Biodegradable Guar-Gum-Based Super-Porous Matrices for Gastroretentive Controlled Drug Release in the Treatment of Helicobacter pylori: A Proof of Concept.

An increase in resistance to key antibiotics has made the need for novel treatments for the gastric colonization of Helicobacter pylori (H. pylori) a matter of the utmost urgency. Recent studies tackling this topic have focused either on the discovery of new compounds to ameliorate therapeutic regimes (such as vonoprazan) or the synthesis of gastroretentive drug delivery systems (GRDDSs) to improve the pharmacokinetics of oral formulations. The use of semi-interpenetrating polymer networks (semi-IPNs) that can act as super-porous hydrogels for this purpose is proposed in the present work, specifically those displaying low ecological footprint, easy synthesis, self-floating properties, high encapsulation efficiency for drugs such as amoxicillin (AMOX), great mucoadhesiveness, and optimal mechanical strength when exposed to stomach-like fluids. To achieve such systems, biodegradable synthetic copolymers containing acid-labile monomers were prepared and interpenetrated with guar gum (GG) in a one-pot polymerization process based on thiol-ene click reactions. The resulting matrices were characterized by SEM, GPC, TGA, NMR, and rheology studies, and the acidic hydrolysis of the acid-sensitive polymers was also studied. Results confirm that some of the obtained matrices are expected to perform optimally as GRDDSs for the sustained release of active pharmaceutical ingredients at the gastrointestinal level, being a priori facilitated by its disaggregation. Therefore, the optimal performance of these systems is assessed by varying the molar ratio of the labile monomer in the matrices.

Impact of the parenting style of foster parents on the behaviour problems of foster children.

BACKGROUND: Few studies have analysed the effects of the parenting style used by foster carers on children's behaviour problems. This study examines the role played by the quality of the emotional relationship with foster carers and the kind of discipline they use as regard internalizing and externalizing problems among foster children. METHODS: Participants were 104 foster children (56 boys and 48 girls) and their respective foster families. The Child Behaviour Checklist, the Affect and Communication Scale, and the Rules and Demands Scale were completed by foster parents. A series of linear regression analyses were performed using the stepwise method. RESULTS: The main findings were as follows: an authoritarian parenting style explained the internalizing problems presented by foster children (11% of the variance); criticism/rejection, authoritarian parenting and permissive parenting explained externalizing problems (37% of the variance); and criticism/rejection and authoritarian parenting explained total problems (29% of the variance). These results indicate that criticism/rejection on the part of foster parents, as well as the use of inappropriate parenting styles (authoritarian and permissive), has an important effect in relation to the behaviour problems of foster children. CONCLUSIONS: This highlights the key role that foster carers play in terms of tackling the behaviour problems that foster children present. The findings also suggest that preparation for fostering should focus especially on ways of helping foster parents both to acquire positive parenting strategies and to avoid authoritarian and permissive parenting.

Advanced interpenetrating polymer networks for innovative gastroretentive formulations targeting Helicobacter pylori gastric colonization.

The escalating challenges of Helicobacter pylori-induced gastric complications, driven by rising antibiotic resistance and persistent cancer risks, underscore the demand for innovative therapeutic strategies. This study addresses this urgency through the development of tailored semi-interpenetrating polymer networks (semi-IPN) serving as gastroretentive matrices for amoxicillin (AMOX). They are biodegradable, absorb significant volume of simulated gastric fluid (swelling index > 360 %) and exhibit superporous microstructures, remarkable mucoadhesion, and buoyancy. The investigation includes assessment at pH 1.2 for comparative analysis with prior studies and, notably, at pH 5.0, reflecting the acidic environment in H. pylori-infected stomachs. The semi-IPN demonstrated gel-like structures, maintaining integrity throughout the 24-hour controlled release study, and disintegrating upon completing their intended function. Evaluated in gastroretentive drug delivery system performance, AMOX release at pH 1.2 and pH 5.0 over 24 h (10 %-100 %) employed experimental design methodology, elucidating dominant release mechanisms. Their mucoadhesive, buoyant, three-dimensional scaffold stability, and gastric biodegradability make them ideal for accommodating substantial AMOX quantities. Furthermore, exploring the inclusion of the potassium-competitive acid blocker (P-CAB) vonoprazan (VONO) in AMOX-loaded formulations shows promise for precise and effective drug delivery. This innovative approach has the potential to combat H. pylori infections, thereby preventing the gastric cancer induced by this pathogen.

Simultaneous Formation of Polyhydroxyurethanes and Multicomponent Semi-IPN Hydrogels.

This study introduces an efficient strategy for synthesizing polyhydroxyurethane-based multicomponent hydrogels with enhanced rheological properties. In a single-step process, 3D materials composed of Polymer 1 (PHU) and Polymer 2 (PVA or gelatin) were produced. Polymer 1, a crosslinked polyhydroxyurethane (PHU), grew within a colloidal solution of Polymer 2, forming an interconnected network. The synthesis of Polymer 1 utilized a Non-Isocyanate Polyurethane (NIPU) methodology based on the aminolysis of bis(cyclic carbonate) (bisCC) monomers derived from 1-thioglycerol and 1,2-dithioglycerol (monomers A and E, respectively). This method, applied for the first time in Semi-Interpenetrating Network (SIPN) formation, demonstrated exceptional orthogonality since the functional groups in Polymer 2 do not interfere with Polymer 1 formation. Optimizing PHU formation involved a 20-trial methodology, identifying influential variables such as polymer concentration, temperature, solvent (an aprotic and a protic solvent), and the organo-catalyst used [a thiourea derivative (TU) and 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU)]. The highest molecular weights were achieved under near-bulk polymerization conditions using TU-protic and DBU-aprotic as catalyst-solvent combinations. Monomer E-based PHU exhibited higher Mw¯ than monomer A-based PHU (34.1 kDa and 16.4 kDa, respectively). Applying the enhanced methodology to prepare 10 multicomponent hydrogels using PVA or gelatin as the polymer scaffold revealed superior rheological properties in PVA-based hydrogels, exhibiting solid-like gel behavior. Incorporating monomer E enhanced mechanical properties and elasticity (with loss tangent values of 0.09 and 0.14). SEM images unveiled distinct microstructures, including a sponge-like pattern in certain PVA-based hydrogels when monomer A was chosen, indicating the formation of highly superporous interpenetrated materials. In summary, this innovative approach presents a versatile methodology for obtaining advanced hydrogel-based systems with potential applications in various biomedical fields.

The synthetic molecule stauprimide impairs cell growth and migration in triple-negative breast cancer.

Stauprimide, a semi-synthetic derivative of staurosporine, is known mainly for its potent differentiation-enhancing properties in embryonic stem cells. Here, we studied the effects of stauprimide in cell growth and migration of triple-negative breast cancer cells in vitro, evaluating its potential antitumoral activity in an orthotopic mouse model of breast cancer in vivo. Our results from survival curves, EdU incorporation, cell cycle analysis and annexin-V detection in MDA-MB-231 cells indicated that stauprimide inhibited cell proliferation, arresting cell cycle in G2/M without induction of apoptosis. A decrease in the migratory capability of MDA-MB-231 was also assessed in response to stauprimide. In this work we pointed to a mechanism of action of stauprimide involving the modulation of ERK1/2, Akt and p38 MAPK signalling pathways, and the downregulation of MYC in MDA-MB-231 cells. In addition, orthotopic MDA-MB-231 xenograft and 4T1 syngeneic models suggested an effect of stauprimide in vivo, increasing the necrotic core of tumors and reducing metastasis in lung and liver of mice. Together, our results point to the promising role of stauprimide as a putative therapeutic agent in triple-negative breast cancer.

Pharmacist care in hospital emergency departments: a consensus paper from the Spanish hospital pharmacy and emergency medicine associations. / Atención farmacéutica en los servicios de urgencias: documento de posicionamiento de la Sociedad Española de Farmacia Hospitalaria (SEFH) y la Sociedad Española de Medicina de Urgencias y Emergencias (SEMES).

OBJECTIVES: To draft a list of actions and quality indicators for pharmacist care in hospital emergency departments, based on consensus among a panel of experts regarding which actions to prioritize in this setting. MATERIAL AND METHODS: A panel of experts from the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Emergency Medicine (SEMES) evaluated a preliminary list of potential actions and quality of care indicators. The experts used a questionnaire to assess the proposals on the basis of available evidence. In the first round, each expert individually assessed the importance of each proposed action based on 4 dimensions: evidence base, impact on clinical response and patient safety, ease of implementation, and priority. In the second round the experts attended a virtual meeting to reach consensus on a revised list of proposals; suggestions and comments that had been made anonymously in the first round were included. The group then prioritized each action as basic, intermediate, or advanced. RESULTS: The experts evaluated a total of 26 potential actions and associated quality indicators. No items were eliminated in the analysis of scores and comments from the first round. After the second round, 25 actions survived. Nine were considered basic, 10 intermediate, and 6 advanced. CONCLUSION: The expert panel's list of pharmacist actions and care quality indicators provides a basis for developing a pharmacist care program in Spanish emergency departments on 3 levels of priority. The list can serve as a guide to pharmacists, managers, physicians, and nurses involved in the effort to improve drug therapy in this hospital setting.

OBJETIVO: Desarrollar un conjunto de actividades e indicadores de atención farmacéutica en los servicios de urgencias hospitalarios mediante un consenso colectivo de un panel de expertos que permita priorizar las actividades a realizar por los farmacéuticos en estas unidades. METODO: Un comité formado por miembros de la Sociedad Española de Farmacia Hospitalaria (SEFH) y de la Sociedad Española de Medicina de Urgencias y Emergencias (SEMES) evaluó una propuesta inicial de actividades e indicadores potenciales, basados en la evidencia científica disponible, en formato de cuestionario. En una primera ronda, cada uno de los expertos del panel clasificó de forma individual la relevancia de cada una de las actividades propuestas en cuatro dimensiones: evidencia científica, impacto en la respuesta clínica y seguridad para el paciente, facilidad de implementación y grado de prioridad. La segunda ronda se realizó mediante una reunión grupal de forma virtual, a partir del cuestionario modificado de acuerdo con las sugerencias planteadas, así como los comentarios vertidos por los participantes del panel de forma anónima. En esta ronda, cada actividad fue clasificada por consenso como básica, intermedia o avanzada en función del grado de prioridad de implantación considerado por el grupo de expertos. RESULTADOS: Se propusieron un total de 26 potenciales actividades a los expertos, con indicadores asociados. Tras el análisis de las puntuaciones y los comentarios realizados en la primera ronda, no se eliminó ninguna de las actividades propuestas. Tras la segunda ronda, se mantuvieron 25 actividades, de las cuales se puntuaron 9 como actividades básicas, 10 actividades como intermedias y 6 actividades como avanzadas. CONCLUSIONES: El desarrollo del conjunto de actividades e indicadores de atención farmacéutica en urgencias, priorizados por grado de relevancia para la unidad, es la base para el desarrollo de esta cartera de servicios en los hospitales españoles, y sirve como guía tanto para farmacéuticos como para gestores, médicos y enfermeros de la unidad a fin de mejorar la farmacoterapia los pacientes atendidos en los servicios de urgencias.

Quantitative (1) H MR spectroscopic imaging of the prostate gland using LCModel and a dedicated basis-set: correlation with histologic findings.

Proton magnetic resonance spectroscopic imaging ((1) H-MRSI) has been advocated as a valuable tool for prostate cancer diagnosis. However, a barrier to widespread clinical use of this technique is the lack of robust quantification methods that yield reproducible results in an institution-independent manner. The main goal of this study was to develop a standardized and fully automated approach (LCModel-based) for quantitative prostate (1) H-MRSI. To this end, a dedicated basis set was constructed by the combination of simulated (citrate, Cit; choline, Cho, and creatine, CR) and experimentally acquired (spermine, Spm) spectra. The overlapping Spm, Cho, and Cr could be resolved and quantified individually, thus allowing for the independent assessment of glandular (Cit and Spm) and proliferative (Cho) components. Several metabolite ratios were calculated and compared to the histologic findings of prostatectomy specimens from 10 prostate cancer patients with Gleason scores (3 + 3) and (3 + 4). The Cho mole fraction and the Cho/(Cit + Spm) ratio were found to best discriminate between prostate cancer and healthy tissue. The comparison between the quantitative MRSI results and the histologic findings suggests that no correlation exists between the detected metabolic alterations and the Gleason score of low-grade tumors.

Tacrolimus modulates liver and pancreas nitric oxide synthetase and heme-oxygenase isoforms and cytokine production after endotoxemia.

Cytoprotective effects of tacrolimus are due to its unspecific anti-inflammatory and anti-oxidant properties. Neither the exact mechanisms nor if there is any organ-specificity or dose-dependent response have not been yet elucidated. Our aim was to evaluate the effect of tacrolimus on oxidative stress and mediator production in liver and pancreatic tissue secondary to endotoxemia. Wistar rats were pretreated with intraperitoneal injection of tacrolimus (0.07, 0.15, and 0.3mg/kg) 24h before Escherichia coli LPS was administrated. Animals were sacrificed 24h after LPS administration and iNOS, eNOS, and nNOS and type 1 and 2 heme-oxygenase (HO) expression were measured. TNF-α and IL-1 tissue expression and plasmatic NO, CO, TNF-α, and IL-1 were also determined. LPS exposure increased iNOS expression in both organs, eNOS did not show variations and liver nNOS expression was significantly lower. Tacrolimus diminished both pancreas and liver iNOS and nNOS expression. Both liver and pancreatic eNOS expression augmented when tacrolimus was administrated. High doses of tacrolimus were correlated with ameliorated liver HO-1 plus HO-2 and pancreas HO-1 expression after LPS stimulation. Tacrolimus treatment diminished TNF-α but not IL-1 expression increase after LPS challenge in hepatic tissue. Pancreatic TNF-α and IL-1 values diminished partially when high doses were employed. Plasmatic NO, CO, TNF-α, and IL-1 concentrations increase after LPS challenge was diminished when highest doses of tacrolimus were given. In conclusion, tacrolimus exerts a protective effect on commonly observed harmful phenomena after LPS stimulation by modulating liver and pancreas oxidative enzyme expression and cytokine production.

Carbohydrate-based polyesters made from bicyclic acetalized galactaric acid.

The dimethyl ester of 2,3:4,5-di-O-methylene-galactaric acid (Galx) was made to react in the melt with 1,n-alkanediols HO(CH(2))(n)OH containing even numbers of methylenes (n from 6 to 12) to produce linear polycyclic polyesters. Two sets of poly(alkylene 2,3:4,5-di-O-methylene-galactarate) polyesters (PE-nGalx) with weight-average molecular weights in the ∼ 5000-10000 and ∼ 35000-45000 ranges were obtained using TBT and DBTO catalysts, respectively. For comparative purposes a set of poly(alkylene adipate) polyesters (PE-nAd) was also synthesized with molecular weights in the higher range using a similar procedure. The thermal stability of PE-nGalx was greater than that of PE-nAd although it notably decayed as molecular weight decreased. The replacement of Ad by Galx in the polyesters caused increases in T(g) of up to 70 °C, and almost doubled the tensile mechanical parameters. All PE-nGalx were semicrystalline but only those made from 1,12-dodecanediol were able to crystallize from the melt with a crystallization rate that diminished as the molecular weight increased. In general, the galactarate containing polyesters displayed higher solubility and wettability than polyadipates, they hydrolyzed faster and exhibited comparable sensitivity to the action of lipases.

Prevalence of adverse drug events in emergency departments. FARM-URG multi-center project.

OBJECTIVE: Adverse drug events are a well-known cause of emergency department admissions. FARM-URG is a project promoted by  the REDFASTER working group of the Spanish Society of Hospital  Pharmacy. Its aim is to evaluate these adverse events through regular  prevalence measurements. The present study shows the results of the first observations. The goal was to determine the prevalence of adverse drug  events with respect to the total number of patients treated in emergency  departments and carry out a description of the different events identified. METHOD: This is a multicenter cross-sectional study carried out in the emergency room of 13 Spanish hospitals. The identification and  registration of patients were obtained from the emergency department  patient census at the time of the first prevalence measurement (16 June  2020). The REDCap® platform was used for patient registration. RESULTS: The 2020 FARM-URG registry, which included 13 hospitals, evaluated 772 patients, of whom 57 (7.4%) consulted for  adverse drug events. Antithrombotic drugs were responsible for most of  these episodes, acenocoumarol being the main drug involved (22.8%).  Nine (15.8%) adverse drug events were caused by inappropriate drug  prescriptions according to the STOPP-START criteria. Nineteen (33.0%)  patients returned to the emergency service within 30 days from discharge. CONCLUSIONS: Adverse drug events are a frequent cause of emergency department visits and are commonly associated with a  significant percentage of re-visits. The FARM-URG project has been created with the purpose of obtaining dynamic and updated information on such  events.

Objetivo: Los acontecimientos adversos por medicamentos son una causa conocida de asistencia a los servicios de urgencias. El objetivo del  proyecto FARM-URG, impulsado por el Grupo de Trabajo REDFASTER de la  Sociedad Española de Farmacia Hospitalaria, es evaluar estos  acontecimientos adversos mediante cortes periódicos. En este estudio se  muestran los resultados del primer registro. Sus objetivos fueron  determinar la prevalencia de acontecimientos adversos respecto al total de pacientes atendidos y caracterizarlos.Método: Estudio multicéntrico transversal realizado en los servicios de urgencias de hospitales españoles. La identificación y registro de  pacientes se obtuvo a partir del censo de pacientes atendidos en urgencias en el momento del corte (16 de junio de 2020). Se revisaron las historias  clínicas retrospectivamente y se registraron los datos en la plataforma  REDCap®.Resultados: En este corte FARM-URG de 2020 participaron 13 hospitales, que evaluaron 772 pacientes, de los cuales 57 (7,4%) habían consultado por un acontecimiento adverso por medicamentos. El grupo de  fármacos antitrombóticos fue responsable de la mayor parte de estos  episodios, siendo acenocumarol (22,8%) el principal fármaco implicado.  Nueve (15,8%) de los acontecimientos adversos fueron causados por  fármacos con prescripción inapropiada según los criterios STOPP-START.  Diecinueve (33,0%) pacientes volvieron a visitar el servicio de urgencias  antes de los 30 días del alta.Conclusiones: Los acontecimientos adversos por medicamentos son un motivo frecuente de visita a los servicios de urgencias y están  asociados a un importante porcentaje de visitas posteriores tras el alta. El  proyecto FARM-URG nace con el propósito de obtener información  periódicamente para la posible implementación de medidas preventivas.

Synthetic polymers from readily available monosaccharides.

The low degradability of petroleum-based polymers and the massive use of these materials constitute a serious problem because of the environmental pollution that they can cause. Thus, sustained efforts have been extensively devoted to produce new polymers based on natural renewing resources and with higher degradability. Of the different natural sources, carbohydrates stand out as highly convenient raw materials because they are inexpensive, readily available, and provide great stereochemical diversity. New polymers, analogous to the more accredited technical polymers, but based on chiral monomers, have been synthesized from natural and available sugars. This chapter describes the potential of sugar-based monomers as precursors to a wide variety of macromolecular materials.

In-Depth Study into Polymeric Materials in Low-Density Gastroretentive Formulations.

The extensive use of oral dosage forms for the treatment of diseases may be linked to deficient pharmacokinetic properties. In some cases the drug is barely soluble; in others, the rapid transit of the formulation through the gastrointestinal tract (GIT) makes it difficult to achieve therapeutic levels in the organism; moreover, some drugs must act locally due to a gastric pathology, but the time they remain in the stomach is short. The use of formulations capable of improving all these parameters, as well as increasing the resident time in the stomach, has been the target of numerous research works, with low-density systems being the most promising and widely explored, however, there is further scope to improve these systems. There are a vast variety of polymeric materials used in low-density gastroretentive systems and a number of methods to improve the bioavailability of the drugs. This works aims to expedite the development of breakthrough approaches by providing an in-depth understanding of the polymeric materials currently used, both natural and synthetic, their properties, advantages, and drawbacks.

[The participation of the pharmacist in the design and follow-up of the drug treatment plan for patients with a cardiovascular condition]. / Diseño y seguimiento del plan farmacoterapéutico del paciente con enfermedad cardiovascular.

OBJECTIVES: To systemise the pharmaceutical care provided to patients with chronic diseases. To evaluate the pharmacist's participation in the drug treatment plan, studying their intervention in the reconciliation of the patient's habitual treatment and the detection and resolution of drug-related problems. METHOD: A multicentre study based on the comparison of two cohorts: one with the intervention of the pharmacist and one without. Inclusion criteria were as follows: patients over the age of 70 with chronic cardiovascular conditions being treated with more than 6 drugs. They were selected between 24-48 hours from admittance; a control patient was chosen for each patient in the intervention group. The pharmaceutical intervention consisted of medication reconciliation on admittance, drug treatment monitoring and reconciliation on discharge. Drug-related problems, their seriousness, the pharmaceutical intervention, the degree of resolution and the clinical outcomes on discharge were all recorded. A total of 24 hospitals participated, with a total of 356 patients: 180 in the intervention cohort and 176 in the control one. RESULTS: A total of 602 drug-related problems were identified: 66.9% belonging to the intervention group and 33% to the control group. Interventions were made in 359 (89%) patients belonging to the intervention group, 66% were resolved after the pharmaceutical intervention, producing a total or partial improvement in the patient in 36.3% of cases. CONCLUSIONS: Pharmaceutical care has been systematised, providing an instrument that enables all the hospitals to work in a standardised manner. The active participation of the pharmacist in the healthcare team contributes to preventing and resolving drug-related problems.

Mapping extracellular pH in rat brain gliomas in vivo by 1H magnetic resonance spectroscopic imaging: comparison with maps of metabolites.

The value of extracellular pH (pH(e)) in tumors is an important factor in prognosisand choice of therapy. We demonstrate here that pH(e) can be mappedin vivo in a rat brain glioma by (1)H magnetic resonance spectroscopic imaging (SI) of the pH buffer (+/-)2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA). (1)H SI also allowed us to map metabolites, and, to better understand the determinants of pH(e), we compared maps of pH(e), metabolites, and the distribution of the contrast agent gadolinium1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraaceticacid (Gd-DOTA). C6 cells injected in caudate nuclei of four Wistar rats gave rise to gliomas of approximately 10 mm in diameter. Three mmols of IEPA were injected in the right jugular vein from t = 0 to t = 60 min. From t = 50 min to t = 90 min, spin-echo (1)H SI was performed with an echo time of 40 ms in a 2.5-mm slice including the glioma (nominal voxel size, 2.2 microl). IEPA resonances were detected only within the glioma and were intense enough for pH(e) to be calculated from the chemical shift of the H2 resonance in almost all voxels of the glioma. (1)H spectroscopic images with an echo time of 136 ms were then acquired to map metabolites: lactate, choline-containing compounds (tCho), phosphocreatine/creatine, and N-acetylaspartate. Finally, T(1)-weighted imaging after injection of a bolus of Gd-DOTA gave a map indicative of extravasation. On average, the gradient of pH(e) (measured where sufficient IEPA was present) from the center to the periphery was not statistically significant. Mean pH(e) was calculated for each of the four gliomas, and the average was 7.084 +/- 0.017 (+/- SE; n = 4 rats), which is acid with respect to pH(e) of normal tissue. After normalization of spectra to their water peak, voxel-by-voxel comparisons of peak areas showed that N-acetylaspartate, a marker of neurons, correlated negatively with IEPA (P < 0.0001) and lactate (P < 0.05), as expected of a glioma surrounded by normal tissue. tCho (which may indicate proliferation) correlated positively with pH(e) (P < 0.0001). Lactate correlated positively with tCho (P < 0.0001), phosphocreatine/creatine (P < 0.001), and Gd-DOTA (P < 0.0001). Although lactate is exported from cells in association with protons, within the gliomas, no evidence was observed that pH(e) was significantly lower where lactate concentration was higher. These results suggest that lactate is produced mainly in viable, well-perfused, tumoral tissue from which proton equivalents are rapidly cleared.

Intracellular water motion decreases in apoptotic macrophages after caspase activation.

Triggering of the macrophage cell line RAW 264.7 with lipopolysaccharide and interferon-gamma promoted apoptosis that was prevented by inhibitors of type 2 nitric oxide synthase or caspase. Using (1)H NMR analysis, we have investigated the changes of the intracellular transverse relaxation time (T(2)) and apparent diffusion coefficient (ADC) as parameters reflecting the rotational and translational motions of water in apoptotic macrophages. T(2) values decreased significantly from 287 to 182 ms in cells treated for 18 h with NO-donors. These changes of T(2) were prevented by caspase inhibitors and were not due to mitochondrial depolarization or microtubule depolymerization. The decrease of the intracellular values of T(2) and ADC in apoptotic macrophages was observed after caspase activation, but preceded phosphatidylserine exposure and nucleosomal DNA cleavage. The changes of water motion were accompanied by an enhancement of the hydrophobic properties of the intracellular milieu, as detected by fluorescent probes. These results indicate the occurrence of an alteration in the physicochemical properties of intracellular water during the course of apoptosis.

Usefulness of WISC-IV in Determining Intellectual Giftedness.

Several studies question the usefulness of the Wechsler Intelligence Scale for Children (WISC-IV) in determining giftedness due to the importance of speed in some of its subtests, which may penalize children of high intellectual level. This study analyzes the factor structure of the WISC-IV of gifted children based on confirmatory factor analysis. Participants were eighty-seven gifted children from Spain (6-13 years old). Score discrepancies were also examined for the main indexes: Verbal Comprehension, Processing Speed, Working Memory and Perceptual Organization. Results pointed out four models with a good fit from the five models analyzed: a two-factor model according to GAI subscales (RMSEA = .001, p = .84), a four-factor first-order model including main indexes (RMSEA = .05, p = .19), a four-factor model with g as a direct factor (RMSEA = .001, p = .84) and a four-factor model with g as an indirect higher-order factor (RMSEA = .05, p = .13). Discrepancies were found between Verbal Comprehension and Processing Speed, and between Perceptual Organization and Processing Speed. Verbal Comprehension yielded the highest score, whereas the lowest scores were obtained in Processing Speed and Working Memory. These results support the use of this scale in the assessment and diagnosis of Spanish children with a high intellectual level.

[Clinical practice variation in cataract surgery]. / Variabilidad clínica en la cirugía de la catarata.

PURPOSE: Cataract surgery rates have dramatically increased in the last two decades. However, clinical practice variation in cataract surgery has not been thoroughly studied. The aim of this review is to analyze clinical practice variation, including the causes and consequences of this phenomenon. Then, its role in health care planning and health care quality is focused, emphasizing the importance of reducing it and providing several practical strategies to accomplish it. RECENT FINDINGS: The latest researches are presented in this article. They identify the development and implementation of clinical practice guidelines as the best tool to standardize care processes. CONCLUSION: Managing unwarranted or unwanted variation would improve quality of care and may lead to a significant saving in health care spending.

Exposure to pesticides and cryptorchidism: geographical evidence of a possible association.

Synthetic hormone-disrupting chemicals may play a role in the increased frequency of cryptorchidism observed in some studies. We used a spatial ecological design to search for variations in orchidopexy rates in the province of Granada in Spain and to search for relationships between these differences and geographical variations in exposure to pesticides. Orchidopexy rates were estimated for the period from 1980 to 1991 in all municipalities and health care districts served by the University of Granada Hospital. A random sample of males of the same age (1-16 years) admitted for any reason during the same period was used to estimate inpatient control rates. Each municipality was assigned to one of four levels of pesticide use. We used Poisson homogeneity tests to detect significant differences in rates of orchidopexy between districts and between levels of pesticide use. Poisson and logistic regression models were also used to estimate the strength of association between orchidopexy and level of pesticide use. Orchidopexy rates tended to be higher in districts near the Mediterranean coast where intensive farming is widespread. The city of Granada, where the reference hospital is located, also had higher figures both for orchidopexy and inpatient control rates. Regression models showed that the strength of association between orchidopexy and level of pesticide use tended to increase with higher levels of use, with the exception of level 0 (mainly in the city of Granada). Our results are compatible with a hypothetical association between exposure to hormone-disruptive chemicals and the induction of cryptorchidism. Several methodological limitations in the design make it necessary to evaluate the results with caution.