Using Generative Modeling to Endow with Potency Initially Inert Compounds with Good Bioavailability and Low Toxicity.

In the early stages of drug development, large chemical libraries are typically screened to identify compounds of promising potency against the chosen targets. Often, however, the resulting hit compounds tend to have poor drug metabolism and pharmacokinetics (DMPK), with negative developability features that may be difficult to eliminate. Therefore, starting the drug discovery process with a "null library", compounds that have highly desirable DMPK properties but no potency against the chosen targets, could be advantageous. Here, we explore the opportunities offered by machine learning to realize this strategy in the case of the inhibition of α-synuclein aggregation, a process associated with Parkinson's disease. We apply MolDQN, a generative machine learning method, to build an inhibitory activity against α-synuclein aggregation into an initial inactive compound with good DMPK properties. Our results illustrate how generative modeling can be used to endow initially inert compounds with desirable developability properties.

Multiomic prediction of therapeutic targets for human diseases associated with protein phase separation.

The phenomenon of protein phase separation (PPS) underlies a wide range of cellular functions. Correspondingly, the dysregulation of the PPS process has been associated with numerous human diseases. To enable therapeutic interventions based on the regulation of this association, possible targets should be identified. For this purpose, we present an approach that combines the multiomic PandaOmics platform with the FuzDrop method to identify PPS-prone disease-associated proteins. Using this approach, we prioritize candidates with high PandaOmics and FuzDrop scores using a profiling method that accounts for a wide range of parameters relevant for disease mechanism and pharmacological intervention. We validate the differential phase separation behaviors of three predicted Alzheimer's disease targets (MARCKS, CAMKK2, and p62) in two cell models of this disease. Overall, the approach that we present generates a list of possible therapeutic targets for human diseases associated with the dysregulation of the PPS process.

Fulminant endogenous panophthalmitis caused by Clostridium septicum infection / Panoftalmite endógena fulminante por infecção por Clostridium septicum

ABSTRACT We report an unusual case of fulminant endogenous Clostridium septicum panophthalmitis. A 74-year-old male patient presented with sudden amaurosis in the right eye, which in a few hours, evolved into an orbital cellulitis, endophthalmitis, anterior segment ischemia, and secondary perforation of the eye. A complete diagnostic study, which included cranial and orbital contrast-enhanced computed tomography scan, contrast-enhanced magnetic resonance imaging, blood cultures, and complete blood work, were performed. No causal agent was identified. Clostridium septicum infection caused fulminant gaseous panophthalmitis. Despite broad-spectrum antibiotic treatment, evisceration of the eyeball was necessary. The extension study showed a colon adenocarcinoma as the origin of the infection. Clostridium septicum panophthalmitis is a rare but aggressive orbital infection. This infection warrants the identification of a neoplastic process in the gastrointestinal tract in many cases not previously described.

RESUMO Este é o relato de um caso incomum de panoftalmite endógena fulminante por Clostridium septicum. Um paciente do sexo masculino, 74 anos, apresentou amaurose súbita no olho direito, que em poucas horas evoluiu para celulite orbitária, endoftalmite, isquemia do segmento anterior e perfuração secundária do olho. Foi realizado um estudo diagnóstico completo, que incluiu uma tomografia computadorizada com contraste cranial e orbital, um exame de ressonância magnética, hemocultura e hemograma completo. Nenhum agente causal foi identificado. A infecção por Clostridium septicum causou uma panoftalmite gasosa fulminante. Apesar do tratamento com antibióticos de amplo espectro, foi necessário eviscerar o globo ocular. O estudo de seguimento mostrou um adenocarcinoma de cólon como a origem da infecção. A panoftalmite por Clostridium septicum é um tipo raro, mas muito agressivo de infecção orbitária. Essa infecção deve sugerir a busca por um processo neoplásico no trato gastrointestinal, em muitos casos não diagnosticado anteriormente.

Fulminant endogenous panophthalmitis caused by Clostridium septicum infection.

We report an unusual case of fulminant endogenous Clostridium septicum panophthalmitis. A 74-year-old male patient presented with sudden amaurosis in the right eye, which in a few hours, evolved into an orbital cellulitis, endophthalmitis, anterior segment ischemia, and secondary perforation of the eye. A complete diagnostic study, which included cranial and orbital contrast-enhanced computed tomography scan, contrast-enhanced magnetic resonance imaging, blood cultures, and complete blood work, were performed. No causal agent was identified. Clostridium septicum infection caused fulminant gaseous panophthalmitis. Despite broad-spectrum antibiotic treatment, evisceration of the eyeball was necessary. The extension study showed a colon adenocarcinoma as the origin of the infection. Clostridium septicum panophthalmitis is a rare but aggressive orbital infection. This infection warrants the identification of a neoplastic process in the gastrointestinal tract in many cases not previously described.

A Kinetic Map of the Influence of Biomimetic Lipid Model Membranes on Aß42 Aggregation.

The aggregation of the amyloid ß (Aß) peptide is one of the molecular hallmarks of Alzheimer's disease (AD). Although Aß deposits have mostly been observed extracellularly, various studies have also reported the presence of intracellular Aß assemblies. Because these intracellular Aß aggregates might play a role in the onset and progression of AD, it is important to investigate their possible origins at different locations of the cell along the secretory pathway of the amyloid precursor protein, from which Aß is derived by proteolytic cleavage. Senile plaques found in AD are largely composed of the 42-residue form of Aß (Aß42). Intracellularly, Aß42 is produced in the endoplasmatic reticulum (ER) and Golgi apparatus. Since lipid bilayers have been shown to promote the aggregation of Aß, in this study, we measure the effects of the lipid membrane composition on the in vitro aggregation kinetics of Aß42. By using large unilamellar vesicles to model cellular membranes at different locations, including the inner and outer leaflets of the plasma membrane, late endosomes, the ER, and the Golgi apparatus, we show that Aß42 aggregation is inhibited by the ER and Golgi model membranes. These results provide a preliminary map of the possible effects of the membrane composition in different cellular locations on Aß aggregation and suggest the presence of an evolutionary optimization of the lipid composition to prevent the intracellular aggregation of Aß.

Terapia miofuncional, maloclusión y disfunción orofacial: Evaluación fotogramétrica del perfil / Myofunctional therapy, malocclusion and orofacial dysfunction: Profile photogrammetric evaluation

RESUMEN: El objetivo de este estudio observacional analítico es determinar el efecto de la Terapia Miofuncional en el perfil facial de voluntarios con maloclusión y disfunción orofacial, mediante fotogrametría. En una muestra de 15 pacientes, se midieron indirectamente mediante fotogrametría en el Software Blue Sky Plan® las siguientes variables cefalométricas: Ángulo Nasolabial, Prominencia Labial y Plano Estético. Se realizó toma de fotografías al comenzar la Terapia Miofuncional (primera sesión) y al finalizarla (décima sesión). Para comparar valores obtenidos en el mismo voluntario en cada variable cefalométrica entre principio y final de terapia, análisis estadísticos fueron realizados. Se determinó que no hay diferencia estadística en valores obtenidos en ninguna de las variables cefalométricas al comparar el inicio con el final de terapia. Por consiguiente, se concluyó que la Terapia Miofuncional no tiene un efecto significativo en estas variables de perfil facial en voluntarios con maloclusión y disfunción orofacial medidas mediante fotogrametría, pese a cambios funcionales percibidos por pacientes y evaluadores. Es fundamental poder realizar un diagnóstico riguroso y posterior derivación a Fonoaudiología, si corresponde, para lograr equilibrio funcional en los pacientes y reducir riesgo de progresión o reaparición de Anomalías Dentomaxilares.

ABSTRACT: This analytical observational study aimed to determine the effect of Myofunctional Therapy on the facial profile in volunteers with malocclusion and orofacial dysfunction, through photogrammetry. Fifteen patients were recruited, and the following cephalometric variables were measured indirectly through photogrammetry in the Blue Sky Plan Software (Blue Sky Bio®): Nasolabial Angle, Lip Prominence and Aesthetic Plane. Previous photographs were taken, at the beginning of Myofunctional Therapy (first session) and the end (tenth session). To compare the values of each variable in a volunteer between the beginning and end of therapy, statistical analyses were performed. There was no statistical difference in the values obtained in any of these variables when comparing the beginning and the end of myofunctional therapy. Therefore, it was concluded that myofunctional therapy does not have a statistically significant effect on these facial profile variables in volunteers with malocclusion and orofacial dysfunction measured by photogrammetry, despite the functional changes perceived by patients and evaluators. However, it is essential to perform a rigorous diagnosis and subsequent referral to speech therapy, if applicable, to achieve functional balance in the patients and reduce progression or recurrence risk of Dentomaxillary Abnormalities.

Evolución del embarazo en adolescentes y distribución de sus determinantes en la ciudad de Córdoba, Argentina, periodo 2015-2018 / Teenage pregnancy evolution and distribution of its determinants in the city of Córdoba, Argentina, 2015-2018 period

Este trabajo describe la tendencia del embarazo en adolescentes según determinantes sociales individuales y contextuales en la ciudad de Córdoba, Argentina, para el periodo 2015 a 2018. Se diseñó un estudio descriptivo bietapico. Inició con un estudio ecológico de grupos múltiples, considerando 99 áreas programáticas sanitarias de la ciudad. Luego uno observacional, incluyendo 6171 mujeres menores de 20 años que tuvieron hijos/as durante 2015-2018. Se observó una tendencia decreciente en la proporción de embarazos en adolescentes: 11,52% (2015) a 8,19% (2018), y de la Tasa de Fecundidad Adolescente (TEFA): 46,3‰ (2015) a 28,2‰ (2018). La TEFA resultó mayor en áreas con hogares con NBI superior a la mediana (p<0,05), siendo su geolocalización concentrada mayormente en las periferias de la ciudad. Fue superior la proporción de madres adolescentes sin cobertura de seguro de salud que con cobertura (p<0,05). La proporción de embarazos de adolescentes entre 18 y 19 años fue superior entre quienes presentaban secundario incompleto o menos (p<0,05). La sostenida reducción del embarazo en adolescentes, aquí objetivada, no debiera traducirse en una desatención a esta problemática, sino por el contrario profundizarse las acciones tendientes a sostener esta tendencia, atendiendo especialmente a grupos de mayor vulnerabilidad social (AU)

This paper describes the trend of teenage pregnancy according to individual and contextual social determinants in the city of Córdoba, Argentina, for the period 2015-2018. A descriptive sequential two-stage study was carried out. First, an ecological study of multiple groups, including the 99 'programmatic health areas´ of the city was developed. Then, an observational study including 6171 women under 20 years who had children between 2015-2018. A decreasing trend in the proportion of teenage pregnancies was observed: 11.52% (2015) to 8.19% (2018), and in the Adolescent Fertility Rate (TEFA): 46.3‰ (2015) to 28,2‰ (2018). TEFA was greater in areas with higher proportion of households with unsatisfied basic needs (NBI) (p <0.05), and these areas were mostly located at the city peripheries. The proportion of teenage mothers was higher among those with health coverage (p <0.05). The proportion of mothers of 18 and 19 years was higher among those who has incomplete secondary educational level or less or less (p <0.05). The sustained reduction of pregnancy in adolescents should not translate into a neglect of this problem, but instead into a deepen of the actions tending to sustain this trend, focusing special attention in groups of greater social vulnerability (AU)

El papel de las especies reactivas de oxígeno y de nitrógeno en algunas enfermedades neurodegenerativas / The role of reactive oxygen and nitrogen species in some neurodegenerative diseases

Resumen Las especies reactivas de oxígeno y nitrógeno son moléculas que se generan a partir del metabolismo celular fisiológico; sin embargo, cuando existe un desequilibrio entre la producción de radicales libres y los mecanismos antioxidantes se genera estrés oxidante. El estrés oxidante se ha asociado con el desarrollo y progresión de enfermedades neurodegenerativas como Alzheimer, Parkinson y Huntington. Dado que el inicio del estrés oxidante es imperceptible y aún no se cuenta con estudios de laboratorio que determinen el impacto de los radicales libres en pacientes con enfermedades neurodegenerativas, es importante dilucidar el papel de estos en los procesos neurodegenerativos con el fin de tener indicios sólidos sobre las posibles dianas de tratamiento y prevenir el daño progresivo en este tipo de enfermedades.

Abstract The reactive oxygen and nitrogen species are molecules that are generated from the physiological cellular metabolism. However, when there is an imbalance between the production of free radicals and the antioxidant mechanisms, oxidative stress is generated. Oxidative stress has been associated with the development and progression of neurodegenerative diseases such as Alzheimer, Parkinson and Huntington, given that the onset of oxidative stress is imperceptible and that there are still no laboratory studies that can determine the impact of free radicals in patients with neurodegenerative diseases. It is important to elucidate the role of free radicals in neurodegenerative processes in order to have solid indications about the possible treatment targets and to prevent the progressive damage in this type of diseases.

Alphabet Writing and Allograph Selection as Predictors of Spelling in Sentences Written by Spanish-Speaking Children Who Are Poor or Good Keyboarders.

This study examined the relationship and degree of predictability that the fluency of writing the alphabet from memory and the selection of allographs have on measures of fluency and accuracy of spelling in a free-writing sentence task when keyboarding. The Test Estandarizado para la Evaluación de la Escritura con Teclado ("Spanish Keyboarding Writing Test"; Jiménez, 2012) was used as the assessment tool. A sample of 986 children from Grades 1 through 3 were classified according to transcription skills measured by keyboard ability (poor vs. good) across the grades. Results demonstrated that fluency in writing the alphabet and selecting allographs mediated the differences in spelling between good and poor keyboarders in the free-writing task. Execution in the allograph selection task and writing alphabet from memory had different degrees of predictability in each of the groups in explaining the level of fluency and spelling in the free-writing task sentences, depending on the grade. These results suggest that early assessment of writing by means of the computer keyboard can provide clues and guidelines for intervention and training to strengthen specific skills to improve writing performance in the early primary grades in transcription skills by keyboarding.

Home Palliative Care for Patients with Advanced Chronic Kidney Disease: Preliminary Results.

Healthcare for patients with advanced chronic kidney disease (ACKD) on conservative treatment very often poses healthcare problems that are difficult to solve. At the end of 2011, we began a program based on the care and monitoring of these patients by Primary Care Teams. ACKD patients who opted for conservative treatment were offered the chance to be cared for mainly at home by the Primary Care doctor and nurse, under the coordination of the Palliative Care Unit and the Nephrology Department. During 2012, 2013, and 2014, 76 patients received treatment in this program (mean age: 81 years; mean Charlson age-comorbidity index: 10, and mean glomerular filtration rate: 12.4 mL/min/1.73 m²). The median patient follow-up time (until death or until 31 December 2014) was 165 days. During this period, 51% of patients did not have to visit the hospital's emergency department and 58% did not require hospitalization. Forty-eight of the 76 patients died after a median time of 135 days in the program; 24 (50%) died at home. Our experience indicates that with the support of the Palliative Care Unit and the Nephrology Department, ACKD patients who are not dialysis candidates may be monitored at home by Primary Care Teams.

Programa de atención domiciliaria a pacientes con enfermedad renal crónica avanzada. Experiencia de dos años / Home care programme for patients with advanced chronic kidney disease. A two-year experience

Introducción: La atención sanitaria de los pacientes con enfermedad renal crónica avanzada (ERCA) bajo tratamiento conservador plantea con gran frecuencia problemas asistenciales de difícil solución. Muchos de ellos son enfermos añosos, con dificultad de movilidad, en los que los desplazamientos al centro hospitalario suponen una gran dificultad. A finales del año 2011 iniciamos un programa basado en la asistencia y el control de estos enfermos por los equipos de Atención Primaria. Material y métodos: A los pacientes con ERCA que han elegido tratamiento conservador, se les ofrece la posibilidad de recibir una asistencia fundamentalmente domiciliaria por el médico de Atención Primaria, bajo la coordinación de la Unidad de Cuidados Paliativos y del Servicio de Nefrología. Resultados: Durante los años 2012 y 2013, 50 enfermos recibieron tratamiento en este programa. Edad media: 81 años, índice edad-comorbilidad de Charlson: 10, y filtrado glomerular medio 11,8 ml/min/1,73 m². El tiempo de seguimiento medio por enfermo (hasta el fallecimiento o hasta el 31/12/2013) fue de 184 días. Durante este período, el 44 % de los enfermos no tuvo que acudir al Servicio de Urgencias del hospital, y el 58 % no precisó ingreso hospitalario. Fallecieron 29 de los 50 enfermos, tras un tiempo medio de permanencia en el programa de 163 días; en 14 de ellos (48 %), el sitio de fallecimiento fue su domicilio. Conclusiones: Nuestra experiencia indica que con soporte de la Unidad de Cuidados Paliativos y del Servicio de Nefrología, el paciente con ERCA no candidato a diálisis puede ser controlado en su domicilio por Atención Primaria (AU)

Introduction: Healthcare for patients with advanced chronic kidney disease (ACKD) on conservative treatment very often poses healthcare problems that are difficult to solve. Many patients are elderly and have mobility problems, and it is very difficult for them to travel to hospital. At the end of 2011, we began a programme based on the care and monitoring of these patients by Primary Care teams. Material and method: ACKD patients who opted for conservative treatment were offered the chance to be cared for mainly at home by the Primary Care doctor, under the coordination of the Palliative Care Unit and the Nephrology Department. Results: During 2012 and 2013, 50 patients received treatment in this programme. Mean age: 81 years, Charlson age-comorbidity index: 10 and mean glomerular filtration rate: 11.8ml/min/1.73.m². The mean patient follow-up time (until death or until 31/12/2013) was 184 days. During this period, 44% of patients did not have to visit the hospital’s Emergency Department and 58% did not require hospitalisation. 29 of the 50 patients died after a mean time of 163 days on the programme; 14 (48%) died at home. Conclusions: Our experience indicates that with the support of the Palliative Care Unit and the Nephrology Department, ACKD patients who are not dialysis candidates may be monitored at home by Primary Care (AU)

Home care programme for patients with advanced chronic kidney disease. A two-year experience.

INTRODUCTION:  Healthcare for patients with advanced chronic kidney disease (ACKD) on conservative treatment very often poses healthcare problems that are difficult to solve. Many patients are elderly and have mobility problems, and it is very difficult for them to travel to hospital. At the end of 2011, we began a programme based on the care and monitoring of these patients by Primary Care teams.  MATERIAL AND METHOD:  ACKD patients who opted for conservative treatment were offered the chance to be cared for mainly at home by the Primary Care doctor, under the coordination of the Palliative Care Unit and the Nephrology Department.  RESULTS:  During 2012 and 2013, 50 patients received treatment in this programme. Mean age: 81 years, Charlson age-comorbidity index: 10 and mean glomerular filtration rate: 11.8ml/min/1.73.m². The mean patient follow-up time (until death or until 31/12/2013) was 184 days. During this period, 44% of patients did not have to visit the hospital’s Emergency Department and 58% did not require hospitalisation. 29 of the 50 patients died after a mean time of 163 days on the programme; 14 (48%) died at home.  CONCLUSIONS:  Our experience indicates that with the support of the Palliative Care Unit and the Nephrology Department, ACKD patients who are not dialysis candidates may be monitored at home by Primary Care.

Necesidades y acceso a los servicios de salud de la población adolescente en el norte argentino / Adolescents in northern Argentina: needs and cccess to health services

INTRODUCCION: Los/as adolescentes tienen bajos indicadores de morbimortalidad. Sin embargo, presentan problemáticas particulares que pueden condicionar su desarrollo saludable y que deben ser analizadas, ya que se trata de una población prioritaria desde la prevención sanitaria y con larga expectativa de vida.OBJETIVOS: Conocer la situación de salud/enfermedad de los/asadolescentes en el norte argentino. Identificar sus necesidades realesy percibidas, así como las barreras de acceso a los servicios de salud,particularmente en materia de salud sexual, adicciones, alimentacióny suicidio. METODOS: El estudio incluyó los siguientes pasos: 1) revisiónde bibliografía y normativa sobre salud adolescente; 2) mapeo de actores y entrevistas a referentes locales; 3) aplicación de una encuesta autoadministrada a adolescentes de escuelas públicas en seis provincias argentinas; 4) análisis cuanticualitativo de las encuestas y entrevistas. RESULTADOS: Aunque la percepción y las dolencias correspondieron a perfiles de baja necesidad, del total de adolescentes que consignaron problemas de salud, sólo la mitad consultó al sistema, y la mayoría dijo que prefería recurrir a su entorno cercano (padres, amigos). Las preocupaciones adolescentes no estuvieron vinculadas necesariamente con el estado de salud, sino con planteosy problemas emergentes de su edad. Más allá de las barreras geográficas,se observaron limitaciones institucionales y familiares querestringen el vínculo entre el sistema de salud y los/as adolescentes.CONCLUSIONES: Los resultados muestran espacios vacantes departicipación (del sistema y del entorno familiar, comunitario y escolar) para que los requerimientos de información y atención de los/as adolescentes se traduzcan en demandas y en un mejor acceso.

INTRODUCTION: Adolescents have low mortality and morbidity rates. However, there are certain problemsconditioning a healthy development which should be analyzed as a priority, from a prevention perspective, for this population with long life expectancy. OBJECTIVES: To know the health/disease status of adolescents in Northern Argentina. To identify real andperceived needs as well as barriers in access to health services, focusing on sexual health, addictions, nutrition and suicide. METHODS: The study included following steps: 1) literature review and survey of current legislation on adolescent health; 2) mapping of actors and interviews with local key informants; 3) self-administered survey to adolescents of public schools in six Argentine provinces; 4) qualitative and quantitative analysis of surveys and interviews. RESULTS: Although perceptions and complaints belonged to low-need profiles, only half of theadolescents reporting health problems used the health system to get information, and most of them said they preferred to talk with parents and friends. Adolescent concerns were notnecessarily related to health status, but to issues of their age group. Apart from geographical barriers, family and institutional reasons were found to limit the relationship between healthsystem and adolescents. CONCLUSIONS: Results show spacesfor participation which should be occupied by the health care system and family, community and school environment, so that information and attention requirements can be reflectedin demands and a better access.

Prevalence of metabolic syndrome and associated cardiovascular risk factors in Guatemalan school children.

Guatemala is experiencing a nutritional and lifestyle transition. While chronic malnutrition is prevalent, overweight, obesity and chronic diseases have increased substantially in the country. This study was conducted to investigate the prevalence of metabolic syndrome and the associated cardiovascular risk factors in the pre-adolescent Guatemalan population. A cross-sectional study was conducted among 302 Guatemalan children (8-13 years old) attending public and private schools in the Municipality of Chimaltenango. Demographic data and anthropometric and blood pressure measurements were collected. A blood sample was taken after an 8 h overnight fast and analyzed for glucose, triglyceride and high-density lipoprotein cholesterol levels. The data were analyzed to identify factors associated with metabolic syndrome and with its components. The prevalence of metabolic syndrome in the study population was 2.0 %. However, approximately 54 % of the children had at least one component of metabolic syndrome, while none had four or five of the components. The three most prevalent risk factors were high triglycerides (43.4 %), low HDL cholesterol (17.2 %) and obesity (12.3 %). Boys were more likely to be obese than girls and rural children were more likely to have higher triglyceride levels than urban children. Although the prevalence of metabolic syndrome is low, the fact that majority of the children already have at least one component of metabolic syndrome is cause for concern since components of metabolic syndrome can continue into adulthood and increase the risk for chronic diseases later in life. Therefore, immediate action should be taken to address the problem.

Multicenter study of subcutaneous alemtuzumab administered at reduced dose in patients with fludarabine-relapsed/refractory chronic lymphocytic leukemia: final analysis.

Optimal management of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) has been the motive behind a large number of studies in recent years, and previous response, its duration, and development of clonal evolution appear to be the best indicators for the choice of a new regimen. Although alemtuzumab in relapsed/refractory CLL may be beneficial, the optimal dosage and risk of infection related to its use remain thus far deeply controversial issues. In this pilot phase II study we investigated the feasibility of, toxicity of, and response to alemtuzumab at a reduced dose (30 mg s.c. for 2 weeks and then once a week at extended intervals: every 2, 4, 6 weeks up to 1 year). The overall response rate was 95%, with 51% complete response. The complete response range was 55% in fludarabine-relapsed patients and 28% in patients with fludarabine-refractory disease, without significant difference between the two groups. The regimen was well tolerated with mild toxicity and few cytomegalovirus (CMV) infections. With a median follow-up of 27 months, the overall survival (46% at 3 years) appears to be similar to that with other regimens although with fewer adverse events. In conclusion, treatment with alemtuzumab at a reduced dose seems to be safe and increases the event-free survival of patients with relapsed/refractory CLL, compared with the standard dose. A randomized study comparing both regimens including a larger number of patients is warranted.

Recombinant S3Pvac-phage anticysticercosis vaccine: Simultaneous protection against cysticercosis and hydatid disease in rural pigs.

This paper provides macroscopic and histological evidence on the statistically significant protective effects of S3Pvac-phage vaccination against porcine cysticercosis and hydatidosis. The study included 391 rustically bred pigs (187 vaccinated and 204 controls). Vaccination significantly reduced the prevalence of cysticercosis by 61.7%. Vaccination also significantly reduced by 56.1% the prevalence of hydatidosis caused by Echinococcus granulosus in pigs. The presence of the vaccine epitopes in both cestodes is probably involved in the cross-protection observed. Increased inflammation was found in 5% of cysticerci recovered from controls, versus 24% from vaccinated pigs (P<0.01). Hydatid cysts were non-inflammatory in either group. Vaccination was effective to prevent one single disease, but it failed to prevent the simultaneous infections with both parasites in a same pig. The widening of the S3Pvac-phage vaccine protective repertoire to include hydatidosis is a convenient feature that should reduce the prevalence of two frequent zoonoses that affect rustic porcine breading with a single action. Thus, the costs of two different vaccination programs would be reduced to a single one with significant reduction in both zoonoses.

Nitric oxide binding and photodelivery based on ruthenium(II) complexes of 4-arylazo-3,5-dimethylpyrazole.

Two fluorescent ligands, 3,5-dimethyl-4-(6'-sulfonylammonium-1'-azonaphthyl)pyrazole (dmpzn, 1) and 3,5-dimethyl-4-(4'-N,N'-dimethylaminoazophenyl)pyrazole (dmpza, 2) were obtained by condensation of ketoenolic derivatives with hydrazine. 1 and 2 formed the novel dinuclear complexes [(H(2)O)(3)ClRu(micro-L)(2)RuCl(H(2)O)(3)] (3 or 4) and [(H(2)O)(NO)Cl(2)Ru(micro-L)(2)RuCl(2)(NO)(H(2)O)] (6 or 7) (where L 1 = 2 or , respectively) which were characterized by IR, NMR and elemental analysis. The nitrosyl complexes were prepared by bubbling purified nitric oxide through methanol solutions of the corresponding ruthenium(II) chloroderivative or by reaction of the appropriate ligands with Ru(NO)Cl(3). Complexes 3 and 4 were found to bind NO, resulting in an increase in fluorescence. Ligand 1 also formed the mononuclear nitrosyl complex [Ru(NO)(bpy)(2)(dmpzn)]Cl(2) (8) which released NO in water at physiological pH and in the solid state as revealed by fluorescence and IR measurements, respectively.

Discordancia entre cultivos de vellosidades coriónicas, de corto y largo plazo. Presentación de un caso y revisión del tema / Short and long term chorion villi culture discordance. Presentation of a case and theme review

Presentamos un caso de diagnóstico prenatal en el que se halló un resultado falso negativo en un cultivo a largo plazo de vellosidades coriónicas, discordante con los resultados del cultivo a corto plazo, que mostraba trisomía 21. Se discute las posibles causas de discrepancia en éste y otros casos similares, y la mejor manera de proceder para asegurar el diagnóstico correcto.

We present a prenatal diagnosis case with false negative result in long term villi culture discordant with short term villi culture showing trisomy 21. We discuss possible causes of discordance in this and similar cases and the best way to proceed to ensure correct diagnosis.