Novel 1-hydroxy-1,1-bisphosphonates derived from indazole: synthesis and characterization

Bisphosphonates (BPs) are an important class of drugs used in the treatment of abnormal calcium metabolism diseases. The first syntheses of bisphosphonates derived from indazole, substituted at the N-1, N-2 and C-3 positions are reported. The 1-hydroxy-1,1-bisphosphonates were synthesized from the corresponding carboxylic acid or acyl chloride compounds, by two different methods. These BPs have a side chain with different lengths ((CH2)n, n = 0-5) between the indazole ring and the bisphosphonate group

Asymmetric synthesis of secondary benzylic alcohols via arene chromium tricarbonyl complexes

ABSTRACT: The use of O-methyl-N-(alpha-methylbenzyl)hydroxylamine as a novel chiral auxiliary in asymmetric ortho-deprotonation of the (eta(6)-arene) chromium tricarbonyl complexes is described. Upon quenching of the resultant ortho-lithiated complex with an electrophile, 1,2-disubstituted (eta(6)-arene) chromium tricarbonyl complexes were obtained in good yield and excellent levels of diastereoselectivity.info:eu-repo/semantics/publishedVersio

Synthesis and characterization of novel hydroxy- and aminobisphosphonates

Bisphosphonates (BPs) are a family of drugs that are successfully used in the treatment of various calcium-related disorders such as Pagetμs disease, osteoporosis and bone metastases. In addition, functional BPs have been also used in the treatment of metal intoxication and as novel ligands for well-defined radioactive metal complexes that can be used in imagiology, scintigraphy and radiotherapy applications [1,2]. The indazole derivatives are pharmacologically important compounds and the indazole ring system forms the basis of a number of drug molecules. Condensed pyrazoles are also known as pharmacophoric elements in numerous active compounds. However, in comparison with other heteroaromatic compounds, the chemistry of indazole and condensed pyrazoles remains less studied [3]. The present work is to extend the previous studies in indazolebisphosphonates [4] in order to obtain new BPs derived from indazole and condensed pyrazole with potential biological/therapeutical activities. Herein, we report the synthesis and characterization of a series of new 1-hydroxybisphosphonates (1) and aminobisphosphonates (2) (substituted at different C- or N-positions of the indazole ring - N-1, C-5, C-6, C-7

Nightside condensation of iron in an ultra-hot giant exoplanet

Ultra-hot giant exoplanets receive thousands of times Earth's insolation. Their high-temperature atmospheres (>2,000 K) are ideal laboratories for studying extreme planetary climates and chemistry. Daysides are predicted to be cloud-free, dominated by atomic species and substantially hotter than nightsides. Atoms are expected to recombine into molecules over the nightside, resulting in different day-night chemistry. While metallic elements and a large temperature contrast have been observed, no chemical gradient has been measured across the surface of such an exoplanet. Different atmospheric chemistry between the day-to-night ("evening") and night-to-day ("morning") terminators could, however, be revealed as an asymmetric absorption signature during transit. Here, we report the detection of an asymmetric atmospheric signature in the ultra-hot exoplanet WASP-76b. We spectrally and temporally resolve this signature thanks to the combination of high-dispersion spectroscopy with a large photon-collecting area. The absorption signal, attributed to neutral iron, is blueshifted by -11+/-0.7 km s-1 on the trailing limb, which can be explained by a combination of planetary rotation and wind blowing from the hot dayside. In contrast, no signal arises from the nightside close to the morning terminator, showing that atomic iron is not absorbing starlight there. Iron must thus condense during its journey across the nightside.Comment: Published in Nature (Accepted on 24 January 2020.) 33 pages, 11 figures, 3 table

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake