Neocortical Sox9+ radial glia generate glutamatergic neurons for all layers, but lack discernible evidence of early laminar fate restriction.

Glutamatergic neurons in the cerebral cortex are derived from embryonic neural stem cells known as radial glial progenitors (RGPs). Early RGPs, present at the onset of cortical neurogenesis, are classically thought to produce columnar clones of glutamatergic neurons spanning the cortical layers. Recently, however, it has been reported that a subset of early RGPs may undergo early commitment to upper layer neuron fates, thus bypassing genesis of deep layer neurons. However, the latter mode of early RGP differentiation was not confirmed in some other studies, and remains controversial. To further investigate the clonal output from early RGPs, we employed genetic lineage tracing driven by Sox9, a transcription factor gene that is expressed in all early RGPs. We found that early RGPs produced columnar clones spanning all cortical layers, with no evidence of significant laminar fate restriction. These data support the classic progressive restriction model of cortical neurogenesis, and suggest that early RGPs do not undergo early commitment to only upper or lower layer fates.

AGEP sistémico, un diagnóstico oculto en una falsa psoriasis paradójica por anti-TNF / Systemic AGEP, a hidden diagnosis in a false psoriasis paradoxical by anti-TNF

La pustulosis exantemática generalizada aguda (AGEP, en inglés) es una enfermedad poco frecuente, causada por drogas, caracterizada por aparición aguda de numerosas pústulas estériles en una base eritematosa, asociada en ocasiones a fiebre y leucocitosis, en algunos casos puede causar un compromiso de piel severo pero que resuelve rápidamente con la suspensión del fármaco sin tratamiento especial requerido. Puede confundirse con otras entidades como la psoriasis pustular e inusualmente produce compromiso sistémico. Presentamos un caso de AGEP secundario a terapia anti-TNF con compromiso sistémico.

The acute generalized exanthematous pustulosis (AGEP, in english)is a rare disease caused by drugs, characterized by acute onsetof numerous sterile pustules on an erythematous base, sometimesassociated with fever and leukocytosis, in some cases may causea severe skin involvement reaction but solved quickly with the drugsuspension without special treatment required. It can be confusedwith other entities such as pustular psoriasis and unusually producesystemic involvement. We present a case of secondary to anti-TNFtherapy AGEP systemic involvement.

Simple measurement of the apparent viscosity of a cell from only one picture: Application to cardiac stem cells.

Mechanical deformability of cells is a key property that influences their ability to migrate and their contribution to tissue development and regeneration. We analyze here the possibility of characterizing the overall deformability of cells by their apparent viscosity, using a simplified method to estimate that parameter. The proposed method simplifies the quantitative analysis of micropipette-aspiration experiments. We have studied by this procedure the overall apparent viscosity of cardiac stem cells, which are considered a promising tool to regenerate damaged cardiac tissue. Comparison with the apparent viscosity of low-viscosity cells such as immune-system cells suggests that treatments to reduce the viscosity of these cells could enhance their ability to repair damaged cardiac tissue.

Identification and dynamics of polyglycine II nanocrystals in Argiope trifasciata flagelliform silk.

Spider silks combine a significant number of desirable characteristics in one material, including large tensile strength and strain at breaking, biocompatibility, and the possibility of tailoring their properties. Major ampullate gland silk (MAS) is the most studied silk and their properties are explained by a double lattice of hydrogen bonds and elastomeric protein chains linked to polyalanine ß-nanocrystals. However, many basic details regarding the relationship between composition, microstructure and properties in silks are still lacking. Here we show that this relationship can be traced in flagelliform silk (Flag) spun by Argiope trifasciata spiders after identifying a phase consisting of polyglycine II nanocrystals. The presence of this phase is consistent with the dominant presence of the -GGX- and -GPG- motifs in its sequence. In contrast to the passive role assigned to polyalanine nanocrystals in MAS, polyglycine II nanocrystals can undergo growing/collapse processes that contribute to increase toughness and justify the ability of Flag to supercontract.

Minor ampullate silks from Nephila and Argiope spiders: tensile properties and microstructural characterization.

The mechanical behavior and microstructure of minor ampullate gland silk (miS) of two orb-web spinning species, Argiope trifasciata and Nephila inaurata, were extensively characterized, enabling detailed comparison with other silks. The similarities and differences exhibited by miS when compared with the intensively studied major ampullate gland silk (MAS) and silkworm (Bombyx mori) silk offer a genuine opportunity for testing some of the hypotheses proposed to correlate microstructure and tensile properties in silk. In this work, we show that miSs of different species show similar properties, even when fibers spun by spiders that diverged over 100 million years are compared. The tensile properties of miS are comparable to those of MAS when tested in air, significantly in terms of work to fracture, but differ considerably when tested in water. In particular, miS does not show a supercontraction effect and an associated ground state. In this regard, the behavior of miS in water is similar to that of B. mori silk, and it is shown that the initial elastic modulus of both fibers can be explained using a common model. Intriguingly, the microstructural parameters measured in miS are comparable to those of MAS and considerably different from those found in B. mori. This fact suggests that some critical microstructural information is still missing in our description of silks, and our results suggest that the hydrophilicity of the lateral groups or the large scale organization of the sequences might be routes worth exploring.

Transmission permeability of tuberculosis involving immigrants, revealed by a multicentre analysis of clusters.

In recent years, the number of cases of tuberculosis (TB) among immigrants in Spain has increased markedly, and led to this analysis of the recent transmission patterns of TB in the immigrant population in Madrid. The countries from which the highest number of immigrant cases have been reported were Ecuador (21%), Romania (16%), Morocco (12%), Peru (11%) and Bolivia (9%). Fifty-one per cent of the cases were from South America. In a multicentre study (2004-2006), IS6110 restriction fragment length polymorphism and spoligotyping were used to genotype the Mycobacterium tuberculosis isolates from 632 immigrant cases from 47 countries. A total of 183 cases (29%) were grouped into 59 clusters, which are markers of potential transmission events. Most of the clusters (81%) included patients living in different healthcare districts, and 54% of the clusters were multinational. When a sample of 478 autochthonous cases was included, 53% of the clusters involving immigrants also included autochthonous cases. This study revealed marked transmission permeability among nationalities and between the immigrant and the autochthonous populations.

Cirugía endovascular de los aneurismas aislados de la arteria hipogástrica / Endovascular surgery of isolated hypogastric artery aneurysms

Introducción. Los aneurismas aislados de la arteria hipogástrica son entidades de difícil diagnóstico. Tradicionalmente se habían tratado mediante la ligadura del origen de la hipogástrica más una endoaneurismorrafia. Caso clínico. Varón de 72 años con un aneurisma de hipogástrica de 4 cm de diámetro tratado mediante la embolización con coils metálicos del saco aneurismático y el cierre del origen de la hipogástrica con un stent cubierto de politetraflouroetileno expandido con balón. Tanto los controles inmediatos como los realizados a los seis meses mostraron una correcta exclusión del aneurisma, así como la permeabilidad de la ilíaca externa. Conclusión. Actualmente la cirugía endovascular es una alternativa menos agresiva

Introduction. Isolated hypogastric artery aneurisms are very difficult to diagnose. They have traditionally been treated by means of tying of the entrance of the hypogastric artery in addition to an endoaneurysmorrhaphy. Case report. A 72 year-old man presented a hypogastric aneurysm with a diameter of 4 cm treated by embolization of the aneurysm sack with metallic coils and the closure of the origin of the affected artery with one polytetrafluoroethylene covered stent expanded by balloon. Both controls carried out immediately and after six months show a correct exclusion of the aneurysms in addition to a functioning flow through the external iliac artery. Conclusion. Nowadays, endovascular surgery is a less aggressive method

Prolonged survival of an HIV-infected patient with multidrug-resistant Mycobacterium bovis infection treated with surgical resection.

We describe a case of multidrug-resistant tuberculosis due to Mycobacterium bovis in a human immunodeficiency virus-infected woman with good immunologic status. The patient presented with a hard mass measuring 10 cm in diameter on the lower left ribs and a lung nodule measuring 3 cm in diameter in the left superior lobe. No adequate pharmacological treatment was available. Both lesions were surgically resected. The patient has remained asymptomatic (without fever, cough, lymphadenopathy, or cutaneous masses) for 20 months, after discharge from the hospital.

Postnatal shifts of interneuron position in the neocortex of normal and reeler mice: evidence for inward radial migration.

During development, interneurons migrate to precise positions in the cortex by tangential and radial migration. The objectives of this study were to characterize the net radial migrations of interneurons during the first postnatal week, and to investigate the role of reelin signaling in regulating those migrations. To observe radial migrations, we compared the laminar positions of interneurons (immunoreactive for GABA or Dlx) in mouse neocortex on postnatal days (P) 0.5 and P7.5. In addition, we used bromodeoxyuridine birthdating to reveal the migrations of different interneuron cohorts. To study the effects of reelin deficiency, experiments were performed in reeler mutant mice. In normal P0.5 cortex, interneurons were most abundant in the marginal zone and layer 5. By P7.5, interneurons were least abundant in the marginal zone, and were distributed more evenly in the cortical plate. This change was attributed mainly to inward migration of middle- to late-born interneurons (produced on embryonic days (E) 13.5 to E16.5) from the marginal zone to layers 2-5. During the same interval, late-born projection neurons (non-immunoreactive for GABA or Dlx) migrated mainly outward, from the intermediate zone to upper cortical layers. In reeler cortex, middle- and late-born interneurons migrated from the superplate on P0.5, to the deep cortical plate on P7.5. Late-born projection neurons in reeler migrated in the opposite direction, from the intermediate zone to the deep cortical plate. We conclude that many middle- and late-born interneurons migrate radially inward, from the marginal zone (or superplate) to the cortical plate, during the first postnatal week in normal and reeler mice. We propose that within the cortical plate, interneuron laminar positions may be determined in part by interactions with projection neurons born on the same day in neurogenesis.

Antibiotic susceptibility of bacterial strains isolated from patients with community-acquired urinary tract infections.

Isolates from urine samples obtained during 1999 were identified and their susceptibility to antimicrobial agents studied along with any production of extended-spectrum beta-lactamases (ESBL) by Escherichia coli and Klebsiella pneumoniae. A total of 13774 samples were analysed using an automatic system for the detection of bacterial ATP (Coral, USA). Of these samples, 49% were reported to be positive and uncontaminated; bacteria most frequently isolated were E. coli (47%), Proteus mirabilis (7%), Enterococcus faecalis (6%) and K. pneumoniae (5%). The susceptibility studies showed 37% E. coli strains resistant to amoxycillin+clavulanate 33% to cotrimoxazole and 22% to ciprofloxacin. Seven strains of E. coli produced ESBL. Thirteen per cent of strains were resistant to cefuroxime but only (1%) to fosfomycin. Resistance to nitrofurantoin in K. pneumoniae was 38%. P. mirabilis showed 52% resistance to cotrimoxazole and 13% Staphylococcus aureus, were methicillin-resistant. E. faecalis did not show any special resistance to normal medication. Fosfomycin continued to show high activity against Gram-negative bacilli. However, enterococci, some species of staphylococci and yeasts were difficult to treat empirically. ESBL were detected in the isolates of E. coli and there were some methicillin-resistant strains of S. aureus.

Tsukamurella strandjordae sp. nov., a proposed new species causing sepsis.

We have isolated a gram-positive, weakly acid-alcohol-fast, irregular rod-shaped bacterium from cultures of blood from a 5-year-old girl with acute myelogenous leukemia. This isolate was compared with 14 other strains including reference strains of Tsukamurella species by a polyphasic approach based on physiological and biochemical properties, whole-cell short-chain fatty acid and mycolic acid analyses, DNA-DNA hybridization, and sequencing of the 16S rRNA gene. This isolate represents a new taxon within the genus Tsukamurella for which we propose the name Tsukamurella strandjordae sp. nov. Our study also revealed that Tsukamurella paurometabola ATCC 25938 represents a misnamed Tsukamurella inchonensis isolate and confirms that Tsukamurella wratislaviensis belongs to the genus Rhodococcus.

Data acquisition, data storage, and data presentation in a modern genetics laboratory.

Modern genetic analysis can be divided into three main areas of investigation. The first is data acquisition, in the form of genomic sequence and the cataloguing of polymorphism data of the single nucleotide polymorphism variety (so called SNPs). Once identified, such genetic information can be adapted into high throughput tests to examine genetic information in large populations, making the analysis of sufficiently large numbers both cost and time effective so that relatively low-penetrant genetic effects can be accurately detected. The third step is correlating variation with phenotype (e.g. disease susceptibility or resistance) for a variety of disorders is paramount in our motivation and indeed is a common goal of modern human genetic analysis. While the technology to acquire vast amounts of genetic data is now well established and continues to expand, the ability to deal with such data, from the process of acquisition, storage, and analysis depends fundamentally on a solid informatics infrastructure as an essential component. Indeed, most of the major gains in productivity in this field are to be realized on the informatics front, and involve automating data acquisition, defining and sorting data in databases for quality control and analysis and facilitating access to data for the large variety of data analyses. Informatics-related issues including those relating to data acquisition, database structure, and analysis tools are summarized here in an effort to define some of the issues relevant to establishing informatics infrastructure in a small genetics laboratory focused on resequencing human immune response genes. From inherited diseases to drug efficacy to the specific genetic changes occurring during tumor development, this new field of medical genetics promises a profound impact on the state of human health. Ultimately, any and all advances in this field will continue to depend on major investments in informatics.

Estrógenos en la terapia hormonal de reemplazo / Estrogens in the hormonal therapy available

Analiza que la expectativa de vida de la mujer y su participación activa en la sociedad la enfrenta con una prolongada etapa postmenopáusica, con manifestaciones que requieren terapia de remplazo hormonal. Los estrógenos tanto endógenos como sintéticos tienen acciones en los ácidos nucleicos de las células blanco, necesarias para la homeostasis. La curva de la actividad hormonal a lo largo de la vida termina en una baja producción de estróganos en la postmenopausia. Existen varias alternativas para una Terapia de Reemplazo Hormonal, en la que se prefieren los esestrógenos naturales administrados de tal manera que los niveles hormonales obtenidos semejen los fisiológicos. El estriol, aunque sintético, tiene una estructura idéntica al estrógeno endógeno. Su administración puede ser oral, vaginal, transdérmica, percutánea, en implantes subcutáneos o por vía vaginal u oral. Los estrógenos conjugados son también efectivos en el tratamiento de los síntomas de la menopausia y se usan por vía oral. Existe consenso sobre los diversos beneficios de la Terapia de Reemplazo Hormonal, que incluyen la reducción tanto de la sintomatología cuanto de los riesgos cardiovasculares y ostearticulares asociados, así como una mejor calidad de vida que se refleja en un incremento de los puntajes de bienestar general. Los esquemas son muy bien tolerados y toda mujer que enfrenta la menopausia amerita se considere seriamente iniciar y mantener terapia hormonal de reemplazo...