnosis

Women's appraisal, interpretation and help-seeking for possible symptoms of breast and cervical cancer in South Africa: a qualitative study.

BACKGROUND: In South Africa, breast cancer is the most commonly diagnosed cancer and cervical cancer the leading cause of cancer mortality. Most cancers are diagnosed at a late-stage and following symptomatic presentation. The overall purpose of the study was to inform interventions aimed at improving timely diagnosis of breast and cervical cancer. METHODS: In-depth interviews were conducted with women with potential breast or cervical cancer symptoms from urban and rural South Africa. Participants were recruited from a community-based cross-sectional study on breast and cervical cancer awareness. Data were analysed using a thematic analysis approach. RESULTS: Eighteen women were interviewed (10 urban, 8 rural): the median age was 34.5 years (range 22-58). Most were unemployed, and five were HIV positive. Themes included impact and attribution of bodily changes; influence of social networks and health messaging in help-seeking; management of symptoms and help-seeking barriers. Breast changes were often attributed to manual activities or possible cancer. Women were often unsure how to interpret vaginal symptoms, attributing them to HIV, hormonal contraceptives, or partner infidelity. Concerns about cancer were based on health information from the radio, social networks, or from primary care providers. Prompt care seeking was triggered by impact of symptoms on personal lives. Rural women, especially with possible symptoms of cervical cancer, experienced challenges during help-seeking including judgmental attitudes of clinic staff. Most participants were skeptical of traditional medicine. CONCLUSIONS: This is the first study exploring interpretation of possible breast and cervical cancer symptoms at a community level in South Africa. The process of interpreting bodily changes, symptom attribution and help-seeking is complex and influenced by women's everyday life experiences. Timely diagnosis interventions should not only include cancer symptom awareness but also address individual, structural and health systems related barriers to care

Chiral metallohelices enantioselectively target hybrid human telomeric G-quadruplex DNA

The design and synthesis of metal complexes that can specifically target DNA secondary structure has attracted considerable attention. Chiral metallosupramolecular complexes (e.g. helicates) in particular display unique DNA-binding behavior, however until recently few examples which are both water-compatible and enantiomerically pure have been reported. Herein we report that one metallohelix enantiomer , available from a diastereoselective synthesis with no need for resolution, can enantioselectively stabilize human telomeric hybrid G-quadruplex and strongly inhibit telomerase activity with IC 50 of 600 nM. In contrast, no such a preference is observed for the mirror image complex . More intriguingly, neither of the two enantiomers binds specifically to human telomeric antiparallel G-quadruplex. To the best of our knowledge, this is the first example of one pair of enantiomers with contrasting selectivity for human telomeric hybrid G-quadruplex. Further studies show that can discriminate human telomeric G-quadruplex from other telomeric G-quadruplexes

Impact of the COVID-19 pandemic on cancer assessment in primary care: a qualitative study of GP views

Funding This research was co-funded by the National Institute for Health Research (NIHR) Policy Research Programme, conducted through the Policy Research Unit in Cancer Awareness, Screening and Early Diagnosis, PR-PRU-1217–21601. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The study was also supported by the CanTest Collaborative funded by Cancer Research UK C8640/A23385, of which Fiona Walter is director, Richard Neal is associate director, Suzanne Scott is co-investigator, and Natalia Calanzani and Stephanie Honey are researchers. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.Peer reviewedPublisher PD

Impact of the COVID-19 global pandemic on symptomatic diagnosis of cancer - the view from primary care

The entire landscape of cancer management in primary care, from case identification to the management of those living with and beyond cancer, is evolving rapidly in the face of the coronavirus (COVID-19) pandemic.1 In a climate of fear and mandated avoidance of all but essential clinical services, delays in patient, population and healthcare system responses to suspected cancer symptoms seem inevitable