Inclusion of radiation in the collective coordinate method approach of the ϕ

We present an effective Lagrangian for the ϕ^{4} model that includes radiation modes as collective coordinates. The coupling between these modes to the discrete part of the spectrum, i.e., the zero mode and the shape mode, gives rise to different phenomena which can be understood in a simple way in our approach. In particular, some aspects of the short time evolution of the energy transfer among radiation, translation, and shape modes is carefully investigated in the single-kink sector. Finally, we also discuss in this framework the inclusion of radiation modes in the study of oscillons. This leads to relevant phenomena such as the oscillon decay and the kink-antikink creation.

Conocimiento y opinión sobre la atención integrada del niño con parálisis cerebral desde Atención Primaria / Knowledge and opinion on integrated care for children with cerebral palsy in Primary Car

Introducción: los pacientes con parálisis cerebral infantil (PCI) precisan de múltiples cuidados y terapias. El objetivo principal del estudio es describir la opinión, percepción y conocimiento sobre el abordaje integral del niño con PCI de pediatras de Atención Primaria (AP), así como su manejo actual sobre el mismo. Material y métodos: estudio transversal, descriptivo y de ámbito nacional, mediante encuesta en línea, a pediatras y médicos de familia dedicados a la pediatría que ejercían en AP entre enero y febrero de 2021. Resultados: se recibieron 335 respuestas. El 91% piensa que no dispone de formación suficiente y que su conocimiento es limitado, reconociendo el 65% que no está capacitado para el manejo del niño con PCI. Un 97,3% opina que es necesaria la formación en esta patología y el 99% que es necesaria la creación de protocolos específicos. Al 57,2% le gustaría ser pediatra coordinador trabajando con el pediatra hospitalario. El 75% estima que los cuidadores no están satisfechos con la atención que reciben, considerando que la atención integral al niño con PCI desde AP o disponer de unidades específicas para ello mejoraría la satisfacción familiar, resultando estadísticamente significativo. Conclusiones: la mayoría de los pediatras no se sienten capacitados para llevar a cabo el manejo del niño con PCI desde AP y consideran necesario la formación y creación de guías específicas. Opinan que la atención integral del paciente con PCI mejoraría la calidad de vida de las familias, abogando para ello por modelos mixtos de coordinación (AU)

Objective: patients with cerebral palsy (CP) require multiple treatments and services. The primary objective of the study was to describe the opinion, perception and knowledge of primary care (PC) paediatricians about the comprehensive approach to the care of children with CP and their current management of this condition.Material and methods: cross-sectional, descriptive and nationwide study carried out through an online survey of paediatricians and family physicians dedicated to paediatric care and practicing in the PC level in January and February 2021.Results: we received a total of 335 responses. Ninety-one percent of respondents thought they had insufficient training and limited knowledge, and 65% did not considered themselves adequately qualified to manage children with CP. In addition, 97.3% believed that training on CP is necessary and 99% that specific protocols need to be developed. Of all respondents, 57.2% would like to be the care coordinator working in collaboration with hospital paediatricians. Last of all, 75% believed that the caregivers were not satisfied with the care received, and that the provision of comprehensive care to children with CP from PC or the availability of specific units for their management would improve family satisfaction, a result that was statistically significant.Conclusions: most paediatricians do not feel qualified for the management of children with CP from PC and consider that training and the development of specific guidelines are necessary. Professionals believe that an integrated, comprehensive approach to the care of these patients would improve the quality of life of families, and advocated for hybrid care coordination models. (AU)

Evaluación positiva de medicamentos: enero, febrero y marzo de 2020 / Positive assessment of drugs: January, February, March 2020

Se reseñan los medicamentos evaluados y con dictamen positivo por comisión de expertos de la Agencia Española de Medicamentos y Productos Sanitarios o de la Agencia Europea del Medicamento hechos públicos en abril y junio de 2020, y considerados de mayor interés para el profesional sanitario. Se trata de opiniones técnicas positivas que son previas a la autorización y puesta en el mercado del medicamento

The drugs assessed by the Spanish Agency for Medicines and Health Products or European Medicines Agency made public in April and June of 2020, and considered of interest to the healthcare professional, are reviewed. These are positive technical reports prior to the authorization and placing on the market of the product

[ADCY5-associated dyskinesia in young children: a case report of a family and an updated review]. / Discinesia asociada a ADCY5 en la infancia: a propósito de una familia y revisión actualizada.

INTRODUCTION: Dyskinesia of the ADCY5 mutation is a rare movement-onset disorder in childhood. It is characterized by isolated chorea movements or associated with myoclonus and dystonia affecting the limbs, neck and face. The low number of patients and families still does not allow an adequate genotype-phenotype relationship. AIMS: The case of a child with movement disorders of early onset is presented in a family with three generations of affected members. An updated review of the casuistry and management of this rare disease is made. CASE REPORT: A 6-year-old boy referred for language delay and hyperactivity. After six months of follow-up he begins to show chorea movements of predominantly facial and limb roots, especially when waking up. At one year of follow-up, generalized chorea at rest with orofacial involvement and awkward gait begins to show. His family history includes his mother, grandfather, maternal uncle and cousin, who were diagnosed with Meige's syndrome (oromandibular dystonia and periorbital muscles) with choreiform-like movement disorders without affiliation since childhood. The brain study by MRI showed no alterations. A clinical exome targeting movement disorders was performed that discovered the pathogenic mutation in the ADCY5 gene causing autosomal familial dyskinesia. CONCLUSION: The c.1126G>A p.A376T mutation shows a natural history with a non-progressive clinical phenotype in three generations of affected members, with childhood debut and response to guanfacine treatment.

TITLE: Discinesia asociada a ADCY5 en la infancia: a propósito de una familia y revisión actualizada.Introducción. La discinesia de la mutación ADCY5 es un raro trastorno del movimiento de inicio en la infancia. Se caracteriza por movimientos coreicos aislados o asociados a mioclonías y distonías que afectan a las extremidades, el cuello y la cara. El escaso número de pacientes y familias no permite aún una adecuada relación genotipo-fenotipo. Objetivos. Presentar el caso de un niño con trastornos del movimiento de inicio precoz en el seno de una familia con tres generaciones de afectados, y realizar una revisión actualizada de la casuística y el tratamiento de esta rara enfermedad. Caso clínico. Varón de 6 años, remitido por retraso del lenguaje e hiperactividad. Tras seis meses de seguimiento, comenzó a presentar movimientos coreicos de predominio facial y de la raíz de los miembros, especialmente al despertar. Al año de seguimiento, se evidenció corea generalizado en reposo con afectación orofacial y torpeza en la marcha. Como antecedentes familiares destacaban su madre, abuelo, tío y prima maternos, que fueron diagnosticados de síndrome de Meige (distonía oromandibular y músculos periorbitarios) con trastornos del movimiento de tipo coreiforme sin filiar desde la infancia. El estudio cerebral por resonancia magnética no presentó alteraciones. Se realizó un exoma clínico dirigido a trastornos del movimiento que descubrió la mutación patógena en el gen ADCY5 causante de la discinesia familiar autosómica. Conclusión. La mutación c.1126G>A p.A376T muestra una historia natural con un fenotipo clínico no progresivo en tres generaciones de afectados, con inicio en la infancia y respuesta al tratamiento con guanfacina.

Análisis integrado clínico, molecular e histopatológico de la médula ósea en las neoplasias mieloproliferativas crónicas / Comprehensive clinical, molecular and histopathological analysis of bone marrow in chronic myeloproliferative neoplasia

OBJETIVOS: Análisis de las posibles correlaciones entre las alteraciones moleculares en los genes JAK2, MPL y CALR, el patrón morfológico de la médula ósea y el perfil clínico-hematológico de los pacientes. PACIENTES Y MÉTODOS: Se trata de un estudio retrospectivo que incluye 140 pacientes con diagnóstico de neoplasias mieloproliferativas Filadelfia negativas (NMP Fi−) de un único centro. RESULTADOS: En la TE, los pacientes con la mutación el JAK2 V617F, presentaron un mayor número de leucocitos y neutrófilos que aquellos que presentaron la mutación en CALR. Los CALR mutados obtuvieron un mayor número de plaquetas y mayor necesidad de tratamiento citorreductor. Estos hallazgos apoyan el hecho de que el estado mutacional en la TE parece definir subtipos de pacientes con un curso clínico y pronóstico substancialmente diferentes. En la MF el estado mutacional parece influir en los cambios histopatológicos encontrados en la BMO, lo que no ocurrió en PV y TE

OBJECTIVES: To analyse the possible correlation between molecular changes in the JAK2, MPL and CALR genes, the morphological pattern of bone marrow and the clinical-haematologic profile of patients. PATIENTS AND METHODS: We conducted a retrospective study that included 140 patients diagnosed with Philadelphia-negative myeloproliferative neoplasia (Ph-MPN) in a single centre. RESULTS: In essential thrombocythaemia (ET), the patients with the JAK2 V617F mutation presented more leucocytes and neutrophils than patients who presented the CALR mutation, who had more platelets and a greater need for cytoreductive therapy. These findings support the fact that the mutational state in ET appears to define subtypes of patients with substantially different clinical courses and prognoses. In myelofibrosis, the mutational state appears to influence the histopathological changes found in the bone marrow biopsy, which did not occur in polycythaemia vera or ET

Comprehensive clinical, molecular and histopathological analysis of bone marrow in chronic myeloproliferative neoplasia. / Análisis integrado clínico, molecular e histopatológico de la médula ósea en las neoplasias mieloproliferativas crónicas.

OBJECTIVES: To analyse the possible correlation between molecular changes in the JAK2, MPL and CALR genes, the morphological pattern of bone marrow and the clinical-haematologic profile of patients. PATIENTS AND METHODS: We conducted a retrospective study that included 140 patients diagnosed with Philadelphia-negative myeloproliferative neoplasia (Ph-MPN) in a single centre. RESULTS: In essential thrombocythaemia (ET), the patients with the JAK2 V617F mutation presented more leucocytes and neutrophils than patients who presented the CALR mutation, who had more platelets and a greater need for cytoreductive therapy. These findings support the fact that the mutational state in ET appears to define subtypes of patients with substantially different clinical courses and prognoses. In myelofibrosis, the mutational state appears to influence the histopathological changes found in the bone marrow biopsy, which did not occur in polycythaemia vera or ET.

Serum hepatitis B core-related antigen is more accurate than hepatitis B surface antigen to identify inactive carriers, regardless of hepatitis B virus genotype.

OBJECTIVES: To investigate whether hepatitis B surface antigen (HBsAg) and hepatitis B core-related antigen (HBcrAg) levels are useful to identify inactive carriers among HBeAg-negative patients infected by different hepatitis B virus (HBV) genotypes. METHODS: In all, 202 consecutive HBeAg-negative patients with chronic hepatitis B, 135 inactive carriers and 67 with HBV activity, were prospectively followed for 1 year. RESULTS: In HBeAg-negative patients, HBsAg levels differed across the different genotypes (p <0.001). The highest levels were observed in genotypes F or H (4.2 ± 0.6 logIU/mL), followed by genotype E (3.4 ± 1.1 logIU/mL), genotype A (3.4 ± 0.8 logIU/mL), and the lowest in genotype D (2.7 ± 1.1 logIU/mL). Variations in HBsAg levels were similar in inactive carriers and patients with HBV activity. HBsAg <3 logIU/mL showed good performance for identifying genotype D inactive carriers: 76% of genotype D inactive carriers met this cut-off versus ≤31% for genotypes A, E, F or H. However, in patients with genotype A, HBsAg levels ≤3.7 logIU/mL better classified inactive carriers. The combination of a single measurement of HBcrAg ≤3 logU/mL plus HBV DNA ≤2000 IU/mL yielded a positive predictive value and diagnostic accuracy >85% in all HBV genotypes, except genotype H or F, with values of 62.5% and 72.7%, respectively, for the two parameters. CONCLUSIONS: HBsAg levels varied across genotypes in HBeAg-negative patients. HBsAg levels <3 logIU/mL were only useful for identifying genotype D inactive carriers. A single HBcrAg measurement ≤3 logU/mL plus HBV DNA ≤2000 IU/mL was highly accurate for identifying inactive carriers, regardless of their HBV genotype.

Comparison of myocardial damage among dogs at different stages of clinical leishmaniasis and dogs with idiopathic chronic kidney disease.

Canine leishmaniasis (CanL) is a systemic disease caused by the protozoan parasite Leishmania infantum. Myocarditis in CanL has been described previously in CanL by histopathological analysis of post-mortem specimens and by evaluation of cardiac troponin I (cTnI) levels. However, the degree of myocardial damage at different stages of CanL and the role that concurrent azotaemia plays in this myocardial injury are unknown. The aim of this study was to prospectively evaluate and compare the presence of myocardial injury in dogs at different stages of clinical CanL and in dogs with severe idiopathic chronic kidney disease (CKD) by measuring cTnI. Forty-eight dogs were included in the study, divided into four groups: (1) group A (10 healthy dogs); (2) group B (17 dogs with CanL without renal azotaemia, classified as mild to severe in the LeishVet scheme); (3) group C (11 dogs with CanL and renal azotaemia, classified as very severe in the LeishVet scheme); and (4) group D (10 dogs with idiopathic CKD). Dogs in group C had significantly higher cTnI than dogs in groups B and D, although cTnI was also elevated in these groups. Dogs in group A had normal cTnI values. Dogs in groups D and C had similar renal IRIS classification scorers. Severe lymphoplasmocytic myocarditis and a positive real time PCR of L. infantum DNA were observed in all dogs in group C. Dogs with very severe CanL exhibit more myocardial injury than dogs with milder CanL or dogs with idiopathic CKD.

Cistectomía radical tipo Bricker ubicada en cuadrante izquierdo. Caso clínico / No disponible

El cáncer de vejiga es el sexto tipo de cáncer más común en los Estados Unidos, después del cáncer de pulmón, cáncer de próstata, cáncer de mama, cáncer de colon y linfoma. Es el tercer tipo de cáncer más común en hombres, pero el onceavo cáncer más común en mujeres. La cistectomía radical tipo Bricker es una técnica descrita por el doctor Bricker en 1950 y que sigue siendo una de las técnicas más utilizadas a pesar de los años transcurridos. Consiste en la creación de un conducto con un segmento aislado de íleon de unos 12 cm, anastomosando los uréteres al extremo proximal del íleon y abocando el extremo distal a la pared abdominal. Es una intervención mutilante que conlleva importantes secuelas para el paciente, tanto físicas como psicológicas, debido al trastorno de la imagen corporal, pérdida de la erección en el varón y sacrificio de la micción, entre otros. El tratamiento de los pacientes cistectomizados es un reto que afrontamos a diario en nuestro hospital los profesionales de enfermería, tanto antes como después de la intervención. En este póster queremos remarcar la importancia de la consulta preoperatoria y, dentro de ella, la importancia del marcaje del estoma. Esta intervención enfermera (aprobada por el Consejo de Enfermería en diciembre de 2014) influye favorablemente en la calidad de vida del paciente urostomizado

Bladder cancer is the sixth most common cancer in the United States, after lung cancer, prostate cancer, breast cancer, colon cancer, and lymphoma. It is the third most common cancer in men, but the eleventh most common cancer in women. Radical cystectomy Bricker is a technique described by Dr. Bricker in 1950 and remains one of the most used techniques despite the years. It involves the creation of a conduct with an isolated segment of ileum about 12 cm, anastomosing the ureters to the proximal end of the ileum and joining to the distal end of the abdominal wall. It is a mutilating intervention that has important consequences for both physical and psychological patient due to body image disorder, loss of erection in men and sacrifice of urination, among others. Treatment of patients with a cystectomy is a challenge that nurses should face every day in our Hospital, both before and after the intervention. In this poster we would like to emphasize the importance of preoperative counseling and specially the importance of marking the stoma. This nurse intervention (approved by the College of Nurses in December 2014) influences positively the quality of life of the patient ostomized

Preclinical evaluation of collagen type I scaffolds, including gelatin-collagen microparticles and loaded with a hydroglycolic Calendula officinalis extract in a lagomorph model of full-thickness skin wound.

Previously, we have developed collagen type I scaffolds including microparticles of gelatin-collagen type I (SGC) that are able to control the release of a hydroglycolic extract of the Calendula officinalis flower. The main goal of the present work was to carry out the preclinical evaluation of SGC alone or loaded with the C. officinalis extract (SGC-E) in a lagomorph model of full-thickness skin wound. A total of 39 rabbits were distributed in three groups, of 13 animals each. The first group was used to compare wound healing by secondary intention (control) with wound healing observed when wounds were grafted with SGC alone. Comparison of control wounds with wounds grafted with SGC-E was performed in the second group, and comparison of wounds grafted with SGC with wounds grafted with SGC-E was performed in the third group. Clinical follow-ups were carried in all animals after surgery, and histological and histomorphometric analyses were performed on tissues taken from the healed area and healthy surrounding tissue. Histological and histomorphometric results indicate that grafting of SGC alone favors wound healing and brings a better clinical outcome than grafting SGC-E. In vitro collagenase digestion data suggested that the association of the C. officinalis extract to SGC increased the SGC-E cross-linking, making it difficult to degrade and affecting its biocompatibility.

Molecular interference in antibody-antigen interaction studied with magnetic force immunoassay.

Molecular interferences are an important challenge in biotechnologies based on antibody-antigen interactions, such as sandwich immunoassays. We report how a sandwich immunoassay with magnetic particles as label can be used to probe interference by surfactants. Surfactants are often used to improve the performance of immunoassays, however the surfactants can affect the involved proteins and the mechanism of action of surfactant molecules on the antibody-antigen system is mostly unknown. As an example, we investigated molecular interference by a nonionic surfactant (Pluronic F-127) in a cardiac troponin (cTn) sandwich immunoassay with two monoclonal antibodies. The influence of the surfactant below the critical micelle concentration (0.00-0.04%) on dissociation properties was quantified in a magnetic tweezers setup, where a force is applied to the molecules via magnetic particle labels. The force-dependent dissociation curves revealed the existence of two distinct cTn-dependent bond types, namely a weak bond attributable to non-specific binding of cTn, and a strong bond attributable to the specific binding of cTn. The dissociation rate constant of the strong bonds increased with the surfactant concentration by about a factor of two. Circular dichroism spectroscopy data showed that the nonionic surfactant influences the conformation of cTn while not noticeably affecting the two monoclonal antibodies. This suggests that the surfactant-induced increase of the dissociation rate of the specific sandwich-type cTn binding may be related to a conformational change of the antigen molecule. The described methodology is an effective tool to study the influence of surfactants and other interferences on assays based on protein interactions.

Clostridium difficile in the ICU: Study of the incidence, recurrence, clinical characteristics and complications in a University Hospital / Clostridium difficile en UCI: estudio de la incidencia, recurrencias, características clínicas y complicaciones en un hospital universitario

OBJECTIVE: Although several studies have established the association between antibiotics and Clostridium difficile infection (CDI), there is a lack of epidemiological studies on the incidence of CDI in European Intensive Care Units outside the context of infection outbreaks. The present study describes the incidence, patient characteristics, complications, and recurrence rates of CDI in a Spanish ICU. DESIGN: A retrospective study was carried out. SETTING: A clinical---surgical ICU with 34 beds, a tertiary referral hospital with 1400 beds. PATIENTS: All patients over 18 years of age admitted to the ICU from January 2010 to December2011 with diarrhea for more than 48 h.INTERVENTIONS: None. Study variables: Underlying diseases, risk factors, fever, leukocyte count, complications, recurrence of infection. RESULTS: A total of 1936 adult patients were admitted. Seven patients acquired CDI (0.36%),representing an infection rate of 3.1 per 10,000 bed-days and a cumulative incidence rate of3.6 in two years. The mean age was 61 years. Six patients showed some degree of immunosuppression. The mean APACHE II score at ICU admission was 17 (IQR 13---24). Severe sepsis was reported in 5 cases of CDI, three of which presented shock and multiorgan dysfunction. Four patients presented recurrence of CDI during hospitalization. ICU admission was prolonged for a mean of 24 days (SD 17.8) after diagnosis. CONCLUSIONS: Less than 1% of the patients admitted to a clinical---surgical ICU in a large teaching institution in Spain developed CDI. However, a high risk of recurrence/complications was associated with prolonged ICU stay

OBJETIVO: El objetivo de este estudio es describir la incidencia, características de los pacientes, complicaciones y la recurrencia de infección por Clostridium difficile en una UCI de un hospital universitario en un período fuera de brote. DISEÑO: Serie de casos. Ámbito: UCI médico-quirúrgica de 34 camas en hospital de referencia de 1.400 camas. Pacientes o participantes: Todo paciente mayor de 18 años ingresado en la UCI desde enero de2010 hasta diciembre de 2011 que tuviese diarrea durante más de 48 h. INTERVENCIONES: Sin intervención. Variables de interés principales: Enfermedades de base, factores de riesgo, recurrencia de infección. RESULTADOS: Un total de 1.936 pacientes fueron ingresados en el periodo de estudio, de los cuales 177 presentaron diarrea durante más de 48 h y 7 cumplieron criterios de infección por Clostridium difficile (0,36%). Una tasa de infección de 3,1 pacientes por cada 10.000 camas/día y una incidencia acumulada de 3,6×1.000, en 2 años. La edad media fue de 61 años. Seis mostraron algún grado de inmunosupresión. La media del score APACHE II al ingreso fue de17. Cinco casos presentaron sepsis grave, 3 de los cuales tuvieron shock y disfunción multiorgánica. Un paciente de los 7 (14%) falleció. Cuatro pacientes sufrieron recurrencia durante la hospitalización (57%). La estancia media se prolongó 24 días (DE 17,8) después del diagnóstico. CONCLUSIONES: Menos del 1% de los pacientes hospitalizados en una UCI médico-quirúrgica desarrollaron infección por Clostridium difficile. Sin embargo, se asoció a un alto grado de recurrencia/complicaciones y a una larga estancia en la UCI

Clostridium difficile in the ICU: study of the incidence, recurrence, clinical characteristics and complications in a university hospital.

OBJECTIVE: Although several studies have established the association between antibiotics and Clostridium difficile infection (CDI), there is a lack of epidemiological studies on the incidence of CDI in European Intensive Care Units outside the context of infection outbreaks. The present study describes the incidence, patient characteristics, complications, and recurrence rates of CDI in a Spanish ICU. DESIGN: A retrospective study was carried out. SETTING: A clinical-surgical ICU with 34 beds, a tertiary referral hospital with 1400 beds. PATIENTS: All patients over 18 years of age admitted to the ICU from January 2010 to December 2011 with diarrhea for more than 48 h. INTERVENTIONS: None. STUDY VARIABLES: Underlying diseases, risk factors, fever, leukocyte count, complications, recurrence of infection. RESULTS: A total of 1936 adult patients were admitted. Seven patients acquired CDI (0.36%), representing an infection rate of 3.1 per 10,000 bed-days and a cumulative incidence rate of 3.6 in two years. The mean age was 61 years. Six patients showed some degree of immunosuppression. The mean APACHE II score at ICU admission was 17 (IQR 13-24). Severe sepsis was reported in 5 cases of CDI, three of which presented shock and multiorgan dysfunction. Four patients presented recurrence of CDI during hospitalization. ICU admission was prolonged for a mean of 24 days (SD 17.8) after diagnosis. CONCLUSIONS: Less than 1% of the patients admitted to a clinical-surgical ICU in a large teaching institution in Spain developed CDI. However, a high risk of recurrence/complications was associated with prolonged ICU stay.

Experimental model for reproduction of canine visceral leishmaniosis by Leishmania infantum.

In this report an experimental model of Leishmania infantum (L. infantum) infection in dogs is described. The data presented are derived from an overall and comparative analysis of the clinical outcomes of three groups of dogs intravenously infected with 500,000 promastigotes on different dates (2003, 2006 and 2008). The parasites used for challenge were isolated from a dog having a patent form of leishmaniosis, classified as MCAN/ES/1996/BCN150 zymodeme MON-1. Late-log-phase promastigote forms derived from cultured amastigotes obtained from the spleen of the heavily infected hamsters were used for infection. Only one single infective dose was administered to each dog. After challenge, the animals were monitored for 12 months. To analyze the disease outcome, several biopathological, immunological and parasitological end-points were considered. The analysis of the infected dogs indicated that the development of the clinical disease was very similar in the three experimental challenges, as shown by the immune response, the parasite load and the clinical and histopathological lesions detected at necropsy. A high similarity was also observed between the disease development after the experimental challenge and the one reported to occur in endemic natural infection areas, as various degrees of susceptibility to the disease and even resistance were observed in the experimentally infected animals. We believe that this challenge model faithfully reproduces and mimics the course of a natural infection and that it could be used as a suitable tool for analyzing the efficacy of anti-Leishmania drugs and vaccines.

ATR controls cellular adaptation to hypoxia through positive regulation of hypoxia-inducible factor 1 (HIF-1) expression.

Tumor cells adaptation to severe oxygen deprivation (hypoxia) plays a major role in tumor progression. The transcription factor HIF-1 (hypoxia-inducible factor 1), whose α-subunit is stabilized under hypoxic conditions is a key component of this process. Recent studies showed that two members of the phosphoinositide 3-kinase-related kinases (PIKKs) family, ATM (ataxia telangiectasia mutated) and DNA-PK (DNA-dependent protein kinase), regulate the hypoxic-dependent accumulation of HIF-1. These proteins initiate cellular stress responses when DNA damage occurs. In addition, it has been demonstrated that extreme hypoxia induces a replicative stress resulting in regions of single-stranded DNA at stalled replication forks and the activation of ATR (ataxia telangiectasia and Rad3 related protein), another member of the PIKKs family. Here, we show that even less severe hypoxia (0.1% O2) also induces activation of ATR through replicative stress. Importantly, in using either transiently silenced ATR cells, cells expressing an inactive form of ATR or cells exposed to an ATR inhibitor (CGK733), we demonstrate that hypoxic ATR activation positively regulates the key transcription factor HIF-1 independently of the checkpoint kinase Chk1. We show that ATR kinase activity regulates HIF-1α at the translational level and we find that the elements necessary for the regulation of HIF-1α translation are located within the coding region of HIF-1α mRNA. Finally, by using three independent cellular models, we clearly show that the loss of ATR expression and/or kinase activity results in the decrease of HIF-1 DNA binding under hypoxia and consequently affects protein expression levels of two HIF-1 target genes, GLUT-1 and CAIX. Taken together, our data show a new function for ATR in cellular adaptation to hypoxia through regulation of HIF-1α translation. Our work offers new prospect for cancer therapy using ATR inhibitors with the potential to decrease cellular adaptation in hypoxic tumors.

Risk in dosing regimens for 25-OH vitamin D supplementation in chronic haemodialysis patients.

INTRODUCTION: 25-OH vitamin D (25-OHvitD) insufficiency or deficiency should be treated in haemodialysis (HD) patients, although the 25-OHvitD target, drug or dosing regimens are unclear. AIMS: To describe factors associated with 25-OHvitD levels in HD patients and to assess the effect of three dosing regimens to supplement 25-OHvitD (calcifediol) on serum calcium (Ca), phosphate (P), parathyroid hormone (PTH), 25-OHvitD and 1,25-OHvitD. METHODS: Two hundred and seventeen patients from three HD units were studied. Demographic and biochemical data were collected at baseline. Two different 25-OHvitD assays were used. One hundred and sixty-seven patients were treated with various calcifediol dosing regimens. The same biochemical determinations were repeated after 3 months of treatment. RESULTS: At baseline, 12.9% of patients had 25-OHvitD <10 ng/ml. In multivariate linear regression, the season (lower in winter) and the assay method were determinants of 25-OHvitD concentration. Following calcifediol supplementation, 25-OHvitD, calcium and phosphate increased, while PTH diminished with statistical significance. After treatment, there were positive correlations between 25-OHvitD and Ca (r = 0.28, p < 0.0001) or 1,25-OHvitD (r = 0.75, p < 0.0001) that were not observed in the baseline dataset. High concentrations of post-treatment 25-OHvitD were associated with higher 1,25-OHvitD levels. Calcemia increased more in those treated with concomitant active vitamin D or those having suppressed baseline PTH, while PTH decreased more in those having above-target PTH levels. CONCLUSIONS: Standardisation of methods to determine 25-OHvitD blood levels is needed. In HD patients, calcifediol increased 25-OHvitD, calcemia and phosphatemia and lowered PTH. Caution should be exercised with the higher calcifediol dosing regimens, especially in patients with suppressed PTH or on vitamin D receptor activators.

Estudio epidemiológico multivariable del paciente con fractura osteoporótica de fémur proximal / Multivariate epidemiological study of the patient with osteoporotic proximal femoral fracture

Objetivo: Revisar las fracturas de cadera en personas mayores de 50 años para valorar cómo afectan las comorbilidades asociadas al pronóstico. Material y método: Estudiamos 200 pacientes mayores de 50 años tratados de fractura de fémur proximal mediante un análisis retrospectivo de las variables, con el fin de valorar el pronóstico y la calidad de vida residual. Resultados: Observamos una tendencia, sin significación estadística, de a mayor edad del paciente, mayor probabilidad de que su fractura sea extracapsular. El índice de Singh no se correlacionó con el tipo de fractura. La carencia de vitamina D fue una constante. Hallamos una correlación entre la comorbilidad y el grado de insuficiencia renal (creatinina). No hubo incremento de estancia media en pacientes con mayor número de patologías. La demora quirúrgica no prolongó el tiempo de hospitalización postquirúrgica. Conclusión: El paciente osteoporótico con fractura de cadera ha de ser tratado de una manera multidisciplinar. Son muchos los factores que condicionarán su pronóstico y situación funcional final (AU)

Objective: To review hip fractures in patients over 50 years of age, with a view to assessing how they affect the comorbidities associated to the prognosis. Material and method: The study comprised a total of 200 patients over 50 years of age treated for proximal femoral fractures, based on a retrospective analysis of the variables, in order to define the prognosis and residual quality of life. Results: Increased patient age was found to be associated to an increased probability of extracapsular fracture, though statistical significance was not reached. The Singh index was not correlated to the type of fracture. Vitamin D deficiency was a constant finding. A correlation was observed between comorbidity and the degree of renal failure (creatinine). There was no increase in hospital stay in patients with a larger number of disorders. Surgical delay did not prolong postoperative hospital stay. Conclusion: Osteoporotic hip fracture patients require multidisciplinary management. Many factors condition the prognosis and ultimate functional outcome (AU)

Perfil socio-laboral de los profesionales en Administración en Salud de la Universidad de Antioquia 1999-2008 / Social and work profile of the Health Administration professionals from Universidad de Antioquia, 1999–2008

Objetivo: caracterizar el perfil socio-laboral de los profesionales egresados del programa Administración en Salud de la Universidad de Antioquia. Metodología: estudio descriptivo de corte transversal basado en información primaria mediante encuesta a 356 profesionales egresados del programa entre 1999 y 2008. Se aplicaron técnicas de análisis estadístico descriptivo e inferencial. Según la naturaleza de las variables, se reportan valores absolutos, proporciones, medidas de resumen y tendencia central. Resultados: se trata de un grupo de profesionales jóvenes con edad promedio de 32,5 años, principalmente mujeres, en su mayoría con experiencia laboral profesional después de haberse graduado y con vínculo laboral al momento de la encuesta. El 12,1% reportó estar desempleado. El principal sector de la economía donde laboran es el de servicios, seguido de la construcción. El cargo desempeñado durante su historia laboral más frecuente es el administrativo seguido del operativo. Para la mayoría, sus ingresos salariales no superan los 4 Salarios Mínimos Legales Vigentes (SMLV). Discusión: algunos hallazgos se corresponden con estudios previos de 2001 y 2004. Otras variables contrastan con esos estudios y con otros referentes nacionales. Se concluye que las condiciones de precariedad laboral no son inherentes a la profesión en sí misma sino a las características del mercado laboral del mundo capitalista actual.

OBJECTIVE: To characterize the social and work profiles of the professionals from Universidad de Antioquia (University of Antioquia) who hold a degree in Health Administration.METODHOLOGY: A cross–sectional study based on primary data obtained by surveying 356 graduate professionals between 1999 and 2008. Descriptive and inferential statistical analysis techniques were applied. Depending on the nature of the variables, absolute values, ratios, and summary measures of central tendency were reported. RESULTS: It was a group of young professionals with an average age of 32.5 years. They were mainly women with professional work experience after graduation. They were employed at the time of the survey, but 12.1% of them reported being unemployed. The main sector of the economy where they work is services, followed by construction. Their most common position is that of administrator, followed by operational positions. In most cases, their income doesn't exceed 4 legal minimum wages.DISCUSSION: some findings are consistent with previous studies conducted in 2001 and 2004. Other variables contrast with these studies and with other national references. We conclude that the conditions of job insecurity are not inherent to the profession itself but to the labor market characteristics of the current capitalist world.

Fragmentation of extracellular DNA by long-term exposure to radiation from uranium in aquatic environments.

Persistent harmful scenarios associated with disposal of radioactive waste, high-background radiation areas and severe nuclear accidents are of great concern regarding consequences to both human health and the environment. Of particular concern is the extracellular DNA in aquatic environments contaminated by radiological substances. Strand breaks induced by radiation promote decrease in the transformation efficiency for extracellular DNA. The focus of this study is the quantification of DNA damage following long-term exposure (over one year) to low doses of natural uranium (an alpha particle emitter) to simulate natural conditions, since nothing is known about alpha radiation induced damage to extracellular DNA. A high-resolution Atomic Force Microscope was used to evaluate DNA fragments. Double-stranded plasmid pBS as a model for extracellular DNA was exposed to different amounts of natural uranium. It was demonstrated that low concentrations of U in water (50 to 150 ppm) produce appreciable numbers of double strand breaks, scaling with the square of the average doses. The importance of these findings for environment monitoring of radiological pollution is addressed.