Predictors of mortality and short-term physical and cognitive dependence in critically ill persons 75 years and older: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to identify predictors of 3-month mortality in critically ill older persons under medical care and to assess the clinical impact of an ICU stay on physical and cognitive dependence and subjective health status in survivors.</p> <p>Methods</p> <p>We conducted a prospective observational cohort study including all older persons 75 years and older consecutively admitted into ICU during a one-year period, except those admitted after cardiac arrest, All patients were followed for 3 months or until death. Comorbidities were assessed using the Charlson index and physical dependence was evaluated using the Katz index of Activity of Daily Living (ADL). Cognitive dependence was determined by a score based on the individual components of the Lawton index of Daily Living and subjective health status was evaluated using the Nottingham Health Profile (NHP) score.</p> <p>Results</p> <p>One hundred patients were included in the analysis. The mean age was 79.3 ± 3.4 years. The median Charlson index was 6 [IQR, 4 to 7] and the mean ADL and cognitive scores were 5.4 ± 1.1 and 1.2 ± 1.4, respectively, corresponding to a population with a high level of comorbidities but low physical and cognitive dependence. Mortality was 61/100 (61%) at 3 months. In multivariate analysis only comorbidities assessed by the Charlson index [Adjusted Odds Ratio, 1.6; 95% CI, 1.2-2.2; <it>p </it>< 0.003] and the number of organ failures assessed by the SOFA score [Adjusted Odds Ratio, 2.5; 95% CI, 1.1-5.2; <it>p </it>< 0.02] were independently associated with 3-month mortality. All 22 patients needing renal support after Day 3 died. Compared with pre-admission, physical (<it>p </it>= 0.04), and cognitive (<it>p </it>= 0.62) dependence in survivors had changed very little at 3 months. In addition, the mean NHP score was 213.1 <b>± </b>132.8 at 3 months, suggesting an acceptable perception of their quality of life.</p> <p>Conclusions</p> <p>In a selected population of non surgical patients 75 years and older, admission into the ICU is associated with a 3-month survival rate of 38% with little impact on physical and cognitive dependence and subjective health status. Nevertheless, a high comorbidity level (ie, Charlson index), multi-organ failure, and the need for extra-renal support at the early phase of intensive care could be considered as predictors of death.</p

Botany, Genetics and Ethnobotany: A Crossed Investigation on the Elusive Tapir's Diet in French Guiana

While the populations of large herbivores are being depleted in many tropical rainforests, the importance of their trophic role in the ecological functioning and biodiversity of these ecosystems is still not well evaluated. This is due to the outstanding plant diversity that they feed upon and the inherent difficulties involved in observing their elusive behaviour. Classically, the diet of elusive tropical herbivores is studied through the observation of browsing signs and macroscopic analysis of faeces or stomach contents. In this study, we illustrate that the original coupling of classic methods with genetic and ethnobotanical approaches yields information both about the diet diversity, the foraging modalities and the potential impact on vegetation of the largest terrestrial mammal of Amazonia, the lowland tapir. The study was conducted in the Guianan shield, where the ecology of tapirs has been less investigated. We identified 92 new species, 51 new genera and 13 new families of plants eaten by tapirs. We discuss the relative contribution of our different approaches, notably the contribution of genetic barcoding, used for the first time to investigate the diet of a large tropical mammal, and how local traditional ecological knowledge is accredited and valuable for research on the ecology of elusive animals

Concentration Dependent Ion Selectivity in VDAC: A Molecular Dynamics Simulation Study

The voltage-dependent anion channel (VDAC) forms the major pore in the outer mitochondrial membrane. Its high conducting open state features a moderate anion selectivity. There is some evidence indicating that the electrophysiological properties of VDAC vary with the salt concentration. Using a theoretical approach the molecular basis for this concentration dependence was investigated. Molecular dynamics simulations and continuum electrostatic calculations performed on the mouse VDAC1 isoform clearly demonstrate that the distribution of fixed charges in the channel creates an electric field, which determines the anion preference of VDAC at low salt concentration. Increasing the salt concentration in the bulk results in a higher concentration of ions in the VDAC wide pore. This event induces a large electrostatic screening of the charged residues promoting a less anion selective channel. Residues that are responsible for the electrostatic pattern of the channel were identified using the molecular dynamics trajectories. Some of these residues are found to be conserved suggesting that ion permeation between different VDAC species occurs through a common mechanism. This inference is buttressed by electrophysiological experiments performed on bean VDAC32 protein akin to mouse VDAC

Ion selectivity in VDAC1: a Molecular Dynamics Study of wild-type and mutant proteins

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Origin of ion selectivity in Phaseolus coccineus mitochondrial VDAC.

The mitochondrial voltage-dependent anion-selective channel (VDAC) is the major permeation pathway for small ions and metabolites. Although a wealth of electrophysiological data has been obtained on different VDAC species, the physical mechanisms of their ionic selectivity are still elusive. We addressed this issue using electrophysiological experiments performed on plant VDAC. A simple macroscopic electrodiffusion model accounting for ion diffusion and for an effective fixed charge of the channel describes well its selectivity. Brownian Dynamics simulations of ion permeation performed on plant and mammalian VDACs point to the role of specific charged residues located at about the middle of the pore.JOURNAL ARTICLESCOPUS: ar.jSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Dual mechanism of ion permeation through VDAC revealed with inorganic phosphate ions and phosphate metabolites.

In the exchange of metabolites and ions between the mitochondrion and the cytosol, the voltage-dependent anion channel (VDAC) is a key element, as it forms the major transport pathway for these compounds through the mitochondrial outer membrane. Numerous experimental studies have promoted the idea that VDAC acts as a regulator of essential mitochondrial functions. In this study, using a combination of molecular dynamics simulations, free-energy calculations, and electrophysiological measurements, we investigated the transport of ions through VDAC, with a focus on phosphate ions and metabolites. We showed that selectivity of VDAC towards small anions including monovalent phosphates arises from short-lived interactions with positively charged residues scattered throughout the pore. In dramatic contrast, permeation of divalent phosphate ions and phosphate metabolites (AMP and ATP) involves binding sites along a specific translocation pathway. This permeation mechanism offers an explanation for the decrease in VDAC conductance measured in the presence of ATP or AMP at physiological salt concentration. The binding sites occur at similar locations for the divalent phosphate ions, AMP and ATP, and contain identical basic residues. ATP features a marked affinity for a central region of the pore lined by two lysines and one arginine of the N-terminal helix. This cluster of residues together with a few other basic amino acids forms a "charged brush" which facilitates the passage of the anionic metabolites through the pore. All of this reveals that VDAC controls the transport of the inorganic phosphates and phosphate metabolites studied here through two different mechanisms.info:eu-repo/semantics/publishe

The mitochondrial VDAC of bean seeds recruits phosphatidylethanolamine lipids for its proper functioning.

The voltage-dependent anion-selective channel (VDAC) is the main pathway for inorganic ions and metabolites through the mitochondrial outer membrane. Studies recently demonstrated that membrane lipids regulate its function. It remains, however, unclear how this regulation takes place. In this study, we show that phospholipids are key regulators of Phaseolus VDAC function and, furthermore, that the salt concentration modulates this regulation. Both selectivity and voltage dependence of Phaseolus VDAC are very sensitive to a change in the lipid polar head from PC to PE. Interestingly enough, this dependence is observed only at low salt concentration. Furthermore, significant changes in VDAC functional properties also occur with the gradual methylation of the PE group pointing to the role of subtle chemical variations in the lipid head group. The dependence of PcVDAC gating upon the introduction of a small mole fraction of PE in a PC bilayer has prompted us to propose the existence of a specific interaction site for PE on the outer surface of PcVDAC. Eventually, comparative modeling and molecular dynamics simulations suggest a potential mechanism to get insight into the anion selectivity enhancement of PcVDAC observed in PE relative to PC.info:eu-repo/semantics/publishe

Protein residues interacting with ATP or AMP in the pore.

<p>Time-averaged number of interactions (N_int) of each of the five positively charged residues (K12-blue, R15-red, K20-cyan, K119-green, R218-orange) with (A-B) the phosphate group of AMP and (C-D) the α-, β-, and γ-phosphate groups (P_α, P_β, and P_γ) of ATP along the pore axis as defined by the position of the terminal phosphate in the presence a KCl concentration of either 0.1 M (A,C) or 1 M (B,D).</p