Epidemiological changes and outcomes of people living with HIV admitted to the intensive care unit: a 14-year retrospective study.

PURPOSES: Since 2016, the World Health Organization has recommended universal antiretroviral therapy (ART) for all people living with Human Immunodeficiency Virus (PLHIV). This recommendation may have influenced the characteristics and outcomes of PLHIV admitted to the Intensive Care Unit (ICU). This study aims to identify changes in the epidemiological and clinical characteristics of PLHIV admitted to the ICU, and their short- and medium-term outcomes before and after the implementation of universal ART (periods 2006-2015 and 2016-2019). METHODS: This retrospective, observational, single-center study included all adult PLHIV admitted to the ICU of a University Hospital in Barcelona from 2006 to 2019. RESULTS: The study included 502 admissions involving 428 patients, predominantly men (75%) with a median (P25-P75) age of 47.5 years (39.7-53.9). Ninety-one percent were diagnosed with HIV before admission, with 82% under ART and 60% admitted from the emergency department. In 2016-2019, there were more patients on ART pre-admission, reduced needs for invasive mechanical ventilation (IMV) and fewer in-ICU complications. ICU mortality was also lower (14% vs 7%). Predictors of in-ICU mortality included acquired immunodeficiency syndrome defining event (ADE)-related admissions, ICU complications, higher SOFA scores, IMV and renal replacement therapy (RRT) requirement. ART use during ICU admission was protective. Higher SOFA scores, admission from hospital wards, and more comorbidities predicted one-year mortality. CONCLUSIONS: The in-ICU mortality of critically ill PLHIV has decreased in recent years, likely due to changes in patient characteristics. Pre- and ICU admission features remain the primary predictors of short- and medium-term outcomes.

Impact of a Nurse-Driven Patient Empowerment Intervention on the Reduction in Patients' Anxiety and Depression During ICU Discharge: A Randomized Clinical Trial.

OBJECTIVES: To assess the impact of a nurse-driven patient empowerment intervention on anxiety and depression of patients during ICU discharge. DESIGN: A prospective, multicenter, randomized clinical trial. SETTING: Three ICUs (1 medical, 1 medical and surgical, and 1 coronary) of three tertiary hospitals. PATIENTS: Adults admitted to the ICU greater than 18 years old for greater than or equal to 48 hours with preserved consciousness, the ability to communicate and without delirium, who were randomized to receive the nurse-driven patient empowerment intervention (NEI) (intervention group [IG] or standard of care [control group (CG)]) before ICU discharge. INTERVENTION: The NEI consisted of an individualized intervention with written information booklets, combined with verbal information, mainly about the ICU process and transition to the ward, aimed at empowering patients in the transition process from the ICU to the general ward. MEASUREMENTS AND RESULTS: Patients completed the Hospital Anxiety and Depression Scale before and after (up to 1 wk) ICU discharge. IG ( n = 91) and CG ( n = 87) patients had similar baseline characteristics. The NEI was associated with a significant reduction in anxiety and depression ( p < 0.001) and the presence of depression ( p = 0.006). Patients with comorbidities and those without family or friends had greater reductions in anxiety and depression after the NEI. After the intervention, women and persons with higher education levels had lower negative outcomes. CONCLUSIONS: We found that a NEI before ICU discharge can decrease anxiety and depression in critically ill survivors. The long-term effect of this intervention should be assessed in future trials. TRIAL REGISTRATION: NCT04527627 ( https://clinicaltrials.gov/ct2/show/NCT04527627 ).

Effects of α-, ß- and maltosyl-ß-cyclodextrins use on the glucoraphanin-sulforaphane system of broccoli juice.

Cyclodextrins (CDs) are macromolecules with several industrial applications, being particularly used in the food industry as health-promoting compounds protection agents, as flavour stabilizers, or to eliminate undesired tastes and browning reactions, among others. This study shows the effects of α- (10, 30 and 40 mmol L-1 ), ß- (3, 6 and 10 mmol L-1 ) and maltosyl-ß-CDs (30, 60 and 90 mmol L-1 ) use on the health-promoting glucoraphanin-sulforaphane system of a broccoli juice up to 24 h at 22 °C. Maltosyl-ß-CD (90 mmol L-1 ) highly retained glucoraphanin content after 24 h at 22 °C, showing better effectiveness than ß-CD (10 mmol L-1 ). Sulforaphane was efficiently encapsulated with ß-CD at just 3 mmol L-1 , and the sulforaphane formed was stable during 3 h at 22 °C. On the other hand, 40 mmol L-1 α-CD retained a high glucoraphanin content in broccoli juice. In contrast, glucoraphanin levels in juice without CDs decreased by 71% after 24 h. Consequently, CDs addition may potentially preserve glucoraphanin in this broccoli juice during industrial processing with the possibility to be later transformed by endogenous myrosinase after ingestion to the health-promoting sulforaphane. © 2018 Society of Chemical Industry.

Distinctive physiological and molecular responses to cold stress among cold-tolerant and cold-sensitive Pinus halepensis seed sources.

BACKGROUND: Forest species ranges are confined by environmental limitations such as cold stress. The natural range shifts of pine forests due to climate change and proactive-assisted population migration may each be constrained by the ability of pine species to tolerate low temperatures, especially in northern latitudes or in high altitudes. The aim of this study is to characterize the response of cold-tolerant versus cold-sensitive Pinus halepensis (P. halepensis) seedlings at the physiological and the molecular level under controlled cold conditions to identify distinctive features which allow us to explain the phenotypic difference. With this objective gas-exchange and water potential was determined and the photosynthetic pigments, soluble sugars, glutathione and free amino acids content were measured in seedlings of different provenances under control and cold stress conditions. RESULTS: Glucose and fructose content can be highlighted as a potential distinctive trait for cold-tolerant P. halepensis seedlings. At the amino acid level, there was a significant increase and accumulation of glutathione, proline, glutamic acid, histidine, arginine and tryptophan along with a significant decrease of glycine. CONCLUSION: Our results established that the main difference between cold-tolerant and cold-sensitive seedlings of P. halepensis is the ability to accumulate the antioxidant glutathione and osmolytes such as glucose and fructose, proline and arginine.

Acute Care Diagnostic Collaboration: Bayesian modeling comparative diagnostic assessment of lactate, procalcitonin and CRP in risk stratified population by Mortality in ED (MEDS) score.

OBJECTIVE: To assess and compare the diagnostic value of lactate, procalcitonin (PCT) and C-reactive protein (CRP) in low, moderate, and high-risk stratified population applying Mortality in Emergency Department (MEDS) risk score using Bayesian statistical modeling. METHODS: MEDS criteria was used to risk stratify into low, moderate and high risk. Each population was attributed a percentage risk, and used as pre-test probability in the Bayesian nomogram. Sensitivity and specificity lactate, PCT and CRP were attained from pooled meta-analysis data. Absolute and relative diagnostic gains were calculated. RESULTS: Pooled diagnostic quality data obtained from a meta-analysis reflected sensitivity for PCT of 77% and specificity of 79%, for lactate sensitivity 49.1% and specificity 74.3% and CRP yielded a sensitivity of 75% and specificity 67%. likelihood ratios (LR) calculations for PCT were LR+ 3.67 and LR- 0.29; for lactate LR+ 1.88 and LR- 0.69; CRP LR+ 2.27 and LR- 0.37. When computed in Bayesian nomogram post-test probabilities for LR+ were as follows: for PCT low risk absolute gain of 11.7% and relative gain of 220%; moderate absolute gain 25.7% relative gain 148.5%; for high risk absolute gain 25.1% and relative gain 42.6%. Lactate LR+ results for low risk absolute gain of 4.7% and relative gain of 88.6%; moderate absolute gain 10.7% and relative gain 61.8%; high risk relative gain 14.1% and relative gain 23.9%. CRP results for low population and LR+ absolute gain 5.7% and relative gain 107.5%; moderate risk 14.7% absolute gain and 84.9% relative gain; high risk 77% post-test 18.1% absolute gain and 30.7% relative gain. CONCLUSION: Bayesian statistical model demonstrated the superior diagnostic quality of PCT. For ruling out severe disease, lactate yielded a higher benefit with increased relative gain with negative LR.

Incremental diagnostic quality gain of CTA over V/Q scan in the assessment of pulmonary embolism by means of a Wells score Bayesian model: results from the ACDC collaboration.

OBJECTIVE: Our objective was to evaluate the diagnostic value of computed tomography angiography (CTA) and ventilation perfusion (V/Q) scan in the assessment of pulmonary embolism (PE) by means of a Bayesian statistical model. METHODS: Wells criteria defined pretest probability. Sensitivity and specificity of CTA and V/Q scan for PE were derived from pooled meta-analysis data. Likelihood ratios calculated for CTA and V/Q were inserted in the nomogram. Absolute (ADG) and relative diagnostic gains (RDG) were analyzed comparing post- and pretest probability. Comparative gain difference was calculated for CTA ADG over V/Q scan integrating ANOVA p value set at 0.05. RESULTS: The sensitivity for CT was 86.0% (95% CI: 80.2%, 92.1%) and specificity of 93.7% (95% CI: 91.1%, 96.3%). The V/Q scan yielded a sensitivity of 96% (95% CI: 95%, 97%) and a specificity of 97% (95% CI: 96%, 98%). Bayes nomogram results for CTA were low risk and yielded a posttest probability of 71.1%, an ADG of 56.1%, and an RDG of 374%, moderate-risk posttest probability was 85.1%, an ADG of 56.1%, and an RDG of 193.4%, and high-risk posttest probability was 95.2%, an ADG of 36.2%, and an RDG of 61.35%. The comparative gain difference for low-risk population was 46.1%; in moderate-risk 41.6%; and in high-risk a 22.1% superiority. ANOVA analysis for LR+ and LR- showed no significant difference (p = 0.8745, p = 0.9841 respectively). CONCLUSIONS: This Bayesian model demonstrated a superiority of CTA when compared to V/Q scan for the diagnosis of pulmonary embolism. Low-risk patients are recognized to have a superior overall comparative gain favoring CTA.

Physiological and Molecular Characterization of the Differential Response of Broccoli (Brassica oleracea var. Italica) Cultivars Reveals Limiting Factors for Broccoli Tolerance to Drought Stress.

Broccoli is a cruciferous crop rich in health-promoting metabolites. Due to several factors, including anthropogenic global warming, aridity is increasing in many cultivation areas. There is a great demand to characterize the drought response of broccoli and use this knowledge to develop new cultivars able to maintain yield under water constraints. The aim of this study is to characterize the drought response at the physiological and molecular level of different broccoli (Brassica oleracea L. var. Italica Plenck) cultivars, previously characterized as drought-sensitive or drought-tolerant. This approach aims to identify different traits, which can constitute limiting factors for drought stress tolerance in broccoli. For this purpose, we have compared several physiological parameters and the complete profiles of amino acids, primary metabolites, hormones, and ions of drought-tolerant and drought-sensitive cultivars under stress and control conditions. We have found that drought-tolerant cultivars presented higher levels of methionine and abscisic acid and lower amounts of urea, quinic acid, and the gluconic acid lactone. Interestingly, we have also found that a drought treatment increases the levels of most essential amino acids in leaves and in florets. Our results have established physiological and molecular traits useful as distinctive markers to predict drought tolerance in broccoli or which could be reliably used for breeding new cultivars adapted to water scarcity. We have also found that a drought treatment increases the content of essential amino acids in broccoli.

Distinctive Traits for Drought and Salt Stress Tolerance in Melon (Cucumis melo L.).

Melon (Cucumis melo L.) is a crop with important agronomic interest worldwide. Because of the increase of drought and salinity in many cultivation areas as a result of anthropogenic global warming, the obtention of varieties tolerant to these conditions is a major objective for agronomical improvement. The identification of the limiting factors for stress tolerance could help to define the objectives and the traits which could be improved by classical breeding or other techniques. With this objective, we have characterized, at the physiological and biochemical levels, two different cultivars (sensitive or tolerant) of two different melon varieties (Galia and Piel de Sapo) under controlled drought or salt stress. We have performed physiological measurements, a complete amino acid profile and we have determined the sodium, potassium and hormone concentrations. This has allowed us to determine that the distinctive general trait for salt tolerance in melon are the levels of phenylalanine, histidine, proline and the Na+/K+ ratio, while the distinctive traits for drought tolerance are the hydric potential, isoleucine, glycine, phenylalanine, tryptophan, serine, and asparagine. These could be useful markers for breeding strategies or to predict which varieties are likely perform better under drought or salt stress. Our study has also allowed us to identify which metabolites and physiological traits are differentially regulated upon salt and drought stress between different varieties.

UGT2B7_-161C>T polymorphism is associated with lamotrigine concentration-to-dose ratio in a multivariate study.

Lamotrigine (LTG) is metabolized by UGT1A4 but UGT2B7 also contributes to its glucuronidation. The aim of this study was to determine whether UGT2B7_- 161C>T and UGT2B7_372A>G polymorphisms contribute to the intersubject variability in LTG concentration-to-dose ratio (LTG-CDR) in epileptic patients. Fifty-three white epileptic patients attending the Neuropediatric and Neurology Services at the Marqués de Valdecilla University Hospital, in whom LTG serum concentration was to be measured for pharmacokinetic monitoring, were selected according to predefined criteria for LTG-CDR evaluation. All patients had at least one steady-state LTG serum concentration obtained before the first dose in the morning. Patients were classified in 3 groups of comedication: (1) LTG in combination with metabolism-inducer anticonvulsants (n = 22), (2) LTG in combination with valproate (n = 13), and (3) LTG as monotherapy (n = 16) or in combination with valproate and inducers (n = 2). Genotypes were determined by Applied Biosystems Genotyping Assays with TaqMan probes. A significant association was found between LTG-CDR and UGT2B7_-161C>T polymorphism (P = 0.021) when patient age and concomitant antiepileptic drugs were taken into account. Comedication explained 70% of the LTG-CDR variability, patient age 24%, and UGT2B7_-161C>T 12%. In contrast, a significant association between LTG-CDR and this polymorphism was not found in the bivariate study when age and comedication groups were not considered. A significant association between UGT2B7_372A>G and LTG-CDR was not found in the bivariate or the multivariate studies. UGT2B7_-161C>T polymorphism is significantly associated with LTG-CDR when comedication with other antiepileptic drugs and patient age are taken into account in a multivariate analysis.

Molecular and cellular events in alcohol-induced muscle disease.

Alcohol consumption induces a dose-dependent noxious effect on skeletal muscle, leading to progressive functional and structural damage of myocytes, with concomitant reductions in lean body mass. Nearly half of high-dose chronic alcohol consumers develop alcoholic skeletal myopathy. The pathogenic mechanisms that lie between alcohol intake and loss of muscle tissue involve multiple pathways, making the elucidation of the disease somewhat difficult. This review discusses the recent advances in basic and clinical research on the molecular and cellular events involved in the development of alcohol-induced muscle disease. The main areas of recent research interest on this field are as follows: (i) molecular mechanisms in alcohol exposed muscle in the rat model; (ii) gene expression changes in alcohol exposed muscle; (iii) the role of trace elements and oxidative stress in alcoholic myopathy; and (iv) the role of apoptosis and preapoptotic pathways in alcoholic myopathy. These aforementioned areas are crucial in understanding the pathogenesis of this disease. For example, there is overwhelming evidence that both chronic alcohol ingestion and acute alcohol intoxication impair the rate of protein synthesis of myofibrillar proteins, in particular, under both postabsorptive and postprandial conditions. Perturbations in gene expression are contributory factors to the development of alcoholic myopathy, as ethanol-induced alterations are detected in over 400 genes and the protein profile (i.e., the proteome) of muscle is also affected. There is supportive evidence that oxidative damage is involved in the pathogenesis of alcoholic myopathy. Increased lipid peroxidation is related to muscle fibre atrophy, and reduced serum levels of some antioxidants may be related to loss of muscle mass and muscle strength. Finally, ethanol induces skeletal muscle apoptosis and increases both pro- and antiapoptotic regulatory mechanisms.

Use of cyclodextrins as secondary antioxidants to improve the color of fresh pear juice.

In this paper, the color of fresh pear juice was evaluated for the first time in the presence of some natural and modified cyclodextrins (CDs) and the effect of these compounds as browning inhibitors was determined using the color space CIELAB system. Furthermore, because contradictory claims have been published concerning the mechanism by which enzymatic browning is inhibited by CDs, a kinetic model in the presence of CDs is proposed and the corresponding apparent complexation constants between the mixtures of diphenols present in pear juice and alpha-, beta-, and maltosyl-beta-CD have been calculated. Moreover, pear juice color was studied in the presence of different polyphenoloxidase inhibitors. Finally, we show that maltosyl-beta-CD enhances the ability of ascorbic acid to prevent enzymatic browning because of the protection that maltosyl-beta-CD offers against ascorbic acid oxidation. In this respect, maltosyl-beta-CD seems to act as a "secondary antioxidant", reducing pear juice browning and enhancing the naturally occurring antioxidant capacity of pear juice.

Use of natural and modified cyclodextrins as inhibiting agents of peach juice enzymatic browning.

UNLABELLED: Although cyclodextrins (CDs) have been successfully used as antibrowning agents in different fruit juices, no research has studied the effect of these compounds on enzymatic browning in peach juice. In this paper, the color of fresh peach juice was evaluated in the presence of two types of natural (alpha-CD and beta-CD) and a modified (maltosyl-beta-CD) CD, and the effectiveness of these compounds as browning inhibitors was determined using the color space CIELAB system. Moreover, to clarify the mechanism by which CDs inhibit peach juice enzymatic browning, the process was kinetically modeled in the absence and presence of CDs using a colorimetric method; the apparent complexation constants between the mixtures of diphenols present in peach juice and some types of CD were calculated. The results show that the highest affinity constant was presented by alpha-CD (Kc = 18.31 mM-1) followed by maltosyl-beta-CD (Kc = 11.17 mM-1), whereas beta-CD was incapable of inhibiting peach juice enzymatic browning. KEYWORDS: Cyclodextrin; browning; peach; juice; color; polyphenol oxidase.

Kinetic study of the activation of banana juice enzymatic browning by the addition of maltosyl-beta-cyclodextrin.

In recent years, the use of cyclodextrins (CDs) as antibrowning agents in fruit juices has received growning attention. However, there has been no detailed study of the behavior of these molecules as substances, which can lead to the darkening of foods. In this paper, when the color of fresh banana juice was evaluated in the presence of different CDs, the evolution of several color parameters was the opposite of that observed in other fruit juices. Moreover, a kinetic model based on the complexation by CDs of the natural browning inhibitors present in banana is developed for the first time to clarify the enzymatic browning activation of banana juice. Finally, the apparent complexation constant between the natural polyphenoloxidase inhibitors present in banana juice and maltosyl-beta-CD was calculated (Kci = 27.026 +/- 0.212 mM (-1)).

Drought Tolerance in Pinus halepensis Seed Sources As Identified by Distinctive Physiological and Molecular Markers.

Drought is one of the main constraints determining forest species growth, survival and productivity, and therefore one of the main limitations for reforestation or afforestation. The aim of this study is to characterize the drought response at the physiological and molecular level of different Pinus halepensis (common name Aleppo pine) seed sources, previously characterized in field trials as drought-sensitive or drought-tolerant. This approach aims to identify different traits capable of predicting the ability of formerly uncharacterized seedlings to cope with drought stress. Gas-exchange, water potential, photosynthetic pigments, soluble sugars, free amino acids, glutathione and proteomic analyses were carried out on control and drought-stressed seedlings in greenhouse conditions. Gas-exchange determinations were also assessed in field-planted seedlings in order to validate the greenhouse experimental conditions. Drought-tolerant seed sources presented higher values of photosynthetic rates, water use efficiency, photosynthetic pigments and soluble carbohydrates concentrations. We observed the same pattern of variation of photosynthesis rate and maximal efficiency of PSII in field. Interestingly drought-tolerant seed sources exhibited increased levels of glutathione, methionine and cysteine. The proteomic profile of drought tolerant seedlings identified two heat shock proteins and an enzyme related to methionine biosynthesis that were not present in drought sensitive seedlings, pointing to the synthesis of sulfur amino acids as a limiting factor for drought tolerance in Pinus halepensis. Our results established physiological and molecular traits useful as distinctive markers to predict drought tolerance in Pinus halepensis provenances that could be reliably used in reforestation programs in drought prone areas.

Life-threatening cryoglobulinemia: clinical and immunological characterization of 29 cases.

OBJECTIVES: To analyze the etiology, clinical presentation, and outcomes of patients with life-threatening cryoglobulinemic vasculitis. METHODS: We studied 209 consecutive patients with cryoglobulinemic vasculitis. A potentially life-threatening cryoglobulinemia was considered as the development of renal failure, vasculitic abdominal involvement, pulmonary hemorrhage, or central nervous system involvement. RESULTS: Twenty-nine (14%) patients had life-threatening cryoglobulinemic vasculitis. There were 17 women and 12 men, with a mean age of 57 years. In 17 (59%) patients, life-threatening cryoglobulinemia was the initial clinical feature of the disease. The 29 patients had a total of 33 life-threatening episodes, which included renal failure due to cryoglobulinemic glomerulonephritis (n = 18), intestinal vasculitis (n = 8), pulmonary hemorrhage (n = 4), and central nervous system involvement (n = 3). In comparison with a control group of age-sex-matched patients with milder cryoglobulinemic vasculitis, those with severe cryoglobulinemic vasculitis had a higher frequency of fever (28% versus 7%, P = 0.017), type II cryoglobulins (100% versus 59%, P = 0.008), low C3 levels (55% versus 20%, P = 0.001), and a higher mean value of cryocrit (11.4% versus 3.3%, P = 0.004). Nineteen (66%) of the 29 patients with life-threatening involvement died, with the mortality rate reaching 100% in patients with intestinal ischemia and pulmonary hemorrhage. CONCLUSION: Life-threatening cryoglobulinemic vasculitis was observed in 14% of our patients, with almost two-thirds of episodes occurring at the onset of the disease. Fever, high cryocrit levels, and low C3 levels were associated with this severe presentation. Two-thirds of the patients died, with mortality for pulmonary hemorrhage and intestinal ischemia reaching 100%.

Influence of nutritional status on alcoholic myopathy.

BACKGROUND: Muscle weakness and structural changes in striated skeletal muscle are common in persons with chronic alcoholism. OBJECTIVE: The objective of the study was to assess the role of malnutrition in the development of chronic alcoholic myopathy. DESIGN: We prospectively evaluated 146 men who reported an intake >/=100 g ethanol/d for the previous 5 y and 73 well-nourished control subjects. Alcohol consumption, energy and protein nutritional status, and deltoid muscle strength were determined. Deltoid muscle tissue specimens were taken from alcoholics and from 14 control subjects for histochemical studies and morphometric measurements of the fibers. RESULTS: Deltoid muscle strength was less in alcoholics than in control subjects (P < 0.001). Muscle strength correlated with lifetime consumption of ethanol (r = -0.56, P < 0.001), and a decrease in muscle strength was significantly greater in the presence of energy malnutrition. Using logistic regression analysis, we observed that alcoholics with muscle strength < 18 kg had the independent risk factors of an arm muscle area < 50 cm(2) (odds ratio: 5.4; 95% CI: 2.3, 12.3), consumption of > 1600 kg ethanol throughout their lives (odds ratio: 4.5; 95% CI: 2.0, 10.1), and protein malnutrition (odds ratio: 4.2; 95% CI: 1.4, 12.7). Protein malnutrition was also associated with muscle inefficiency (P < 0.001). Histologic myopathy was present in 58% of alcoholics, was related to lifetime ethanol consumption (P = 0.001), and was more severe in the presence of protein malnutrition (P = 0.01). CONCLUSION: Malnutrition is an additional developmental factor in the functional and structural muscle damage induced by chronic ethanol consumption.

Cell membrane stretch modulates the high-conductance Ca2+-activated K+ channel in bovine trabecular meshwork cells.

PURPOSE: Anterior chamber structures are subjected to changes in intraocular pressure (IOP). Several studies have pointed out that trabecular meshwork (TM) cells are sensitive to mechanical stretch and that cell-signaling mechanisms are activated in response to elevated pressure. Because membrane stretch has been shown to be a modulator of several ionic conductances, this study was conducted to determine its effects on the high-conductance Ca(2+)-activated K(+) (BK(Ca)) channels present in TM cells. METHODS: Primary cultures of TM cells from bovine eyes were used. Patch-clamp recordings were performed in the cell-attached, inside-out, and whole-cell configurations. To stretch the cell membrane, both suction to the rear end of the patch pipette and hypotonic shock were used. Intracellular calcium concentration ([Ca(2+)](i)) was measured in TM cells loaded with fura-2, using an epifluorescence microscope coupled to a charge-coupled device (CCD) camera. RESULTS: Electrophysiological characterization of BK(Ca) channels was in agreement with previous studies. In cell-attached patches, the open probability of the BK(Ca) channel (i.e., the amount of time the channel is open) increased consistently when 14- to 45-mm Hg suctions were applied at a constant depolarized voltage. At a constant pressure (25 or 45 mm Hg), channel openings increased when depolarizing pulses were applied to the patch. Stretch activation of the BK(Ca) channel was not mediated by increases in [Ca(2+)](i), because it was present in inside-out patches maintained at a constant Ca(2+) concentration. Nevertheless, it cannot be ruled out that at low suction levels, a minimum Ca(2+) concentration is necessary for channel activation. Whole-cell currents carried by BK(Ca) channels increased when the isotonic solution in the bath was exchanged with a hypotonic solution and were selectively blocked by iberiotoxin. In our conditions, the hypotonic shock did not modify [Ca(2+)](i). CONCLUSIONS: The data show that in TM cells, open probability of the BK(Ca) channel is enhanced by membrane stretching as well as by membrane depolarization and [Ca(2+)](i). Changes in membrane tension induced by cell volume increase also activated whole-cell BK(Ca) currents. Homeostatic mechanisms in TM cells may involve BK(Ca) channel activation in response either to changes in cell volume or changes in IOP.

[Central-venous catheter-related infections and intensive care unit organization systems (EPIC Study, Spain)]. / Infecciones relacionadas con el uso de catéteres venosos centrales y sistemas organizativos de las unidades de cuidados intensivos (estudio EPIC).

BACKGROUND AND OBJECTIVE: Central venous catheter (CVC)-related nosocomial bacteremia is an important problem at the ICU. The possible role of organizational factors, as well as health care workers experience, for developing these infections is not well known. We aimed to identify the possible relationships and differences between the health care process, organizational features of the institutions and the development of CVC-related nosocomial infections. We also compared the results of the Spanish participating hospital with those of an international group of hospitals. PATIENTS AND METHOD: The EPIC study (Evaluation of Processes and Indicators in Infection Control) includes a total of 56 hospitals from different countries. The Hospital Clínic of Barcelona was the only Spanish participant. Each Hospital selects, by means of a random process, 5 ICU patients per month with a recently placed CVC. Data related to the CVC insertion process, follow-up and care of the CVC, time dedication of nursing personnel, days of stay and episodes of CVC-related bacteremia per 1000 patient-days of CVC use were recorded. RESULTS: A total of 3,298 patients with a CVC were included, and 89 episodes of CVC-related nosocomial bacteremia were identified (3.86 episodes per 1000 CVC-days). The Hospital Clínic included 67 patients with a CVC and identified 1.96 episodes of CVC-related nosocomial bacteremia per 1000 CVC-days. When compared to the international group of hospitals, the Spanish centre used sterile drapes more frequently for fixing the CVC (70% vs. 23%), each Health Care Worker inserted fewer CVC (average over last 6 months: 24 vs 50) and CVC were more frequently inserted by Registered Nurses (48% vs. 4%). The type of CVC more commonly used in Spain was a peripherically-inserted CVC (48% vs. 6%), and the CVC was withdrawn from patients less commonly before discharge from the ICU (16% vs. 43%). Mean total number of hours of nursing dedication was lower in Spain, with lower personnel ratios (number of nurses' hours) per day of stay (12 vs. 15). CONCLUSIONS: The EPIC study provides a valid tool for assessing the results of the process of health care, and for linking the outcomes to this process. The results registered at the Spanish hospital seem to be adequate, yet some differences in the health care process are identified.

Inactivation of lipoxygenase and cyclooxygenase by natural betalains and semi-synthetic analogues.

Betalains are natural pigments characteristic of plants of the order Caryophyllales. In this work, the role of betalains in the anti-inflammatory activity described for plant extracts is analysed in terms of the inactivation of the enzymes involved in the biochemical response (lipoxygenase and cyclooxygenase). Pure natural betalains and semi-synthetic analogues are demonstrated to promote a significant reduction of the enzymes activity. Reactions were followed spectrophotometrically and by HPLC-DAD. Phenethylamine-betaxanthin was the most potent in the inactivation of cyclooxygenase, with a reduction of 32% of the control activity at 125µM, while the natural pigment betanidin and a betalain analogue derived from indoline resulted as the most potent inactivators of lipoxygenase, with IC50 values of 41.4 and 40.1µM, respectively. Molecular docking studies revealed that betalains interact with the lipoxygenase amino acids involved in substrate binding and with Tyr-385 and Ser-530 close to the cyclooxygenase active site, interfering in enzyme catalysis.

Effects of different antigenic stimuli on thymic function and interleukin-7/CD127 system in patients with chronic HIV infection.

BACKGROUND: We tested if an increase in immune activation and a decrease in CD4⁺ T cells induced by different antigenic stimuli could be associated with changes in the thymic function and the interleukin (IL)-7/CD127 system. METHODS: Twenty-six HIV-infected patients under combined antiretroviral therapy (cART) were randomized to receive, during 12 months, a complete immunization schedule (7 vaccines and 15 doses) or placebo. Thereafter, cART was interrupted during 6 months. Changes in the thymic function and the IL-7/CD127 system after 3 different antigenic stimuli (vaccines, episodes of low-level intermittent viremia before cART interruption, or viral load rebound after cART interruption) were assessed. RESULTS: During the period on cART, neither vaccines nor low-level viremia influenced thymic function or IL-7/CD127 system parameters. By analyzing the cohort as a whole while on cART, a significant improvement was observed in the thymic function as measured by an increase in the thymic volume (P = 0.024), T-cell receptor excision circle-bearing cells (P = 0.012), and naive CD4⁺ and CD8⁺ T cells (P = 0.069 both). No significant changes were observed in the IL-7/CD127 system. After cART interruption, a decrease in T-cell receptor excision circles (P < 0.001) and naive CD8⁺ T cells (P < 0.001), an increase in IL-7 and expression of CD127 on naive and memory CD4⁺ T cells (P = 0.028, P = 0.088, and P = 0.04, respectively), and a significant decrease in CD127 on naive and memory CD8⁺ T cells (P = 0.01, P = 0.006, respectively) were observed. CONCLUSIONS: Low-level transient antigenic stimuli during cART were not associated with changes in the thymic function or the IL-7/CD127 system. Conversely, viral load rebound very early after cART interruption influenced the thymic function and the IL-7/CD127 system. Clinical Trials.gov number NCT00329251.