Regulatory and metabolic adaptations in the nitrogen assimilation of marine picocyanobacteria.

Prochlorococcus and Synechococcus are the two most abundant photosynthetic organisms on Earth, with a strong influence on the biogeochemical carbon and nitrogen cycles. Early reports demonstrated the streamlining of regulatory mechanisms in nitrogen metabolism and the removal of genes not strictly essential. The availability of a large series of genomes, and the utilization of latest generation molecular techniques have allowed elucidating the main mechanisms developed by marine picocyanobacteria to adapt to the environments where they thrive, with a particular interest in the strains inhabiting oligotrophic oceans. Given that nitrogen is often limited in those environments, a series of studies have explored the strategies utilized by Prochlorococcus and Synechococcus to exploit the low concentrations of nitrogen-containing molecules available in large areas of the oceans. These strategies include the reduction in the GC and the cellular protein contents; the utilization of truncated proteins; a reduced average amount of N in the proteome; the development of metabolic mechanisms to perceive and utilize nanomolar nitrate concentrations; and the reduced responsiveness of key molecular regulatory systems such as NtcA to 2-oxoglutarate. These findings are in sharp contrast with the large body of knowledge obtained in freshwater cyanobacteria. We will outline the main discoveries, stressing their relevance to the ecological success of these important microorganisms.

Mixotrophy in marine picocyanobacteria: use of organic compounds by Prochlorococcus and Synechococcus.

Marine picocyanobacteria of the Prochlorococcus and Synechococcus genera have been longtime considered as autotrophic organisms. However, compelling evidence published over the last 15 years shows that these organisms can use different organic compounds containing key elements to survive in oligotrophic oceans, such as N (amino acids, amino sugars), S (dimethylsulfoniopropionate, DMSP), or P (ATP). Furthermore, marine picocyanobacteria can also take up glucose and use it as a source of carbon and energy, despite the fact that this compound is devoid of limiting elements and can also be synthesized by using standard metabolic pathways. This review will outline the main findings suggesting mixotrophy in the marine picocyanobacteria Prochlorococcus and Synechococcus, and its ecological relevance for these important primary producers.

Have there been changes in the application of mechanical ventilation in relation to scientific evidence? A multicenter observational study in Mexico. / ¿Se han producido cambios en la aplicación de la ventilación mecánica en relación con la evidencia científica? Estudio multicéntrico en México.

OBJECTIVE: The main study objectives were to describe the practice of mechanical ventilation over an 18-year period in Mexico, and estimate changes in mortality among critical patients subjected to invasive mechanical ventilation (IMV). DESIGN: A retrospective subanalysis of a prospective observational study conducted in 1998, 2004, 2010 and 2016 was carried out. SETTING: Intensive Care Units (ICUs) in Mexico. PARTICIPANTS: Adult patients consecutively enrolled in the ICU during one month and who underwent IMV for more than 12hours or noninvasive mechanical ventilation for more than one hour. Follow-up was performed up to a maximum of 28 days after inclusion. INTERVENTIONS: None. PRINCIPAL VARIABLES OF INTEREST: Age, sex, severity upon admission as estimated by SAPS II, parameters of daily arterial blood gases, treatment and complication variables, date and status at discharge from the ICU and from hospital. RESULTS: A total of 959 patients were included in 81 ICUs. Tidal volume (vt) decreased significantly both in patients with acute respiratory distress syndrome (ARDS) criteria (estimated 8.5ml/kg b.w. in 1998 to 6ml/kg in 2016; P<0.001) and in patients without ARDS (estimated 9ml/kg b.w. in 1998 to 6ml/kg in 2016; P<0.001). The ventilatory protective strategy (defined as vt < 6ml/kg or < 8ml/kg and a plateau pressure < 30cmH2O) was: 19% in 1998, 44% in 2004, 58% in 2010 and 75% in 2016 (P<0.001). The adjusted mortality rate in ICU over the 4 periods was: in 2004, odds ratio (OR) 1.05 (95% confidence interval, 95%CI: 0.73-1.72; P=0.764); in 2010, OR 1.68 (95%CI: 1.13-2.48; P=0.009); in 2016, OR 0.85 (95%CI: 0.60-1.20; P=0.368). CONCLUSIONS: The clinical practice of IMV in Mexican ICUs has been modified over a period of 18 years. The most significant change is the ventilatory strategy based on low vt. These changes have not been associated with significant changes in mortality.

Resistance to ethanol sensitization is associated with a loss of synaptic plasticity in the hippocampus.

Behavioral sensitization to repeated ethanol (EtOH) exposure induces an increase in locomotor activity in mice. However, not all animals express such sensitization. Although the literature indicated that the hippocampus may play a role in EtOH sensitization, it is not known whether behavioral sensitization to EtOH is associated with preferential changes in bidirectional synaptic plasticity, i.e., LTP and LTD, two markers of learning capabilities that have also been shown to be involved in addictive behavior. In the present study, we examined whether the vulnerability to develop and express behavioral sensitization to EtOH is associated with altered bidirectional synaptic plasticity in the CA1 area of the dorsal hippocampus. For this purpose, we analyzed both LTP and LTD in resistant and sensitized mice during the expression phase, i.e., 7 days after 10 days of repeated EtOH i.p. administration. We found that resistant mice showed a lack of LTD without changes in LTP. The lack of LTD was associated with an increase in GluN2A protein level and was not due to an altered level of neuronal activity, since no difference was observed between the number of c-FOS positive neurons in sensitized and resistant mice. Given that both types of synaptic plasticity signals may have distinct roles in specific learning and behaviors, our results suggest that resistant mice could exhibit different phenotypes in terms of learning/memory and addictive behaviors compared to sensitized ones. Synapse 71:e21899, 2017. © 2016 Wiley Periodicals, Inc.

p73 is required for endothelial cell differentiation, migration and the formation of vascular networks regulating VEGF and TGFß signaling.

Vasculogenesis, the establishment of the vascular plexus and angiogenesis, branching of new vessels from the preexisting vasculature, involves coordinated endothelial differentiation, proliferation and migration. Disturbances in these coordinated processes may accompany diseases such as cancer. We hypothesized that the p53 family member p73, which regulates cell differentiation in several contexts, may be important in vascular development. We demonstrate that p73 deficiency perturbed vascular development in the mouse retina, decreasing vascular branching, density and stability. Furthermore, p73 deficiency could affect non endothelial cells (ECs) resulting in reduced in vivo proangiogenic milieu. Moreover, p73 functional inhibition, as well as p73 deficiency, hindered vessel sprouting, tubulogenesis and the assembly of vascular structures in mouse embryonic stem cell and induced pluripotent stem cell cultures. Therefore, p73 is necessary for EC biology and vasculogenesis and, in particular, that DNp73 regulates EC migration and tube formation capacity by regulation of expression of pro-angiogenic factors such as transforming growth factor-ß and vascular endothelial growth factors. DNp73 expression is upregulated in the tumor environment, resulting in enhanced angiogenic potential of B16-F10 melanoma cells. Our results demonstrate, by the first time, that differential p73-isoform regulation is necessary for physiological vasculogenesis and angiogenesis and DNp73 overexpression becomes a positive advantage for tumor progression due to its pro-angiogenic capacity.

[Gluteal artery based perforator flaps for sacral pressure sore reconstruction in children]. / Colgajos basados en arterias perforantes glúteas para la reconstrucción de úlceras sacras por presión en niños.

INTRODUCTION: Children have much lower incidence of pressure sores (PS) than adults and furthermore, they are diagnosed in earlier stages. Therefore, the reported experience with surgical treatment of advanced pediatric PS is scarce. MATERIAL AND METHODS: We present the surgical treatment of 2 chronic PS stage IV in children aged 11 and 14 years, by means of perforator flaps based on the gluteal arteries: in the first case we used a free-style flap based on a left medial gluteal perforator and in the second a large reusable rotation-advancement flap based on both right superior and inferior gluteal artery perforators. RESULTS: In both patients we achieved a rapid cure with 100% survival of the flaps and a stable cover over a 6 month and 1 year follow-up respectively. CONCLUSIONS: Gluteal artery perforator flaps can produce excellent and durable results in the reconstructive treatment of sacral pressure sores in children. These flaps carry lower morbidity than musculocutaneous flaps and are more reliable than traditional fasciocutaneous flaps. Furthermore they preserve more reconstructive options in case of recurrence during the children's lifetime.

Regulatory feedback loop between TP73 and TRIM32.

The p73 transcription factor is one of the members of the p53 family of tumor suppressors with unique biological functions in processes like neurogenesis, embryonic development and differentiation. For this reason, p73 activity is tightly regulated by multiple mechanisms, including transcription and post-translational modifications. Here, we identified a novel regulatory loop between TAp73 and the E3 ubiquitin ligase tripartite motif protein 32 (TRIM32). TRIM32, a new direct p73 transcriptional target in the context of neural progenitor cells, is differentially regulated by p73. Although TAp73 binds to the TRIM32 promoter and activates its expression, TAp73-induced TRIM32 expression is efficiently repressed by DNp73. TRIM32 in turn physically interacts with TAp73 and promotes its ubiquitination and degradation, impairing p73-dependent transcriptional activity. This mutual regulation between p73 and TRIM32 constitutes a novel feedback loop, which might have important implications in central nervous system development as well as relevance in oncogenesis, and thus emerges as a possible therapeutic target.

Fimosis: ¿prepucioplastia o circuncisión? / Phimosis: ¿dorsal slit or circumcision?

Objetivos. La fimosis es una de las patologías más frecuentes en la consulta del cirujano pediátrico. El propósito de este estudio es compararlas dos opciones quirúrgicas más extendidas en nuestro medio: prepucioplastia y circuncisión. Material y métodos. Estudio retrospectivo de 1.698 pacientes tratados quirúrgicamente en nuestro servicio por presentar fimosis desde2003 a 2009. Se analizan edad, tiempo quirúrgico y anestésico, técnicaquirúrgica y complicaciones. Se realiza un estudio transversal descriptivo mediante encuesta telefónica a padres y pacientes mayores de16 años en cuanto a dolor postoperatorio, satisfacción estética y funcional .Se considera estadísticamente significativo p<0,05.Resultados. En un 76,6% de los casos (n=1.300) se realizó prepucioplastiay en el otro 23,4% (n= 398) circuncisión. La media de edad fue de 7,15 y la media de seguimiento 42,3 meses. El tiempo quirúrgico fue significativamente mayor en la circuncisión (p<0,0001). Huboun 3% (n= 51) de reintervenciones, sin diferencias entre los grupos. Tampoco encontramos diferencias estadísticamente significativas en cuanto a la reestenosis postoperatoria, aunque la incidencia de sangradosí fue mayor en la circuncisión (1,7%; p=0,03). No encontramos diferencias significativas en cuanto a la apreciación paterna del dolor postoperatorio o la satisfacción estética y funcional entre las dos técnicasquirúrgicas. Conclusiones. No hallamos diferencias en cuanto a la satisfacción subjetiva entre grupos. Aunque sí existen diferencias a nivel de sangrado postoperatorio, la incidencia global es muy baja. En nuestra experiencia ambas técnicas son válidas y seguras, por lo que la elección debe quedar a criterio del cirujano y de los padres (AU)

Introduction. Phimosis is perhaps one of the most frequent consultation on pediatric surgery clinics throught the world. The aim of this study is to compare the two procedures more frequently performed in our hospital: dorsal slit and circumcision. Patients y methods: Retrospective study of 1698 patients who were admitted for elective surgical treatment of phimosis between 2003 and2009. We analyzed age, surgical and anesthethic times, surgical technique and complications. We also did transversal descriptive study through telephonic survey on parents and patients older than 16 years old. Results: There was 76.6% of dorsal slit (n=1300) and 23.4% (n=398) of circumcisions. Mean age was 7.15 years y mean time of follow up was 42.3 months. Surgical time was significantly higher in circumcision(p<0.0001). There were 3% (n= 51) of reoperations, no differences between groups. We didn’t find differences in postoperative stenosis, but bleeding was more frequent in circumcision group (1.7%;p=0.03). There were no differences on parental appreciation of postoperative pain, or functional and esthetic satisfaction between groups. Conclusions: We didn’t find differences on subjective satisfaction between groups. Even if there are differences n postoperative bleeding, global incidence is very low. In our experience both techniques are validand safe, so surgeon and parents must jointly make the decisión (AU)

[Phimosis: dorsal slit or circumcision?]. / Fimosis: prepucioplastia o circuncisión?

INTRODUCTION: Phimosis is perhaps one of the most frequent consultation on pediatric surgery clinics throught the world. The aim of this study is to compare the two procedures more frequently performed in our hospital: dorsal slit and circumcision. PATIENTS Y METHODS: Retrospective study of 1698 patients who were admitted for elective surgical treatment of phimosis between 2003 and 2009. We analyzed age, surgical and anesthethic times, surgical technique and complications. We also did transversal descriptive study through telephonic survey on parents and patients older than 16 years old. RESULTS: There was 76.6% of dorsal slit (n = 1300) and 23.4% (n= 398) of circumcisions. Mean age was 7.15 years y mean time of follow up was 42.3 months. Surgical time was significantly higher in circumcision (p < 0.0001). There were 3% (n = 51) of reoperations, no differences between groups. We didn't find differences in postoperative stenosis, but bleeding was more frequent in circumcision group (1.7%; p = 0.03). There were no differences on parental appreciation of postoperative pain, or functional and esthetic satisfaction between groups. CONCLUSIONS: We didn't find differences on subjective satisfaction between groups. Even if there are differences n postoperative bleeding, global incidence is very low. In our experience both techniques are valid and safe, so surgeon and parents must jointly make the decision.

Relationship of oxidative stress and endothelial dysfunction in sleep apnoea.

The aim of the present study was to evaluate ischaemic reactive hyperaemia (IRH) in obstructive sleep apnoea (OSA) and its relationship with oxidative stress. We studied 69 consecutive patients referred to our Sleep Unit (Reina Sofia University Hospital, Cordoba, Spain). Patients with chronic diseases or those taking medication were excluded. IRH was assessed before and after polysomnography. Morning IRH and oxidative stress markers were compared between patients with (apnoea-hypopnoea index (AHI) ≥ 5) and without (AHI < 5) OSA. Measurements were repeated in 25 severe OSA patients after continuous positive airway pressure (CPAP) therapy. We included 46 OSA patients (mean ± sd AHI 49 ± 32.1) and 23 non-OSA subjects (AHI 3 ± 0.9). The OSA patients showed a significant worsening of morning IRH, and a significant increase in malondialdehyde and 8-hydroxydeoxyguanosine levels. Only the oxygen desaturation index independently explained morning IRH, while malondialdehyde levels showed a weak effect on IRH. In severe OSA patients, IRH improved significantly after CPAP treatment, as did malondialdehyde, 8-hydroxydeoxyguanosine and protein carbonyl levels. In OSA patients, endothelial dysfunction and oxidative stress were observed, and IRH worsened after sleep. The increase in oxidative stress was not associated with IRH, while intermittent hypoxia was strongly associated with IRH. In severe OSA patients, CPAP treatment improved oxidative stress and endothelial function.

Situación de la leishmaniosis en Granada (Sur de España) después de 25 años de estudio / Current status of leishmaniasis in Granada (Southern Spain) after 25 years of study

INTRODUCCIÓN: En España, Leishmania infantum es la única especie responsable de la leishmaniosis cutánea (LC) y visceral (LV) humanas, así como de la leishmaniosis canina (L Ca).Como vectores actúan dípteros nematóceros del género Phlebotomus (Diptera, Phlebotomidae), con las especies Phlebotomus perniciosus y P. ariasi actuando en condiciones simpátricas en un mismo foco. OBJETIVO: Pretendemos analizar los cambios acaecidos en la epidemiología de la leishmaniosis en la provincia de Granada durante los últimos 25 años, prestando atención a la incidencia de la enfermedad humana, la prevalencia de la leishmaniosis canina y la densidad de los vectores. METODOLOGÍA: se han recopilado los casos de leishmaniosis humana declarados entre 1984 y2005. En el caso del reservorio, se ha realizado un estudio epidemiológico de la leishmaniosis canina en 20 pueblos de la Alpujarra, que fueron estudiados previamente hace 22 años. Los cambios en las poblaciones de vectores se han determinado haciendo capturas con papeles adhesivos. RESULTADOS Y DISCUSIÓN: En el periodo 1984-2005, la media de la tasa de incidencia de la leishmaniosis humana en la provincia de Granada ha sido de 0,4 casos anuales/100.000 habitantes, observándose un ligero aumento del número de casos a lo largo de los años. Con respecto a la L Ca, hemos observado un incremento progresivo de la seroprevalencia en el piso bioclimático Mesomediterráneo. La densidad de P.perniciosus y P. ariasi ha quedado constante en el Termomediterráneo y ha caído en el Mesomediterráneo; sin embargo se ha incrementado el periodo de actividad de P. perniciosus(AU)

Introduction: The human and canine leishmaniosis are endemic in Granada province (South Spain)since the beginning of 20th century. Object: to study the variation of the rate of human leishmaniosis, the seroprevalence of canine leishmaniosis, and the density of vectors (phlebotomine sandflies).Methodology: we have compiled the reported cases of human leishmaniosis in the period 1984-2004,we have analysed, by IFAT, the dogs of 20 villages of the Alpujarra region, and the results were compared with those obtained 22 years ago. In the same way, the vectors populations were studied using sticky traps. Results and discussion: we have observed a net increase in the rate of human leishmaniosis, and in the seroprevalence of canine leishmaniosis. Respect the vector there is a increase in the activity period but not in the density(AU)

Síndrome de apnea del sueño, catecolaminas y alteración lipídica / Sleep adnea syndrome, catecholamines and lipid desorder

Objetivos: determinar si el síndrome de apneas-hipopneas del sueño (SAHS) incrementa las cifras de catecolaminas y a través de este mecanismo puede alterar el perfil lipídico. Pacientes y métodos: estudio prospectivo, grupo control y muestreo consecutivo de sujetos con sospecha de SAHS. Fueron excluidos aquellos con enfermedad grave de órgano o ingesta de fármacos con efecto sobre la actividad simpática y/o perfil lipídico. Según el índice de apneas-hipopneas (IAH) obtenido en la polisomnografía, los sujetos se asignaron al grupo clínico (IAH >5) o al grupo control (IAH <5). En ambos se compararon las cifras de colesterol total, HDL-c, triglicéridos y noradrenalina urinaria. Resultados: Fueron incluidos 33 en el grupo clínico y 16 en el control sin existir diferencias en edad, género e índice de masa corporal (IMC). En el grupo clínico, la noradrenalina en orina y colesterol total se elevaron significativamente mientras que disminuyeron las del HDL-colesterol. Se observó una correlación significativa entre los valores de la saturación periférica de O2 (SapO2) y la noradrenalina urinaria, aunque la variabilidad de ésta sólo se asoció independientemente con el índice de desaturación y el IMC. También se detectó correlación significativa entre la noradrenalina urinaria y colesterol total, HDL-c y triglicéridos, sin embargo esta correlación desapareció al ajustar por edad, género e IMC. Conclusiones: el SAHS aumenta la actividad simpática nocturna y el índice de desaturación es el factor de mayor influencia. En los pacientes con SAHS se incrementan significativamente las cifras séricas de colesterol total mientras descienden las del HDL-c, aunque estos resultados no fueron explicados de forma independiente por el aumento en la actividad simpática (AU)

Objectives: To determine whether the syndrome sleep apnea-hypopnea syndrome (SAHS) increases catechilamine value and throught this mechanism may alter the lipid profile. (..) (AU)

p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53.

The question of how neural progenitor cells maintain its self-renewal throughout life is a fundamental problem in cell biology with implications in cancer, aging and neurodegenerative diseases. In this work, we have analyzed the p73 function in embryonic neural progenitor cell biology using the neurosphere (NS)-assay and showed that p73-loss has a significant role in the maintenance of neurosphere-forming cells in the embryonic brain. A comparative study of NS from Trp73-/-, p53KO, p53KO;Trp73-/- and their wild-type counterparts demonstrated that p73 deficiency results in two independent, but related, phenotypes: a smaller NS size (related to the proliferation and survival of the neural-progenitors) and a decreased capacity to form NS (self-renewal). The former seems to be the result of p53 compensatory activity, whereas the latter is p53 independent. We also demonstrate that p73 deficiency increases the population of neuronal progenitors ready to differentiate into neurons at the expense of depleting the pool of undifferentiated neurosphere-forming cells. Analysis of the neurogenic niches demonstrated that p73-loss depletes the number of neural-progenitor cells, rendering deficient niches in the adult mice. Altogether, our study identifies TP73 as a positive regulator of self-renewal with a role in the maintenance of the neurogenic capacity. Thus, proposing p73 as an important player in the development of neurodegenerative diseases and a potential therapeutic target.

Valoración de la oxidación proteica en pacientes con apneas del sueño / Evaluation of protein oxidation in patients with sleep apnea

Introducción: en el síndrome de apneas-hipopneas del sueño (SAHS) son frecuentes los episodios de hipoxemia-reoxigenación que pueden producir sustancias oxígeno reactivas y estrés oxidativo. Pacientes y método: estudio prospectivo, con muestreo consecutivo, para determinar si la hipoxemia nocturna puede provocar oxidación proteica. Fueron incluidos pacientes con sospecha de SAHS, indicación de una polisomnografía, edad comprendida entre 25 y 49 años, y ausencia de enfermedad sistémica. Se compararon los resultados observados en un grupo clínico (IAH > 10) con los de un grupo control (IAH < 5). Resultados: se excluyeron 3 pacientes por presentar un IAH entre 5 y 10. Fueron incluidos 36 sujetos (edad = 40 ± 6,1 años, 30 hombres y 6 mujeres, IMC = 31 ± 5,9), 23 pertenecientesínas carboniladas fueron de al grupo clínico y 13 al grupo control. En el grupo clínico, los valores de prote 0,14 ± 0,179 nmol/mg y de 0,10 ±0,066 nmol/mg en el grupo control (p = 0,348). No se observó correlación significativa entre las cifras de proteínas carboniladas y el índice de apneas-hipopneas (rho = 0,197; p = 0,249), índice de de saturación >3% (rho = 0,129, p = 0,452) y porcentaje de sueño con SaO2 <90% (rho = 0,058, p = 0,736). Conclusiones: en pacientes con edad media y SAHS moderado, las proteínas carboniladas séricas se observaron más elevadas, aunque sin alcanzar diferencias significativas (AU)

Introduction: episodes of hypoxemia-reoxigenation are frequent insleep apnea-hypopnea syndrome (SAHS) and can produce reactiveoxygen substances and oxidative stress.Patients and methods: prospective study, with consecutive sampling to determine if nocturnal hypoxemia can produce oxidation. Patients with SAHS suspicion, polysomnography indication, age between 25-49 years old and without systemic disease were included. Results obtained in clinical group (IAH > 10) were comparedwith control group (IAH < 5). Resul years old, 30 men and 6 women, BMI = 31 ± 5.9), 23 patients were from clinical group and 13 from control group. In clinical group, carbonylated proteins values were 0.14 ± 0.179 nmol/mg and 0.10 ± 0.066 nmol/mg incontrol group (p = 0.348). There was not significative correlation between carbonyl proteins and apnea-hypopnea index (rho = 0.197, p = 0.249), desaturation index >3% (rho = 0.129, p = 0.452) and sleep time spent with SaO2 <90% (rho = 0.058, p = 0.736). Conclusions: in patientes with mean age and moderate SAHS, protein carbonyls were higher althout not reaching significant differences (AU)

n-3 Fatty acid supplementation in burned paediatric patients.

AIM: To determine the effect of dietary supplementation with n-3 fatty acids (FA) in paediatric burned patients who had less than 20% of total body surface affected. METHODS: Burned patients were randomly assigned into two groups, one of them received a supplement of n-3 FA during 5 weeks; the other group was considered as not n-3 supplemented burned group. A third group of no burned patients was selected as control. Blood samples were collected at admission and in burned groups at the final of the study. Plasma and erythrocyte phospholipid FA composition and some biochemical parameters related to the clinical evolution: total plasma proteins and C3 and C4 complement proteins were determined. RESULTS: In the early post-burn patients, there is an increase in saturated and monounsaturated FAs in plasma phospholipids, and a decrease in polyunsaturated FAs compared with control. These alterations are in favour of proinflammatory response to burn injury. In n-3 FA supplemented group, these changes were further reverted, and a favourable response in the amount of total plasma proteins and in C3 and C4 proteins of the complement system was demonstrated. CONCLUSION: Dietary n-3 FA supplementation might be beneficial for patients suffering thermal injury.

Poligrafía domiciliaria en pacientes con patología cardiovascular y sospecha de un SAHS / No disponible

OBJETIVOS: Validar la poligrafía domiciliaria en pacientes con comorbilidad vascular y sospecha de un síndrome de apneas hipopneas del sueño (SAHS) y determinar, en aquellos enfermos con cardiopatía isquémica, si el tratamiento con CPAP influye en el control de esta enfermedad. PACIENTES Y MÉTODOS: Fueron incluidos 42 enfermos (29 hombres y 13 mujeres, edad: 53 ± 7,8 años, IMC: 33 ± 5,2). Se les realizó poligrafía domiciliaria y polisomnografía convencional. Dieciséis pacientes con cardiopatía isquémica fueron evaluados tras el tratamiento con CPAP. El diagnóstico de SAHS se estableció ante un índice de apnea-hipopnea (IAH), en la polisomnografía> 5 y se indicó tratamiento con CPAP si el IAH fue > 15. RESULTADOS: Se observa una correlación y concordancia significativa (p < 0,01) entre la polisomnografía y poligrafía, en el IAH (36 ± 19,9 frente a 32 ± 17,4), r = 0,903 y CCI = 0,938, y en el índice de saturación (33 ± 23,5 frente a 35 ± 22,1), r = 0,896 y CCI = 0,948. Respecto a un IAH > 5 en la polisomnografía, la poligrafía obtiene un área bajo la curva ROC = 1 y para un IAH > 15el área bajo la curva ROC fue de 0,945. Tras el tratamiento con CPAP, los enfermos con cardiopatía isquémica acudieron menos frecuentemente al servicio de urgencias. CONCLUSIONES: La poligrafía domiciliaria es válida para el diagnóstico e indicación de tratamiento. En pacientes con cardiopatía isquémica, la CPAP mejora su control, descendiendo el número de consultas al servicio de urgencias (AU)

OOBJETIVES: To validate home poligraphy in patients with vascular comorbidity and suspicion of obstructive sleep apnea syndrome (OSAS), and to determine in patients with is chemicheart disease if treatment with CPAP influences in their control. PATIENTS AND METHODS: Forty-two patients were included (29 men and 13 women; Age: 53 ± 7.8 years; BMI: 33 ± 5.2)who were made home sleep study and conventional polysomnography. Sixteen patients with ischemic heart disease were evaluate dafter CPAP treatment. Diagnosis of OSAS was stablished when apnea-hypoapnea index (AHI) was > 5 in polysomnography and treatment with CPAP was indicated when AHI > 15. RESULTS: A significative correlation and concordance (p<0.01)were observed between the polysomnography and polygraphy in the AHI (36 ± 19.9 vs 32 ± 17.4), r = 0.903 and CCI = 0.938, and the desaturation index (33 ± 23.5 vs 35 ± 22.1), r = 0.896 and CCI = 0.948.When AHI >5 in polysomnography, the polygraphy obtained an are aunder the ROC curve = 1 and for IAH >15 the area under the ROC curve was 0.945. After CPAP treatment, patients with ischemic heart disease went less frequently to the hospital. CONCLUSIONS: Poligraphy is valid for diagnosis and treatment indication. Patients with ischemic heart disease, CPAP improves their control and reduces visits to the hospital (AU)

Calcium-activated potassium currents differentially modulate respiratory rhythm generation.

The pre-Bötzinger complex (PBC) generates eupnea and sighs in normoxia and gasping during hypoxia through particular mixtures of intrinsic and synaptic properties. Among intrinsic properties, little is known about the role of Ca(2+)-activated potassium channels in respiratory rhythms generation. To examine this role, we tested the effects of openers and blockers of the large-conductance (BK) and small-conductance (SK) Ca(2+)-activated potassium channels on the respiratory rhythms recorded both in vitro and in vivo, as well as on the discharge pattern of respiratory neurons in the PBC. Activation of SK channels with 1-ethyl-2-benzimidazolinone (1-EBIO) abolished sigh-like activity and inhibited eupneic-like activity, whereas blockade of SK channels with apamine (APA) increased frequency in both rhythms. In hypoxia, APA did not affect the transition to gasping-like activity. At the cellular level, activation of SK channels abolished pacemaker activity and decreased non-pacemaker neurons discharge; opposite effects were observed with SK blockade. In contrast to SK channel modulation, either activation or blockade of BK channels with NS 1619 or iberiotoxin and paxilline, respectively, produced mild effects on eupneic-like and sigh-like bursts during normoxia in vitro. However, BK blockers prevented the changes associated with the transition to gasping-like activity in vitro and perturbed gasping generation and autoresuscitation in vivo. At the cellular level BK channel modulation did not affect respiratory neurons discharge. We conclude that K(Ca) participate in rhythm generation in a state-dependent manner; SK channels are preferentially involved in rhythm generation in normoxia whereas BK channels participate in the transition to gasping generation in hypoxia.

Diabetes en la escuela. Percepciones de los niños y adolescentes con diabetes mellitus tipo 1 / Diabetes in the school. Perceptions of children and adolescents with type 1 diabetes

Objetivos: Mejorar el conocimiento sobre las necesidades de los niños y adolescentes con diabetes mellitus tipo 1 en el ámbito escolar, partiendo de la información proporcionada por ellos mismos. Material y métodos: Estudio basado en las opiniones de 414 niños y adolescentes con diabetes tipo 1, de entre 6 y 16 años de edad, asistentes a 18 colonias de verano en 2006, en España. Para la recogidade la información se utilizó un cuestionario estructurado, diseñado por la Fundación para la Diabetes. Resultados: La condición de diabetes es conocida por profesores (92%) y compañeros (91%), y el 12% de los niños menciona algún tipo de problema escolar debido a la enfermedad. El 32% de los escolares se inyecta insulina y el 65% controlala glucemia en el colegio. El 45% (337) de los niños que asisten a un centro escolar con comedor come en el colegio. El 94% hace ejercicio físico. El 36% refiere haber sufrido alguna hipoglucemia grave en el colegio. Por término medio, mencionan 3,3 tipos de medidas para mejorar su vida escolar. Conclusiones: La plena integración del niño con diabetes en la escuela presenta dificultades específicas debido a la naturaleza de la enfermedad y la complejidad de su tratamiento. Se precisan intervenciones para garantizar la seguridad del niño en la escuela, la viabilidad del tratamiento y la igualdad de oportunidades. La necesidad de coordinación entre varios departamentos de las administraciones públicas, como educación, sanidad y asuntos sociales, dificulta la solución del problema

Objective: To improve awareness of the needs, with in school settings, of children and adolescents with type 1 diabetes, based on information provided by the students. Materials and methods: The study was based on beliefs provided by 414 children and adolescents with type 1 diabetes, between 6 and 16 years of age, and participants at 18 summer-campsacross Spain during 2006. A structured questionnaire designed by the Fundación para la Diabetes, was used for evaluation. Results: Ninety-two percent of teachers and 91% of the camps participants were aware about the child’s diabetic condition. Twelve percent of children admitted having some school problems because of diabetes. Thirty-two percent of children and adolescents with diabetes used insulin injections, and 65% performed capillary glucose monitoring at school. From 337 subjects attending a school with catering facilities, only 45% had lunch at school. Ninety-four percent exercise regularly and 36% recognize having suffered severe hypoglycemic episodes at school. An average of 3.3 changes was suggested by diabetic children and adolescents to improve their school life. Conclusions: Full integration at school for diabetic children and adolescents entails specific difficulties inherent to the nature of the condition as well as to the complexities involved in treating it. Measures to guarantee the wellbeing of diabetic children at school, treatment administration viability and equal opportunities must be implemented. The current situation, in which coordination between several departments of public administration as education, health and social services is necessary, make it difficult to find the solution to the problem

Trastornos del sueño en pacientes con hemodiálisis. Estudio polisomnográfico con grupo control / Sleep disfunctions in haemodialysis patients. Polysomnographic study with control group

Objetivos: Respecto a población sana, se evalúan los trastornos del sueño en enfermos con enfermedad renal crónica estadio 4-5 (ERC 4-5) y hemodiálisis. En estos últimos se estudia la prevalencia del síndrome de apneas-hipopneas del sueño (SAHS) y algún marcador analítico asociado independientemente al SAHS. Pacientes y Método: fueron estudiados 32 pacientes en hemodiálisis(24 hombres y 8 mujeres, edad: 54 ± 16, IMC: 25 ± 3.9), 14enfermos con ERC 4-5 y 14 sujetos sanos. Estos dos últimos grupos, pareados por edad, género e IMC con el grupo en hemodiálisis. Se les realizó una historia clínica y una polisomnografía diagnóstica, estableciéndose el diagnóstico de SAHS ante un índice deapnea-hipopnea (IAH) ? 10.Resultados: Respecto al grupo control sano, los pacientes con ERC 4-5 muestran peor calidad de sueño y un mayor IAH, aunque sin significación estadística, mientras el grupo en hemodiálisis presenta menos cantidad y peor calidad de sueño, un IAH significativamente elevado (4.3 ± 1.44 vs 19.1 ± 18.5, p:0.007) y un mayor número de descensos en la SaO2 (9.9 ± 5.15 vs 26.5 ± 17.81,p:0.011). Un 78% de los enfermos en hemodiálisis presentaban algún trastorno del sueño, destacando el SAHS (48%). La creatinina y el eKt/V se asociaron con el IAH (R2:0.219, p: 0.028).Conclusiones: El SAHS es frecuente en la IRC. Los pacientes en hemodiálisis muestran un elevado IAH y de hipoxia intermitente que deben evitarse en estos pacientes con mortalidad cardiovascular elevada. Únicamente las cifras de creatinina y eKt/ Vexplican parcialmente la variabilidad del IAH

Objetives: To evaluate the quality of the sleep and sleep disorders breathing in patients with chronic kidney disease stage 4-5(CKD4-5) and in hemodialysis respect healthy population. In addition, to study in these last ones, the prevalence of the obstructive sleep apnea-hypoapnea syndrome (SAHS) and the existence of some analytical marker associated to SAHS. Patients and methods: There were studied 32 patients with CKD in hemodialysis (24 men and 8 women, age of 54±16, BMI of25±3.9), 14 patients with CKD 4-5 and a group of 14 healthy subjects; these groups were matched for age, gender, and BMI with the hemodialysis group. All of them were studied with a clinical history and a overnight polisomnography. We stablished the diagnostic of SAHS when the apnea-hypoapnea index (AHI) ?10.Results: Patients with CKD 4-5 showed worse quality of sleep and more episodes of AHI respect healthy control group, although without statistic signification. The group in hemodialysis had less quantity and worse quality of sleep than the control group with an AHI significatly higher (4.3 ± 1.44 vs 19.1 ± 18.5, p:0.007) and more decreases of the SaO2 (9.9 ± 5.15 vs 26.5 ± 17.81, p:0.011).78% of the patients in hemodialysis suffered some sleep disorder, emphasizing the SAHS (48%). The serum creatinine and the eKt/ v were independently associated with the AHI (R2: 0.219, p: 0.028).Conclusions: The sleep disorder is a prevalent pathology in the CKD. Patients in hemodialysis show a elevated AHI and of intermittent hypoxia, that must be avoided in these patients with an elevated cardiovascular mortality. Only, the levels of creatinine and the eKt/v explain partially the variability of the AHI

Molecular heterogeneity in chronic lymphocytic leukemia is dependent on BCR signaling: clinical correlation.

Chronic lymphocytic leukemia (CLL), the most frequent form of adult leukemia in Western countries, is characterized by a highly variable clinical course. Expression profiling of a series of 160 CLL patients allowed interrogating the genes presumably playing a role in pathogenesis, relating the expression of functionally relevant signatures with the time to treatment. First, we identified genes relevant to the biology and prognosis of CLL to build a CLL disease-specific oligonucleotide microarray. Second, we hybridized a training series on the CLL-specific chip, generating a biology-based predictive model. Finally, this model was validated in a new CLL series. Clinical variability in CLL is related with the expression of two gene clusters, associated with B-cell receptor (BCR) signaling and mitogen-activated protein kinase (MAPK) activation, including nuclear factor-kappaB1 (NF-kappaB1). The expression of these clusters identifies three risk-score groups with treatment-free survival probabilities at 5 years of 83, 50 and 17%. This molecular predictor can be applied to early clinical stages of CLL. This signature is related to immunoglobulin variable region somatic hypermutation and surrogate markers. There is a molecular heterogeneity in CLL, dependent on the expression of genes defining BCR and MAPK/NF-kappaB clusters, which can be used to predict time to treatment in early clinical stages.