Telemedicina en retinopatía del prematuro: Atravesando fronteras en la salud visual pediátrica. Estudio TELEROP / Telemedicine in retinopathy of prematurity: Crossing borders in pediatric vision health. TELEROP study

Objetivo general Evaluar la precisión y validez de imágenes vía teléfono inteligente en comparación con el sistema RetCam® para el diagnóstico de retinopatía del prematuro (ROP). Metodología Estudio observacional, de corte longitudinal y enmascarado realizado en el hospital Dr. Elías Santana. Se incluyeron infantes con peso al nacer ≤ 1.500 g, edad gestacional ≤ 30 semanas y/o pacientes expuestos a factores de riesgo o complicaciones ligadas a ROP. Estos sujetos fueron tamizados empleando imágenes vía teléfono inteligente o RetCam®, ambos comparados con la fondoscopía convencional. Se utilizó la clasificación de ICROP para la estadificación. Los resultados principales analizados fueron sensibilidad, especificidad, valores predictivos e índice kappa. Resultados Se obtuvieron 915 imágenes (n = 121), distribuidas en grupo teléfono inteligente (50,4%) y grupo RetCam® (49,6%) entre agosto del 2020 y marzo del 2021. Los sujetos que presentaron ROP tuvieron menor edad gestacional (30,2 sem ± 2.8), peso al nacer (1.361 g ± 398) y mayor exposición a oxigenoterapia (12,8 días ± 11,3). El grupo RetCam® presentó sensibilidad = 80%, especificidad = 78%, valor predictivo positivo = 90% e índice kappa = 0,70. El grupo teléfono inteligente presentó sensibilidad = 88%, especificidad = 90%, valor predictivo positivo = 93,75% e índice kappa = 0,81. Conclusiones Ambos métodos diagnósticos fueron precisos para identificar ROP. El grupo teléfono inteligente obtuvo resultados superiores con una excelente resolución, representando un método costo-efectivo para crear un impacto global en la reducción de la ceguera prevenible en población pediátrica (AU)

General objective To evaluate the accuracy and validity of images with smartphone compared to the RetCam® system for the diagnosis of retinopathy of prematurity (ROP). Methodology Observational, longitudinal and masked study carried out at the Dr. Elías Santana hospital. Infants with birth weight ≤ 1500 g, gestational age ≤ 30 weeks and/or patients exposed to risk factors or complications linked to ROP were included. These subjects were screened using images with smartphone or RetCam®, both compared to conventional fundoscopy. The ICROP classification was used for staging. The main results analyzed were sensitivity, specificity, positive predictive values and kappa index. Results 915 images (n = 121) were obtained, distributed in smartphone group (50.4%) and RetCam® group (49.6%) between August 2020 and March 2021. Subjects with ROP had lower gestational age (30.2 sem ± 2.8), birth weight (1361 g ± 398), and greater exposure to oxygen therapy (12.8 days ± 11.3). The RetCam® group presented sensitivity = 80%, specificity = 78%, positive predictive value = 90% and kappa index = 0.70. The smartphone group presented sensitivity = 88%, specificity = 90%, positive predictive value = 93.75% and kappa index = 0.81. Conclusions Both diagnostic methods were accurate to identify ROP. The smartphone group obtained superior results with excellent resolution, representing a cost-effective method to create a global impact on reducing preventable blindness in the pediatric population (AU)

Telemedicine in retinopathy of prematurity: Crossing borders in pediatric vision health. TELEROP study.

GENERAL OBJECTIVE: To evaluate the accuracy and validity of images with smartphone compared to the RetCam® system for the diagnosis of retinopathy of prematurity (ROP). METHODOLOGY: Observational, longitudinal and masked study carried out at the Dr. Elías Santana hospital. Infants with birth weight ≤1500 g, gestational age ≤30 weeks and/or patients exposed to risk factors or complications linked to ROP were included. These subjects were screened using images with smartphone or RetCam®, both compared to conventional fundoscopy. The ICROP classification was used for staging. The main results analyzed were sensitivity, specificity, positive predictive values and kappa index. RESULTS: 915 images (n = 121) were obtained, distributed in smartphone group (50.4%) and RetCam® group (49.6%) between August 2020 and March 2021. Subjects with ROP had lower gestational age (30.2 sem ± 2.8), birth weight (1361 g ± 398), and greater exposure to oxygen therapy (12.8 days ± 11.3). The RetCam® group presented sensitivity = 80%, specificity = 78%, positive predictive value = 90% and kappa index = 0.70. The smartphone group presented sensitivity = 88%, specificity = 90%, positive predictive value = 93.75% and kappa index = 0.81. CONCLUSIONS: Both diagnostic methods were accurate to identify ROP. The smartphone group obtained superior results with excellent resolution, representing a cost-effective method to create a global impact on reducing preventable blindness in the pediatric population.

Study of guided wave propagation on a plate between two solid bodies with imperfect contact conditions.

In this work, fundamental symmetric Lamb wave S0 mode is characterized in terms of its velocity variation as function of the interfacial conditions between solid bodies in contact. Imperfect contact conditions are numerically and experimentally determined by using ultrasonic Lamb wave propagation parameters. For the study, an experimental system was used, formed by two solid aluminum rods (25.4mm in diameter) axially loading a thin aluminum plate to control contact interfacial stiffness. The axially applied load on the aluminum plate was varied from 0MPa to 10MPa. Experimental Lamb wave signals were excited on the plate through two longitudinal contact transducers (1MHz of central frequency) using a pitch-catch configuration. Numerical simulations of contact conditions and Lamb wave propagation were performed through Finite Element Analysis (FEA) in commercial software, ANSYS 15®. Simulated Lamb wave signals were generated by means of a 5 cycles tone burst signals with different frequency values. Results indicate a velocity change in both, experimental and simulated Lamb wave signals as function of the applied load. Finally, a comparison between numerical results and experimental measurements was performed obtaining a good agreement.

Off-Clamp Renal Tumourectomy by Retroperitoneoscopy in Posterior Renal Tumours of Medium Complexity (Padua score 8-9).

BACKGROUND: The guidelines recommend partial surgery for T1 renal tumours. Various aspects of this surgery have evolved in recent years, including the clamping method and duration, enucleation, the retroperitoneoscopic approach and the use of 3mm ports. We present our initial series on laparoscopic renal tumourectomy by retroperitoneoscopy (LRTR) and analyse our learning curve and use of 3-mm instrumentation. MATERIAL AND METHODS: From January 2011 to January 2015, we performed LRTR on 50 patients with posterior or convex T1 renal tumours. After 10 cases, the technique changed to off-clamp, and 11 cases were subsequently performed with 3mm instrumentation. RESULTS: The mean tumour size was 34.36 mm (14-62), with a mean PADUA score of 8.42 (5-12). The mean operative time was 163.1 minutes (75-300), and the mean warm ischaemia time was 4.21 minutes (0-28). The main renal artery was not clamped in 41 (82%) patients, and no vessel (zero ischaemia) was clamped in 39 (78%) patients. Seven cases had positive margins (6 focal). Eleven LRTRs were performed with 3mm instrumentation, with shorter surgical times, less intraoperative bleeding and shorter hospital stays. CONCLUSIONS: Retroperitoneoscopy coupled with enucleation enables the extirpation without clamping of posterior renal tumours, with a relatively short learning curve. The 3-mm material enables the technique to be performed, although in our experience it has resulted in a higher rate of positive surgical margins.

Effects of parathyroid hormone on cortical porosity, non-enzymatic glycation and bone tissue mechanics in rats with type 2 diabetes mellitus.

Type 2 diabetes mellitus increases skeletal fragility; however, the contributing mechanisms and the efficacy of bone-forming agents are unclear. We studied diabetes and parathyroid hormone (PTH) treatment effects on cortical porosity (Ct.Po), non-enzymatic glycation (NEG) and bone mechanics in Zucker diabetic fatty (ZDF) rats. Eleven-week old ZDF diabetic (DB) and non-diabetic (ND) rats were given 75µg/kg PTH (1-84) or vehicle 5days per week over 12weeks. The right femora and L4 vertebrae were excised, micro-CT scanned, and tested in 3-point bending and uniaxial compression, respectively. NEG of the samples was determined using fluorescence. Diabetes increased Ct.Po (vertebra (vert): +40.6%, femur (fem): +15.5% vs. ND group, p<0.05) but had no effect on NEG. PTH therapy reduced vertebral NEG in the ND animals only (-73% vs untreated group, p<0.05), and increased femoral NEG in the DB vs. ND groups (+63%, p<0.05). PTH therapy had no effect on Ct.Po. Diabetes negatively affected bone tissue mechanics where reductions in vertebral maximum strain (-22%) and toughness (-42%) were observed in the DB vs. ND group (p<0.05). PTH improved maximum strain in the vertebra of the ND animals (+21%, p<0.05) but did not have an effect in the DB group. PTH increased femoral maximum strain (+21%) and toughness (+28%) in ND and decreased femoral maximum stress (-13%) and toughness (-27%) in the DB animals (treated vs. untreated, p<0.05). Ct.Po correlated negatively with maximum stress (fem: R=-0.35, p<0.05, vert: R=-0.57, p<0.01), maximum strain (fem: R=-0.35, p<0.05, vert: R=-0.43, p<0.05) and toughness (fem: R=-0.34, p<0.05, vert: R=-0.55, p<0.01), and NEG correlated negatively with toughness at the femur (R=-0.34, p<0.05) and maximum strain at the vertebra (R=-0.49, p<0.05). Diabetes increased cortical porosity and reduced bone mechanics, which were not improved with PTH treatment. PTH therapy alone may worsen diabetic bone mechanics through formation of new bone with high AGEs cross-linking. Optimal treatment regimens must address both improvements of bone mass and glycemic control in order to successfully reduce diabetic bone fragility. This article is part of a Special Issue entitled "Bone and diabetes".

[Scuba diving in children: Physiology, risks and recommendations]. / Buceo en la edad pediátrica: fisiología, riesgos y recomendaciones.

INTRODUCTION: The increase in recreational scuba diving in recent years, including children, involves risks and the possibility of accidents. While legislation, conditions and risks of scuba diving are well documented in adults, scientific evidence in scuba diving by children and adolescents is sparse and isolated. Furthermore, existing guidelines and recommendations for adults cannot be transferred directly to children. METHODS: These circumstances have led to the Group on Techniques of the Spanish Society of Pediatric Pulmonology (SENP) to perform a literature search to review and update the knowledge about scuba diving in children. RESULTS: Physiological adaptations of the body are examined during the dive, as well as the anatomical and physiological characteristics of children that should be taken into account in scuba diving. The most common types of accidents and its causes, as well as the risks of scuba diving practice in children with previous diseases are discussed, along with details of the medical and psychological requirements for scuba diving to be considered in the assessment of child and adolescent. CONCLUSIONS: A list of recommendations for scuba diving with compressed air in children is presented by a group of experts.

Is there a limit for the laparoscopic approach of a retroperitoneal residual mass postchemotherapy?

OBJECTIVES: Rescue lymphadenectomy for testicular cancer is a complex surgery, with a high number of complications. The laparoscopic approach appears to offer faster recovery and improved quality of life compared with open surgery. The aim of our study is to report on our experience and to define whether there is a limit (oncological, anatomical or technical) for laparoscopic management. MATERIAL AND METHODS: A retrospective study was conducted of 15 patients who underwent laparoscopic retroperitoneal lymphadenectomy after chemotherapy. In addition to epidemiological and oncologic variables, we analyzed the mean surgical time, intraoperative and postoperative complications, the mean hospital stay and the mean follow-up time. RESULTS: The mean surgical time was 294 minutes (range, 180-240). There were 4 large-vessel vascular lesions, all of which were large-volume retroperitoneal masses, with diameters >7 cm. The rate of postoperative complications was 33%; there was only 1 case of Clavien >III. The mean hospital stay was 5.38 days (range, 2-9), and the mean patient follow-up was 28.9 months (range, 1-79). There was no recurrence in any of the cases. CONCLUSIONS: The laparoscopic approach is an oncologically safe option for the rescue treatment of testicular cancer. The complex location of these masses entails the onset of severe intraoperative complications. We have observed a clear relationship between vascular complications and large masses (>7 cm). We therefore believe that it would be appropriate to establish a limit on the size for laparoscopic treatment.

[Combined approach of laparoscopic and open surgery for complex renal lesions]. / Abordaje combinado para la nefrectomía parcial en lesiones renales complejas.

OBJECTIVE: To develop a combined surgical approach (laparoscopic and open) that allows an increased vascular control and decreased ischemia time, maintaining the advantages of pure laparoscopic partial nephrectomy (LPN). MATERIAL AND METHODS: During the laparoscopic phase, dissection of the kidney and its pedicle is achieved. Then, an open approach is initiated through a mini-laparotomy, with the kidney being brought to the incision, improving the identification and exposition of the tumors. Following tumor identification by ultrasound, exeresis of the lesion is performed with or without vascular clamping. RESULTS: Through this approach we performed the excision of complex lesions in 6 patients. Mean surgical time was 192 minutes (range 180-210) and mean warm ischemia time was 13 minutes (0-22), with a mean blood loss of 267 mL (100-500). Average pre and postoperative glomerular filtration rate was 51.5 (28-90) and 48.8 mL/min/1.73 m(2) (19-90), respectively. In one patient, suture repair of the pelvicaliceal system was needed, with no other perioperative morbidities being reported. CONCLUSIONS: This combined approach is a minimally invasive surgical alternative, reproducible and safe which preserves the virtues of pure LPN. It allows a better control of the vascular pedicle, reducing the risk of hemorrhage and the warm ischemia time. This technique may be either considered in the treatment of renal masses with indication for partial nephrectomy but of complex laparoscopic approach or as a surgical approach in the early learning curve of the LPN.

Evaluation of the i-STAT point-of-care capillary whole blood prothrombin time and international normalized ratio: comparison to the Tcoag MDAII coagulation analyzer in the central laboratory.

BACKGROUND: Point-of-care devices for performing a prothrombin time/international normalized ratio (PT/INR) using capillary blood samples are being increasingly used to monitor patients receiving anticoagulation therapy. However, the performance of some devices has been shown to be suboptimal and there are only limited published data comparing specific devices to various central laboratory coagulation analyzers. We report an evaluation of the iSTAT PT/INR with a comparison to the Tcoag MDA II analyzer. METHODS: We obtained simultaneous capillary/venous samples on 20 healthy volunteers for a normal range study and on 50 anticoagulated patients for a clinical evaluation. Testing was performed by phlebotomists. We also obtained 68 near simultaneous capillary/venous test results for assessment of performance by non-laboratory personnel. The criteria for determining clinical equivalence of the iSTAT to the MDA II were (1) same clinical category (subtherapeutic INR<2, therapeutic INR 2-3, and supratherapeutic INR>3) or (2) paired values within ≤ 0.4 INR. RESULTS: Forty nine of 50 patient sample pairs collected by phlebotomists showed acceptable clinical agreement. Sixty one (61) of 68 patient sample pairs collected by nurses showed acceptable agreement. In all discordant cases the differences were minor and would have resulted in either no or minimal change in therapy. CONCLUSIONS: The iSTAT PT/INR compares well to the MDA II when performed by phlebotomists or nurses.

Microsatellites and Alu elements from the human MHC in Valencia (Spain): analysis of genetic relationships and linkage disequilibrium.

Two different sets of noncoding markers (microsatellites and Alu elements) from the human chromosome six were analysed in 106 individuals from Valencia (Spain), with the aim of exploring the effect of evolutionary forces on the genetic variability of the major histocompatibility complex (MHC) and assessing the potential usefulness of these genetic loci in phylogenetic studies. Linkage disequilibrium (LD) analyses revealed statistically significant associations among markers located in the MHC class I region, and also between the microsatellite D6S2792 and several genetic loci from MHC class I, II and III regions. Results of the Ewens-Watterson test indicated that only D6S2792 showed significant departure from selective neutrality. Despite the paucity of haplotype data in the literature, results of the phylogenetic analyses at world scale (Alu elements) showed that the genetic relationships of Valencia were mainly determined by the ethnic ancestry of the populations considered, whereas at European scale (microsatellites) population affinities were strongly influenced by geography. Our findings suggest that noncoding markers from the MHC such as Alu and microsatellite loci might have a potential value as lineage (ancestry) markers in investigations into evolutionary, medical and forensic perspectives.

Genetic variability in autochthonous Basques from Guipuzcoa: a view from MHC microsatellites.

Five short tandem repeats (STRs) located at human chromosome 6 were analysed in 97 autochthonous Basques from Guipuzcoa (northern Spain), with the aim of assessing the genetic relationships of Basques at a European scale, based on the variability of the major histocompatibility complex (MHC) region, and comparing the phylogenetic information obtained from STRs, and from HLA class I genes (HLA-A and HLA-B) for the same set of European populations. The integrative approach was focused on D6S265 and D6S2792, according to availability of population databases. F(ST) genetic distances obtained from STRs and from HLA loci were very similar, thereby describing a comparable pattern of genetic structuring among the European populations. These findings were supported by results of the Mantel test of matrix correspondence (r = 0.796, P = 0.0022) and by significant correlations between the first two F(ST) eigenvectors of STRs and HLA genes. Coinciding with previous phylogenetic studies, Basques showed substantial genetic differentiation within the European context, probably as a result of the impact of random genetic drift and high inbreeding levels for extended periods of isolation even from adjacent populations. Analysis of the geographical distribution of the allele frequencies revealed a great number of latitudinal frequency clines in both the MHC STRs and the HLA class I genes, which supports the notion of the post-glacial resettlement of Europe being a crucial factor in the genetic make-up of Europeans. Our results indicate that analysing the genetic variability of MHC microsatellites could be a suitable strategy in evaluating the role of evolutionary forces such as natural selection (because of genetic hitchhiking effect), genetic drift and gene flow in the maintenance of polymorphism at the MHC region, because STRs can efficiently complement the genetic information obtained from HLA genes.

Alterations in myeloid dendritic cell innate immune responses in the Galphai2-deficient mouse model of colitis.

BACKGROUND: The G protein alpha subunit type-2 (Galpha(i)2)-deficient mouse develops inflammatory bowel disease (IBD) with increased severity in mice on a 129SvEv (129) background compared to the C57BL/6 (B6) background. Since dendritic cells (DCs) are key cells of innate immunity, we determined whether Galpha(i)2(-/-) DCs have functional defects, influenced by strain background, that predispose to IBD. METHODS: By breeding these strains to homozygosity for the first time, it became possible to study innate immunity in this animal model with more precision than ever before. Immature DCs were generated using bone marrow monoblasts cultured in the presence of GM-CSF (BMDCs), DC subsets sorted and responses to TLR9 activation were assayed. RESULTS: In contrast to Galpha(i)2(-/-) B6, Galpha(i)2(-/-) 129 mice display accelerated onset and increased severity of colitis, abnormal mucosal DC distribution, accompanied by preponderance for Th1 and Th17-associated gut cytokine expression. TLR9 activation of BMDCs induces sustained p38 MAPK activation and greater Th1- and Th17-type cytokine secretion in both strains of Galpha(i)2-deficient compared to wildtype BMDCs. However, only B6 Galpha(i)2(-/-) BMDCs concomitantly produces IL-10 while Galpha(i)2(-/-) 129 BMDCs do not. CONCLUSIONS: Loss of Galpha(i)2 promotes a Th1/Th17 phenotype and relative IL-10 insufficiency in Galpha(i)2(-/-) 129 BMDCs may account for the striking difference in disease.

Cognitive functioning in children with multiple sclerosis.

OBJECTIVE: To examine the cognitive functioning of children with multiple sclerosis (MS). METHODS: Six children with a diagnosis of clinically definite MS were evaluated using a neuropsychological test battery. RESULTS: The majority of the children showed deficits in at least two of the administered subtests, with IQ scores within the deficient classification. CONCLUSIONS: Verbal and non-verbal skills were equally impaired, and patients who were older at the moment of the onset of the disease had a better cognitive performance. Cognitive deficits should be regarded as a common occurrence in the course of MS in children.

On modelling nonlinear viscoelastic effects in ligaments.

Experiments in human ligaments revealed that the rate of stress relaxation in such materials is strain dependent. This nonlinear behavior requires therefore a modified description of the standard quasilinear viscoelasticity theory commonly used in tissue biomechanics. The goal of this study is to characterize and demonstrate the importance of the nonlinear stress-relaxation behavior of ligaments undergoing finite deformation. The structural model presented herein is based on a local additive decomposition of the stress tensor into initial and non-equilibrium parts as resulted from the assumed structure of the free energy density function that generalizes Kelvin-Voigt nonlinear viscous models. We consider different viscoelastic behavior for the matrix and the fibers and the need of considering the strain dependency of this effect is clearly demonstrated. Model parameters were fit to experimental data obtained in specimens undergoing finite deformation in two directions: longitudinal and transversal with respect to the directions of the collagen fibers. The model was then tested against several multi-axial loading situations. The strain dependent relaxation and the strain rate dependent behavior of the human medial collateral ligament were accurately predicted.

Mitochondrial DNA haplogroup diversity in Basques: a reassessment based on HVI and HVII polymorphisms.

This study provides a more complete characterization of the mitochondrial genome variability of the Basques, including data on the hypervariable segment HVII of the D-loop region, which remains relatively unknown. To that end, genomic DNA from 55 healthy men living in the Arratia Valley (Biscay province) and the Goiherri region (Guipúzcoa province) was examined by direct sequencing. Three-generation pedigree charts were compiled to ensure the collection from autochthonous individuals. The most notable findings emerging from the analysis of haplogroup composition are: (i) lack of U8a mitochondrial lineage, a rare subhaplogroup recently identified in Basques and proposed as a Paleolithic marker, (ii) low frequency of haplogroup V, which conflicts with results of earlier analyses describing high frequencies in southwestern Europe, and (iii) high frequency of haplogroup J, especially subhaplogroups J1c1 and J2a. The frequency of haplogroup J does not coincide with previous mtDNA studies in present-day Basques, but is congruent with frequencies found in prehistoric and historic Basque populations. In explaining divergence in haplogroup composition between modern Basque samples, we hypothesized spatial heterogeneity promoted by population fragmentation due to extreme limitation of dispersal opportunities during the Pleistocene glaciations. Similarities between extinct and extant Basque populations as for the high frequency of lineage J, as well as the abundance of this haplogroup in northern Spain endorse a shift in the focus of attention of mtDNA analysts. A refined dissection of haplogroup J might provide more solid evidence about the process of postglacial recolonization of Europe, and thus about the shaping of the European gene pool.

Polymorphic Alu insertions and the genetic structure of Iberian Basques.

Eight Alu sequences (ACE, TPA25, PV92, APO, FXIIIB, D1, A25 and B65) were analyzed in two samples from Navarre and Guipúzcoa provinces (Basque Country, Spain). Alu data for other European, Caucasus and North African populations were compiled from the literature for comparison purposes to assess the genetic relationships of the Basques in a broader geographic context. Results of both MDS plot and AMOVA revealed spatial heterogeneity among these three population clusters clearly defined by geography. On the contrary, no substantial genetic heterogeneity was found between the Basque samples, or between Basques and other Europeans (excluding Caucasus populations). Moreover, the genetic information obtained from Alu data conflicts with hypotheses linking the origin of Basques with populations from North Africa (Berbers) or from the Caucasus region (Georgia). In order to explain the reduced genetic heterogeneity detected by Alu insertions among Basque subpopulations, values of the Wright's F(ST )statistic were estimated for both Alu markers and a set of short tandem repeats (STRs) in terms of two geographical scales: (1) the Basque Country, (2) Europe (including Basques). In the Basque area, estimates of Wahlund's effect for both genetic markers showed no statistical difference between Basque subpopulations. However, when this analysis was performed on a European scale, F(ST) values were significantly higher for Alu insertions than for STR alleles. From these results, we suggest that the spatial heterogeneity of the Basque gene pool identified in previous polymorphism studies is relatively recent and probably caused by a differential process of genetic admixture with non-Basque neighboring populations modulated by the effect of a linguistic barrier to random mating.

Genetic position of Valencia (Spain) in the Mediterranean basin according to Alu insertions.

In this work, eight human-specific Alu insertion polymorphisms (ACE, TPA25, PV92, APO, FXIIIB, D1, A25, and B65) were typed in 106 unrelated healthy individuals born in the province of Valencia (Spain), with the aim of analyzing the genetic relationships between this region of the Iberian Peninsula and other Mediterranean populations. To that end, Alu data on Eastern European, Western European, and North African populations were compiled from previous studies. The genetic information was stressed by means of genetic distances (R matrix method), nonmetric multidimensional scaling (MDS) and analyses of molecular variance (AMOVA). In Valencia, the most common Alu insertion was APO (0.940), and the least frequent was A25 (0.104). The average gene diversity (GD) computed for the sample examined was comparatively high (0.382). The insertion frequencies estimated for the eight Alu markers were very similar to the mean frequencies calculated for the whole set of populations included in the study, suggesting the hybrid nature of the Valencia's gene pool. MDS and AMOVA results generated from Alu data reveal that the Mediterranean has acted as a strong genetic boundary between the north (Europe) and the south (Northern Africa), resulting in significant gene diversity between the populations of the two regions. Restricted exclusively to the European scope, we suggest the possibility that the Mediterranean could have also acted as a migratory passageway, propitiating the dissemination of cultures and genes between the east and west of Europe and giving rise to some homogenization of gene frequencies among coastal dwelling populations.

[Current evidence about atomoxetine. A therapeutic alternative for the treatment of attention deficit hyperactivity disorder]. / Evidencia actual sobre la atomoxetina. Alternativa terapéutica para el trastorno por déficit de atención e hiperactividad.

AIMS: To conduct an updated review of the mechanisms of action, pharmacokinetics, clinical effectiveness and safety of atomoxetine in the treatment of the symptoms of ADHD. DEVELOPMENT: Atomoxetine is the first of the group of non-stimulant drugs to be approved by the US Food and Drug Administration to treat this disorder in children, adolescents and adults. Atomoxetine has a direct effect on noradrenalin and dopamine concentrations by exerting a strong and highly selective inhibiting action on the pre-synaptic noradrenalin transporter, with a minimum affinity for other transporters and receptors. After adjustment of the dosage for body weight, the pharmacokinetic parameters are similar across all age and gender groups. Maximal plasma concentration is reached one to two hours after oral administration. Data concerning the effectiveness and safety from the clinical trials and studies reported in the literature are discussed. CONCLUSIONS: Atomoxetine is an effective and well-tolerated drug when used for the pharmacological treatment of ADHD symptoms. Despite being a drug that has only recently been developed, evidence from the large number of comparative studies that have been carried out endorse its widespread use in the treatment of this syndrome.