CTX-M-15-H30Rx-ST131 subclone is one of the main causes of healthcare-associated ESBL-producing Escherichia coli bacteraemia of urinary origin in Spain.

OBJECTIVES: The objective of this study was to assess the prevalence and molecular epidemiology of ESBL-producing Escherichia coli causing healthcare-associated (HCA) and community-associated (CA) bacteraemia of urinary origin (BUO) in Spain. METHODS: An observational cohort study was conducted at eight hospitals from different Spanish geographical areas (2010-11). BUO episodes (n = 425) were classified as HCA (n = 215) and CA (n = 210), and one blood isolate per episode was collected. Susceptibility testing was performed, ESBLs were screened by double-disc diffusion test and ESBL and OXA-1 genes were characterized (PCR and sequencing). Population structure (phylogenetic groups, XbaI-PFGE and MLST) and ST131 subtyping (PCR) were determined. Virulence genes were detected by PCR and virulence score, profiles and extraintestinal pathogenic E. coli (ExPEC) status calculated. RESULTS: ESBL-producing E. coli prevalence was 9.2% (39/425). ESBL-producing E. coli episodes were significantly associated with HCA-BUO episodes [14% (30/215) versus 4.3% (9/210); P = 0.001]. The highest non-susceptibility proportions corresponded to ciprofloxacin (97.4%), amoxicillin/clavulanate (74.4%), co-trimoxazole (69.2%) and tobramycin (61.5%). Of the 39 ESBL-producing E. coli isolates, 34 produced CTX-M enzymes (21 CTX-M-15, 11 CTX-M-14 and 2 CTX-M-1). Fifteen STs were identified, the B2-ST131 clone being the most prevalent (54%; 21/39). All ST131 isolates were ExPEC and had the highest virulence scores, but they showed less diversity in virulence profiles than other STs. The H30Rx subclone accounted for most ST131 isolates (20/21), co-produced CTX-M-15 (20/20) and OXA-1 (19/20) enzymes and was associated with HCA episodes (16/20). CONCLUSIONS: The CTX-M-15-ST131-H30Rx subclone is a relevant MDR pathogen causing BUO, mainly HCA episodes. The dominance of this subclone with comparatively less diversity of virulence profiles reflects the spread of a successful and MDR ESBL ST131 lineage in Spain.

Multi-ancestry Genome-Wide Association Study of Early Childhood Caries.

Early childhood caries (ECC) is the most common non-communicable childhood disease. It is an important health problem with known environmental and social/behavioral influences that lacks evidence for specific associated genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multi-ancestry population of U.S. preschool-age children (n=6,103) participating in a community-based epidemiologic study of early childhood oral health. Calibrated examiners used ICDAS criteria to measure ECC with the primary trait using the dmfs index with decay classified as macroscopic enamel loss (ICDAS ≥3). We estimated heritability, concordance rates, and conducted genome-wide association analyses to estimate overall genetic effects; the effects stratified by sex, household water fluoride, and dietary sugar; and leveraged the combined gene/gene-environment effects using the 2-degree-of-freedom (2df) joint test. The common genetic variants explained 24% of the phenotypic variance (heritability) of the primary ECC trait and the concordance rate was higher with a higher degree of relatedness. We identified 21 novel non-overlapping genome-wide significant loci for ECC. Two loci, namely RP11-856F16 . 2 (rs74606067) and SLC41A3 (rs71327750) showed evidence of association with dental caries in external cohorts, namely the GLIDE consortium adult cohort (n=∼487,000) and the GLIDE pediatric cohort (n=19,000), respectively. The gene-based tests identified TAAR6 as a genome-wide significant gene. Implicated genes have relevant biological functions including roles in tooth development and taste. These novel associations expand the genomics knowledge base for this common childhood disease and underscore the importance of accounting for sex and pertinent environmental exposures in genetic investigations of oral health.

[Analysis of the valproic acid-meropenem interaction in hospitalised patients]. / Análisis de la interacción ácido valproico-meropenem en pacientes hospitalizados.

INTRODUCTION: Published data demonstrate a serious interaction between valproic acid and meropenem. However, recommendations about the management of concomitant treatment are contradictory; some experts recommend closer monitoring of valproic acid serum concentrations and others recommend avoiding concurrent therapy. The purpose of this study is to critically analyse the interaction and to evaluate the impact of pharmaceutical intervention in the use of these drugs in hospitalised patients. MATERIAL AND METHODS: Study of the concomitant prescription of valproic acid and meropenem in a general hospital of 1,080 beds divided in to two periods; the first period was retrospective and observational and it was followed by a prospective period involving pharmaceutical intervention. The prescription habits between both periods were compared. RESULTS: A total of 26 patients received concurrent treatment with valproic acid and meropenem (13 per period) and none of them maintained therapeutic serum levels of the antiepileptic drug. Pharmaceutical intervention modified prescription habits, reducing by half the number of days of concomitant treatment, changing the antibiotherapy and/or monitoring serum concentrations more often. CONCLUSIONS: The interaction between valproic acid and meropenem is serious, especially because of the dramatic decrease in the antiepileptic serum concentrations. The concomitant use of both drugs should be avoided, replacing the antibiotherapy empirically, or according to the resistance profiles of the microorganism and maintaining the same the anti-epileptic treatment.

[Analysis of errors in manual versus electronic prescriptions in trauma patients]. / Análisis de errores de la prescripción manual comparados con la prescripción electrónica asistida en pacientes traumatológicos.

OBJECTIVE: To detect, quantify, and compare the medication error produced with manual versus electronically assisted prescription systems. METHODS: A descriptive, observational, prospective study in two traumatology hospitalisation units; one with manual prescriptions and the other with electronically assisted prescriptions. Prescription errors were determined. RESULTS: We analysed 1,536 lines of treatment (393 treatment forms) from 164 patients. With manual prescriptions, we detected errors in 19.54% of cases, compared to 9.4% in electronically assisted prescriptions. Omission errors were significantly lower with electronically assisted prescriptions, especially with drugs that act upon the central nervous system. CONCLUSIONS: Prescription error has decreased by 53% since computerising the prescription process. This is particularly useful for omission errors, as prescription is more complete. The decrease in error regarding drugs that act on the central nervous system stands out.

Transcultural adaptation and validity of a pictogram to assess communication needs in adults with artificial airway in intensive care.

OBJECTIVE: To perform the cross-cultural adaptation and validity of a pictogram to assess communication needs in adults with artificial airway in ICU in Cartagena, Colombia. METHOD: Scale validation study, population comprising all the patients who were hospitalized in six ICU of Cartagena-Colombia. The sample was made up of 181 adult patients with artificial airway, the adaptation to Spanish was determined (translation, backtranslation, expert review, pre-final version, pilot test, final version), facial validity by expert agreement, content validity with the Lawshe index modified by Tristan (cut-off point 0.58), exploratory factor analysis (AFE) with the Bartlett's test of sphericity and Cattell's graph; internal consistency measured through the Cronbach alpha statistic. RESULTS: Patients between the ages of 19 and 88 years participated (mean = 54 ±â€¯17), 91.71% expressed frequent needs for accompaniment, knowing date and time; 61% of the experts agreed with the cross-culturally adapted items, the overall Content Validity Index (CVI) was 0.86 with agreement in understanding eleven items. The AFE suggested retaining 13 items and 3 factors (perception/cognition, elimination and exchange, comfort), which explain the construct. The internal alpha Cronbach consistency was 0.64. CONCLUSIONS: The pictographic material, Spanish version, was shown to be a multidimensional instrument composed of 18 items grouped in 3 factors. Therefore, it is recommended it be applied to the patient with artificial airway and to establish communication as a preliminary point of care in nursing.

Transcultural adaptation and validity of a pictogram to assess communication needs in adults with artificial airway in intensive care. / Adaptación transcultural y validez de un pictograma para evaluar necesidades de comunicación en adultos con vía aérea artificial en cuidados intensivos.

OBJECTIVE: To perform the cross-cultural adaptation and validity of a pictogram to assess communication needs in adults with artificial airway in ICU in Cartagena, Colombia. METHOD: Scale validation study, population comprising all the patients who were hospitalized in six ICU of Cartagena-Colombia. The sample was made up of 181 adult patients with artificial airway, the adaptation to Spanish was determined (translation, backtranslation, expert review, pre-final version, pilot test, final version), facial validity by expert agreement, content validity with the Lawshe index modified by Tristan (cut-off point 0.58), exploratory factor analysis (AFE) with the Bartlett's test of sphericity and Cattell's graph; internal consistency measured through the Cronbach alpha statistic. RESULTS: Patients between the ages of 19 and 88years participated (mean: 54±17); 91.71% expressed frequent needs for accompaniment, knowing date and time; 61% of the experts agreed with the cross-culturally adapted items, the overall Content Validity Index (CVI) was 0.86 with agreement in understanding eleven items. The AFE suggested retaining 13 items and 3 factors (perception/cognition, elimination and exchange, comfort), which explain the construct. The internal alpha Cronbach consistency was 0.64. CONCLUSIONS: The pictographic material, Spanish version, was shown to be a multidimensional instrument composed of 18 items grouped in 3 factors. Therefore, it is recommended it be applied to the patient with artificial airway and to establish communication as a preliminary point of care in nursing.

Effects of hospital pharmacist interventions on health outcomes in older polymedicated inpatients: a scoping review.

PURPOSE: To identify the evidence that supports the effect of interventions made by hospital pharmacists, individually or in collaboration with a multidisciplinary team, in terms of healthcare outcomes, a more effective utilization of resources and lower costs in older polymedicated inpatients. METHODS: We searched the following databases: MEDLINE, EMBASE and the Cochrane Library. We also conducted a hand search by checking the references cited in the primary studies and studies included in reviews identified during the process of research. Four review authors working by pairs searched for studies, extracted data, and drew up the results tables. RESULTS: Twenty-six studies were included in the review. In 13 of them pharmacists carried out their intervention exclusively while the patients were in hospital, whereas in 13 interventions were delivered during admission and after hospital discharge. Outcomes identified were mortality, length of stay, visits to the emergency department, readmissions and reported quality of life, among others. Pharmacist interventions were found to be beneficial in fifteen studies, specifically on hospital readmissions, visits to the emergency department and healthcare costs. CONCLUSION: There is no hard evidence demonstrating the effectiveness of hospital pharmacist interventions in older polymedicated patients. Mortality does not show as a relevant outcome. Other health care outcomes, such as hospital readmissions, visits to the emergency department and healthcare costs, seem to be more relevant and amenable to change. Interventions that include pharmacists in multidisciplinary geriatric teams seem to be more promising that isolated pharmacist interventions. Interventions prolonged after hospital discharge seem to be more appropriate that interventions delivered only during hospital admission. Better-designed studies should be conducted in the future to provide further insight into the effect of hospital pharmacist interventions.

Metabolomics Insights in Early Childhood Caries.

Dental caries is characterized by a dysbiotic shift at the biofilm-tooth surface interface, yet comprehensive biochemical characterizations of the biofilm are scant. We used metabolomics to identify biochemical features of the supragingival biofilm associated with early childhood caries (ECC) prevalence and severity. The study's analytical sample comprised 289 children ages 3 to 5 (51% with ECC) who attended public preschools in North Carolina and were enrolled in a community-based cross-sectional study of early childhood oral health. Clinical examinations were conducted by calibrated examiners in community locations using International Caries Detection and Classification System (ICDAS) criteria. Supragingival plaque collected from the facial/buccal surfaces of all primary teeth in the upper-left quadrant was analyzed using ultra-performance liquid chromatography-tandem mass spectrometry. Associations between individual metabolites and 18 clinical traits (based on different ECC definitions and sets of tooth surfaces) were quantified using Brownian distance correlations (dCor) and linear regression modeling of log2-transformed values, applying a false discovery rate multiple testing correction. A tree-based pipeline optimization tool (TPOT)-machine learning process was used to identify the best-fitting ECC classification metabolite model. There were 503 named metabolites identified, including microbial, host, and exogenous biochemicals. Most significant ECC-metabolite associations were positive (i.e., upregulations/enrichments). The localized ECC case definition (ICDAS ≥1 caries experience within the surfaces from which plaque was collected) had the strongest correlation with the metabolome (dCor P = 8 × 10-3). Sixteen metabolites were significantly associated with ECC after multiple testing correction, including fucose (P = 3.0 × 10-6) and N-acetylneuraminate (p = 6.8 × 10-6) with higher ECC prevalence, as well as catechin (P = 4.7 × 10-6) and epicatechin (P = 2.9 × 10-6) with lower. Catechin, epicatechin, imidazole propionate, fucose, 9,10-DiHOME, and N-acetylneuraminate were among the top 15 metabolites in terms of ECC classification importance in the automated TPOT model. These supragingival biofilm metabolite findings provide novel insights in ECC biology and can serve as the basis for the development of measures of disease activity or risk assessment.

A post-training intrahippocampal anxiogenic dose of the neurosteroid pregnenolone sulfate impairs passive avoidance retention.

Pregnenolone sulfate (PregS) is a neurosteroid that acts as a negative modulator of the GABA(A) receptor complex and a positive modulator of glutamate NMDA receptors. PregS improves learning and memory when centrally or systemically administered. However, systemic high doses of PregS, which facilitate the passive avoidance retention, have been shown to impair this learning when a high foot-shock punishment was used. Moreover, moderate or high PregS doses present a well documented anxiogenic-like profile in several animal models of anxiety. In previous experiments, we have shown that unilateral intrahippocampal 5 ng of PregS improves spatial recognition memory and reverses learning impairment induced by co-administration of alcohol and nicotine. In the present experiment, we analyzed the effects of bilateral intrahippocampal 5 ng of PregS on the passive avoidance task, using a high foot-shock punishment (0.5 mA), as well as on anxiety-like behaviour measured in the open field test in the same experimental subjects. As a control, we have injected the neurosteroid allopregnanolone (AlloP) into the hippocampus, which produces opposite behavioural and neurochemical profiles to those of PregS, by acting as a positive GABA(A) modulator and showing anxiolytic and sedative behavioural effects. Results showed that bilateral intrahippocampal 5 ng of PregS deteriorated passive avoidance retention but also presented an anxiogenic-like profile in the open field test, decreasing the locomotion and the time spent in the central zone without affecting either total activity or time spent in the periphery of the field (thigmotaxis). AlloP administration did not affect passive avoidance retention, and also showed a non anxiolytic-like profile, possibly related to fluctuations of endogenous AlloP concentrations induced by the stress generated by the high foot-shock punishment received before the anxiety tests. In conclusion, a post-training intrahippocampal anxiogenic dose of the neurosteroid PregS impairs passive avoidance retention. These results highlight the important role of the hippocampus in several behavioural effects of neurosteroids on learning, memory processes and anxiety.

[Involvement of neurosteroids in normal and pathological behaviour]. / Implicación de los neuroesteroides en la conducta normal y patológica.

INTRODUCTION: The nervous system synthesises steroids (then called neurosteroids) de novo from cholesterol. These substances play a role in a number of functions related to the allosteric modulation of the main ionotropic receptors in the central nervous system (CNS). AIM: To describe the most important behavioural and cognitive processes in which neurosteroids are involved and which can open up new perspectives for research focused above all on their possible therapeutic use in pathologies affecting the CNS, such as the cognitive impairment associated to neurodegenerative diseases, addictions like alcoholism, anxiety disorders, and epilepsy and convulsive behaviour. DEVELOPMENT: We provide a brief outline of the concept of neurosteroids, their synthesis, how they act on receptors for neurotransmitters and their distribution throughout nerve tissue. We then offer an extensive, up-to-date, critical review of the main psychological processes that they are involved in. CONCLUSIONS: Neurosteroids offer an important therapeutic potential. In epileptiform behaviour, no tolerance is developed to the anticonvulsive effects of these substances with repeated administration, unlike the case of benzodiazepines, although the study of synthetic analogues and agents that step up the synthesis of neurosteroids in the CNS seems to be decisive owing to the limitation imposed by the long-term systemic use of hormones. In anxiety disorders, they offer several advantages that are comparable to the prototypical anxiolytic agents, that is, benzodiazepines, but also their chief side effects, such as sedation. In cognitive impairment, the enormous potential for cognitive enhancement in animal models is not reproduced in humans with dementia, although controlled clinical trials are needed to evaluate the benefits and risks of replacement therapy with steroids.

MIRAgel: the immunohistochemical expression of CD3, CD34, and CD68 in the surrounding capsule.

PurposeTo study the immunohistochemical features of the capsule tissue surrounding MIRAgel episcleral buckles.Patients and methodsThis Institutional interventional clinical cohort study examined a consecutive series of 21 referred patients who required MIRAgel removal from July 2009 to July 2013. All patients with hydrated and fragmented MIRAgel episcleral buckles were included in this study. Capsule biopsies from MIRAgel episcleral buckles were obtained from all patients. Capsule specimens of seven patients with extruded silicone bands were processed as controls. Paraffin-embedded specimens were examined using light microscopy and immunohistochemistry (via the PAP horseradish peroxidase technique) to detect the expression of CD3, CD20, CD34 and CD68, and S-100 protein.ResultsInflammation with granuloma, which was primarily related to sutures, was found in all (n=36) of the MIRAgel specimens and foreign body granulomas with multinucleated giant cells, histiocytes, and macrophages (CD68+ cells) surrounded the MIRAgel fragments. Average number of CD68+ cells was higher (P<0.001) for MIRAgel than for silicone rubber. The lymphocytic inflammatory infiltrate related to the MIRAgel fragments was CD3+ and CD20- (delayed T cell-mediated immune response). Moderate neoangiogenesis was indicated by the presence of CD34+ cells.ConclusionsThe immunohistochemical analysis revealed that the immune system is able to identify the fragments of MIRAgel (after its hydrolytic degradation) as a foreign body during a delayed T cell-mediated immune response. The phagocytosis by macrophages likely triggers and perpetuates local disease. Removal of MIRAgel explants before hydrolysis should be considered.

On the origin of the highest ozone episodes in Spain.

The 2000-2015 occurrences of the highest ozone (O3) pollution episodes in Spain were evaluated to investigate their origin. To this end, data series available for urban and regional background (UB and RB), traffic (TR) and industrial (IN) sites were analysed separately and intercompared. Results evidenced that during these 16years mean O3 levels in the RB sites did not change significantly, and remained constantly high. However, there is a clear increase at the TR and UB sites. Although sensitivity analysis is needed to interpret the cause of this increasing trend, this might be caused probably by the lower O3 titration intensity due to the preferential abatement of NO vs NO2, as supported from the neutral trend of OX (NO2+O3) at these sites. We found that the exceedances of the hourly information threshold for O3 (>180µg/m3) are recorded mostly at UB and IN sites located in seven areas of Spain (specific hotspots or at the tail end of large urban plumes), and that these increased during summer heatwaves (i.e. 2003 and 2015). Although the external contribution of regional-to-subcontinental transported O3 might be relevant during the highest O3 episodes in the Western Mediterranean, our results evidenced that in the above specific areas, regional-local O3 production decisively contributes to the exceedances of the information threshold. Also that the human protection threshold and the AOT40 are more frequently exceeded in the Central, Southern and Mediterranean sides of the Iberian Peninsula. The design of effective episode abatement measures is quite complex in those conditions, due to both the nonlinearity of the chemical processes of O3 formation and destruction, and to the interplay with the complex meteorological setting, causing frequent recirculation and in situ aging of air masses. However, the combination of meteorological forecasting of the main recirculation processes and sensitivity analysis of NOX/VOC emission abatement measures might be powerful tools to evaluate the effectiveness of potential O3 mitigation strategies. Finally we would like to highlight that the current UB, RB, IN and TR classification (somewhat subjective) is not adequate to interpret the origin of O3 exceedances in complex areas of Southern Europe. Thus, a UB station recording exceedances, and located in a small city in the tail end of an urban plume of a large city, receives not only the contribution from its own UB, but mainly from the specific high O3 RB caused by the urban plume transport.

The neurosteroid pregnenolone sulfate neutralized the learning impairment induced by intrahippocampal nicotine in alcohol-drinking rats.

The effects of intrahippocampal administration of nicotine and the neurosteroids pregnenolone sulfate and allopregnanolone on acquiring the lever-press response and extinction in a Skinner box were examined using voluntary alcohol-drinking rats. A free-choice drinking procedure that implies early availability of the alcoholic solution (10% ethanol v/v+3% glucose w/v in distilled water) was used. Alcohol and control rats were deprived of food and assigned at random to six groups. Each group received two consecutive intrahippocampal (dorsal CA1) injections immediately after 1-h of drinking ethanol and before the free lever-press response shaping and extinction session. The groups were: saline-saline; saline-pregnenolone sulfate (5 ng, 24 microM); saline-allopregnanolone (0.2 microg, 1.26 microM); nicotine (4.6 microg, 20 mM)-saline; nicotine-pregnenolone sulfate; nicotine-allopregnanolone. Blood alcohol concentrations were assessed the day before conditioning. The combination of the oral self-administration of ethanol and the intrahippocampal injection of nicotine deteriorated the ability to acquire the lever-press response. This effect was neutralized by intrahippocampal pregnenolone sulfate (negative modulator of the GABA(A) receptor complex), and it was not affected by intrahippocampal allopregnanolone (positive GABA receptor complex A modulator). Pregnenolone sulfate and allopregnanolone had no effects per se on lever-press acquisition, neither in alcohol-drinking rats nor in controls. Alcohol consumption facilitated operant extinction just as anxiolytics that act as positive modulators of the GABA receptor complex A receptors do, possibly reducing the anxiety or aversion related to non-reinforcement. This effect was increased by intrahippocampal nicotine.

Finasteride administration potentiates the disruption of prepulse inhibition induced by forced swim stress.

Acute stress has been demonstrated to alter sensory gating processes, measured by the prepulse inhibition of the startle response (PPI). It is well known that brain and plasma levels of the neurosteroid allopregnanolone (ALLO) increase after acute environmental stress, fact that has been considered a homeostatic mechanism in restoring normal function following stress. Thus, it is of great interest to study the contribution of stress-altered plasma ALLO levels on PPI function. For this purpose, animals were injected with finasteride, an ALLO synthesis inhibitor, and submitted to swim stress before PPI testing. In order to obtain ALLO plasma levels, a separate set of animals that followed the same experimental procedure was used. We hypothesize that the blockade of ALLO production in response to stress can increase the stress-induced PPI disruption. In accordance with other authors, our results indicate that acute swim stress disrupted the normal PPI evolution (increase) related to the increase in prepulse intensities, and also decreased PPI at the highest prepulse intensity level (15 db above background). Finasteride potentiated the PPI decrease induced by swim stress in the intermediate prepulse intensity (10 db above background). As expected, plasma ALLO levels were increased in stressed animals and this increase was neutralized by prior finasteride administration. These results indicate that the neutralization of the physiological plasma ALLO levels increase after acute stress potentiates stress-induced PPI disruption. This data suggests that alterations in homeostatic ALLO synthesis mechanism may be linked to some neuropsychiatric disorders related to stress, such as anxiety/depression disorders.

Risk factors for severe sepsis in community-onset bacteraemic urinary tract infection: impact of antimicrobial resistance in a large hospitalised cohort.

OBJECTIVE: To determine risks factors associated with severe sepsis or septic shock (SS) at admission in patients with community-onset bacteraemic urinary tract infection (CO-BUTI) including the impact of multidrug-resistant (MDR) bacteria. METHODS: We analysed a prospective cohort of all consecutive episodes of CO-BUTI requiring hospitalisation in 8 tertiary hospitals of Spain between October 2010 and June 2011. RESULTS: Of an overall of 525 CO-BUTI episodes, 175 (33%) presented with SS at admission. MDR bacteria were isolated in 29% (51/175) of episodes with SS and in 33% (117/350) of those without SS (p = 0.32). The main MDR microorganism was Escherichia coli in both groups (25% and 28% respectively). Independent risk factors associated with SS at admission were: having fatal underlying conditions, McCabe score II/III (OR 1.90; 95%CI 1.23-2.92; p = 0.004), presence of an indwelling urethral catheter (OR 3.01; 95%CI 1.50-6.03; p = 0.002) and a history of urinary tract obstruction (OR 1.56; 95%CI 1.03-2.34; p = 0.03). After considering interactions, indwelling urethral catheters were a risk factor only for patients without fatal underlying conditions. CONCLUSIONS: SS at hospital admission occurred in a third of CO-BUTI. Mainly host factors, and not the causative microorganisms or antimicrobial resistance patterns had an impact on the presence of SS.

[Improving drug prescribing in the elderly: a new edition of STOPP/START criteria]. / Mejorando la prescripción de medicamentos en las personas mayores: una nueva edición de los criterios STOPP-START.

Inappropriate use of drugs in older patients may have an adverse impact on several individual health outcomes, such as increasing the prevalence of adverse drug reactions, morbidity and mortality, and geriatric syndromes, as well as on health care systems, such as increased costs and longer hospital stays. Explicit criteria of drug appropriateness are increasingly used to detect and prevent inappropriate use of drugs, either within a comprehensive geriatric assessment or as tool used by different multidisciplinary geriatric teams. STOPP-START criteria, first published in 2008 (in Spanish in 2009), are being adopted as reference criteria throughout Europe. The Spanish version of the new 2014 edition (recently published in English) of the STOPP-START criteria is presented here. A review of all the papers published in Spain using the former version of these criteria is also presented, with the intention of promoting their use and for research in different health care levels.

The neurosteroid pregnenolone sulfate infused into the nucleus basalis increases both acetylcholine release in the frontal cortex or amygdala and spatial memory.

The effects of an infusion (5 ng) of the neurosteroid pregnenolone sulfate into the nucleus basalis magnocellularis on acetylcholine release in the frontoparietal cortex and basolateral amygdala were evaluated during the 130 min post-injection in male Sprague-Dawley rats using in vivo microdialysis coupled "on line" with high performance liquid chromatography detection. One week later, the same animals were tested for spatial memory after another infusion of pregnenolone sulfate (5 ng) into the nucleus basalis. Results show that pregnenolone sulfate enhanced acetylcholine release by more than 50% of baseline concentrations in the two structures relative to a control injection. The duration of this effect was longer in cortex (130 min) than in amygdala (30 min). Furthermore, pregnenolone sulfate improved memory performance in a task based upon spatial recognition of a familiar environment. A significant positive correlation (r=0.49) was found between the recognition score in the spatial memory test and the levels of acetylcholine release in the frontoparietal cortex but not in the basolateral amygdala. Therefore, our results suggest that the nucleus basalis magnocellularis-cortical pathway could be in part responsible for the promnesic effect of pregnenolone sulfate. This neurosteroid acts as a negative modulator of the GABA(A) receptor complex and positively modulates the N-methyl-D-aspartate receptor, possibly resulting in a global stimulatory effect on central cholinergic neurotransmission.

Infusion of neurosteroids into the rat nucleus basalis affects paradoxical sleep in accordance with their memory modulating properties.

The neurosteroids pregnenolone sulfate and allopregnanolone affect memory processes in an opposite manner, pregnenolone sulfate acts as a potent memory-enhancer whereas allopregnanolone impairs memory performance. The mechanisms underlying these memory modulating properties have yet to be elucidated. We have previously reported that infusions of either neurosteroid into the nucleus basalis magnocellularis, one of the main forebrain cholinergic nuclei, differentially affect spatial memory in rats. The relationships between memory performance and paradoxical sleep are well documented, therefore we investigated whether neurosteroids infused into the nucleus basalis magnocellularis affected the sleep-wakefulness cycle in rats, measured by electroencephalographic recordings. Results show that pregnenolone sulfate (5 ng) increased by 12%, whereas allopregnanolone (2 ng) decreased by 24%, the duration of paradoxical sleep in the 24 h interval following injection compared to control recordings. Pregnenolone sulfate inhibits GABA(A) receptors whereas allopregnanolone stimulates them. Since cholinergic neurons of the nucleus basalis magnocellularis are GABA-modulated, it may be postulated that these neurosteroids modify paradoxical sleep by acting on the cholinergic transmission. This may account, at least in part, for the memory modulating properties of these compounds.

Long-term complications of silicone and hydrogel explants in retinal reattachment surgery.

OBJECTIVE: To compare long-term complications of silicone sponge, silicone rubber, and MIRAgel used as episcleral buckling elements. METHODS: Medical reports were reviewed of 805 patients with cryotherapy and episcleral buckle for rhegmatogenous retinal detachment who were operated on by 1 of us (M.R.-P.) between March 1984 and December 1997. Average follow-up was 76 months. Symptoms and signs of infection or rejection were considered. Care was taken in buckling element removal, considering the material used for scleral buckling (detailed operative note), duration of the buckle, cause of removal, and culture of the removed element. RESULTS: A total of 757 patients were included in the study. Removal of the implant was necessary in 10 patients (1.3%). Silicone sponge (3 [9%] of 32 patients) was more frequently removed than was silicone rubber (2 [0.6%] of 360 patients) or MIRAgel (5 [1.3%] of 386 patients). Silicone sponge needed to be removed a short time after surgery, showing symptoms of acute infection and positive cultures. Silicone rubber was removed 1 year after surgery with symptoms of chronic infection and positive cultures, and MIRAgel implants were removed after long-term follow-up (7-10 years), showing positive cultures in only 20%. CONCLUSION: Periodic long-term follow-up previously recommended for use of other materials also must be recommended for MIRAgel use because of long-term alterations in its chemical composition and eventual swelling of material.