Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

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

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

Conolodinines A–D, Aspidosperma–Aspidosperma Bisindole Alkaloids with Antiproliferative Activity from Tabernaemontana corymbosa

Examination of the EtOH extract of the leaves of the Malayan Tabernaemontana corymbosa resulted in the isolation of four new (1-4) and two known bisindole alkaloids (5, 6) of the Aspidosperma-Aspidosperma type. The structures of these alkaloids were determined based on analysis of the spectroscopic data (NMR and HRESIMS). X-ray diffraction analyses of the related bisindole alkaloids conophylline (5) and conophyllinine (6) established the absolute configurations. Treatment of the bisindole alkaloid conophylline (5) with benzeneselenic anhydride gave, in addition to the known bisindole polyervinine (7) previously isolated from another Malayan Tabernaemontana, another bisindole product, 8, an isolable tautomer of 7. X-ray diffraction analyses yielded the absolute configurations of both bisindoles and in addition showed that polyervinine (7) exists primarily as the neutral dione structure. The bisindoles (1-8) and the related conophylline-type bisindoles (9-13) showed pronounced in vitro growth inhibitory activity against an array of human cancer cell lines, including KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, A549, HT-29, and HCT 116 cells, with IC50 values for the active compounds in the 0.01-5 μM range. © 2019 American Chemical Society and American Society of Pharmacognosy

Cytotoxic Vobasine, Tacaman, and Corynanthe-Tryptamine Bisindole Alkaloids from <i>Tabernaemontana</i> and Structure Revision of Tronoharine

Seven new indole alkaloids (<b>1</b>–<b>7</b>) comprising four vobasine, two tacaman, and one corynanthe-tryptamine bisindole alkaloid were isolated from the stem-bark extract of a Malayan <i>Tabernaemontana</i>. Two of the new vobasine alkaloids (<b>1</b>, <b>3</b>), as well as 16-epivobasine (<b>15</b>) and 16-epivobasenal (<b>17</b>), showed appreciable cytotoxicity toward KB cells (IC₅₀ ca. 5 μg/mL). The structure of the known <i>Tabernaemontana</i> alkaloid tronoharine (<b>8</b>) was revised based on newly acquired NMR data, as well as X-ray diffraction analysis

Cytotoxic Vobasine, Tacaman, and Corynanthe-Tryptamine Bisindole Alkaloids from <i>Tabernaemontana</i> and Structure Revision of Tronoharine

Seven new indole alkaloids (<b>1</b>–<b>7</b>) comprising four vobasine, two tacaman, and one corynanthe-tryptamine bisindole alkaloid were isolated from the stem-bark extract of a Malayan <i>Tabernaemontana</i>. Two of the new vobasine alkaloids (<b>1</b>, <b>3</b>), as well as 16-epivobasine (<b>15</b>) and 16-epivobasenal (<b>17</b>), showed appreciable cytotoxicity toward KB cells (IC₅₀ ca. 5 μg/mL). The structure of the known <i>Tabernaemontana</i> alkaloid tronoharine (<b>8</b>) was revised based on newly acquired NMR data, as well as X-ray diffraction analysis

Unusual phenethylamine-containing alkaloids from Elaeocarpus tectorius

From the leaves of Elaeocarpus tectorius (Lour.) Poir. four previously undescribed phenethylamine-containing alkaloids were isolated, namely, tectoricine, possessing an unprecedented isoquinuclidinone ring system incorporating a phenethylamine moiety, tectoraline, representing a rare alkamide incorporating two phenethylamine moieties, and tectoramidines A and B, representing the first naturally occurring trimeric and dimeric phenethylamine alkaloids incorporating an amidine function. The structures of these alkaloids were established by detailed spectroscopic analysis. The absolute configuration of tectoricine was determined by comparison of the experimental and calculated ECD spectra. Plausible biosynthetic pathways to the four alkaloids are proposed

Vobatensines A–F, Cytotoxic Iboga-Vobasine Bisindoles from <i>Tabernaemontana corymbosa</i>

Six new bisindole alkaloids of the iboga-vobasine type, vobatensines A–F (<b>1</b>–<b>6</b>), in addition to four known bisindoles (<b>8</b>–<b>11</b>), were isolated from a stem bark extract of a Malayan <i>Tabernaemontana corymbosa</i>. The structures of these alkaloids were determined based on analysis of the spectroscopic data and in the case of vobatensines A (<b>1</b>), B (<b>2</b>), and 16′-decarbomethoxyvoacamine (<b>8</b>) also confirmed by partial syntheses. Nine of these alkaloids (<b>1</b>–<b>5</b>, <b>8</b>–<b>11</b>) showed pronounced in vitro growth inhibitory activity against human KB, PC-3, LNCaP, HCT 116, HT-29, MCF7, MDA-MB-231, and A549 cancer cells