Hypertrophic cardiomyopathy in a dog: a systematic diagnostic approach.

A seven-year-old female neutered Parson Russel terrier was referred for syncopal episodes. An electrocardiogram revealed paroxysmal atrial flutter followed by periods of sinus arrest, suggesting sick sinus syndrome. Echocardiography showed severe biventricular wall thickening (hypertrophic cardiomyopathy (HCM) phenotype) with no signs of fixed or dynamic left ventricular outflow tract obstruction. Blood pressure, abdominal ultrasound, serum total thyroxin and thyroid-stimulating hormone, and insulin-like growth factor-1 were all within normal limits. Cardiac troponin I was elevated (1.7 ng/mL, ref<0.07). Serological tests for common infectious diseases were negative. A 24-h Holter confirmed that the syncopal episodes were associated with asystolic pauses (sinus arrest after runs of atrial flutter) ranging between 8.5 and 9.6 s. Right ventricular endomyocardial biopsies (EMB) were performed at the time of pacemaker implantation to assess for storage or infiltrative diseases that mimic HCM in people. Histological analysis of the EMB revealed plurifocal inflammatory infiltrates with macrophages and lymphocytes (CD3+ > 7/mm2) associated with myocyte necrosis, but no evidence of myocyte vacuolisation or infiltrative myocardial disorders. These findings were compatible with myocardial ischaemic injury or acute lymphocytic myocarditis. Molecular analysis of canine cardiotropic viruses were negative. The dog developed refractory congestive heart failure and was euthanised 16 months later. Cardiac post-mortem examination revealed cardiomyocyte hypertrophy and disarray with diffuse interstitial and patchy replacement fibrosis, and small vessel disease, confirming HCM. We described a systemic diagnostic approach to an HCM phenotype in a dog, where a diagnosis of HCM was reached by excluding HCM phenocopies.

Multifocal lymphangioendotheliomatosis with thrombocytopenia: phenotypic variability and response to rapamycin. / Linfagioendoteliomatosis multifocal con trombopenia: variabilidad fenotípica y respuesta a rapamicina.

INTRODUCTION: Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is characterized by multiple maculopapular lesions involving the stomach and the lungs, associated with thrombocytopenia as a result of platelet entrapment. Episodes of severe digestive bleeding, which are sometimes unmanageable, are one of its most frequent presentations and a cause of mortality. Our objective was to describe the various phenotypes, as well as our treatment experience. MATERIALS AND METHODS: A retrospective analysis of patients diagnosed with MLT in our vascular abnormality unit from 2007 to 2018 was carried out. Epidemiological, clinical, and evolution data were analyzed, and a long-term follow-up was performed. RESULTS: Five patients (3 boys and 2 girls) had congenital macules and erythematous papules of various sizes. They were later associated with episodes of severe hematemesis along with thrombocytopenia, which required blood product transfusion. The most frequently involved areas were the stomach and the colon. In two patients, multiple bilateral pulmonary nodules were noted. The anatomical pathology examination showed extended vessels with a prominent, hobnail endothelium, as well as intraluminal papillary projections in the dermis. Immunohistochemical analysis was CD-31 positive and CD-34 positive in a characteristic manner. Two patients were treated with mTOR inhibitors (rapamycin), with a progressive decrease in extracutaneous involvement and platelet recovery, but with a poor response in dermal lesions. Two patients were treated with vincristine, with a reduction of digestive bleeding episodes. No deaths were reported in our series. CONCLUSION: MLT is characterized by hematological and cutaneous involvement - sometimes minimal -, with potential lesions in other internal organs. Its heterogeneous presentation, which may start with severe digestive bleeding, makes this rare pathology difficult to diagnose. mTOR inhibitors have opened up new treatment possibilities.

INTRODUCCION: La linfangioendoteliomatosis multifocal con trombopenia (LMT) es una anomalía, caracterizada por múltiples lesiones maculo-papulosas con afectación visceral gástrica y pulmonar, asociado a trombopenia por atrapamiento plaquetar. Una de sus presentaciones más frecuentes es en forma de episodios de hemorragia digestiva severa, en ocasiones inmanejable, y que es la responsable de su mortalidad. Nuestro objetivo es describir los diferentes fenotipos, así como nuestra experiencia en su tratamiento. MATERIAL Y METODOS: Hemos realizado un análisis retrospectivo de los pacientes diagnósticos de LMT según las características histológicas típicas entre 2007 y 2018 en nuestra unidad de anomalías vasculares. Se analizaron datos epidemiológicos, clínicos y de evolución, así como seguimiento a largo plazo. RESULTADOS: Cinco pacientes (3 hombres y 2 mujeres) presentaron al nacimiento máculas y pápulas eritematosas de diferentes tamaños a los que más adelante se les asoció episodios de hematemesis graves junto a trombopenia, que llegaron a requerir transfusión de hemoderivados. Las regiones más afectadas fueron el estómago seguido del colon. En dos pacientes se detectaron múltiples nódulos pulmonares bilaterales. La anatomía patológica describió vasos alargados con endotelio prominente y en tachuela junto a proyecciones papilares intraluminales en dermis. La inmunohistoquímica fue positiva de forma característica para CD-31 y CD-34. Dos pacientes fueron tratados con inhibidores de mTOR (rapamicina) con disminución progresiva de la afectación extracutánea y recuperación plaquetar, pero con una pobre respuesta de las lesiones dérmicas. Dos pacientes fueron tratados con vincristina con reducción de los episodios de sangrado digestivo. No se registró ningún fallecimiento en nuestra serie. CONCLUSION: La LMT se caracteriza por una afectación cutánea, a veces mínima, y hematológica que puede asociar lesiones en otros órganos internos. La presentación heterogénea, pudiendo debutar con hemorragias digestivas severas, hacen de esta entidad una patología de difícil diagnóstico. Los inhibidores de mTOR han abierto una nueva vía que arroja cierta esperanza para el tratamiento de esta patología tan poco frecuente.

Linfagioendoteliomatosis multifocal con trombopenia: variabilidad fenotípica y respuesta a rapamicina / Multifocal lymphangioendotheliomatosis with thrombocytopenia: phenotypic variability and response to rapamycin

Introducción: La linfangioendoteliomatosis multifocal con trom-bopenia (LMT) es una anomalía, caracterizada por múltiples lesionesmaculo-papulosas con afectación visceral gástrica y pulmonar, asociadoa trombopenia por atrapamiento plaquetar. Una de sus presentacionesmás frecuentes es en forma de episodios de hemorragia digestiva severa,en ocasiones inmanejable, y que es la responsable de su mortalidad.Nuestro objetivo es describir los diferentes fenotipos, así como nuestraexperiencia en su tratamiento. Material y métodos: Hemos realizado un análisis retrospectivo delos pacientes diagnósticos de LMT según las características histológicastípicas entre 2007 y 2018 en nuestra unidad de anomalías vasculares.Se analizaron datos epidemiológicos, clínicos y de evolución, así comoseguimiento a largo plazo. Resultados: Cinco pacientes (3 hombres y 2 mujeres) presentaron alnacimiento máculas y pápulas eritematosas de diferentes tamaños a losque más adelante se les asoció episodios de hematemesis graves juntoa trombopenia, que llegaron a requerir transfusión de hemoderivados. Las regiones más afectadas fueron el estómago seguido del colon. Endos pacientes se detectaron múltiples nódulos pulmonares bilaterales. Laanatomía patológica describió vasos alargados con endotelio prominentey en tachuela junto a proyecciones papilares intraluminales en dermis. Lainmunohistoquímica fue positiva de forma característica para CD-31 y CD-34. Dos pacientes fueron tratados con inhibidores de mTOR (rapamicina)con disminución progresiva de la afectación extracutánea y recuperaciónplaquetar, pero con una pobre respuesta de las lesiones dérmicas. Dospacientes fueron tratados con vincristina con reducción de los episodiosde sangrado digestivo. No se registró ningún fallecimiento en nuestra serie. Conclusión: La LMT se caracteriza por una afectación cutánea,a veces mínima, y hematológica que puede asociar lesiones en otrosórganos internos...(AU)

Introduction: Multifocal lymphangioendotheliomatosis with throm-bocytopenia (MLT) is characterized by multiple maculopapular lesionsinvolving the stomach and the lungs, associated with thrombocytopeniaas a result of platelet entrapment. Episodes of severe digestive bleed-ing, which are sometimes unmanageable, are one of its most frequentpresentations and a cause of mortality. Our objective was to describe thevarious phenotypes, as well as our treatment experience. Materials and methods: A retrospective analysis of patients diag-nosed with MLT in our vascular abnormality unit from 2007 to 2018 wascarried out. Epidemiological, clinical, and evolution data were analyzed,and a long-term follow-up was performed. Results: Five patients (3 boys and 2 girls) had congenital maculesand erythematous papules of various sizes. They were later associatedwith episodes of severe hematemesis along with thrombocytopenia,which required blood product transfusion. The most frequently involvedareas were the stomach and the colon. In two patients, multiple bilateralpulmonary nodules were noted. The anatomical pathology examinationshowed extended vessels with a prominent, hobnail endothelium, as wellas intraluminal papillary projections in the dermis. Immunohistochemi-cal analysis was CD-31 positive and CD-34 positive in a characteristicmanner. Two patients were treated with mTOR inhibitors (rapamycin),with a progressive decrease in extracutaneous involvement and plateletrecovery, but with a poor response in dermal lesions. Two patients weretreated with vincristine, with a reduction of digestive bleeding episodes. No deaths were reported in our series. Conclusion: MLT is characterized by hematological and cutaneousinvolvement – sometimes minimal –, with potential lesions in otherinternal organs...(AU)

Author Correction: Unrevealed genetic diversity of GII Norovirus in the swine population of North East Italy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Unrevealed genetic diversity of GII Norovirus in the swine population of North East Italy.

Noroviruses (NoVs) are one of the major causative agents of non-bacterial gastroenteritis in humans worldwide. NoVs, belonging to Caliciviridae, are classified into ten genogroups (G) and eight P-groups based on major capsid protein (VP1) and of the RNA-dependent-RNA-polymerase (RdRp), respectively. In swine, the main genogroup and P-group identified are GII and GII.P; which can infect humans too. To date, only one case of GIIP.11 have been identified in swine in Italy while the circulation of other P-types is currently unknown. In the present study, 225 swine faecal samples were collected from 74 swine herds in Veneto region through on-farm monitoring. NoV circulation was particularly high in older pigs. The phylogenetic analysis showed the co-circulation of NoVs belonging to two different P-types: GII.P11 and GII.P18, here described for the first time in Italy, presenting an extensive genetic diversity, never described before worldwide. Distinct NoV genetic subgroups and unique amino acid mutations were identified for each P-type for the first time. This study demonstrated the co-circulation of diverse swine NoVs subgroups in Italy, raising questions on the origin of such diversity and suggesting that continuous monitoring of swine NoVs is needed to track the emergence of potentially zoonotic viruses by recombination events.

Nearly Complete Genome Sequence of a Sapelovirus A Strain Identified in Swine in Italy.

We report the first nearly complete genome sequence of a porcine sapelovirus (PSV) A strain that was identified from feces of piglets suffering from diarrhea in Italy in 2015. Phylogenetic investigations revealed a separate clustering for the Italian PSV, indicating unique molecular features.

Epidemiology and natural history of cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa patients: 20 years' experience of a reference centre in Spain.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the leading cause of death in patients with recessive dystrophic epidermolysis bullosa (RDEB). We provide the management and prognosis of cSCC in RDEB patients at a Spanish reference center. MATERIALS AND METHODS: We retrospectively included patients with RDEB attended in La Paz University Hospital from November 1988 to October 2018. RESULTS: Fourteen patients developed at least one cSCC. Tumors were predominantly well differentiated. Nearly half of the tumors have recurred. Median time to first recurrence was 23.4 months (95% CI: 17.2-29.5). Five patients have developed distant metastases. Median overall survival (mOS) was 136.5 months since the diagnosis of the first cSCC (95% CI: 30.6-242.3). When distant metastases occurred, mOS was 6.78 months (95% CI: 1.94-11.61). CONCLUSIONS: cSCC is a life-threatening complication of RDEB patients. Although tumors are usually well differentiated, they tend to relapse. This is the first Spanish report of cSCC arising in RDEB patients.

Abordaje cerrado en patología de vía aérea superior con el uso de microelectrodos: nuestra experiencia / Approach closed upper airway pathology using microelectrodes: our experience

El láser como alternativa a la cirugía abierta de la vía aérea superior ha venido a modificar la forma de abordaje de las patologías en esta área, pero no deja de ser un procedimiento costoso que no está al alcance de todos los servicios. Por este motivo se han reinventado nuevas formas de abordaje que cumplan los mismos requisitos tanto de la cirugía abierta como con láser pero con un menor coste. Presentamos una serie de 30 casos realizados en un período de 6 años por motivos tanto tumorales como no, en los que se realizaron abordajes cerrados a través de microcirugía con disección mediante microelectrodos. Obteniendo pocas complicaciones y una disminución de la estancia hospitalaria significativa. Con lo cual nos parece una técnica eficiente para abordajes de este tipo.

The laser as an alternative to open surgery of the upper airway has come to change the form of approaching the disease in this area, but it is still an expensive procedure that is not available to all services. For this reason a new ways of approach to meet the same requirements both open as laser but at a lower cost surgery. We present a series of 30 cases performed over a period of 6 years for reasons as much tumor, which closed approaches through microsurgical dissection were performed using microelectrodes. Obtaining few complications and significant decreased hospital stay. Our considerations is it seems an efficient technique for such approaches.

Linker histones in hormonal gene regulation.

In the present review, we summarize advances in our knowledge on the role of the histone H1 family of proteins in breast cancer cells, focusing on their response to progestins. Histone H1 plays a dual role in gene regulation by hormones, both as a structural component of chromatin and as a dynamic modulator of transcription. It contributes to hormonal regulation of the MMTV promoter by stabilizing a homogeneous nucleosome positioning, which reduces basal transcription whereas at the same time promoting progesterone receptor binding and nucleosome remodeling. These combined effects enhance hormone dependent gene transcription, which eventually requires H1 phosphorylation and displacement. Various isoforms of histone H1 have specific functions in differentiated breast cancer cells and compact nucleosomal arrays to different extents in vitro. Genome-wide studies show that histone H1 has a key role in chromatin dynamics of hormone regulated genes. A complex sequence of enzymatic events, including phosphorylation by CDK2, PARylation by PARP1 and the ATP-dependent activity of NURF, are required for H1 displacement and gene de-repression, as a prerequisite for further nucleosome remodeling. Similarly, during hormone-dependent gene repression a dedicated enzymatic mechanism controls H1 deposition at promoters by a complex containing HP1γ, LSD1 and BRG1, the ATPase of the BAF complex. Thus, a broader vision of the histone code should include histone H1, as the linker histone variants actively participate in the regulation of the chromatin structure. How modifications of the core histones tails affect H1 modifications and vice versa is one of the many questions that remains to be addressed to provide a more comprehensive view of the histone cross-talk mechanisms.

Action and resistance of monoclonal CD20 antibodies therapy in B-cell Non-Hodgkin Lymphomas.

Anti-CD20 monoclonal antibodies (mAbs) have improved patient's survival with Non-Hodgkin Lymphoma, when combined with chemotherapy. Several mechanisms of action have been reported, including antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and induction of apoptosis. Despite the large amount of studies and published data, the role each mechanism played in vivo is not fully understood. Furthermore, the reason why a significant percentage of patients are refractory or resistant remains unknown. Several activated intracellular signaling pathways have been implicated in the mechanisms of resistance of rituximab. In the present manuscript, we review those mechanisms and new anti-CD20 mAbs, as well as the efforts being accomplished to overcome it, focusing on new drugs targeting pathways implicated in resistance to rituximab.

Infecciones virales de las vías respiratorias en la Unidad de Cuidados Intensivos Neonatales / Infecciones virales de las vías respiratorias en la Unidad de Cuidados Intensivos Neonatales Viral respiratory tract infections in the Neonatal Intensive Care Unit

INTRODUCCIÓN: Las infecciones virales respiratorias son causa de importante morbimortalidad en recién nacidos prematuros. Hemos realizado un estudio prospectivo en nuestra unidad de cuidados intensivos neonatales (UCIN) para determinar la incidencia de infecciones respiratorias, su impacto, epidemiología y pronóstico en neonatos de alto riesgo. PACIENTES Y MÉTODOS: Estudio prospectivo realizado entre septiembre del 2011 y mayo del 2013 entre todos los recién nacidos < 32 semanas de edad gestacional y aquellos niños cuya patología pudiera dar lugar a pensar en un ingreso superior a las 2 semanas. Se recogieron aspirados nasofaríngeos (ANF) el primer día de vida y semanalmente hasta el alta para estudio virológico mediante reacción en cadena de polimerasa. En los casos en los que los niños presentaban síntomas respiratorios, se procedió a recoger un nuevo ANF. El pediatra cumplimentó un cuestionario con los datos clínicos. RESULTADOS: Se estudió a 60 niños; 30 (50%) de ellos con una edad gestacional < 32 semanas y 36 (60%) con un peso < 1.500 g. Se recogió un total de 256 ANF, 24 de los cuales resultaron positivos (9,3%). Estas 24 muestras positivas correspondieron solo a 13 niños (21,6% de los pacientes). De ellos, 9 resultaron sintomáticos y presentaron 11 episodios de infección (2 pacientes experimentaron 2 episodios diferentes con control negativo entre ellos). El virus más frecuentemente identificado -el 79% de las muestras (19)- fue el rinovirus (RV). El dato clínico más frecuente fue la presencia o incremento de apneas (75%) y la necesidad de oxigenoterapia. CONCLUSIONES: Las infecciones por RV son frecuentes en la UCIN y los recién nacidos pretérmino tienen un alto riesgo de presentar infecciones de relevancia clínica

INTRODUCTION: Viral respiratory infections cause major morbidity and mortality in preterm infants. We have performed a prospective study in our neonatal intensive care unit (NICU) to determine the incidence of respiratory infections, their impact and the epidemiology and outcome in high risk neonates. PATIENTS AND METHODS: From September 2011 to May 2013 a prospective study was conducted in all preterm infants < 32 weeks gestational age and in all term newborns admitted to NICU for any pathology that are anticipated to have an income exceeding two weeks. A nasopharyngeal aspirate (NPA) was collected the first day of life and weekly until discharge for virologic study with polymerase chain reaction. When these babies presented respiratory symptoms a new NPA was collected in this moment. A clinical form was filled by the physician. RESULTS: A total of 60 infants were analyzed: 30 (50%) had a gestational age < 32 weeks and 36 (60%) weighing less than 1500 grams. We collected a total of 256 nasopharyngeal aspirate samples, 24 of them being positive (9.3%). These 24 positive samples corresponded to 13 infants in our cohort (21.6% of the patients). Of them, 9 were symptomatic and had 11 episodes of infection (2 patients had two different episodes with negative control between them). The most frequently identified virus was rhinovirus in (19) 79% of cases. The most frequent clinical data was the presence or increased of apneas (75%) and the needed of oxygenotherapy. CONCLUSIONS: HRV infections are prevalent in the NICU, and preterm infants have a high risk of infections with clinical relevance

Viral respiratory tract infections in the neonatal intensive care unit.

INTRODUCTION: Viral respiratory infections cause major morbidity and mortality in preterm infants. We have performed a prospective study in our neonatal intensive care unit (NICU) to determine the incidence of respiratory infections, their impact and the epidemiology and outcome in high risk neonates. PATIENTS AND METHODS: From September 2011 to May 2013 a prospective study was conducted in all preterm infants <32 weeks gestational age and in all term newborns admitted to NICU for any pathology that was anticipated to have an admission exceeding two weeks. A nasopharyngeal aspirate (NPA) was collected the first day of life and weekly until discharge for virologic study with polymerase chain reaction. When these babies presented respiratory symptoms a new NPA was collected at this moment. A clinical form was filled by the physician. RESULTS: A total of 60 infants were analysed: 30 (50%) had a gestational age <32 weeks and 36 (60%) weighed less than 1500 g. We collected a total of 256 nasopharyngeal aspirate samples, 24 of them being positive (9.3%). These 24 positive samples corresponded to 13 infants in our cohort (21.6% of the patients). Of them, 9 were symptomatic and had 11 episodes of infection (2 patients had two different episodes with negative control between them). The most frequently identified virus was rhinovirus in (19) 79% of cases. The most frequent clinical data was the presence or increase in apneas (75%) and the need for oxygenotherapy. CONCLUSIONS: HRV infections are prevalent in the NICU, and preterm infants have a high risk of infections with clinical relevance.

INTRODUCCIÓN: Las infecciones virales respiratorias son causa de importante morbimortalidad en recién nacidos prematuros. Hemos realizado un estudio prospectivo en nuestra unidad de cuidados intensivos neonatales (UCIN) para determinar la incidencia de infecciones respiratorias, su impacto, epidemiología y pronóstico en neonatos de alto riesgo. PACIENTES Y MÉTODOS: Estudio prospectivo realizado entre septiembre del 2011 y mayo del 2013 entre todos los recién nacidos < 32 semanas de edad gestacional y aquellos niños cuya patología pudiera dar lugar a pensar en un ingreso superior a las 2 semanas. Se recogieron aspirados nasofaríngeos (ANF) el primer día de vida y semanalmente hasta el alta para estudio virológico mediante reacción en cadena de polimerasa. En los casos en los que los niños presentaban síntomas respiratorios, se procedió a recoger un nuevo ANF. El pediatra cumplimentó un cuestionario con los datos clínicos. RESULTADOS: Se estudió a 60 niños; 30 (50%) de ellos con una edad gestacional <32 semanas y 36 (60%) con un peso <1.500 g. Se recogió un total de 256 ANF, 24 de los cuales resultaron positivos (9,3%). Estas 24 muestras positivas correspondieron solo a 13 niños (21,6% de los pacientes). De ellos, 9 resultaron sintomáticos y presentaron 11 episodios de infección (2 pacientes experimentaron 2 episodios diferentes con control negativo entre ellos). El virus más frecuentemente identificado ­ el 79% de las muestras (19) ­ fue el rinovirus (RV). El dato clínico más frecuente fue la presencia o incremento de apneas (75%) y la necesidad de oxigenoterapia. CONCLUSIONES: Las infecciones por RV son frecuentes en la UCIN y los recién nacidos pretérmino tienen un alto riesgo de presentar infecciones de relevancia clínica.

[Viral respiratory tract infections in the Neonatal Intensive Care Unit]. / Infecciones virales de las vías respiratorias en la Unidad de Cuidados Intensivos Neonatales.

INTRODUCTION: Viral respiratory infections cause major morbidity and mortality in preterm infants. We have performed a prospective study in our neonatal intensive care unit (NICU) to determine the incidence of respiratory infections, their impact and the epidemiology and outcome in high risk neonates. PATIENTS AND METHODS: From September 2011 to May 2013 a prospective study was conducted in all preterm infants < 32 weeks gestational age and in all term newborns admitted to NICU for any pathology that are anticipated to have an income exceeding two weeks. A nasopharyngeal aspirate (NPA) was collected the first day of life and weekly until discharge for virologic study with polymerase chain reaction. When these babies presented respiratory symptoms a new NPA was collected in this moment. A clinical form was filled by the physician. RESULTS: A total of 60 infants were analyzed: 30 (50%) had a gestational age < 32 weeks and 36 (60%) weighing less than 1500 grams. We collected a total of 256 nasopharyngeal aspirate samples, 24 of them being positive (9.3%). These 24 positive samples corresponded to 13 infants in our cohort (21.6% of the patients). Of them, 9 were symptomatic and had 11 episodes of infection (2 patients had two different episodes with negative control between them). The most frequently identified virus was rhinovirus in (19) 79% of cases. The most frequent clinical data was the presence or increased of apneas (75%) and the needed of oxygenotherapy. CONCLUSIONS: HRV infections are prevalent in the NICU, and preterm infants have a high risk of infections with clinical relevance.

Activation of mitogen- and stress-activated kinase 1 is required for proliferation of breast cancer cells in response to estrogens or progestins.

Growth of breast cancers is often dependent on ovarian steroid hormones making the tumors responsive to antagonists of hormone receptors. However, eventually the tumors become hormone independent, raising the need to identify downstream targets for the inhibition of tumor growth. One possibility is to focus on the signaling mechanisms used by ovarian steroid hormones to induce breast cancer cell proliferation. Here we report that the mitogen- and stress-activated kinase 1 (MSK1) could be a potential druggable target. Using the breast cancer cell line T47D, we show that estrogens (E2) and progestins activate MSK1, which forms a complex with the corresponding hormone receptor. Inhibition of MSK1 activity with H89 or its depletion by MSK1 short hairpin RNAs (shRNAs) specifically abrogates cell proliferation in response to E2 or progestins without affecting serum-induced cell proliferation. MSK1 activity is required for the transition from the G1- to the S-phase of the cell cycle and inhibition of MSK1 compromises both estradiol- and progestin-dependent induction of cell cycle genes. ChIP-seq experiments identified binding of MSK1 to progesterone receptor-binding sites associated with hormone-responsive genes. MSK1 recruitment to epigenetically defined enhancer regions supports the need of MSK1 as a chromatin remodeler in hormone-dependent regulation of gene transcription. In agreement with this interpretation, expression of a histone H3 mutated at S10 eliminates the hormonal effect on cell proliferation and on induction of relevant target genes. Finally, we show that E2- or progestin-dependent growth of T47D cells xenografted in immunodefficient mice is inhibited by depletion of MSK1, indicating that our findings are not restricted to cultured cells, and that MSK1 plays an important role for hormone-dependent breast cancer growth in a more physiological context.

Cross-clade protection against H5N1 HPAI strains recently isolated from commercial poultry in Egypt with a single dose of a baculovirus based vaccine.

The current avian influenza epidemic in Egypt caused by circulation of genetically and antigenically diverse H5N1 HPAI viruses in poultry is controlled by applying vaccination among other measures. In this context, the use of a DIVA (differentiating infected from vaccinated animals) vaccination strategy utilizing a vaccine capable of inducing protection against multiple antigenic variants may result as an additional control tool to the existing ones. In this study the efficacy of a single-shot recombinant baculovirus-based vaccine in specific-pathogen-free chickens was tested by experimental challenge with genetically and antigenically diverse H5N1 HPAI viruses belonging to clades 2.2.1 and 2.2.1.1, which have been circulating in Egypt since 2010. A single dose of vaccine, administration at 10 days of age, was shown to confer 100% clinical protection, with a decrease or suppression of virus shedding.

Antigenic and genetic analyses of isolate APMV/wigeon/Italy/3920-1/2005 indicate that it represents a new avian paramyxovirus (APMV-12).

Isolate wigeon/Italy/3920-1/2005 (3920-1) was obtained during surveillance of wild birds in November 2005 in the Rovigo province of Northern Italy and shown to be a paramyxovirus. Analysis of cross-haemagglutination-inhibition tests between 3920-1 and representative avian paramyxoviruses showed only a low-level relationship to APMV-1. Phylogenetic analysis of the whole genome and each of the six genes indicated that while 3920-1 grouped with APMV-1 and APMV-9 viruses, it was quite distinct from these two. In the whole-genome analysis, 3920-1 had 52.1 % nucleotide sequence identity to the closest APMV-1 virus, 50.1 % identity to the APMV-9 genome, and less than 42 % identity to representatives of the other avian paramyxovirus groups. We propose isolate wigeon/Italy/3920-1/2005 as the prototype strain of a further APMV group, APMV-12.