Coordination chemistry and catalysis with secondary phosphine oxides

Secondary phosphine oxides present a tautomeric equilibrium between the pentavalent oxide form (SPO) and the trivalent phosphinous acid (PA). This dichotomy is the origin of the rich coordination chemistry of this class of compounds. As the pentavalent oxide form usually predominates, SPOs are air-stable but at the same time metal coordination can shift the tautomerism towards the PA form, making the ligand act as an ordinary trivalent phosphine. For this reason this class of ligands have found application in numerous homogeneously catalysed reactions, including some enantioselective transformations. This review aims to give an up to date account on the synthesis, coordination chemistry and homogeneous catalysis with SPOs

Self‐assembled highly positively charged allyl‐Pd crowns: cavity‐pocket driven interactions of fluoroanions

A series of dodecanuclear highly positively charged homo‐ and heterometallamacrocycles [{Pd(η 3 ‐2‐Me‐C 3 H 4 )} 6 (4‐PPh 2 py) 12 {M 2 (tpbz)} 3 ] 18+ (M = Pd, Pt; tpbz = 1,2,4,5‐tetrakis(diphenylphosphanylbenzene) were synthesized by the quantitative self‐assembly of {Pd(η 3 ‐2‐Me‐C 3 H 4 )} + , {M 2 (tpbz)} 4+ and 4‐PPh 2 py moieties in 2:1:4 molar ratio. The cationic assemblies were obtained as salts of different fluorinated anions that display diverse sizes and electronic properties, namely BF 4 ‐ , PF 6 ‐ , SbF 6 ‐ and CF 3 SO 3 ‐ . The new crown‐like metallamacrocycles showed remarkable differences in their NMR spectra due to the presence of the different counteranions. On the basis of the observed variations, the metallacycles have been tested as catalytic precursors in allylic alkylation reactions. The anion‐dependent activity and selectivity has been analysed and compared with that of the corresponding monometallic allylic corners [Pd(η 3 ‐2‐Me‐C 3 H 4 )(4‐PPh 2 py) 2 ]X (X = BF 4 ‐ , PF 6 ‐ , SbF 6 ‐ , CF 3 SO 3 ‐ ). DFT calculations have been employed in order to help to the interpretation of the experimental data and to model the anion‐crown interactions

Inhibition of Neuraminidase Inhibitor-Resistant Influenza Virus by DAS181, a Novel Sialidase Fusion Protein

Antiviral drug resistance for influenza therapies remains a concern due to the high prevalence of H1N1 2009 seasonal influenza isolates which display H274Y associated oseltamivir-resistance. Furthermore, the emergence of novel H1N1 raises the potential that additional reassortments can occur, resulting in drug resistant virus. Thus, additional antiviral approaches are urgently needed. DAS181 (Fludase®), a sialidase fusion protein, has been shown to have inhibitory activity against a large number of seasonal influenza strains and a highly pathogenic avian influenza (HPAI) strain (H5N1). Here, we examine the in vitro activity of DAS181 against a panel of 2009 oseltamivir-resistant seasonal H1N1 clinical isolates. The activity of DAS181 against nine 2009, two 2007, and two 2004 clinical isolates of seasonal IFV H1N1 was examined using plaque number reduction assay on MDCK cells. DAS181 strongly inhibited all tested isolates. EC50 values remained constant against isolates from 2004, 2007, and 2009, suggesting that there was no change in DAS181 sensitivity over time. As expected, all 2007 and 2009 isolates were resistant to oseltamivir, consistent with the identification of the H274Y mutation in the NA gene of all these isolates. Interestingly, several of the 2007 and 2009 isolates also exhibited reduced sensitivity to zanamivir, and accompanying HA mutations near the sialic acid binding site were observed. DAS181 inhibits IFV that is resistant to NAIs. Thus, DAS181 may offer an alternative therapeutic option for seasonal or pandemic IFVs that become resistant to currently available antiviral drugs

Plasma p217+tau versus NAV4694 amyloid and MK6240 tau PET across the Alzheimer\u27s continuum

Introduction: We evaluated a new Simoa plasma assay for phosphorylated tau (P-tau) at aa217 enhanced by additional p-tau sites (p217+tau). Methods: Plasma p217+tau levels were compared to 18F-NAV4694 amyloid beta (Aβ) positron emission tomography (PET) and 18F-MK6240 tau PET in 174 cognitively impaired (CI) and 223 cognitively unimpaired (CU) participants. Results: Compared to Aβ− CU, the plasma levels of p217+tau increased 2-fold in Aβ+ CU and 3.5-fold in Aβ+ CI. In Aβ− the p217+tau levels did not differ significantly between CU and CI. P217+tau correlated with Aβ centiloids P =.67 (CI, P =.64; CU, P =.45) and tau SUVRMT P =.63 (CI, P =.69; CU, P =.34). Area under curve (AUC) for Alzheimer\u27s disease (AD) dementia versus Aβ− CU was 0.94, for AD dementia versus other dementia was 0.93, for Aβ+ versus Aβ− PET was 0.89, and for tau+ versus tau− PET was 0.89. Discussion: Plasma p217+tau levels elevate early in the AD continuum and correlate well with Aβ and tau PET

The promotion of children's health and wellbeing:the contributions of England's charity sector

Background. Sports and arts based services for children have positive impacts on their mental and physical health. The charity sector provides such services, often set up in response to local communities expressing a need. The present study maps resilience promoting services provided by children's charities in England. Specifically, the prominence of sports and arts activities, and types of mental health provisions including telephone help-lines, are investigated. Findings. The study was a cross-sectional web-based survey of chief executives, senior mangers, directors and chairs of charities providing services for children under the age of 16. The aims, objectives and activities of participating children's charities and those providing mental health services were described overall. In total 167 chief executives, senior managers, directors and chairs of charities in England agreed to complete the survey. From our sample of charities, arts activities were the most frequently provided services (58/167, 35%), followed by counselling (55/167, 33%) and sports activities (36/167, 22%). Only 13% (22/167) of charities expected their work to contribute to the health legacy of the 2012 London Olympics. Telephone help lines were provided by 16% of the charities that promote mental health. Conclusions. Counselling and arts activities were relatively common. Sports activities were limited despite the evidence base that sport and physical activity are effective interventions for well-being and health gain. Few of the charities we surveyed expected a health legacy from the 2012 London Olympics

Perfluorinated alkyl substances (PFASs) in northern Spain municipal solid waste landfill leachates

Landfill leachates have been recognized as significant secondary sources of poly- and perfluoroalkyl substances (PFASs). This study presents data on the occurrence and concentration of 11 perfluoroalkyl carboxylates (PFCAs) and 5 perfluoroalkyl sulfonates (PFSAs) in leachates from 4 municipal solid waste landfill sites located across northern Spain. To the best of our knowledge, this is the first report of the presence of PFASs in Spanish landfill leachates. Two of the landfill sites applied on-site treatment using membrane bioreactors (MBR), and its effect on PFASs occurrence is also reported. Total PFASs (∑PFASs) in raw leachates reached 1378.9 ng/L, while in treated samples ∑PFASs was approximately two-fold (3162.3 ng/L). PFCAs accounted for the majority of the detected PFASs and perfluorooctanoic acid (PFOA) was the dominant compound in raw leachates (42.6%), followed by shorter chain PFHxA (30.1%), PFPeA and PFBA. The age of the sites might explain the PFASs pattern found in raw leachates as all of them were stabilized leachates. However, PFASs profile was different in treated samples where the most abundant compound was PFHxA (26.5%), followed by linear perfluorobutane sulfonate (L-PFBS) (18.7%) and PFOA (17.7%). The overall increase of the PFASs content as well as the change in the PFASs profile after the MBR treatment, could be explained by the possible degradation of PFASs precursors such as fluorotelomer alcohols or fluorotelomer sulfonates. Using the volume of leachates generated in the landfill sites, that served 1.8 million people, the discharge of 16 ∑PFASs contained in the landfill leachates was estimated as 1209 g/year.The authors thank financial support from the Spanish Ministry of Economy and Competitiveness (Project CTM2013-44081-R)

Consensus Recommendations for the Use of Automated Insulin Delivery (AID) Technologies in Clinical Practice

International audienceThe significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past six years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment