Inhibition of mitochondrial fission by Drp-1 blockade by short-term leptin and Mdivi-1 treatment improves white adipose tissue abnormalities in obesity and diabetes.

BACKGROUND: Obesity and type 2 diabetes are chronic diseases characterized by insulin resistance, mitochondrial dysfunction and morphological abnormalities. OBJECTIVE: We have investigated if dysregulation of mitochondrial dynamics and biogenesis is involved in an animal model of obesity and diabetes. METHODS: The effect of short-term leptin and mdivi-1 - a selective inhibitor of Drp-1 fission-protein - treatment on mitochondrial dynamics and biogenesis was evaluated in epididymal white adipose tissue (WAT) from male ob/ob mice. RESULTS: An increase in Drp-1 protein levels and a decrease in Mfn2 and OPA-1 protein expression were observed with enhanced and sustained mitochondrial fragmentation in ob/ob mice compared to wt C57BL/6 animals (p < 0.05). The content of mitochondrial DNA and PGC-1α mRNA expression -both parameters of mitochondrial biogenesis- were reduced in ob/ob mice (p < 0.05). Treatment with leptin and mdivi-1 significantly increased mitochondrial biogenesis, improved fusion-to-fission balance and attenuated mitochondrial dysfunction, thus inducing white-to-beige adipocyte transdifferentiation. Measurements of glucose and lipid oxidation in adipocytes revealed that both leptin and mdivi-1 increase substrates oxidation while in vivo determination of blood glucose concentration showed decreased levels by 50% in ob/ob mice, almost to the wt level. CONCLUSIONS: Pharmacological targeting of Drp-1 fission protein may be a potential novel therapeutic tool for obesity and type 2 diabetes.

Statistical inference for unreliable grading using the maximum entropy principle.

Quantitatively assessing the level of confidence on a test score can be a challenging problem, especially when the available information is based on multiple criteria. A concrete example beyond the usual grading of tests occurs with recommendation letters, where a recommender assigns a score to a candidate, but the reliability of the recommender must be assessed as well. Here, we present a statistical procedure, based on Bayesian inference and Jaynes' maximum entropy principle, that can be used to estimate the most probable and expected score given the available information in the form of a credible interval. Our results may provide insights on how to properly state and analyze problems related to the uncertain evaluation of performance in learning applied to several contexts, beyond the case study of the recommendation letters presented here.

Improvement in fetal pulmonary hypertension and maturity after reversal of ductal constriction: prospective cohort study.

OBJECTIVES: To test the hypotheses that estimated mean pulmonary arterial pressure (MPAP) decreases and pulmonary vascular maturation, assessed by the ratio of pulmonary arterial flow acceleration time to ejection time (AT/ET ratio), increases after reversal of fetal ductus arteriosus constriction by reducing maternal intake of the causal agent (prostaglandin inhibitors, such as polyphenol-rich foods or non-steroidal anti-inflammatory drugs), and that these effects are independent of gestational age, which are inferences not yet demonstrated in the clinical setting. METHODS: This was a prospective cohort study comparing Doppler echocardiographic ductal flow dynamics, MPAP and pulmonary arterial flow AT/ET ratio in third-trimester fetuses (≥ 28 weeks' gestation) with ductus arteriosus constriction, at the time of diagnosis and after 2 weeks of reduced maternal intake of prostaglandin inhibitors either by suspending the use of pharmacological agents with potential for prostaglandin inhibition or by restricting the consumption of polyphenol-rich foods. MPAP was estimated using the Dabestani equation (MPAP = 90 - (0.62 × AT)), and pulmonary vascular maturity was assessed using the AT/ET ratio, according to reported validation studies. Student's t-test was used for comparison of variables at diagnosis with those after reversal of ductal constriction. Change in MPAP and pulmonary AT/ET ratio between the two assessments was compared with the expected change in the same gestational period in normal fetuses based on reference curves of MPAP and pulmonary AT/ET ratio constructed in normal fetuses from healthy pregnant women at 19-37 weeks' gestation, encompassing the same gestational age range as the study group (28-37 weeks). RESULTS: Seventy pregnancies with fetal ductus arteriosus constriction were included in the study. After 2 weeks of reduced maternal intake of prostaglandin inhibitors, normalization of mean systolic (change from 1.86 ± 0.34 m/s at diagnosis to 1.38 ± 0.41 m/s; P < 0.001) and diastolic (change from 0.41 ± 0.11 m/s to 0.21 ± 0.065 m/s; P < 0.001) ductal velocities and of mean pulsatility index (change from 1.99 ± 0.20 to 2.55 ± 0.42; P < 0.001) was demonstrated. MPAP decreased between the assessments (change from 66.7 ± 6.90 mmHg at diagnosis to 54.5 ± 6.70 mmHg after 2 weeks; P < 0.001) and mean pulmonary AT/ET ratio increased (change from 0.20 ± 0.06 to 0.33 ± 0.07; P < 0.001). Change in MPAP between diagnosis and after 2 weeks of reduced maternal intake of prostaglandin inhibitors was -12.2 ± 0.30 mmHg, which was 5.3-times higher than that in 305 normal fetuses over 2 weeks during the same gestational period (-2.3 ± 0.19 mmHg) (P < 0.001), and change in pulmonary AT/ET ratio between the two assessments was 0.13 ± 0.08, which was 8.7-times higher than that in normal fetuses in the same gestational period (0.015 ± 0.08) (P < 0.001). CONCLUSIONS: Resolution of fetal ductal constriction is followed by a fall in MPAP and by an increase in pulmonary vascular maturity, to a significantly greater degree than is observed in normal fetuses in the same gestational-age period. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Increase of prostaglandin E2 in the reversal of fetal ductal constriction after polyphenol restriction.

OBJECTIVE: Anti-inflammatory substances that inhibit the synthesis of prostaglandins, such as non-steroidal anti-inflammatory drugs (NSAIDs) and polyphenol-rich foods, can cause constriction of the fetal ductus arteriosus. This study aimed to test the hypothesis that reversal of fetal ductal constriction after maternal restriction of polyphenol-rich foods, in the third trimester of pregnancy, is accompanied by increased plasma levels of prostaglandin E2 (PGE2). METHODS: This was a controlled clinical trial of women with singleton pregnancy ≥ 28 weeks undergoing fetal echocardiography. The intervention group included pregnancies with diagnosis of fetal ductal constriction and not exposed to NSAIDs. The control group consisted of third-trimester normal pregnancies. Both groups answered a food frequency questionnaire to assess the amount of total polyphenols in their diet, underwent Doppler echocardiographic examination and had blood samples collected for analysis of plasma levels of PGE2. Intervention group participants received dietary guidance to restrict the intake of polyphenol-rich foods. The assessments were repeated after 2 weeks in both groups. RESULTS: Forty normal pregnancies were assessed in the control group and 35 with fetal ductal constriction in the intervention group. Mean maternal age (26.6 years) and mean body mass index (30.12 kg/m2 ) were similar between the two groups. Intragroup analysis showed that dietary guidance reduced the median consumption of polyphenols (from 1234.82 to 21.03 mg/day, P < 0.001), increasing significantly the plasma concentration of PGE2 (from 1091.80 to 1136.98 pg/mL, P < 0.05) in the intervention group after 2 weeks. In addition, Doppler echocardiography showed reversal of fetal ductal constriction in the intervention group. No significant changes were observed in the control group. CONCLUSIONS: Dietary intervention for maternal restriction of polyphenol-rich foods in the third trimester of pregnancy is accompanied by increase in plasma levels of PGE2 and reversal of fetal ductal constriction. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Activation by ACA induces pluripotency in human blood progenitor cells.

Reprogramming of human somatic cells by transcription factors to pluripotent state holds great promise for regenerative medicine. However, low efficiencies of current reprogramming methods, immunogenicity and lack of understanding regarding the molecular mechanisms responsible for their generation, limits their utilization and raises questions regarding safety for therapeutic application. Here we report that ACA signaling via PI3K/Akt/mTor induces sustained de-differentiation of human blood progenitor cells leading to generation of ACA pluripotent stem cells. Blood-derived pluripotent stem cells differentiate in vitro into cell types of all three germ layers, exhibiting neuronal, liver, or endothelial characteristics. Our results reveal insight into the molecular events regulating cellular reprogramming and also indicate that pluripotency might be controlled in vivo through binding of a natural ligand(s) to ACA receptor enabling reprogramming through defined pathway(s) and providing a safe and efficient method for generation of pluripotent stem cells which could be a breakthrough in human therapeutics.

Expression and intracellular localization of ACA and TRA-1-81 in smooth muscle cell tumors.

We studied the expression and intracellular localization of ACA and TRA-1-81 in smooth muscle cell tumors. The study was performed on tissue specimens obtained during surgery from patients with uterine leiomyoma and leiomyosarcoma (mean age 34 and 51 years, respectively). ACA was present in leiomyoma, leiomyosarcoma, and control myometrium. Intracellular expression of ACA varied in different types of tumors and was minimum in normal myometrium and maximum in leiomyosarcoma. Membrane localization of the protein is typical of common and cellular leiomyoma, while in the growth zones of mitotically active leiomyoma and leiomyosarcoma the reaction product was primarily located in tumor cell cytoplasm. TRA was detected in some leiomyosarcoma cells. Thus, ACA dysregulation was revealed in the growth zones of leiomyomas and in leiomyosarcomas, which manifested in enhanced expression of this protein and its detachment from the plasma membrane, which leads ACA translocation into the cytoplasm and nucleus of tumor cells and potentiates their proliferative activity.

A novel human glycoprotein ACA is an upstream regulator of human hematopoiesis.

A central issue in stem cell biology is a better understanding of the molecular mechanisms that regulate self-renewal of human hematopoietic stem cells (HSCs). Control of the specific function of HSCs like self-renewal and differentiation might be regulated by a common set of critical genes. However, the regulation among these genes is yet to be elucidated. Here, we show that activation by a novel human GPI-linked glycoprotein ACA at the surface of human peripheral blood progenitor cells induces via PI3K/Akt/mTor/PTEN upregulation of WNT, Notch1, Bmi-1 and HoxB4 genes thus, promoting self-renewal and generation of primitive HSCs. ACA-generated self-renewing cells retained their lympho-myeloid repopulating potential in NOD/SCID mouse xeno-transplantation model with long term functional capacity. We conclude that ACA is an essential regulator of the genes involved in maintaining hematopoiesis and its use in clinical praxis could overcome many of the barriers present so far in transplantation medicine.

Gene expression and molecular modeling of the HSP104 chaperone of Trypanosoma cruzi.

Heat shock protein (HSP) 104 is a highly conserved molecular chaperone that catalyzes protein unfolding, disaggregation and degradation under stress conditions. We characterized HSP104 gene structure and expression in Trypanosoma cruzi, a protozoan parasite that causes Chagas' disease. The T. cruzi HSP104 is an 869 amino-acid protein encoded by a single-copy gene that has the highest sequence similarity (76%) with that of T. brucei and the lowest (23%) with that of the human protein. HSP104 transcripts were detected at room temperature, and levels increased after incubation at 37° or 40°C. The HSP104 protein was found at low levels in non-heat-shocked cells, and accumulated continuously up to 24 h at elevated temperatures. We developed a predicted structural model of hexameric T. cruzi HSP104, which showed some conserved features.

Atomic structure and Mott nature of the insulating charge density wave phase of 1T-TaS2.

Using x-ray pair distribution function (PDF) analysis and computer modeling, we explore structure models for the complex charge density wave (CDW) phases of layered 1T-TaS2that both well capture their atomic-level features and are amenable to electronic structure calculations. The models give the most probable position of constituent atoms in terms of 3D repetitive unit cells comprising a minimum number of Ta-S layers. Structure modeling results confirm the emergence of star-of-David (SD) like clusters of Ta atoms in the high-temperature incommensurate (IC) CDW phase and show that, contrary to the suggestions of recent studies, the low-temperature commensurate (C) CDW phase expands upon cooling thus reducing lattice strain. The C-CDW phase is also found to preserve the stacking sequence of Ta-S layers found in the room temperature, nearly commensurate (NC) CDW phase to a large extent. DFT based on the PDF refined model shows that bulk C-CDW 1T-TaS2also preserves the insulating state of individual layers of SD clusters, favoring the Mott physics description of the metal-to-insulator (NC-CDW to C-CDW) phase transition in 1T-TaS2. Our work highlights the importance of using precise crystal structure models in determining the nature of electronic phases in complex materials.

Candidate gene association study conditioning on individual ancestry in patients with type 2 diabetes and metabolic syndrome from Mexico City.

BACKGROUND: Type 2 diabetes (T2D) is influenced by diverse environmental and genetic risk factors. Metabolic syndrome (MS) increases the risk of cardiovascular disease and diabetes. We analysed 14 cases of polymorphisms located in 10 candidate loci, in a sample of patients with T2D and controls from Mexico City. METHODS: We analysed the association of 14 polymorphisms located within 10 genes (TCF7L2, ENPP1, ADRB3, KCNJ11, LEPR, PPARgamma, FTO, CDKAL1, SIRT1 and HHEX) with T2D and MS. The analysis included 519 subjects with T2D defined according to the ADA criteria, 389 with MS defined according to the AHA/NHLBI criteria and 547 controls. Association was tested with the program ADMIXMAP including individual ancestry, age, sex, education and in some cases body mass index (BMI), in a logistic regression model. RESULTS: The two markers located within the TCF7L2 gene showed strong associations with T2D (rs7903146, T allele, odd ratio (OR) = 1.76, p = 0.001 and rs12255372, T allele, OR = 1.78, p = 0.002), but did not show significant association with MS. The non-synonymous rs4994 polymorphism of the ADRB3 gene was associated with T2D (Trp allele, OR = 0.62, p = 0.001) and MS (Trp allele, OR = 0.74, p = 0.018). Nominally significant associations were also observed between T2D and the SIRT1 rs3758391 SNP and MS and the HHEX rs5015480 polymorphism. CONCLUSIONS: Variants located within the gene TCF7L2 are strongly associated with T2D but not with MS, providing support to previous evidence indicating that polymorphisms at the TCF7L2 gene increase T2D risk. In contrast, the non-synonymous ADRB3 rs4994 polymorphism is associated with T2D and MS.

Understanding Allogrooming Through a Dynamic Social Network Approach: An Example in a Group of Dairy Cows.

For gregarious species such as domestic cattle, the social environment is a very important determinant of their welfare and fitness. Understanding the complexity of cows' relationships can assist the development of management practices that are more integrated with the cows' social behavioral processes. The two aims of this study were: (1) to determine the dynamics of affiliative relationships, as indicated by allogrooming, by means of stochastic actor-oriented modeling, in dairy cows during early lactation; (2) to explore the underlying processes and the individual attributes, such as age, social rank and reproductive state, that could shape network pattern changes in grooming contacts between individual. We observed the allogrooming behavior of a dynamic group of 38 dairy cows for 4 h per day for 30 days. Using stochastic actor-oriented models, we modeled the dynamics of weekly contacts and studied how structural processes (e.g., reciprocity, transitivity, or popularity) and individual attributes (i.e., age, social rank, and reproductive state) influence network changes. We found that cows tended to groom individuals that had previously groomed them, implying a possible cooperation. Cows that groomed more actively did not appear to have a preference for specific individuals in the herd, and in return, tended to be groomed by fewer cows over time. Older individuals groomed more cows than younger ones, indicating that allogrooming could be related to seniority. Cows groomed mainly individuals of similar age, suggesting that familiarity and growing up together enhanced social grooming. Over time, cows with higher social rank were groomed by fewer cows and individuals recently reintroduced to the group groomed more herdmates. The study of social network dynamics can be used to better understand the complexity and non-linearity of cow relationships. Our findings, along with further research, can complement and strengthen the design of improved management practices that are more in line with the natural social behavior of cows.

Multilayer hazes over Saturn's hexagon from Cassini ISS limb images.

In June 2015, Cassini high-resolution images of Saturn's limb southwards of the planet's hexagonal wave revealed a system of at least six stacked haze layers above the upper cloud deck. Here, we characterize those haze layers and discuss their nature. Vertical thickness of layers ranged from 7 to 18 km, and they extended in altitude ∼130 km, from pressure level 0.5 bar to 0.01 bar. Above them, a thin but extended aerosol layer reached altitude ∼340 km (0.4 mbar). Radiative transfer modeling of spectral reflectivity shows that haze properties are consistent with particles of diameter 0.07-1.4 µm and number density 100-500 cm-3. The nature of the hazes is compatible with their formation by condensation of hydrocarbon ices, including acetylene and benzene at higher altitudes. Their vertical distribution could be due to upward propagating gravity waves generated by dynamical forcing by the hexagon and its associated eastward jet.

Need for lung resection in patients with intact or ruptured hydatid cysts.

BACKGROUND: Lung hydatid cyst caused by Echinococcus granulosus is endemic in many areas of the world. We aimed to compare the outcome of surgical treatment in intact and ruptured (infected or noninfected) cysts. METHODS: We reviewed the medical records of 115 patients with lung hydatid disease who were surgically treated between 2001 and 2005 in a tertiary hospital in Lima, Peru. Patients were divided into 3 groups based on cyst characteristics: intact cysts (n = 41), ruptured noninfected cysts (n = 47) and ruptured infected cysts (n = 27). If a patient had more than one type of cyst, the most severe form of disease was recorded. Data related to symptoms, morbidity and mortality were recorded and compared. We also calculated direct patient costs. RESULTS: Mean age of patients was 23.6 +/- 15.1 years old. Ruptured cysts were present in 64 % of patients and giant cysts (> 10 cm diameter) were present in 26 % of patients. Hemoptysis was present in 47.0 % of patients and was more frequent in patients with ruptured infected cysts. Lung resection was performed in 58 % of patients. The most common postoperative complication was infection of the operative wound (6.08 %). Perioperative mortality was zero. Patients with ruptured cysts had a longer hospitalization time and higher total cost (12.28 +/- 0.92 days, US$ 890.34 +/- 303.35) than patients with intact cysts (10.17 +/- 0.79 days, US$ 724.81 +/- 14.38). CONCLUSION: Surgical treatment of lung hydatid disease is safe, with a good outcome and a low mortality rate. The lung resection rate was higher than most published series and reflects the relatively high proportion of patients with giant and ruptured infected cysts.

Pleural empyema as a late complication of liver cystectomy for hydatid cyst.

Cystectomy without capitonnage is a widely used surgical technique for liver hydatid disease. A residual cavity can be left during the procedure, which can turn into an abscess. We report the case of a patient who developed right pleural empyema as a late complication of this procedure. She was successfully managed with antibiotics and a right thoracotomy.

[Uveitis and idiopathic juvenile arthritis in Spain. Epidemiological and therapeutic aspects]. / Uveítis y artritis idiopática juvenil. Epidemiología, pronóstico y tratamiento.

PURPOSE: The purpose of this paper is to describe the frequency and characteristics of uveitis associated with juvenile idiopathic arthritis at a tertiary referral centre in Spain. METHODS: Review of clinical records. 205 children diagnosed with chronic juvenile arthritis over the last 15 years, of whom 26 presented anterior uveitis. Patients were classified according to their pattern of evolution, the time the uveitis was diagnosed with respect to the onset of arthritis, and the severity of uveitis at diagnosis. RESULTS: The prevalence of uveitis was 12.7%. Of the patients affected with uveitis 71% were girls. The average age at which the arthritis was diagnosed was significantly earlier in the group of patients who developed uveitis (4.06 years). No differences were observed in the incidence of uveitis in girls and boys, nor in pauci/polyarticular affectation. ANA positivity was found in 84.6% of the uveitis-affected patients, this being significantly different to the ANA- group. The average age at which uveitis was diagnosed is 5.87 years. 48.1% of uveitis patients develop uveitis within 12 months of the onset of arthritis. This group presented more complications during the evolution of the condition. A total of 84.7% of the uveitis-affected patients presented with a final visual acuity of >0.5 during the observation period. CONCLUSIONS: In our study, the development of uveitis was significantly associated with an earlier age of diagnosis of the arthritis and with the presence of ANA positivity. No differences were observed between boys and girls, or between pauci and polyarticular groups. A greater prevalence of complications was observed in cases presenting with a shorter time interval between the diagnosis of arthritis and uveitis and in those that presented with complications on diagnosis.

[Transient reading disorders associated with interictal epileptiform paroxysmal discharges in invasive videocorticography]. / Trastornos transitorios de la lectura asociados a descargas paroxisticas epileptiformes interictales en videocorticografia invasiva.

INTRODUCTION: Epilepsy in pediatric age are frequently associated with cognitive disorders. Different studies correlated the presence of transient cognitive disorders with the presence of interictal epileptiform discharges (IEDs). CASE REPORT: A 23-year-old woman with pharmacoresistant focal epilepsy was evaluated with invasive videoEEG in the context of epilepsy surgery. There were selected 300 periods of 10 seconds duration from the invasive videoEEG, which were classified into two groups. Group 1 showed IEDs restricted to the cortex of the middle frontal gyrus, inferior temporal gyrus, left lateral and medial occipitotemporal gyrus (dominant hemisphere). In group 2, IEDs was observed in the upper and middle frontal gyrus, precentral, the inferior and middle temporal left gyrus. The patient read the same text during the selected peirods. The number of words read in each period was counted. The working memory was evaluated by the inverse digit test. In group 1, the average number of words read was 10.2 (95% CI: 10.04-10.35); in group 2 it was 2.3 (95% CI: 2.12-2.27; t(146) = 94.55; p < 0.0001). In group 1, the average of inverse digits was 4.05 (95% CI: 3.81-4.30); in group 2 it was 2.67 (95% CI: 2.48-2.86; t(33) = 10.34; p < 0.0001). CONCLUSIONS: Our finding allows us to infer that the interference of IEDs in the cortex of the upper and middle frontal gyrus, precentral, middle and lower temporal gyrus of the dominant hemisphere, causes a dysfunction of neural networks involved in reading.

TITLE: Trastornos transitorios de la lectura asociados a descargas paroxisticas epileptiformes interictales en videocorticografia invasiva.Introduccion. La epilepsia en la edad pediatrica se asocia frecuentemente a trastornos cognitivos. Distintos estudios correlacionaron la presencia de trastornos cognitivos transitorios con la presencia de descargas epilepticas interictales (DEI). Caso clinico. Mujer de 23 años, con epilepsia focal farmacorresistente evaluada con videoelectroencefalograma (video-EEG) invasivo en el contexto de cirugia de la epilepsia. Del video-EEG invasivo se seleccionaron 300 epocas de 10 s de duracion, que se clasificaron en dos grupos. El grupo 1 evidencio DEI restringidas a la corteza del giro frontal medio, el giro temporal inferior y los giros occipitotemporales lateral y medial izquierdos (hemisferio dominante). En el grupo 2 se observaron DEI en el giro frontal superior y medio, el giro precentral y los giros temporales medio e inferior izquierdos. La paciente leyo el mismo texto durante las epocas seleccionadas. Se contabilizo el numero de palabras leidas en cada epoca. Se evaluo la memoria de trabajo mediante la prueba de digitos inversos. En el grupo 1, la media de palabras leidas fue de 10,2 (IC 95%: 10,04-10,35); en el grupo 2, de 2,3 (IC 95%: 2,12-2,27; t(146) = 94,55; p < 0,0001). En el grupo 1, la media de digitos inversos fue de 4,05 (IC 95%: 3,81-4,30); en el grupo 2, de 2,67 (IC 95%: 2,48-2,86; t(33) = 10,34; p < 0,0001). Conclusion. El hallazgo permite inferir que la interferencia de las DEI en la corteza del giro frontal superior y medio, el giro precentral, y los giros temporales medio e inferior del hemisferio dominante provoca una disfuncion de las redes neuronales implicadas en los mecanismos de la lectura.

Healthcare accreditation as trigger of organisational change: The view of professionals.

BACKGROUND: Healthcare accreditation seeks to promote the organisational change in healthcare organisations from an approach that values the level of progress achieved through a validated reference framework. The aim of this paper is to analyse the role played by accreditation through the experience perceived by health professionals during the process of self-assessment and external evaluation, taking into account three dimensions of analysis: focus on the patient, internal organisation and leadership, and impact on the clinical aspects of healthcare. MATERIAL AND METHODS: Design: Semi-structured interviews with key informants from clinical management units (CMU) within the Andalusian Health System (Spain). PARTICIPANTS: The key informants in each CMU were the clinical leader, the head of nursing and two health professionals (doctors and nurses). A qualitative research protocol was employed to conduct the semi-structured interviews (n=52 interviews) with physicians and nurses, in order to analyse their experience with the accreditation process. RESULTS: The analysis identified four main outcomes related to the accreditation process perceived by professionals: (1) A benchmarking conceptualisation of the process; (2) Improvements in patient-centred care, quality of clinical records, and organisational culture of the units; (3) Improvement of patient safety culture; (4) As negative outcomes, a slight perception of bureaucratisation and standardisation of the clinical practice. CONCLUSIONS: The described initiative of accreditation process in Andalusia (Spain) is widely perceived as positive by health professionals since it fosters the organisational change, although it also has a slightly negative bureaucratisation effect on clinical practice.

Eye lens radiation exposure in paediatric interventional treatment of retinoblastoma.

Retinoblastoma represents 3% of cancers in children under fifteen years of age. The standard paediatric treatment for saving the affected eye is supraselective intra-arterial chemotherapy performed in interventional rooms. In order to address the radiation toxicity due to the angiography, the aim of this study was to determine the typical dose value corresponding to the procedure, estimate the paediatric patients' eye lens dose and study the relationship between dose indicators and dose to the lens. An automatic dose management software was installed in two interventional rooms to obtain the distribution of the dose indicators kerma-area product and reference-point air kerma, getting a typical value 16 Gy·cm2 and 130 mGy, respectively (n = 35). The eye lens dose estimates were obtained with photoluminescent dosimeters placed on the patient's eyelids. In the left eye, the entrance surface air kerma was 44.23 ± 2.66 mGy, and 12.72 ± 0.89 mGy in the right eye (n = 10). There was a positive correlation between dose to the lens per procedure and dose indicators, with R2 > 0.65 for both eyes. Based on this information, the threshold for the onset of radiation-induce cataracts (500 mGy) will be exceeded if the treatment is performed for more than 8 sessions.

Apolipoprotein E genotype does not associate with disease severity measured by Multiple Sclerosis Severity Score.

OBJECTIVES: During the last years, the association between apolipoprotein E (APOE) polymorphism and disease severity in multiple sclerosis (MS) has been studied with conflicting results. As a result of a considerable individual variation in the clinical course of MS, there is no consensus method for measuring progression using single assessments of disability. Recently, Multiple Sclerosis Severity Score (MSSS) method has been proposed for comparing disease progression using single data. We evaluate in our population if there is any correlation between APOE genotype and severity according to MSSS. METHODS: We studied 82 patients followed up in our Neurology Unit throughout the year 2005, diagnosed with MS, and with disease duration of at least 2 years. We collected data concerning demographic and clinical variables including age of onset, disease duration, Expanded Disability Status Scale (EDSS) score and the total number of relapses. When reached, we determined the latency to EDSS scores of 4.0 and 6.0. We calculated progression index (PI) and relapse rate (RR). We ascertained MSSS for our patients in the global MSSS table. RESULTS: We found four patients heterozygous for the E2 allele and 16 for the E4 allele. No patient was homozygous for E2 or E4. RR (P = 0.017 with 95% CI: 0.005-0.57) and PI (P = 0.016 with 95% CI: 0.004-0.38) were significantly lower in E4 carriers. MSSS scores were not associated with carriership of E2 or E4. CONCLUSION: Our results show no effect of the APOE genotype on the severity of MS measured by MSSS, as a recently published meta-analysis has noticed. So, our data do not support a role for APOE in MS severity, in spite of the seeming influence shown using other measures such as PI. MSSS is probably the best method to measure severity with a single measure of disability and should be used more frequently when performing genetic research.