Novel chemotherapeutic agent FX-9 activates NF-κB signaling and induces G1 phase arrest by activating CDKN1A in a human prostate cancer cell line.

BACKGROUND: The aminoisoquinoline FX-9 shows pro-apoptotic and antimitotic effects against lymphoblastic leukemia cells and prostate adenocarcinoma cells. In contrast, decreased cytotoxic effects against non-neoplastic blood cells, chondrocytes, and fibroblasts were observed. However, the actual FX-9 molecular mode of action is currently not fully understood. METHODS: In this study, microarray gene expression analysis comparing FX-9 exposed and unexposed prostate cancer cells (PC-3 representing castration-resistant prostate cancer), followed by pathway analysis and gene annotation to functional processes were performed. Immunocytochemistry staining was performed with selected targets. RESULTS: Expression analysis revealed 0.83% of 21,448 differential expressed genes (DEGs) after 6-h exposure of FX-9 and 0.68% DEGs after 12-h exposure thereof. Functional annotation showed that FX-9 primarily caused an activation of inflammatory response by non-canonical nuclear factor-kappa B (NF-κB) signaling. The 6-h samples showed activation of the cell cycle inhibitor CDKN1A which might be involved in the secondary response in 12-h samples. This secondary response predominantly consisted of cell cycle-related changes, with further activation of CDKN1A and inhibition of the transcription factor E2F1, including downstream target genes, resulting in G1-phase arrest. Matching our previous observations on cellular level senescence signaling pathways were also found enriched. To verify these results immunocytochemical staining of p21 Waf1/Cip1 (CDKN1A), E2F1 (E2F1), PAI-1 (SERPNE1), and NFkB2/NFkB p 100 (NFKB2) was performed. Increased expression of p21 Waf1/Cip1 and NFkB2/NFkB p 100 after 24-h exposure to FX-9 was shown. E2F1 and PAI-1 showed no increased expression. CONCLUSIONS: FX-9 induced G1-phase arrest of PC-3 cells through activation of the cell cycle inhibitor CDKN1A, which was initiated by an inflammatory response of noncanonical NF-κB signaling.

Combination of the PI3K inhibitor Idelalisib with the conventional cytostatics cytarabine and dexamethasone leads to changes in pathway activation that induce anti-proliferative effects in B lymphoblastic leukaemia cell lines.

BACKGROUND: The introduction of combined conventional cytostatics and pathway-specific inhibitors has opened new treatment options for several cancer types including hematologic neoplasia such as leukaemias. As the detailed understanding of the combination-induced molecular effects is often lacking, the identification of combination-induced molecular mechanisms bears significant value for the further development of interventional approaches. METHODS: Combined application of conventional cytostatic agents (cytarabine and dexamethasone) with the PI3K-inhibitor Idelalisib was analysed on cell-biologic parameters in two acute pro-B lymphoblastic leukaemia (B-ALL) cell lines. In particular, for comparative characterisation of the molecular signatures induced by the combined and mono application, whole transcriptome sequencing was performed. Emphasis was placed on pathways and genes exclusively regulated by drug combinations. RESULTS: Idelalisib + cytostatics combinations changed pathway activation for, e.g., "Retinoblastoma in cancer", "TGF-b signalling", "Cell cycle" and "DNA-damage response" to a greater extent than the two cytostatics alone. Analyses of the top-20 regulated genes revealed that both combinations induce characteristic gene expression changes. CONCLUSION: A specific set of genes was exclusively deregulated by the drug combinations, matching the combination-specific anti-proliferative cell-biologic effects. The addition of Idelalisib suggests minor synergistic effects which are rather to be classified as additive.

Suitability of ultrasound-guided fine-needle aspiration biopsy for transcriptome sequencing of the canine prostate.

Ultrasound-guided fine-needle aspiration (US-FNA) biopsy is a widely used minimally invasive sampling procedure for cytological diagnosis. This study investigates the feasibility of using US-FNA samples for both cytological diagnosis and whole transcriptome RNA-sequencing analysis (RNA-Seq), with the ultimate aim of improving canine prostate cancer management. The feasibility of the US-FNA procedure was evaluated intra vitam on 43 dogs. Additionally, aspirates from 31 euthanised dogs were collected for standardising the procedure. Each aspirate was separated into two subsamples: for cytology and RNA extraction. Additional prostate tissue samples served as control for RNA quantity and quality evaluation, and differential expression analysis. The US-FNA sampling procedure was feasible in 95% of dogs. RNA isolation of US-FNA samples was successfully performed using phenol-chloroform extraction. The extracted RNA of 56% of a subset of US-FNA samples met the quality requirements for RNA-Seq. Expression analysis revealed that only 153 genes were exclusively differentially expressed between non-malignant US-FNAs and tissues. Moreover, only 36 differentially expressed genes were associated with the US-FNA sampling technique and unrelated to the diagnosis. Furthermore, the gene expression profiles clearly distinguished between non-malignant and malignant samples. This proves US-FNA to be useful for molecular profiling.

Histopathological Terminology Standards for the Reporting of Prostatic Epithelial Lesions in Dogs.

The terminology applied to canine prostatic epithelial lesions, especially carcinomas, is currently not standardized and this hampers the ability of pathologists to study the biological and clinical significance of these lesions. The aim of this review is to present the essential histomorphological diagnostic attributes of a wide spectrum of prostatic epithelial lesions in dogs. In addition to the traditionally recognized prostatic hyperplasia, hormonal atrophy, prostatitis, squamous metaplasia, adenocarcinoma and transitional cell (urothelial) carcinoma, new entities are described and discussed in order to provide veterinary pathologists with a basic atlas of common histological lesions of the canine prostate that is comprehensive and easy to use.

Decitabine demonstrates antileukemic activity in B cell precursor acute lymphoblastic leukemia with MLL rearrangements.

BACKGROUND: Promotor hypermethylation of CpG islands is common in B cell precursor acute lymphoblastic leukemia (BCP-ALL) with mixed lineage leukemia (MLL) gene rearrangements. Hypomethylating agents (HMA) such as azacitidine (AZA) and decitabine (DEC) reduce DNA hypermethylation by incorporation into DNA and were successfully introduced into the clinic for the treatment of myeloid neoplasias. METHODS: Here, we investigated whether HMA induce comparable biological effects in MLL-positive BCP-ALL. Further, efficacy of HMA and concomitant application of cytostatic drugs (cytarabine and doxorubicin) were evaluated on established SEM and RS4;11 cell lines. In addition, promising approaches were studied on BCP-ALL cell line- and patient-derived xenograft models. RESULTS: In general, DEC effects were stronger compared to AZA on MLL-positive BCP-ALL cells. DEC significantly reduced proliferation by induction of cell cycle arrest in G0/G1 phase and apoptosis. Most sensitive to HMA were SEM cells which are characterized by a fast cell doubling time. The combination of low-dose HMA and conventional cytostatic agents revealed a heterogeneous response pattern. The strongest antiproliferative effects were observed when ALL cells were simultaneously exposed to HMA and cytostatic drugs. Most potent synergistic effects of HMA were induced with cytarabine. Finally, the therapeutic potential of DEC was evaluated on BCP-ALL xenograft models. DEC significantly delayed leukemic proliferation in xenograft models as demonstrated longitudinally by non-invasive bioluminescence as well as 18F-FDG-PET/CT imaging. Unexpectedly, in vivo concomitant application of DEC and cytarabine did not enhance the antiproliferative effect compared to DEC monotherapy. CONCLUSIONS: Our data reveal that DEC is active in MLL-positive BCP-ALL and warrant clinical evaluation.

The impact of neurally adjusted ventilatory assist mode on respiratory severity score and energy expenditure in infants: a randomized crossover trial.

OBJECTIVE: Examine respiratory severity scores (RSS) (mean airway pressure × fraction of inspired oxygen) and resting energy expenditure (REE) on neurally adjusted ventilatory assist (NAVA) compared with synchronized intermittent mandatory ventilation with pressure controlled and supported breath (SIMV (PC)PS). STUDY DESIGN: A randomized, crossover trial in a level IV neonatal intensive care unit. Twenty-four patients were ventilated with NAVA or SIMV (PC) PS for 12 h and then crossed over to the alternative mode for 12 h. The primary outcome (RSS) and additional secondary respiratory outcomes were analyzed. RESULTS: RSS and measured REE were not different between modes. On NAVA, peak inspiratory pressures were lower (17.8 vs 19.9 cmH2O (P<0.05)) without higher oxygen requirements. Respiratory rates were higher on NAVA (52 vs 39 (P<0.05)), estimated work of breathing (WOB) (0.01 vs 0.04 J l-1 (P<0.05)) was improved. CONCLUSION: NAVA mode can be safe without increase in RSS or REE. Although respiratory rates were higher, this was offset by lower peak inspiratory pressures and WOB during NAVA.

Anomalías en los ductos Müllerianos: Evaluación diagnóstica por resonancia magnética / Müllerian Duct Anomalies: Diagnostic Evaluation with Magnetic Resonance Imaging

Los ductos Müllerianos son dos estructuras embrionarias que en su desarrollo pasan por tres procesos fundamentales: desarrollo, fusión ductal y reabsorción septal. Las anomalías de los ductos Müllerianos (ADM) incluyen un gran espectro de malformaciones que comprometen el útero, trompas de Falopio, cuello uterino y los dos tercios superiores de la vagina. La gravedad de las ADM y sus características morfológicas están dadas por el momento embriológico específico en el que aparece el trastorno. Las mujeres con estas anomalías consultan principalmente por amenorrea primaria, infertilidad y complicaciones obstétricas. La resonancia magnética (RM) se ha convertido en una herramienta muy útil para su adecuada evaluación por tratarse de una técnica no invasiva, que no utiliza radiación ionizante y permite una evaluación multiplanar con adecuada valoración del contorno uterino externo, lo que la constituye en una técnica necesaria para el diagnóstico preciso, así como para la planeación quirúrgica de las pacientes

The Müllerian ducts are two embryological structures that undergo three main processes during their formation: development, ductal fusion, and septal resorption. Müllerian duct anomalies (MDAs) include a large spectrum of malformations that involve the uterus, fallopian tubes, cervix, and the upper two-thirds of the vagina. The severity and morphological characteristics are given by the specific embryological moment in which the disorder occurs. Women with these anomalies present symptoms such as primary amenorrhea, infertility, and obstetric complications. Magnetic resonance imaging (MRI) has become a very useful tool for evaluation, given that it is a noninvasive technique that does not use ionizing radiation, while allowing multiplanar evaluation for a proper assessment of the external uterine contour, which makes this method a useful technique for accurate diagnosis and surgical planning

Claudin-1, -3, -4 and -7 gene expression analyses in canine prostate carcinoma and mammary tissue derived cell lines.

Claudins (CLDNs) are transmembrane proteins localised in the cell membrane of epithelial cells composing a structural and functional component of the tight junction protein complexes. In canine tumors deregulations of the CLDN expression patterns were described immunohistochemically. Targeting of claudin proteins has further been evaluated to establish novel therapeutic approaches by directed claudin binding. Precondition for the development of claudin targeting approaches in canine cells is the possibility to characterise claudin expression specifically and the availability of claudin positive cell lines. Herein PCR/qPCR assays were established allowing a rapid qualitative and quantitative characterisation of CLDN-1, -3, -4 and -7 gene expression in canine cell lines and tissues. Further commercially available antibodies were used to verify CLDN gene expression on protein level by Western blots. The developed assays were used to analyse six canine cell lines derived from mammary and prostate tissue for their CLDN-1, -3, -4 and -7 expressions. The canine cell line DT08/40 (prostate transitional cell carcinoma) was used for the establishment of specific CLDNs -1, -3, -4 and -7PCR/qPCR. The designed assays were verified by amplicon cloning and sequencing. Gene expressions were verified on protein level by Western blot. Additionally further cell lines were analysed for their CLDN-1, -3, -4 and -7 expression on mRNA and protein level (mammary derived cell lines: MTH53A (non-neoplastic), ZMTH3 (adenoma), MTH52C (carcinoma); prostate derived cell lines: DT08/46 and CT1258 (both adenocarcinoma).The screened cell lines showed expression for the CLDNs as follows: DT08/46 and DT08/40: CLDN-1, -3, -4 and -7 positive; CT1258: CLDN-1, -3, -4 and -7 negative; ZMTH3 and MTH52C: CLDN-1 and -7 positive, CLDN-3 and -4 negative; MTH53A: CLDN-1, -3 and -4 negative, CLDN-7 positive. Western blot analyses reflect the detected CLDN-1, -3, -4 and -7 expressions in the analysed cell lines. The established CLDN-1, -3, -4 and -7 PCR/qPCR assays allow a qualitative and quantitative characterisation of canine CLDN gene expression. Characterisation of CLDN expression in six canine cell lines led to the identification of two canine prostate tissue derived CLDN expressing cell lines. These cell lines serve as candidates for further research on CLDN-based functional and therapeutic approaches.

Anomalías quísticas congénitas de la vía biliar: aproximación diagnóstica mediante resonancia magnética / Congenital Cystic Biliary Ducts Diseases: Diagnostic Approach by Magnetic Resonance

Las enfermedades fibropoliquísticas hepáticas configuran un grupo de patologías bien diferenciadas que comparten en su etiología una malformación de la placa ductal y de la vía biliar durante el desarrollo intrauterino. La anomalía congénita encontrada depende del nivel donde el árbol biliar se ve afectado durante la embriogénesis. En este artículo se presenta el espectro de las anomalías congénitas de la vía biliar en pacientes evaluados mediante resonancia magnética (RM) y se describen los aspectos anatómicos y embriológicos, así como los hallazgos más relevantes de cada patología en los estudios por RM.

Fibropolycystic liver disease encompasses a unique group of entities that share in their etiology a malformation of the ductal plate and biliary ducts during intrauterine growth. The congenital abnormality found depends on the point where the biliary ducts are affected during embryogenesis. In our review, we describe the spectrum of congenital biliary abnormalities in patients studied with magnetic resonance imaging (MRI). Anatomical and embryological findings are described, as well as the most relevant MRI findings for each disease.

Posibilidades dietéticas en el trastorno por déficit de atención e hiperactividad / Dietary possibilities in attention deficit and hyperactivity disorder

El trastorno por déficit de atención e hiperactividad (TDAH) es el trastorno del neurodesarrollo más frecuente en la edad pediátrica. Se han sugerido etiologías bioquímicas diversas en relación con la dieta: alergias a alimentos y aditivos, toxicidad por metales pesados y otros tóxicos ambientales, dietas bajas en proteínas con alto contenido en hidratos de carbono, desequilibrios de minerales y micronutrientes, ingesta inadecuada de ácidos grasos esenciales y déficit de fosfolípidos, deficiencias de aminoácidos, deficiencias en el complejo vitamínico B y fitonutrientes y trastornos de tiroides. El tratamiento de este trastorno con fármacos estimulantes no está exento de efectos secundarios, como los que ejercen sobre el sueño y el apetito. La aparición de estos efectos secundarios, junto con una falta de respuesta al tratamiento médico, hace que muchos padres lo cuestionen y rechacen, llegando a recurrir a terapias alternativas, como los «tratamientos dietéticos». Por este motivo, los pediatras debemos estar familiarizados con estas terapias alternativas para poder valorar y aconsejar acerca de sus repercusiones nutricionales sobre el niño (AU)

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children. There has been suggested various biochemical etiologies in relation to diets: food allergies and additives, heavy metals toxicity and other environmental toxins, low protein diets with high levels in carbohydrate, imbalances of minerals and micronutrients, inadequate intake of essential fatty acids and phospholipids deficit, aminoacids deficiencies, deficiencies in B vitamins and phytonutrients and thyroid disorders. The treatment of this disorder with stimulant drugs are not free of side effects on sleep and appetite. The occurrence of these side effects joined with a lack of response to medical treatment causes that many parents question and reject the medical treatment, using alternative treatments like the 'dietary treatments'. Therefore pediatricians should be familiar with these alternative therapies to advise and to assess the nutritional impact on the child (AU)

Immune response of healthy horses to DNA constructs formulated with a cationic lipid transfection reagent.

BACKGROUND: Deoxyribonucleic acid (DNA) vaccines are used for experimental immunotherapy of equine melanoma. The injection of complexed linear DNA encoding interleukin (IL)-12/IL-18 induced partial tumour remission in a clinical study including 27 grey horses. To date, the detailed mechanism of the anti-tumour effect of this treatment is unknown. RESULTS: In the present study, the clinical and cellular responses of 24 healthy horses were monitored over 72 h after simultaneous intradermal and intramuscular application of equine IL-12/IL-18 DNA (complexed with a transfection reagent) or comparative substances (transfection reagent only, nonsense DNA, nonsense DNA depleted of CG). Although the strongest effect was observed in horses treated with expressing DNA, horses in all groups treated with DNA showed systemic responses. In these horses treated with DNA, rectal temperatures were elevated after treatment and serum amyloid A increased. Total leukocyte and neutrophil counts increased, while lymphocyte numbers decreased. The secretion of tumour necrosis factor alpha (TNFα) and interferon gamma (IFNγ) from peripheral mononuclear blood cells ex vivo increased after treatments with DNA, while IL-10 secretion decreased. Horses treated with DNA had significantly higher myeloid cell numbers and chemokine (C-X-C motif) ligand (CXCL)-10 expression in skin samples at the intradermal injection sites compared to horses treated with transfection reagent only, suggesting an inflammatory response to DNA treatment. In horses treated with expressing DNA, however, local CXCL-10 expression was highest and immunohistochemistry revealed more intradermal IL-12-positive cells when compared to the other treatment groups. In contrast to non-grey horses, grey horses showed fewer effects of DNA treatments on blood lymphocyte counts, TNFα secretion and myeloid cell infiltration in the dermis. CONCLUSION: Treatment with complexed linear DNA constructs induced an inflammatory response independent of the coding sequence and of CG motif content. Expressing IL-12/IL-18 DNA locally induces expression of the downstream mediator CXCL-10. The grey horses included appeared to display an attenuated immune response to DNA treatment, although grey horses bearing melanoma responded to this treatment with moderate tumour remission in a preceding study. Whether the different immunological reactivity compared to other horses may contributes to the melanoma susceptibility of grey horses remains to be elucidated.

Dietas «milagro» en pediatría. Posibilidades dietéticas en los trastornos del espectro autista / Miracle diets in Pediatrics. Dietary possibilities in autism spectrum disorders

Los trastornos del espectro autista (TEA) son alteraciones del neurodesarrollo caracterizadas por una afectación de la interacción social y de la comunicación asociada a comportamientos rituales, estereotipados y repetitivos, que habitualmente son diagnosticados en los niños. Su prevalencia parece estar aumentando, aunque este incremento podía deberse a un mejor conocimiento del problema y, por tanto, a una mayor sospecha clínica. Los clínicos, y sobre todo los pediatras que tratan a niños diagnosticados de TEA, deberían adquirir conocimientos científicos sobre los tratamientos considerados en este momento alternativos, para poder proporcionar información y consejos sobre sus posibles riesgos y beneficios (AU)

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by impairment of social interaction and communication associated to rituals, stereotyped and repetitive behaviors, which are usually diagnosed in children. Its prevalence appears to be increasing although this increase could be due to a better understanding of the problem and therefore to a greater clinical suspicion. Clinical and especially pediatricians who treat children diagnosed with ASD should acquire scientific knowledge about treatments considered, at this time, alternative to provide information and advice about potential risks and benefits (AU)

Influences of age and sex on leukocytes of healthy horses and their ex vivo cytokine release.

Leukocytes and their functional capacities are used extensively as biomarkers in immunological research. Commonly employed indicators concerning leukocytes are as follows: number, composition in blood, response to discrete stimuli, cytokine release, and morphometric characteristics. In order to employ leukocytes as biomarkers for disease and therapeutic monitoring, physiological variations and influencing factors on the parameters measured have to be considered. The aim of this report was to describe the ranges of selected leukocyte parameters in a sample of healthy horses and to analyse whether age, sex, breed, and sampling time point (time of day) influence peripheral blood leukocyte composition, cell morphology and release of cytokines ex vivo. Flow cytometric comparative characterisation of cell size and complexity in 24 healthy horses revealed significant variance. Similarly, basal release of selected cytokines by blood mononuclear cells also showed high variability [TNFα (65-16,624pg/ml), IFNγ (4-80U/ml), IL-4 (0-5069pg/ml), IL-10 (49-1862pg/ml), and IL-17 (4-1244U/ml)]. Each animal's age influenced leukocyte composition, cell morphology and cytokine release (TNFα, IL-4, IL-10) ex vivo. Geldings showed smaller monocytes and higher spontaneous production of IL-10 when compared to the mares included. The stimulation to spontaneous release ratios of TNFα, IL-4 and IL-17 differed in Warmblood and Thoroughbred types. Sampling time influenced leukocyte composition and cell morphology. In summary, many animal factors - age being the dominant one - should be considered for studies involving the analysis of equine leukocytes. In addition, high inter-individual variances argue for individual baseline measurements.

Delivery of proteins to mammalian cells via gold nanoparticle mediated laser transfection.

Nanoparticle laser interactions are in widespread use in cell manipulation. In particular, molecular medicine needs techniques for the directed delivery of molecules into mammalian cells. Proteins are the final mediator of most cellular cascades. However, despite several methodical approaches, the efficient delivery of proteins to cells remains challenging. This paper presents a new protein transfection technique via laser scanning of cells previously incubated with gold nanoparticles. The laser-induced plasmonic effects on the gold nanoparticles cause a transient permeabilization of the cellular membrane, allowing proteins to enter the cell. Applying this technique, it was possible to deliver green fluorescent protein into mammalian cells with an efficiency of 43%, maintaining a high level of cell viability. Furthermore, a functional delivery of Caspase 3, an apoptosis mediating protein, was demonstrated and evaluated in several cellular assays. Compared to conventional protein transfection techniques such as microinjection, the methodical approach presented here enables high-throughput transfection of about 10 000 cells per second. Moreover, a well-defined point in time of delivery is guaranteed by gold nanoparticle mediated laser transfection, allowing the detailed temporal analysis of cellular pathways and protein trafficking.

Information on quantum states pervades the visible spectrum of the ubiquitous Au144(SR)60 gold nanocluster.

Absorption spectra of very small metal clusters exhibit individual peaks that reflect the discreteness of their localized electronic states. With increasing size, these states develop into bands and the discrete absorption peaks give way to smooth spectra with, at most, a broad localized surface-plasmon resonance band. The widely accepted view over the last decades has been that clusters of more than a few dozen atoms are large enough to have necessarily smooth spectra. Here we show through theory and experiment that for the ubiquitous thiolate cluster compound Au144(SR)60 this view has to be revised: clearly visible individual peaks pervade the full near-IR, VIS and near-UV ranges of low-temperature spectra, conveying information on quantum states in the cluster. The peaks develop well reproducibly with decreasing temperature, thereby highlighting the importance of temperature effects. Calculations using time-dependent density-functional theory indicate the contributions of different parts of the cluster-ligand compound to the spectra.

Impact of intercurrent respiratory infections on lung health in infants born <29 weeks with bronchopulmonary dysplasia.

OBJECTIVE: Assess the impact of intercurrent respiratory infections in infants <29 weeks gestational age (GA). STUDY DESIGN: A retrospective cohort study of 111 infants born <29 weeks GA, controlling for bronchopulmonary dysplasia (BPD) severity and assessing pulmonary health over the first year of life through oxygen, diuretic and inhaled steroid use. RESULT: Regression analysis showed viral infections increased oxygen use (odds ratio (OR) of 15.5 (confidence interval (CI)=3.4, 71.3)). The trend test showed increasing numbers of viral infections were associated with increased oxygen (OR (95% CI)=6.4 (2.3 to 17.4), P=0.0003), diuretic (OR (95% CI)=2.4 (1.1to 5.2), P=0.02) and inhaled steroid use (OR (95% CI)=2.2 (1.003 to 5.2), P=0.049), whereas bacterial infections were not. CONCLUSION: Viral infections caused more long-term pulmonary morbidity/mortality than bacterial infections on premature lung health, even when controlling for BPD.

Infants born at <29 weeks: pulmonary outcomes from a hybrid perinatal system.

OBJECTIVE: To assess pulmonary outcomes of infants <29 weeks gestational age (GA), delivered at level I, II and III facilities, to identify potentially modifiable factors affecting bronchopulmonary dysplasia (BPD) severity and to assess the external generalizability of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) BPD Outcome Estimator. STUDY DESIGN: Outcomes for infants <29 weeks GA born during (2008-2010) and delivered either at an inborn level III center or in a level II or III metropolitan area hospital with transfer to a level IV center, or delivered in a distant level I or II center and then transported to a level IV center were assessed. BPD severity was compared with the NICHD Neonatal BPD Outcome Estimator. RESULT: Of 158 infants who comprised the cohort, 28 (17.8%) had no BPD, 39 (24.2%) had mild BPD, 45 (28.7%) had moderate BPD, 31 (19.7%) had severe BPD and 15 (9.6%) died at ≤36 weeks post menstrual age. Site of birth did not predict severe BPD or death. Receiver operator characteristic curves showed fair predictability for none/mild and severe BPD. CONCLUSION: BPD severity was not dependent on site of birth. The NICHD BPD outcome estimator provides fair prediction for extreme outcomes.

Habilidades parentales para padres con trastorno mental: una prevención necesaria / Parental habilities for parents with mental disorders: a necessary prevention

Pese a que las recomendaciones generales de salud indican la importancia de priorizar el desarrollo de programas de prevención, desde salud mental se tiende, a focalizar la atención en la parte más asistencial, de trinchera. En las unidades de salud mental infantil, al intervenir en la edad pediátrica, se podría considerar que ya se está realizando la tarea preventiva de esos futuros adultos. La presencia de psicopatología en uno o ambos padres puede comprometer la salud mental de los hijos por la exposición a pautas desadaptativas de crianza y problemas en la vinculación afectiva. En algunos países ya se está invirtiendo recursos en apoyar y mejorar las habilidades parentales de pacientes con Trastorno Mental de las Unidades de Salud Mental de Adultos como medida protectora y por tanto preventiva de estos menores en riesgo. En este trabajo se revisa la relevancia de la crianza saludable y el establecimiento de una vinculación segura para el desarrollo de una correcta salud mental. Se describen iniciativas llevadas a cabo con el objetivo de prevenir alteraciones en los hijos de personas con Trastorno Mental. Y tras este análisis, conscientes de la importancia preventiva de intervenir en este ámbito, desde nuestra Unidad de Salud Mental Infantil, proponemos realizar de forma grupal un trabajo de fortalecimiento de lazos vinculares y pautas de crianza en padres usuarios de los servicios de salud mental y los dispositivos de las Unidades de Conductas Adictivas

Although the general health recommendations indicate the importance of prioritizing the development of prevention programs, in mental health services we tend to focus the attention only on care. In child mental health units, as we intervene on children, we could think that the preventive task is being performed for these future adults The presence of psychopathology in one or both parents may compromise the mental health of children from exposure to aladaptive patterns of parenting and bonding problems. Some countries are already investing resources to support and improve parenting skills for patients with a mental disorder as a protective and preventive action for these children at risk. In this paper we discuss the importance of healthy parenting and the establishment of a secure attachment for the development of a proper mental health. It describes initiatives taken in order to prevent disturbances in children whose parents have a mental disorder.And after this analysis, aware of the importance of preventive actions in this field, from our Children's Mental Health Unit, we propose to work with groups of parents from Adult Mental Health and Addictive Behaviour Units to strengthen attachment and improve parenting skills

Evaluation of the reactivity of commercially available monoclonal antibodies with equine cytokines.

Research on equine cytokines is often performed by analyses of mRNA. For many equine cytokines an analysis on the actual protein level is limited by the availability of antibodies against the targeted cytokines. Generation of new antibodies is ongoing but time consuming. Thus, testing the reactivity of commercially available antibodies for cross-reactivity with equine cytokines is of particular interest. Fifteen monoclonal antibodies against IL-1ß, IL-6, IL-8, IL-12, IL-18 and Granulocyte Macrophage Colony stimulating factor (GM-CSF) of different species were evaluated for reactivity with their corresponding equine cytokines. Dot Blot (DB) and Western Blot (WB) analyses were performed using recombinant equine cytokines as positive controls. Immunohistochemistry (IHC) was carried out on equine tissue and flow cytometry on equine PBMC as positive controls. As expected, three equine IL-1ß antibodies detected equine IL-1ß in DB, WB and IHC. For these, reactivity in IHC has not been described before. One of them was also found to be suitable for intracellular staining of equine PBMC and flow cytometric analysis. Two antibodies raised against ovine GM-CSF cross-reacted with equine GM-CSF in DB, WB and IHC. For these anti-GM-CSF mAbs this is the first experimental description of cross-reactivity with equine GM-CSF (one mAb was predicted to be cross-reactive in WB in the respective data sheet). The other clone additionally proved to be appropriate in flow cytometric analysis. Two mAbs targeting porcine IL-18 cross-reacted in IHC, but did not show specificity in the other applications. No reactivity was shown for the remaining five antibodies in DB, although cross-reactivity of two of the antibodies was described previously. The results obtained in this study can provide beneficial information for choosing of antibodies for immunological tests on equine cytokines.