Metagene projection characterizes GEN2.2 and CAL-1 as relevant human plasmacytoid dendritic cell models.

MOTIVATION: Plasmacytoid dendritic cells (pDC) play a major role in the regulation of adaptive and innate immunity. Human pDC are difficult to isolate from peripheral blood and do not survive in culture making the study of their biology challenging. Recently, two leukemic counterparts of pDC, CAL-1 and GEN2.2, have been proposed as representative models of human pDC. Nevertheless, their relationship with pDC has been established only by means of particular functional and phenotypic similarities. With the aim of characterizing GEN2.2 and CAL-1 in the context of the main circulating immune cell populations we have performed microarray gene expression profiling of GEN2.2 and carried out an integrated analysis using publicly available gene expression datasets of CAL-1 and the main circulating primary leukocyte lineages. RESULTS: Our results show that GEN2.2 and CAL-1 share common gene expression programs with primary pDC, clustering apart from the rest of circulating hematopoietic lineages. We have also identified common differentially expressed genes that can be relevant in pDC biology. In addition, we have revealed the common and differential pathways activated in primary pDC and cell lines upon CpG stimulatio. AVAILABILITY AND IMPLEMENTATION: R code and data are available in the supplementary material. CONTACT: pedro.carmona@genyo.es or concepcion.maranon@genyo.es. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

New iPAD-based test for the detection of color vision deficiencies.

PURPOSE: To develop and validate a new iPad-based color vision test (Optopad). METHODS: A total of 341 student eyes were enrolled in a first comparative study between Optopad and the Isihara tests. In a second comparative study, Optopad vs. the Farnworth-Munsell test (FM 100H), a total of 66 adult eyes were included. Besides the agreement between tests, the correlation between FM 100H and Optopad outcomes were investigated. Multiple regression analysis was used to predict the total error score (TES) from contrast thresholds measured with the Optopad test. RESULTS: The Ishihara and Optopad tests detected the same anomalous patients. Concerning FM 100H vs. Optopad, 10 subjects were diagnosed as anomalous with both tests, 3 mild anomalous cases based on TES were classified as normal with Optopad, and 2 anomalous subjects based on Optopad test showed normal TES values. Statistically significant correlations of TES and partial error red-green (PTESRG) with thresholds measured with the red-green Optopad stimuli were found. A multiple quadratic regression model was obtained relating TES and chromatic contrast values from Optopad (R2 = 0.855), with only 13 cases showing residuals of ≥ 25 units. CONCLUSIONS: The design and implementation of a chromatic contrast discrimination test has been carried out, with promising clinical results. This test seems to provide comparable outcomes to those obtained with Ishihara and FM 100H tests.

Can Applications Designed to Evaluate Visual Function Be Used in Different iPads?

SIGNIFICANCE: Apple devices could be suitable for vision tests, provided that the test has been correctly adapted to the device, after considering the spatial and colorimetric characterization of the screen. PURPOSE: The majority of vision applications has not been developed by vision or colorimetry experts and suffers from conceptual and design errors that may lead average users to an erroneous assessment of their visual capabilities. The reliability of vision tests depends on the accurate generation of the necessary visual stimuli in a particular device. Our aim was to ascertain whether a given color test, designed for a colorimetrically characterized device, might be used in another similar device. METHODS: We evaluated color reproduction errors in three iPad tablets of different models with Retina screens, using their individual color characterization models and the model derived for another device. RESULTS: Our results showed, even with this small sample, the high degree of error caused when disregarding the fact that the colorimetric design valid for a given device may not be correct when displayed in another. CONCLUSIONS: The distortion of the chromatic content may lead to subjects with vision defects to pass as normal or vice versa, compromising diagnosis reliability.

Colorimetric Characterization of Mobile Devices for Vision Applications.

PURPOSE: Available applications for vision testing in mobile devices usually do not include detailed setup instructions, sacrificing rigor to obtain portability and ease of use. In particular, colorimetric characterization processes are generally obviated. We show that different mobile devices differ also in colorimetric profile and that those differences limit the range of applications for which they are most adequate. METHODS: The color reproduction characteristics of four mobile devices, two smartphones (Samsung Galaxy S4, iPhone 4s) and two tablets (Samsung Galaxy Tab 3, iPad 4), have been evaluated using two procedures: 3D LUT (Look Up Table) and a linear model assuming primary constancy and independence of the channels. The color reproduction errors have been computed with the CIEDE2000 color difference formula. RESULTS: There is good constancy of primaries but large deviations of additivity. The 3D LUT characterization yields smaller reproduction errors and dispersions for the Tab 3 and iPhone 4 devices, but for the iPad 4 and S4, both models are equally good. The smallest reproduction errors occur with both Apple devices, although the iPad 4 has the highest number of outliers of all devices with both colorimetric characterizations. CONCLUSIONS: Even though there is good constancy of primaries, the large deviations of additivity exhibited by the devices and the larger reproduction errors make any characterization based on channel independence not recommendable. The smartphone screens show, in average, the best color reproduction performance, particularly the iPhone 4, and therefore, they are more adequate for applications requiring precise color reproduction.

Treatment outcomes of obstructive sleep apnoea in obese community-dwelling children: the NANOS study.

The first line of treatment of obstructive sleep apnoea syndrome (OSAS) in children consists of adenotonsillectomy (T&A). The aim of the present study was to evaluate treatment outcomes of OSAS among obese children recruited from the community.A cross-sectional, prospective, multicentre study of Spanish obese children aged 3-14 years, with four groups available for follow-up: group 1: non-OSAS with no treatment; group 2: dietary treatment; group 3: surgical treatment; and group 4: continuous positive airway pressure treatment.117 obese children (60 boys, 57 girls) with a mean age of 11.3±2.9 years completed the initial (T0) and follow-up (T1) assessments. Their mean body mass index (BMI) at T1 was 27.6±4.7 kg·m(-2), corresponding to a BMI Z-score of 1.34±0.59. Mean respiratory disturbance index (RDI) at follow-up was 3.3±3.9 events·h(-1). Among group 1 children, 21.2% had an RDI ≥3 events·h(-1) at T1, the latter being present in 50% of group 2, and 43.5% in group 3. In the binary logistic regression model, age emerged as a significant risk factor for residual OSAS (odds ratio 1.49, 95% confidence interval 1.01-2.23; p<0.05) in obese children surgically treated, and RDI at T0 as well as an increase in BMI emerged as significant risk factors for persistent OSAS in obese children with dietary treatment (OR 1.82, 95% CI 1.09-3.02 (p<0.03) and OR 8.71, 95% CI 1.24-61.17 (p=0.03)).Age, RDI at diagnosis and obesity are risk factors for relatively unfavourable OSAS treatment outcomes at follow-up.

Effectiveness of the Nursing Methodology in Pain Management after Major Ambulatory Surgery.

Patients undergoing a surgical intervention for the first time are unfamiliar with the perioperative context, and they usually have no knowledge of postoperative pain management. In the preoperative circuit, there is no time to educate the patient in these terms. The professional profile of nurses allows this need to be addressed, and provides a regulated language to evaluate their effectiveness. This study evaluates the effectiveness of nursing counseling during a preoperative consultation for the management of postoperative pain and its effects on patient satisfaction at hospital discharge. This quasi-experimental study assesses the efficacy of preoperative nursing intervention in two groups, control (n = 185) and intervention (n = 195). Those in the intervention group attended a preoperative session during which they received information from nursing staff and took part in activities to learn about postoperative pain management and the perioperative circuit. Control group patients underwent the standard preoperative protocol. Data were compiled from January to December 2009. Statistically significant differences existed between the two groups regarding postoperative pain (visual analogue scale >3, 20.5% versus 11.5%; p = .023), patient satisfaction (87.1% versus 78.7%; p = .041), and surgical wound complications (13.9% versus 5.5%; p = .010). The results confirm the benefits of applying the nursing methodology in preoperative clinics.

Inflammatory markers and obstructive sleep apnea in obese children: the NANOS study.

INTRODUCTION: Obesity and obstructive sleep apnea syndrome (OSA) are common coexisting conditions associated with a chronic low-grade inflammatory state underlying some of the cognitive, metabolic, and cardiovascular morbidities. AIM: To examine the levels of inflammatory markers in obese community-dwelling children with OSA, as compared to no-OSA, and their association with clinical and polysomnographic (PSG) variables. Methods. In this cross-sectional, prospective multicenter study, healthy obese Spanish children (ages 4-15 years) were randomly selected and underwent nocturnal PSG followed by a morning fasting blood draw. Plasma samples were assayed for multiple inflammatory markers. RESULTS: 204 children were enrolled in the study; 75 had OSA, defined by an obstructive respiratory disturbance index (RDI) of 3 events/hour total sleep time (TST). BMI, gender, and age were similar in OSA and no-OSA children. Monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) levels were significantly higher in OSA children, with interleukin-6 concentrations being higher in moderate-severe OSA (i.e., AHI > 5/hrTST; P < 0.01), while MCP-1 levels were associated with more prolonged nocturnal hypercapnia (P < 0.001). CONCLUSION: IL-6, MCP-1, and PAI-1 are altered in the context of OSA among community-based obese children further reinforcing the proinflammatory effects of sleep disorders such as OSA. This trial is registered with ClinicalTrials.gov NCT01322763.

Visual perception alterations in COVID-19: a preliminary study.

AIM: To compare the visual perception (color and chromatic-achromatic contrast vision) of a small cohort of COVID-19 patients at the time of infection and after 6mo with that of a healthy population matched for sex and age. METHODS: A total of 25 patients (9 females, 16 males, mean age: 54±10y) with COVID-19 hospitalized in the COVID-19 Unit of the University Clinical Hospital of Valladolid were recruited for this preliminary study. Visual perception, as determined by monocular measurement of contrast sensitivity function (CSF) and color vision was assessed in each patient using the Optopad test. The results obtained were then compared with those of a sample of 16 age- and sex-matched healthy controls (5 females, 11 males, mean age: 50±6y) in which the same measurement procedure was repeated. Statistically significant differences between groups were assessed using the Mann-Whitney U test. Measurements were repeated after a minimum follow-up period of 6mo and statistically significant differences between the two time points in each group were assessed using the Wilcoxon signed rank test. RESULTS: Discrimination thresholds (color and chromatic-achromatic contrast vision) and their corresponding sensitivity, calculated as the inverse of the discrimination threshold, were evaluated. Analysis of the data revealed higher contrast threshold results (i.e., worse contrast sensitivity) in the COVID-19 group than in the control group for all spatial frequencies studied in the Optopad-CSF achromatic test and most of the spatial frequencies studied in the Optopad-CSF chromatic test for the red-green and blue-yellow mechanisms. In addition, color threshold results in the COVID-19 group were also significantly higher (i.e., worse color sensitivity) for almost all color mechanisms studied in the Optopad-Color test. At 6mo, most of the differences found between the groups were maintained despite COVID-19 recovery. CONCLUSION: The present results provide preliminary evidence that visual perception may be impaired in COVID-19, even when the infection has passed. Although further research is needed to determine the precise causes of this finding, analysis of CSF and color vision could provide valuable information on the visual impact of COVID-19.

SIDT1 plays a key role in type I IFN responses to nucleic acids in plasmacytoid dendritic cells and mediates the pathogenesis of an imiquimod-induced psoriasis model.

BACKGROUND: Type I IFN (IFN-I) is a family of cytokines involved in the pathogenesis of autoimmune and autoinflammatory diseases such as psoriasis. SIDT1 is an ER-resident protein expressed in the lymphoid lineage, and involved in anti-viral IFN-I responses in vivo, through an unclear mechanism. Herein we have dissected the role of SIDT1 in the natural IFN-producing cells, the plasmacytoid dendritic cells (pDC). METHODS: The function of SIDT1 in pDC was determined by silencing its expression in human primary pDC and GEN2.2 cell line. SIDT1 role in vivo was assessed using the imiquimod-induced psoriasis model in the SIDT1-deficient mice (sidt1-/-). FINDINGS: Silencing of SIDT1 in GEN2.2 led to a blockade of the IFN-I response after stimulation of TLR7 and TLR9, without affecting the pro-inflammatory responses or upregulation of maturation markers. We found that SIDT1 migrates from the ER to the endosomal and lysosomal compartments together with TLR9 after CpG stimulation, participating in the access of the TLR9-CpG complex to lysosome-related vesicles, and therefore mediating the activation of TBK1 and the nuclear migration of IRF7, but not of NF-κB. sidt1-/- mice showed a significant decrease in severity parameters of the imiquimod-induced acute psoriasis-like model, associated with a decrease in the production of IFN-I and IFN-dependent chemokines. INTERPRETATION: Our findings indicate that SIDT1 is at the cross-road between the IFN-I and the proinflammatory pathways and constitutes a promising drug target for psoriasis and other diseases mediated by IFN-I responses. FUNDING: This work was supported by the Consejería de Salud y Familias de la Junta de Andalucía (PIER_S1149 and C2_S0050) and Instituto de Salud Carlos III (PI18/00082 and PI21/01151), partly supported by European FEDER funds, and prior funding to MEAR from the Alliance for Lupus Research and the Swedish Research Council.

Sleep disturbances in autism spectrum disorder without intellectual impairment: relationship with executive function and psychiatric symptoms.

The autism spectrum disorder (ASD) is a neurodevelopmental condition, frequently accompanied by medical and psychiatric pathology. One of the most commonly found problems associated with ASD is sleep disturbances, which are estimated to affect approximately 80% of the people with ASD, not only during childhood but also in the adolescence and adult stages. Nevertheless, the relationship of these sleep difficulties with autism severity, as well as other associated impairments such as executive functioning and psychiatric disorders (eg, depression), has not yet been widely studied. The main objective of the present study was to explore the relationship between sleep disturbances, subjective measures of executive function, and psychiatric pathology in the ASD population. To reach that goal, a group of 89 participants with ASD (44 children/adolescents and 45 adults) was recruited and evaluated with self-reported measures of executive function performance and psychiatric pathology tests. Multivariate analysis showed a significant association between sleep disturbances and psychiatric symptoms in both ASD groups, with greater sleep disturbances predicting more severe psychiatric pathology. No significant association was found with executive function in any group. Limitations included a small sample size and lack of objective measures. Sleep problems seem to be associated with the severity of psychiatric pathology throughout the lifespan, increasing the chance of developing psychiatric symptoms when they were present. Improving sleep quality in ASD at all ages may result in preventing and/or decreasing psychiatric pathology in this population.

MEK inhibition induces caspases activation, differentiation blockade and PML/RARalpha degradation in acute promyelocytic leukaemia.

The hallmark of acute promyelocytic leukaemia (APL) is the reciprocal translocation t(15;17), which leads to the expression of the promyelocytic leukaemia/retinoic acid receptor alpha (PML/RARalpha) fusion protein and a cell differentiation blockade at the promyelocytic stage. PML/RARalpha is directly targeted by all-trans-retinoic acid (ATRA), which degrades the oncoprotein and induces complete remission of malignancies. The aberrant function of PML/RARalpha, together with the constitutive activation of the mitogen-activated protein/extracellular signal-regulated kinase (MEK/ERK) signalling pathway, regulates the ability of haematopoietic cells to proliferate, differentiate, and escape from apoptotic episodes. The role of the MEK/ERK pathway in PML/RARalpha expression, differentiation, proliferation and apoptosis in APL cells was analysed using specific MEK inhibitors. The blockade of MEK/ERK pathway resulted in caspase-dependent degradation of PML/RARalpha, and attenuation of the cell differentiation induction. To our knowledge, this is the first report to show that PML/RARalpha was suppressed by MEK/ERK inhibition, through a mechanism dependent on caspase activation. ATRA co-operated with MEK inhibitor to increase degradation of PML/RARalpha and exhibited a convergence point in caspase activation with MEK inhibitors. Taken together, our data suggest a new role of MEK/ERK pathway in the pathogenesis of APL, thus supporting the use of MEK/ERK inhibitors as an efficient therapeutic strategy for this haematological malignancy.

Aflibercept for clinically significant diabetic macular edema: 12-month results in daily clinical practice.

PURPOSE: To assess the effectiveness and safety of intravitreal aflibercept in clinically significant diabetic macular edema (DME) in daily clinical practice. METHODS: Prospective, open-label, single-center study. Anti-vascular endothelial growth factor naïve patients with clinically significant DME received intravitreal injections of aflibercept 2 mg, five monthly doses followed by a fixed schedule every 2 months for 12 months. The mean change in best-corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] letters) was the primary outcome. RESULTS: The mean BCVA improved significantly as compared with baseline at 12 months of treatment (47.3 [14.2] vs 62.2 [13.9] ETDRS letters, P<0.001). Significant improvement in BCVA was already observed at visit 2 after the loading doses of aflibercept. At 12 months, gains in ETDRS letters were documented in all eyes (100%), with gains ≥10 letters in 89.6%, ≥15 letters in 65.5%, and ≥20 letters in 6.9% (n=2). A significant reduction in central macular thickness from a mean of 460.5 (11.8) µm at baseline to 229.0 (43.8) µm at 12 months (P<0.001) was observed. Significant reductions of central macular thickness were already observed after the loading doses and continued lowering throughout the study period. No adverse events occurred. CONCLUSION: Aflibercept as a first-line therapy was effective and well tolerated for treating clinically significant DME in naïve patients in daily practice. Successful results in terms of improvement of visual and reduction in central macular thickness contribute to provide evidence for the positioning of aflibercept as a first-line indication of newly diagnosed clinically significant DME.

[Insomnia in children and adolescents. A consensus document]. / Insomnio en niños y adolescentes. Documento de consenso.

Insomnia is very common during childhood (30% of children under 5), and causes a serious cognitive and emotional consequence in learning, as well as significant medical comorbidity. It also affects the quality of life, not only of the child, but also of the whole family. Paediatrician training in its diagnosis and treatment is usually poor. For this reason a consensus document is presented on the management of insomnia in children and adolescents. This has been developed by members of the Spanish Paediatrics Association, the Spanish Sleep Society, the Spanish Society of Paediatric Outpatient and Primary Care, the Spanish Adolescent Medicine Society, the Spanish Child and Adolescent Society, and the Spanish Paediatric Neurology Society. The group suggests that diagnosis must be clinical and complementary tests will only be required in doubtful cases or when a differential diagnosis is needed. Likewise, treatment should be mainly based on cognitive-behavioural therapy and the modification of sleeping habits. Using medicines and other substances to make the sleep easier is currently quite common, even although there are no clinical guidelines to support this.

Metabolic biomarkers in community obese children: effect of obstructive sleep apnea and its treatment.

OBJECTIVE: Obesity and obstructive sleep apnea in children have been associated with metabolic morbidities. The present study aimed to evaluate the presence of metabolic alterations among obese children recruited from the community, with and without obstructive sleep apnea syndrome (OSAS), and the impact of treatment of OSAS on metabolic profiles. METHODS: A cross-sectional, prospective, multicenter study of Spanish children aged 3-14 years with a body mass index (BMI) ≥95th percentile for age and sex were randomly selected in the first phase. Four groups emerged for follow-up: (1) no treatment; (2) dietary intervention; (3) surgical treatment of OSA; and (4) continuous positive airway pressure (CPAP) treatment of OSA. Fasting blood tests were performed at baseline (T0) and approximately one year after the intervention (T1). RESULTS: A total of 113 obese children with a mean age of 11.3 ± 2.9 years completed T0 and T1 assessments. Their mean BMI z-score at T1 was 1.34 ± 0.59, and mean Respiratory Disturbance Index was 8.6 ± 13.0 at T0 and 3.3 ± 4.0/hour total sleep time at T1. Only glucose fasting levels differed among metabolic parameters in obese children with OSAS and without OSAS at baseline (T0) (p = 0.018). There were statistically significant differences between surgically treated OSAS (p = 0.002), and CPAP-treated OSAS (p = 0.024) versus the non-OSAS group in the glucose levels between baseline (T0) and follow-up (T1) after controlling for age and change in BMI. Significant univariate associations between BMI and C-reactive protein, insulin, and homeostasis model assessment of insulin resistance emerged at both T0 and T1. CONCLUSIONS: Concurrent obesity and OSAS could promote metabolic and inflammatory alterations, and the latter appeared to be sensitive to OSAS treatment outcomes. ClinicalTrials.gov Identifier: NCT01322763.

Obstructive sleep apnea in obese community-dwelling children: the NANOS study.

INTRODUCTION: Obesity in children is assumed to serve as a major risk factor in pediatric obstructive sleep apnea syndrome (OSAS). However, the prevalence of OSAS in otherwise healthy obese children from the community is unknown. AIM: To determine the prevalence of OSAS in obese children identified and recruited from primary care centers. METHODS: A cross-sectional, prospective, multicenter study. Spanish children ages 3-14 y with a body mass index (BMI) greater than or equal to the 95th percentile for age and sex were randomly selected, and underwent medical history, snoring, and Pediatric Sleep Questionnaire (PSQ) assessments, as well as physical examination, nasopharyngoscopy, and nocturnal polysomnography (NPSG) recordings. RESULTS: Two hundred forty-eight children (54.4% males) with mean age of 10.8 ± 2.6 y were studied with a BMI of 28.0 ± 4.7 kg/m(2) corresponding to 96.8 ± 0.6 percentile when adjusted for age and sex. The mean respiratory disturbance index (RDI), obstructive RDI (ORDI), and obstructive apnea-hypopnea index (OAHI) were 5.58 ± 9.90, 5.06 ± 9.57, and 3.39 ± 8.78/h total sleep time (TST), respectively. Using ≥ 3/h TST as the cutoff for the presence of OSAS, the prevalence of OSAS ranged from 21.5% to 39.5% depending on whether OAHI, ORDI, or RDI were used. CONCLUSIONS: The prevalence of obstructive sleep apnea syndrome (OSAS) in obese children from the general population is high. Obese children should be screened for the presence of OSAS. ClinicalTrials.gov identifier: NCT01322763.

Multichannel functional testing in normal subjects, glaucoma suspects, and glaucoma patients.

PURPOSE: To evaluate visual function with a novel multichannel functional test named the ATD Multichannel Functional Test. METHODS: This multicenter study had a prospective and cross-sectional design. A total of 186 eyes were included: 42 with glaucoma, 14 glaucoma suspects due to optic nerve characteristics, 25 ocular hypertensives, and 105 normal eyes. All patients performed standard visual fields (Humphrey 24-2) and ATD with eight stimuli configurations: four achromatic (A), two red-green (T), and two blue-yellow (D). To derive main outcome measures, mean sensitivity, mean defect (MD), and pattern standard deviation (PSD) were calculated and compared among groups and types of stimuli with the Kruskal-Wallis test. The percentage of cases outside normal limits (ONL) was calculated. RESULTS: MD and PSD were significantly different in glaucoma eyes than in normal subjects for all types of stimuli except D-0.5 cycles per degree (cpd)/12Hz. PSD was also lower for normals than for all pathologic groups with A-4cpd/2Hz, A-4cpd/12Hz, D-0.5cpd/2Hz, and T-0.5cpd/2Hz. The highest percentage of ONL cases was obtained with the two low-spatial-frequency chromatic stimuli, with D-0.5cpd/2Hz and T-0.5cpd/2Hz using PSD, which classified as ONL 81.6% and 86.7% of glaucoma eyes, 51.8% and 44.5% of hypertensives, and 72.2% and 41.2% of optic disc suspects, respectively. CONCLUSIONS: ATD assessed different aspects of visual function, and the most sensitive tests to detect glaucomatous damage were the low-temporal-frequency chromatic tests.

Insomnio en niños y adolescentes. Documento de consenso / Insomnia in children and adolescents. A consensus document

El insomnio es una patología muy frecuente en edad pediátrica (30% en niños menores de 5 años) que ocasiona una grave repercusión cognitiva, emocional y en el aprendizaje junto con una importante comorbilidad médica y afectación de la calidad de vida del niño y la familia. La formación de los pediatras en el diagnóstico y el tratamiento del mismo suele ser deficitaria. Por todo ello, se presenta el documento de consenso sobre el manejo del insomnio en la infancia y la adolescencia elaborado por representantes de la Asociación Española de Pediatría, la Sociedad Española de Sueño, la Sociedad Española de Pediatría Extrahospitalaria y de Atención Primaria, la Sociedad Española de Medicina de la Adolescencia, la Sociedad Española de Psiquiatría Infantil y la Sociedad Española de Neurología Pediátrica. Este grupo recomienda que el diagnóstico debe ser clínico y solo en los casos dudosos o en que sea necesario un diagnóstico diferencial serán necesarias pruebas complementarias. Asimismo el tratamiento se debe basar principalmente en terapias cognitivo-conductuales y en una modificación de los hábitos de sueño. El uso de medicamentos y sustancias para facilitar el sueño es elevado, aunque no existen guías clínicas que lo apoyen

Insomnia is very common during childhood (30% of children under 5), and causes a serious cognitive and emotional consequence in learning, as well as significant medical comorbidity. It also affects the quality of life, not only of the child, but also of the whole family. Paediatrician training in its diagnosis and treatment is usually poor. For this reason a consensus document is presented on the management of insomnia in children and adolescents. This has been developed by members of the Spanish Paediatrics Association, the Spanish Sleep Society, the Spanish Society of Paediatric Outpatient and Primary Care, the Spanish Adolescent Medicine Society, the Spanish Child and Adolescent Society, and the Spanish Paediatric Neurology Society. The group suggests that diagnosis must be clinical and complementary tests will only be required in doubtful cases or when a differential diagnosis is needed. Likewise, treatment should be mainly based on cognitive-behavioural therapy and the modification of sleeping habits. Using medicines and other substances to make the sleep easier is currently quite common, even although there are no clinical guidelines to support this

Additive effect of PTK787/ZK 222584, a potent inhibitor of VEGFR phosphorylation, with Idarubicin in the treatment of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a disease with a poor prognosis. It has been demonstrated that AML cells express vascular endothelial growth factor (VEGF) as well as Flt-1 and KDR, resulting in an autocrine pathway for cell survival. PTK787/ZK 222584 is a new oral antiangiogenic molecule that inhibits tyrosine kinase activity of all known VEGF receptors. The present study aimed to investigate the therapeutic efficacy of combining PTK787/ZK 222584 with a chemotherapeutic agent, such as Idarubicin, for treatment of AML. We have analyzed in four AML cell lines and seven AML patient samples, cell proliferation, apoptosis, angiogenesis. and activation of several related intracellular pathways after treatment with PTK787/ZK 222584 alone or combined with Idarubicin. PTK787/ZK 222584 decreased VEGF levels and VEGF receptor phosphorylation in the AML cells showing Fms-like tyrosine kinase 3/internal tandem duplication mutation (Flt3/ITD). Both drugs, given separately, inhibited cell proliferation and promoted apoptosis. Moreover, combined treatment promoted more apoptosis and inhibition of cell proliferation than each compound administered separately in all AML cells. In conclusion, PTK787/ZK 222584 combined with Idarubicin achieved a better therapeutic efficacy than chemotherapy alone in AML cells, especially in those with Flt3/ITD, in which the combination further prevented activation of the angiogenic process.

Sueño saludable: evidencias y guías de actuación. Documento oficial de la Sociedad Española de Sueño / Healthy sleep: evidence and guidelines for action. Official document of the Spanish Sleep Society

La Sociedad Española de Sueño tiene como uno de sus principales objetivos la promoción de un sueño saludable en la población general y profesionales de la salud. El presente documento pretende realizar una revisión de la literatura científica actual sobre hábitos de sueño que sirva de fundamento para establecer unas recomendaciones generales y útiles para la población general española, en el contexto de un sueño saludable, e identificar aquellos principales retos en la investigación sobre hábitos de sueño. El desarrollo del documento se ha realizado por un equipo multidisciplinar de miembros de la Sociedad Española de Sueño integrado por expertos en medicina pediátrica del sueño, neurofisiología clínica, neumología, neurología, cronobiología, fisiología y psicología. Se ha procedido a una revisión de la bibliografía científica existente sobre hábitos de sueño en población general, y se han abordado los siguientes aspectos: estado actual de los hábitos de sueño en la población española; revisión genérica de la cantidad óptima de horas de sueño; impacto del entorno ambiental (ruido, temperatura, iluminación...), horarios de sueño, alimentación y deporte; y apartados específicos para niños y adolescentes, trabajadores a turnos y conducción de vehículos. De todos los aspectos abordados a lo largo de este documento, se concluyen unas recomendaciones generales finales que servirán de guía a la población general y profesionales de la salud, así como se discuten los principales retos ambientales y futuras direcciones de investigación (AU)

One of the main objectives of the Spanish Sleep Society is to promote healthy sleep in both the general population and in health professionals. This document aims to conduct a review of the current scientific literature on sleep habits that can serve as the basis on which to establish a set of general recommendations, regarding healthy sleep, for use by the general population in Spain as well as to identify the main challenges faced by research into sleep habits. The document has been developed by a multidisciplinary team made up of members of the Spanish Sleep Society who are experts in paediatric sleep medicine, clinical neurophysiology, pulmonology, neurology, chronobiology, physiology and psychology. The existing scientific literature dealing with sleep habits in the general population was reviewed, and the following aspects were addressed: the current state of sleep habits in the Spanish population; a generic review of the optimum number of hours of sleep; the impact of the environmental setting (noise, temperature, illumination, etc.), hours of sleep, diet and sport, together with several specific sections for children and teenagers, shift-workers and drivers of different vehicles. The conclusions from all the aspects addressed in this document have resulted in a set of final general recommendations that will serve as a guide for the general population and health professionals. Likewise, the principal environmental challenges and future lines of research are also discussed (AU)