Cpt1a silencing in AgRP neurons improves cognitive and physical capacity and promotes healthy aging in male mice.

Orexigenic neurons expressing agouti-related protein (AgRP) and neuropeptide Y in the arcuate nucleus (ARC) of the hypothalamus are activated in response to dynamic variations in the metabolic state, including exercise. We previously observed that carnitine palmitoyltransferase 1a (CPT1A), a rate-limiting enzyme of mitochondrial fatty acid oxidation, is a key factor in AgRP neurons, modulating whole-body energy balance and fluid homeostasis. However, the effect of CPT1A in AgRP neurons in aged mice and during exercise has not been explored yet. We have evaluated the physical and cognitive capacity of adult and aged mutant male mice lacking Cpt1a in AgRP neurons (Cpt1a KO). Adult Cpt1a KO male mice exhibited enhanced endurance performance, motor coordination, locomotion, and exploration compared with control mice. No changes were observed in anxiety-related behavior, cognition, and muscle strength. Adult Cpt1a KO mice showed a reduction in gastrocnemius and tibialis anterior muscle mass. The cross-sectional area (CSA) of these muscles were smaller than those of control mice displaying a myofiber remodeling from type II to type I fibers. In aged mice, changes in myofiber remodeling were maintained in Cpt1a KO mice, avoiding loss of physical capacity during aging progression. Additionally, aged Cpt1a KO mice revealed better cognitive skills, reduced inflammation, and oxidative stress in the hypothalamus and hippocampus. In conclusion, CPT1A in AgRP neurons appears to modulate health and protects against aging. Future studies are required to clarify whether CPT1A is a potential antiaging candidate for treating diseases affecting memory and physical activity.

Rab18 Drift in Lipid Droplet and Endoplasmic Reticulum Interactions of Adipocytes under Obesogenic Conditions.

The adipose tissue stores excess energy in the form of neutral lipids within adipocyte lipid droplets (LDs). The correct function of LDs requires the interaction with other organelles, such as the endoplasmic reticulum (ER) as well as with LD coat-associated proteins, including Rab18, a mediator of intracellular lipid trafficking and ER-LD interaction. Although perturbations of the inter-organelle contact sites have been linked to several diseases, such as cancer, no information regarding ER-LD contact sites in dysfunctional adipocytes from the obese adipose tissue has been published to date. Herein, the ER-LD connection and Rab18 distribution at ER-LD contact sites are examined in adipocytes challenged with fibrosis and inflammatory conditions, which represent known hallmarks of the adipose tissue in obesity. Our results show that adipocytes differentiated in fibrotic conditions caused ER fragmentation, the expansion of ER-LD contact sites, and modified Rab18 dynamics. Likewise, adipocytes exposed to inflammatory conditions favored ER-LD contact, Rab18 accumulation in the ER, and Rab18 redistribution to large LDs. Finally, our studies in human adipocytes supported the suggestion that Rab18 transitions to the LD coat from the ER. Taken together, our results suggest that obesity-related pathogenic processes alter the maintenance of ER-LD interactions and interfere with Rab18 trafficking through these contact sites.

3D bioprinted functional skeletal muscle models have potential applications for studies of muscle wasting in cancer cachexia.

Acquired muscle diseases such as cancer cachexia are responsible for the poor prognosis of many patients suffering from cancer. In vitro models are needed to study the underlying mechanisms of those pathologies. Extrusion bioprinting is an emerging tool to emulate the aligned architecture of fibers while implementing additive manufacturing techniques in tissue engineering. However, designing bioinks that reconcile the rheological needs of bioprinting and the biological requirements of muscle tissue is a challenging matter. Here we formulate a biomaterial with dual crosslinking to modulate the physical properties of bioprinted models. We design 3D bioprinted muscle models that resemble the mechanical properties of native tissue and show improved proliferation and high maturation of differentiated myotubes suggesting that the GelMA-AlgMA-Fibrin biomaterial possesses myogenic properties. The electrical stimulation of the 3D model confirmed the contractile capability of the tissue and enhanced the formation of sarcomeres. Regarding the functionality of the models, they served as platforms to recapitulate skeletal muscle diseases such as muscle wasting produced by cancer cachexia. The genetic expression of 3D models demonstrated a better resemblance to the muscular biopsies of cachectic mouse models. Altogether, this biomaterial is aimed to fabricate manipulable skeletal muscle in vitro models in a non-costly, fast and feasible manner.

Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice.

Obesity and its associated metabolic comorbidities are a rising global health and social issue, with novel therapeutic approaches urgently needed. Adipose tissue plays a key role in the regulation of energy balance and adipose tissue-derived mesenchymal stem cells (AT-MSCs) have gained great interest in cell therapy. Carnitine palmitoyltransferase 1A (CPT1A) is the gatekeeper enzyme for mitochondrial fatty acid oxidation. Here, we aimed to generate adipocytes expressing a constitutively active CPT1A form (CPT1AM) that can improve the obese phenotype in mice after their implantation. AT-MSCs were differentiated into mature adipocytes, subjected to lentivirus-mediated expression of CPT1AM or the GFP control, and subcutaneously implanted into mice fed a high-fat diet (HFD). CPT1AM-implanted mice showed lower body weight, hepatic steatosis and serum insulin and cholesterol levels alongside improved glucose tolerance. HFD-induced increases in adipose tissue hypertrophy, fibrosis, inflammation, endoplasmic reticulum stress and apoptosis were reduced in CPT1AM-implanted mice. In addition, the expression of mitochondrial respiratory chain complexes was enhanced in the adipose tissue of CPT1AM-implanted mice. Our results demonstrate that implantation of CPT1AM-expressing AT-MSC-derived adipocytes into HFD-fed mice improves the obese metabolic phenotype, supporting the future clinical use of this ex vivo gene therapy approach.

CPT1A in AgRP neurons is required for sex-dependent regulation of feeding and thirst.

BACKGROUND: Fatty acid metabolism in the hypothalamus has an important role in food intake, but its specific role in AgRP neurons is poorly understood. Here, we examined whether carnitinea palmitoyltransferase 1A (CPT1A), a key enzyme in mitochondrial fatty acid oxidation, affects energy balance. METHODS: To obtain Cpt1aKO mice and their control littermates, Cpt1a(flox/flox) mice were crossed with tamoxifen-inducible AgRPCreERT2 mice. Food intake and body weight were analyzed weekly in both males and females. At 12 weeks of age, metabolic flexibility was determined by ghrelin-induced food intake and fasting-refeeding satiety tests. Energy expenditure was analyzed by calorimetric system and thermogenic activity of brown adipose tissue. To study fluid balance the analysis of urine and water intake volumes; osmolality of urine and plasma; as well as serum levels of angiotensin and components of RAAS (renin-angiotensin-aldosterone system) were measured. At the central level, changes in AgRP neurons were determined by: (1) analyzing specific AgRP gene expression in RiboTag-Cpt1aKO mice obtained by crossing Cpt1aKO mice with RiboTag mice; (2) measuring presynaptic terminal formation in the AgRP neurons with the injection of the AAV1-EF1a-DIO-synaptophysin-GFP in the arcuate nucleus of the hypothalamus; (3) analyzing AgRP neuronal viability and spine formations by the injection AAV9-EF1a-DIO-mCherry in the arcuate nucleus of the hypothalamus; (4) analyzing in situ the specific AgRP mitochondria in the ZsGreen-Cpt1aKO obtained by breeding ZsGreen mice with Cpt1aKO mice. Two-way ANOVA analyses were performed to determine the contributions of the effect of lack of CPT1A in AgRP neurons in the sex. RESULTS: Changes in food intake were just seen in male Cpt1aKO mice while only female Cpt1aKO mice increased energy expenditure. The lack of Cpt1a in the AgRP neurons enhanced brown adipose tissue activity, mainly in females, and induced a substantial reduction in fat deposits and body weight. Strikingly, both male and female Cpt1aKO mice showed polydipsia and polyuria, with more reduced serum vasopressin levels in females and without osmolality alterations, indicating a direct involvement of Cpt1a in AgRP neurons in fluid balance. AgRP neurons from Cpt1aKO mice showed a sex-dependent gene expression pattern, reduced mitochondria and decreased presynaptic innervation to the paraventricular nucleus, without neuronal viability alterations. CONCLUSIONS: Our results highlight that fatty acid metabolism and CPT1A in AgRP neurons show marked sex differences and play a relevant role in the neuronal processes necessary for the maintenance of whole-body fluid and energy balance.

Influence of Protein Carbonylation on Human Adipose Tissue Dysfunction in Obesity and Insulin Resistance.

BACKGROUND: Obesity is characterized by adipose tissue dysregulation and predisposes individuals to insulin resistance and type 2 diabetes. At the molecular level, adipocyte dysfunction has been linked to obesity-triggered oxidative stress and protein carbonylation, considering protein carbonylation as a link between oxidative stress and metabolic dysfunction. The identification of specific carbonylated proteins in adipose tissue could provide novel biomarkers of oxidative damage related to metabolic status (i.e prediabetes). Thus, we aimed at characterizing the subcutaneous and omental human adipose tissue carbonylome in obesity-associated insulin resistance. METHODS: 2D-PAGE was used to identify carbonylated proteins, and clinical correlations studies and molecular biology approaches including intracellular trafficking, reactive oxygen species assay, and iron content were performed using in vitro models of insulin resistance. RESULTS: The carbonylome of human adipose tissue included common (serotransferrin, vimentin, actin, and annexin A2) and depot-specific (carbonic anhydrase and α-crystallin B in the subcutaneous depot; and α-1-antitrypsin and tubulin in the omental depot) differences that point out the complexity of oxidative stress at the metabolic level, highlighting changes in carbonylated transferrin expression. Posterior studies using in vitro prediabetic model evidence alteration in transferrin receptor translocation, linked to the prediabetic environment. Finally, ligand-receptor molecular docking studies showed a reduced affinity for carbonylated transferrin binding to its receptor compared to wild-type transferrin, emphasizing the role of transferrin carbonylation in the link between oxidative stress and metabolic dysfunction. CONCLUSIONS: The adipose tissue carbonylome contributes to understanding the molecular mechanism driving adipocyte dysfunction and identifies possible adipose tissue carbonylated targets in obesity-associated insulin resistance.

Ptpn1 deletion protects oval cells against lipoapoptosis by favoring lipid droplet formation and dynamics.

Activation of oval cells (OCs) has been related to hepatocyte injury during chronic liver diseases including non-alcoholic fatty liver disease (NAFLD). However, OCs plasticity can be affected under pathological environments. We previously found protection against hepatocyte cell death by inhibiting protein tyrosine phosphatase 1B (PTP1B). Herein, we investigated the molecular and cellular processes involved in the lipotoxic susceptibility in OCs expressing or not PTP1B. Palmitic acid (PA) induced apoptotic cell death in wild-type (Ptpn1+/+) OCs in parallel to oxidative stress and impaired autophagy. This lipotoxic effect was attenuated in OCs lacking Ptpn1 that showed upregulated antioxidant defences, increased unfolded protein response (UPR) signaling, higher endoplasmic reticulum (ER) content and elevated stearoyl CoA desaturase (Scd1) expression and activity. These effects in Ptpn1-/- OCs concurred with an active autophagy, higher mitochondrial efficiency and a molecular signature of starvation, favoring lipid droplet (LD) formation and dynamics. Autophagy blockade in Ptpn1-/- OCs reduced Scd1 expression, mitochondrial fitness, LD formation and restored lipoapoptosis, an effect also recapitulated by Scd1 silencing. PTP1B immunostaining was detected in OCs from mouse liver and, importantly, LDs were found in OCs from Ptpn1-/- mice with NAFLD. In conclusion, we demonstrated that Ptpn1 deficiency restrains lipoapoptosis in OCs through a metabolic rewiring towards a "starvation-like" fate, favoring autophagy, mitochondrial fitness and LD formation. Dynamic LD-lysosomal interations likely ensure lipid recycling and, overall, these adaptations protect against lipotoxicity. The identification of LDs in OCs from Ptpn1-/- mice with NAFLD opens therapeutic perspectives to ensure OC viability and plasticity under lipotoxic liver damage.

Relationship between the order of permanent tooth eruption and the predominance of motor function laterality: a cross-sectional study.

OBJECTIVES: To assess whether the order of permanent tooth eruption may be a useful indicator of motor function laterality. METHODS: We conducted a cross-sectional study in schoolchildren aged 6-8 years old evaluated in the annual school-based routine dental health examinations conducted by the staff of the primary care centre of an urban district in Barcelona, Spain. We also evaluated hand, foot, eye, and auditory lateralities using a battery of simple exercises. Bivariate and multivariate analysis of data was performed. RESULTS: The study sample included 388 children, 51.3% female, with a mean age of 6.5 years. Right laterality was the predominant side in every variable under study, especially in tooth eruption (310 children; 80%), handedness (349; 89.9%), and footedness (337; 86.8%). In the bivariate analysis, we found a statistically significant association of tooth eruption laterality with handedness and footedness, and of tooth eruption laterality with ocular and auditory lateralities (p<.001). In the multivariate analysis, tooth eruption laterality and foot laterality were independent variables significantly associated with hand laterality. The diagnostic accuracy of tooth eruption laterality and foot laterality in relation to hand laterality as reference, showed a similar sensitivity and positive and negative predictive values, but the specificity of dentition laterality was higher (79% versus 66%). CONCLUSIONS: Laterality in the order of dental eruption is a useful indicator of right or left motor function laterality in developing individuals that may be particularly helpful to determine the main dominance in cases of crossed laterality.

Correlación entre el patrón de erupción de la dentición definitiva y la predominancia de la lateralidad de la función motriz: un estudio transversal / Relationship between the order of permanent tooth eruption and the predominance of motor function laterality: A cross-sectional study

Objetivos: Evaluar si el orden de la erupción dental es un buen indicador de la lateralidad motora.Métodos: Estudio transversal en escolares de ambos sexos de 6 a 8 años tratados mediante las revisiones orales rutinarias anuales realizadas en los colegios incluidos en un área de atención primaria urbana en Barcelona (España). También se evaluaron las lateralidades de manos, pies, ojos y oídos mediante una serie de ejercicios simples. Se realizaron análisis bivariantes y multivariantes de los datos.Resultados: La muestra comprendió 388 escolares, 51,3% niñas, con una edad media de 6,5 años. La lateralidad derecha predominó en todas las variables de estudio, especialmente en la dentición (310 escolares; 80%), la mano (349; 89,9%) y el pie (337; 86.8%). En el estudio bivariante se observó una asociación estadísticamente significativa (p <0,001) entre la lateralidad de la dentición y la de la mano y el pie, así como entre la lateralidad de la dentición y las lateralidades de oído y de ojo. En el estudio multivariante, las lateralidades de la dentición y del pie se asociaron significativamente a la lateralidad de la mano. En lo concerniente a la precisión de la lateralidad de la dentición y del pie como prueba diagnóstica de la lateralidad de la mano, ambas mostraron una sensibilidad y valores predictivos positivos y negativos similares, pero la especificidad de la lateralidad de la dentición fue mayor (79% vs. 66%).Conclusiones: La lateralidad en el orden de la erupción dental es un buen indicador para determinar la lateralidad motora durante el desarrollo, que podría ser particularmente útil para ayudar a precisar la lateralidad más predominante en casos de lateralidad cruzada. (AU)

Objectives: To assess whether the order of permanent tooth eruption may be a useful indicator of motor function laterality.Methods: We conducted a cross-sectional study in schoolchildren aged 6 to 8 years old evaluated in the annual school-based routine dental health examinations conducted by the staff of the primary care centre of an urban district in Barcelona, Spain. We also evaluated hand, foot, eye, and auditory lateralities using a series of simple exercises. Bivariate and multivariate analysis of data was performed.Results: The study sample included 388 children, 51.3% female, with a mean age of 6.5 years. Right laterality was the predominant side in every variable under study, especially in tooth eruption (310 children; 80%), handedness (349; 89.9%), and footedness (337; 86.8%). In the bivariate analysis, we found a statistically significant association of tooth eruption laterality with handedness and footedness, an of tooth eruption laterality with ocular and auditory lateralities (P<.001). In the multivariate analysis, tooth eruption laterality and foot laterality were independent variables significantly associated with hand laterality. The diagnostic accuracy of tooth eruption laterality and foot laterality in relation to hand laterality as reference, showed a similar sensitivity and positive and negative predictive values, but the specificity of dentition laterality was higher (79% versus 66%).Conclusions: Laterality in the order of dental eruption is a useful indicator of right or left motor function laterality in developing individuals that may be particularly helpful to determine the main dominance in cases of crossed laterality. (AU)

Liver CPT1A gene therapy reduces diet-induced hepatic steatosis in mice and highlights potential lipid biomarkers for human NAFLD.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased drastically due to the global obesity pandemic but at present there are no approved therapies. Here, we aimed to revert high-fat diet (HFD)-induced obesity and NAFLD in mice by enhancing liver fatty acid oxidation (FAO). Moreover, we searched for potential new lipid biomarkers for monitoring liver steatosis in humans. We used adeno-associated virus (AAV) to deliver a permanently active mutant form of human carnitine palmitoyltransferase 1A (hCPT1AM), the key enzyme in FAO, in the liver of a mouse model of HFD-induced obesity and NAFLD. Expression of hCPT1AM enhanced hepatic FAO and autophagy, reduced liver steatosis, and improved glucose homeostasis. Lipidomic analysis in mice and humans before and after therapeutic interventions, such as hepatic AAV9-hCPT1AM administration and RYGB surgery, respectively, led to the identification of specific triacylglyceride (TAG) specie (C50:1) as a potential biomarker to monitor NAFFLD disease. To sum up, here we show for the first time that liver hCPT1AM gene therapy in a mouse model of established obesity, diabetes, and NAFLD can reduce HFD-induced derangements. Moreover, our study highlights TAG (C50:1) as a potential noninvasive biomarker that might be useful to monitor NAFLD in mice and humans.

Impact of Adaptive Thermogenesis in Mice on the Treatment of Obesity.

Obesity and associated metabolic diseases have become a priority area of study due to the exponential increase in their prevalence and the corresponding health and economic impact. In the last decade, brown adipose tissue has become an attractive target to treat obesity. However, environmental variables such as temperature and the dynamics of energy expenditure could influence brown adipose tissue activity. Currently, most metabolic studies are carried out at a room temperature of 21 °C, which is considered a thermoneutral zone for adult humans. However, in mice this chronic cold temperature triggers an increase in their adaptive thermogenesis. In this review, we aim to cover important aspects related to the adaptation of animals to room temperature, the influence of housing and temperature on the development of metabolic phenotypes in experimental mice and their translation to human physiology. Mice studies performed in chronic cold or thermoneutral conditions allow us to better understand underlying physiological mechanisms for successful, reproducible translation into humans in the fight against obesity and metabolic diseases.

New approaches targeting brown adipose tissue transplantation as a therapy in obesity.

Brown adipose tissue (BAT) is raising high expectations as a potential target in the fight against metabolic disorders such as obesity and type 2 diabetes. BAT utilizes fuels such as fatty acids to maintain body temperature by uncoupling mitochondrial electron transport to produce heat instead of ATP. This process is called thermogenesis. BAT was considered to be exclusive to rodents and human neonates. However, in the last decade several studies have demonstrated that BAT is not only present but also active in adult humans and that its activity is reduced in several pathological conditions, such as aging, obesity, and diabetes. Thus, tremendous efforts are being made by the scientific community to enhance either BAT mass or activity. Several activators of thermogenesis have been described, such as natriuretic peptides, bone morphogenic proteins, or fibroblast growth factor 21. Furthermore, recent studies have tested a therapeutic approach to directly increase BAT mass by the implantation of either adipocytes or fat tissue. This approach might have an important future in regenerative medicine and in the fight against metabolic disorders. Here, we review the emerging field of BAT transplantation including the various sources of mesenchymal stem cell isolation in rodents and humans and the described metabolic outcomes of adipocyte cell transplantation and BAT transplantation in obesity.

Targeting AgRP neurons to maintain energy balance: Lessons from animal models.

The current obesity epidemic is a major worldwide health and economic burden. In the modern environment, an increase in the intake of high-fat and high-sugar foods plays a crucial role in the development of obesity by disrupting the mechanisms governing food intake and energy balance. Food intake and whole-body energy balance are regulated by the central nervous system through a sophisticated neuronal network located mostly in the hypothalamus. In particular, the hypothalamic arcuate nucleus (ARC) is a fundamental center that senses hormonal and nutrient-related signals informing about the energy state of the organism. The ARC contains two small, defined populations of neurons with opposite functions: anorexigenic proopiomelanocortin (POMC)-expressing neurons and orexigenic Agouti-related protein (AgRP)-expressing neurons. AgRP neurons, which also co-produce neuropeptide Y (NPY) and γ-Aminobutyric acid (GABA), are involved in an increase in hunger and a decrease in energy expenditure. In this review, we summarize the key findings from the most common animal models targeting AgRP neurons and the tools used to discern the role of this specific neuronal population in the control of peripheral metabolism, appetite, feeding-related behavior, and other complex behaviors. We also discuss how knowledge gained from these studies has revealed new pathways and key proteins that could be potential therapeutic targets to reduce appetite and food addictions in obesity and other diseases.

Conciliación de medicación al ingreso mediante un programa de prescripción electrónica asistida / Medicines reconciliation at hospital admission into an electronic prescribing program

Objetivo: Describir y analizar los resultados obtenidos durante un año con un nuevo procedimiento de conciliación de la medicación al ingreso hospitalario basado en un programa de prescripción electrónica asistida. Método: Estudio observacional, prospectivo, no aleatorizado y no controlado de 12 meses de duración, en el que se incluyeron todos los pacientes que ingresaron, durante ese año, en un hospital general concertado de 450 camas. Para la conciliación de la medicación se utilizó el programa de prescripción electró- nica como medio para el abordaje multidisciplinar (enfermería, médicos y farmacéuticos). La conciliación se realizó al ingreso hospitalario y se midieron los errores de conciliación. Resultados: Se incluyeron 23.701 pacientes, conciliándose 53.920 medicamentos, de los cuales no tenían discrepancias 48.744 (90,4%) y 5.176 (9,6%) presentaban discrepancias: 4.731 (8,8 % de los fármacos) justificadas y 445 (0,8% de los fármacos) no justificadas. La mayor parte de las discrepancias no justificadas, (n = 310; 69,7%) se debieron a errores en el registro de la medicación domiciliaria al ingreso: medicación no registrada o errores de medicamentos, dosis, frecuencia o vía de administración, omisiones de prescripción, 23,6% (n = 105) y duplicidades, 6,7% (n = 30). En ningún caso el error de conciliación llegó al paciente. Conclusiones: Mediante las ayudas informáticas incluidas en el programa de prescripción electrónica asistida y el abordaje multidisciplinar del proceso de conciliación se consigue realizar la conciliación de la medicación al ingreso en el 98% de los pacientes en el momento del ingreso, evidenciando errores de conciliación solo en el 1,3% de los pacientes (AU)

Objective: To describe and to analyse a new method of integrated medicines reconciliation in an electronic prescribing program results. Method: 12-month, prospective, observational, non-randomized and uncontrolled study, in which all patients who were admitted, during that year, to a general hospital of 450 beds. The electronic prescribing program was used for medication reconciliation as a means to multidisciplinary approach (nurses, doctors, pharmacists). This reconciliation was done at the time of hospital admission and reconciliation errors were measured. Results: A total of 23 701 patients were included, with 53 920 medications being reconciled, of which 48 744 (90.4%) had no discrepancies and 5 176 (9.6%) had discrepancies: 4 731 (8.7%) justified and 445 (0.8%) not justified. The majority of unjustified discrepancies were due to the drugs in use at home not recorded well on the hospital admission record in 310 (69.7%), prescription omissions in 105 (23.6%) and duplications in 30 (6.7%). In any case the reconciliation errors reached patients. Conclusions: Using an electronic prescribing program and an interdisciplinary approach in the reconciliation of chronic medication, medication reconciliation at the time of hospital admission is achieved in 98% of patients, showing medication errors only in 1.3% of patients (AU)

[Medicines reconciliation at hospital admission into an electronic prescribing program]. / Conciliación de medicación al ingreso mediante un programa de prescripción electrónica asistida.

OBJECTIVE: To describe and to analyse a new method of integrated medicines reconciliation in an electronic prescribing program results. METHOD: 12-month, prospective, observational, non-randomized and uncontrolled study, in which all patients who were admitted, during that year, to a general hospital of 450 beds. The electronic prescribing program was used for medication reconciliation as a means to multidisciplinary approach (nurses, doctors, pharmacists). This reconciliation was done at the time of hospital admission and reconciliation errors were measured. RESULTS: A total of 23 701 patients were included, with 53 920 medications being reconciled, of which 48 744 (90.4%) had no discrepancies and 5 176 (9.6%) had discrepancies: 4 731 (8.7%) justified and 445 (0.8%) not justified. The majority of unjustified discrepancies were due to the drugs in use at home not recorded well on the hospital admission record in 310 (69.7%), prescription omissions in 105 (23.6%) and duplications in 30 (6.7%). In any case the reconciliation errors reached patients. CONCLUSIONS: Using an electronic prescribing program and an interdisciplinary approach in the reconciliation of chronic medication, medication reconciliation at the time of hospital admission is achieved in 98% of patients, showing medication errors only in 1.3% of patients.

Objetivo: Describir y analizar los resultados obtenidos durante un año con un nuevo procedimiento de conciliación de la medicación al ingreso hospitalario basado en un programa de prescripción electrónica asistida. Método: Estudio observacional, prospectivo, no aleatorizado y no controlado de 12 meses de duración, en el que se incluyeron todos los pacientes que ingresaron, durante ese año, en un hospital general concertado de 450 camas. Para la conciliación de la medicación se utilizó el programa de prescripción electrónica como medio para el abordaje multidisciplinar (enfermería, médicos y farmacéuticos). La conciliación se realizó al ingreso hospitalario y se midieron los errores de conciliación. Resultados: Se incluyeron 23.701 pacientes, conciliándose 53.920 medicamentos, de los cuales no tenían discrepancias 48.744 (90,4%) y 5.176 (9,6%) presentaban discrepancias: 4.731 (8,8 % de los fármacos) justificadas y 445 (0,8% de los fármacos) no justificadas. La mayor parte de las discrepancias no justificadas, (n = 310; 69,7%) se debieron a errores en el registro de la medicación domiciliaria al ingreso: medicación no registrada o errores de medicamentos, dosis, frecuencia o vía de administración, omisiones de prescripción, 23,6% (n = 105) y duplicidades, 6,7% (n = 30). En ningún caso el error de conciliación llegó al paciente. Conclusiones: Mediante las ayudas informáticas incluidas en el programa de prescripción electrónica asistida y el abordaje multidisciplinar del proceso de conciliación se consigue realizar la conciliación de la medicación al ingreso en el 98% de los pacientes en el momento del ingreso, evidenciando errores de conciliación solo en el 1,3% de los pacientes.

Utility of measurement of interleukin-1ß and interleukin-8 in the diagnosis of complicated parapneumonic pleural effusions.

OBJECTIVES: Thirty percent of patients with pneumonia develop pleural effusion, and of these, 20% have complicated effusion (CPPE), which may require a chest tube or surgery for resolution. The objective of the study is to compare the diagnostic yield of determining interleukin-1ß and interleukin-8 in pleural fluid (PF) (PFIL-1ß and PFIL-8) with respect to classic criteria (pH <7.2, lactate dehydrogenase [LD] >1,000 IU/mL, and/or glucose <60 mg/dL) in the early diagnosis of CPPE. METHODS: Of the 559 patients studied, 40 had CPPE. All underwent PF analysis: pH, glucose (PFGLUC), LD (PFLD), PFIL-1ß and PFIL-8, and PF/serum ratios (PF/SIL-1ß and PF/SIL-8). RESULTS: The diagnostic criterion that showed the best area under the curve was the combination of PF/SIL-8 and PFIL-1ß (0.906), with a statistically significant difference (P < .05) compared with the classic criterion of pH and PFGLUC or PFLD (0.826). The combination of PF/SIL-8 and PFIL-1ß (cutoffs >5.73 and >9.14 pg/mL, respectively) was significantly more sensitive (72.7%) and more specific (97.9%) (P < .05) than the rest of the parameters used. CONCLUSIONS: Measurement of IL-1ß and IL-8 in pleural fluid may be useful in the early diagnosis of CPPE, although individually, it may not improve the results obtained with the PFLD. Further studies are needed to more firmly establish what role these new parameters can play in the diagnosis of CPPE.

[Titanium metallic clips: easier and faster than conventional suturing for heterotopic renal autotransplant in growing pigs]. / Clips metálicos de titanio: una técnica de sutura más rápida y fácil de utilizar que las suturas convencionales en autotrasplantes renales heterotópicos en cerdos en crecimiento.

INTRODUCTION: When performing vascular reconstruction in growing elements, specifically in paediatric transplant surgery, where a short vascular occlusion time is mandatory, master and easily handled suturing methods are needed. Thus the present study compares conventional continuous suturing with polypropylene and dexon versus easier and faster to apply titanium clips in heterotopic renal autotransplants. MATERIAL AND METHODS: 24 growing pigs were used for this study. Heterotopic renal autotransplant was performed when the animals were 45-days-old using VCS clips, continous Polypropylene or Dexon suturing when anastomosing the renal artery and vein to the aorta and cava in an end-to-side fashion RESULTS: VCS clips were easy to use for the surgeon, significantly (P < or = 0.001) decreasing the time needed for end-to-side anastomosis of the renal artery to the aorta (clips, 5.31 +/- 0.80 min/Polypropylene, 14.25 +/- 2.25 min/Dexon, 14.37 +/- 2.97 min); and also the time needed for end-to-side anastomosis of the renal veins to the cava (clips, 8.25 +/- 1.98 min/Polypropylene, 16.25 +/- 2.96 min/Dexon, 19.00 +/- 4.50 min). CONCLUSIONS: The use of VCS clips in heterotopic renal autotransplants significantly decreases the time needed for vascular reconstruction, compared to conventional suturing.

Multiple simultaneous viral infections in infants with acute respiratory tract infections in Spain.

BACKGROUND: The clinical significance of the presence of more than one type of virus in the respiratory specimens of children with respiratory infections is not clear. OBJECTIVES: To describe the clinical characteristics of multiple viral infections versus single infection by respiratory syncytial virus (RSV) in hospitalized infants. STUDY DESIGN: This is a prospective study conducted in all infants under 2 years of age admitted for acute respiratory infection (September 2000-June 2003) in a secondary teaching hospital. Virological diagnosis was made by two different multiplex reverse transcription-nested polymerase chain reaction (RT-PCR) assays in nasopharyngeal aspirates. We describe the clinical characteristics of the patients with multiple viral infections and compare them to a group of 86 randomly selected patients infected only with RSV. RESULTS: 749 specimens taken were analyzed. Respiratory viruses were detected in 65.9% of the samples. 86 children had multiple viral infections (17.4% of all positive specimens). The most frequent clinical diagnosis in this group was recurrent wheezing in 44% and bronchiolitis in 52%. Fever was significantly more frequent (p<0.001), hospital stays were longer (p=0.05), and antibiotic treatment was used more (p=0.03) in infants with multiple viral infections than in the RSV-infected group. CONCLUSIONS: Multiple viral infections are frequent in hospitalized children with respiratory tract disease (17.4%). Multiple viral infections are linked to higher fever, longer hospital stays and more frequent use of antibiotics than in the case of infants with single RSV infections.