Distorted octahedral coordination of tungstate in a subfamily of specific binding proteins

Bacteria and archaea import molybdenum and tungsten from the environment in the form of the oxyanions molybdate (MoO4 2−) and tungstate (WO4 2−). These substrates are captured by an external, high-affinity binding protein, and delivered to ATP binding cassette transporters, which move them across the cell membrane. We have recently reported a crystal structure of the molybdate/tungstate binding protein ModA/WtpA from Archaeoglobus fulgidus, which revealed an octahedrally coordinated central metal atom. By contrast, the previously determined structures of three bacterial homologs showed tetracoordinate molybdenum and tungsten atoms in their binding pockets. Until then, coordination numbers above four had only been found for molybdenum/tungsten in metalloenzymes where these metal atoms are part of the catalytic cofactors and coordinated by mostly non-oxygen ligands. We now report a high-resolution structure of A. fulgidus ModA/WtpA, as well as crystal structures of four additional homologs, all bound to tungstate. These crystal structures match X-ray absorption spectroscopy measurements from soluble, tungstate-bound protein, and reveal the details of the distorted octahedral coordination. Our results demonstrate that the distorted octahedral geometry is not an exclusive feature of the A. fulgidus protein, and suggest distinct binding modes of the binding proteins from archaea and bacteri

Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry

Background: It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. Methods: Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. Results: Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. Conclusion: Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic. Keywords: ARDS; COVID-19; Disease dynamics; Intensive care unit; Pandemic

Stent thrombosis following bare-metal stent implantation: success of emergency percutaneous coronary intervention and predictors of adverse outcome

Aims To investigate the efficacy and outcome of emergency percutaneous coronary interventions (PCI) in patients with stent thrombosis. Methods and results Between 1995 and 2003, 6058 patients underwent bare-metal stent implantation, of which 95 (1.6%) patients suffered from stent thrombosis. The timing of stent thrombosis was acute in 10 (11%), subacute in 61 (64%), and late in 24 (25%) patients. Procedural and clinical outcomes of emergency PCI for treatment of stent thrombosis were investigated. Emergency PCI was successful in 86 (91%), complicated by death in 2 (2%), and coronary artery bypass grafting in 2 (2%) patients. Myocardial infarction occurred in 77 (81%) patients with a peak creatine kinase level of 1466±1570 U/L. Left ventricular ejection fraction declined from 0.54±0.19 prior to 0.48±0.16 (P<0.05) at the time of stent thrombosis after emergency PCI. A 6 month major adverse clinical events comprised death (11%), reinfarction (16%), and recurrent stent thrombosis (12%) after emergency PCI. Multivariable logistic regression analysis identified the achievement of TIMI 3 flow (OR=0.1, CI 95% 0.01-0.54, P<0.001) and diameter stenosis <50% (OR=0.06, CI 95% 0.01-0.32, P<0.001) during emergency PCI to be independently associated with a reduced risk of cardiac death. Recurrent stent thrombosis was independently predicted by the omission of abciximab (OR=4.3, CI 95% 1.1-17.5). Conclusion Emergency PCI for treatment of stent thrombosis effectively restores vessel patency and flow. Patients presenting with stent thrombosis are at risk for recurrent myocardial infarction and recurrent stent thrombosi

Diagnostic performance of the Minimal Eating Observation and Nutrition Form - Version II (MEONF-II) and Nutritional Risk Screening 2002 (NRS 2002) among hospital inpatients - a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The usefulness of the nutritional screening tool Minimal Eating Observation and Nutrition Form - Version II (MEONF-II) relative to Nutritional Risk Screening 2002 (NRS 2002) remains untested. Here we attempted to fill this gap by testing the diagnostic performance and user-friendliness of the MEONF-II and the NRS 2002 in relation to the Mini Nutritional Assessment (MNA) among hospital inpatients.</p> <p>Methods</p> <p>Eighty seven hospital inpatients were assessed for nutritional status with the 18-item MNA (considered as the gold standard), and screened with the NRS 2002 and the MEONF-II.</p> <p>Results</p> <p>The MEONF-II sensitivity (0.61), specificity (0.79), and accuracy (0.68) were acceptable. The corresponding figures for NRS 2002 were 0.37, 0.82 and 0.55, respectively. MEONF-II and NRS 2002 took five minutes each to complete. Assessors considered MEONF-II instructions and items to be easy to understand and complete (96-99%), and the items to be relevant (87%). For NRS 2002, the corresponding figures were 75-93% and 79%, respectively.</p> <p>Conclusions</p> <p>The MEONF-II is an easy to use, relatively quick and sensitive screening tool to assess risk of undernutrition among hospital inpatients. With respect to user-friendliness and sensitivity the MEONF-II seems to perform better than the NRS 2002, although larger studies are needed for firm conclusions. The different scoring systems for undernutrition appear to identify overlapping but not identical patient groups. A potential limitation with the study is that the MNA was used as gold standard among patients younger than 65 years.</p

Peptidomimetic antibiotics disrupt the lipopolysaccharide transport bridge of drug-resistant Enterobacteriaceae

The rise of antimicrobial resistance poses a substantial threat to our health system, and, hence, development of drugs against novel targets is urgently needed. The natural peptide thanatin kills Gram-negative bacteria by targeting proteins of the lipopolysaccharide transport (Lpt) machinery. Using the thanatin scaffold together with phenotypic medicinal chemistry, structural data, and a target-focused approach, we developed antimicrobial peptides with drug-like properties. They exhibit potent activity against Enterobacteriaceae both in vitro and in vivo while eliciting low frequencies of resistance. We show that the peptides bind LptA of both wild-type and thanatin-resistant Escherichia coli and Klebsiella pneumoniae strains with low-nanomolar affinities. Mode of action studies revealed that the antimicrobial activity involves the specific disruption of the Lpt periplasmic protein bridge

Estado nutricional vinculado a ingesta alimentaria y actividad física que realizan estudiantes de séptimo grado de tres colegios privados. Managua-Nicaragua. Abril-Agosto 2015.

Estudio descriptivo de corte transversal en 150 estudiantes de séptimo grado de los colegios: Mi Redentor, Bautista y Jesús Divino Obrero del departamento de Managua. Se concluye que más de la mitad de estudiantes, presentaron estado nutricional normal. Coexiste malnutrición por déficit, y por exceso, asociado al riesgo cardiovascular y antecedentes patológicos familiares de hipertensión y diabetes. El desayuno es la comida que se saltaron con mayor frecuencia. El patrón alimentario lo conforman trece alimentos. La práctica de actividades físicas que realizan: caminar, correr, montar en bicicleta, jugar futbol, voleibol y baloncesto. En la clase de educación física los alumnos están siempre y algunas veces activos