Fiabilidad diagnóstica comparativa de la mielografía y de la tomografía axial computarizada en la hernia discal lumbar

Un grupo de 137 pacientes con hernia discal lumbar fue estudiado retrospectivamente , contrastando los hallazgos quirúrgicos con los proporcionado s por la mielografía y la tomografía axial computarizada (TAC), con objeto de comparar la fiabilidad de ambas técnicas de diagnóstico. La hernia discal correspondió al nivel L5-S1 en 76 pacientes y al L4-L5 en 61. Preoperatoriamente se había efectuado una TAC lumbar en 99 paciente s y una mielografía en 77. En 39 casos se efectuaron ambas exploraciones. La fiabilidad diagnóstica cuantificada por el porcentaje de resultados "verdaderos positivos" fue similar en ambas exploraciones, elevándose al 89% y 90% para la TAC y la mielografía respectivamente . De los 39 paciente s a quiene s se le s practicó ambas exploraciones, en 12 (39%) de ellos no existía concordancia en el diagnóstico. No se registraron "falsos negativos" con la TAC. Como conclusión, ambas técnicas diagnósticas tienen una alta y similar fiabilidad para detectar hernias discale s a nivel lumbar. No obstante, las ventajas que aporta la TAC respecto a la mielografía en cuanto a confort para el pacient e y ausencia de reaccione s adversas hac e que esta técnica sea considerada como el método diagnóstico de elección. La mielografía queda relegada a casos con imágene s dudosas con la TAC.In orde r to compar e the diagnosti c accurac y of CT sca n and myelo - graphy, a series of 137 patients with herniated lumbar disc was retrospectively analyzed matching the surgical findings with the images obtained by both diagnostic techniques. Ther e wer e 7 6 herniate d disc s a t th e L5-S1 leve l an d 6 1 a t th e L4-L5. Preoperatively, 99 patients wer e assessed by CT scan and 77 by mielography. In 39 cases, both technique s wer e performed. The diagnosti c accuracy, quantified by the percentage of "true positive" results wa s similar in both techniques: 89% in CT scan and 90% in mielography . In 12 of the 39 patients explore d by bot h CT scan and myelo - graphy, the results wer e discordant. "False negative" case s wer e not found using CT scan. In conclusion, both CT scan and myelography provide equal high diagnosti c accuracy for lumbar herniated disc. However, CT scan has become the primary diagnostic tool because of several advantages, such as the confort for the patients and the lack of adverse reactions

Comments to paper entitled "Predicting scleral GP lens entrapped tear layer oxygen tensions"

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Bottlenose dolphins (Tursiops truncatus) do also cast neutrophil extracellular traps against the apicomplexan parasite Neospora caninum

Neutrophil extracellular traps (NETs) are web-like structures composed of nuclear DNA decorated with histones and cytoplasmic peptides which antiparasitic properties have not previously been investigated in cetaceans. Polymorphonuclear neutrophils (PMN) were isolated from healthy bottlenose dolphins (Tursiops truncatus), and stimulated with Neospora caninum tachyzoites and the NETs-agonist zymosan. In vitro interactions of PMN with the tachyzoites resulted in rapid extrusion of NETs. For the demonstration and quantification of cetacean NETs, extracellular DNA was stained by using either Sytox Orange® or Pico Green®. Scanning electron microscopy (SEM) and fluorescence analyses demonstrated PMN-derived release of NETs upon exposure to tachyzoites of N. caninum. Co-localization studies of N. caninum induced cetacean NETs proved the presence of DNA adorned with histones (H1, H2A/H2B, H3, H4), neutrophil elastase (NE), myeloperoxidase (MPO) and pentraxin (PTX) confirming the molecular properties of mammalian NETosis. Dolphin-derived N. caninum-NETosis were efficiently suppressed by DNase I and diphenyleneiodonium (DPI) treatments. Our results indicate that cetacean-derived NETs represent an ancient, conserved and relevant defense effector mechanism of the host innate immune system against N. caninum and probably other related neozoan parasites circulating in the marine environment

Molecular Characterization of the Viroporin Function of Foot-and-Mouth Disease Virus Nonstructural Protein 2B

Nonstructural protein 2B of foot-and-mouth disease (FMD) virus (FMDV) is comprised of a small, hydrophobic, 154-amino-acid protein. Structure-function analyses demonstrated that FMDV 2B is an ion channel-forming protein. Infrared spectroscopy measurements using partially overlapping peptides that spanned regions between amino acids 28 and 147 demonstrated the adoption of helical conformations in two putative transmembrane regions between residues 60 and 78 and between residues 119 and 147 and a third transmembrane region between residues 79 and 106, adopting a mainly extended structure. Using synthetic peptides, ion channel activity measurements in planar lipid bilayers and imaging of single giant unilamellar vesicles (GUVs) revealed the existence of two sequences endowed with membrane-porating activity: one spanning FMDV 2B residues 55 to 82 and the other spanning the C-terminal region of 2B from residues 99 to 147. Mapping the latter sequence identified residues 119 to 147 as being responsible for the activity. Experiments to assess the degree of insertion of the synthetic peptides in bilayers and the inclination angle adopted by each peptide regarding the membrane plane normal confirm that residues 55 to 82 and 119 to 147 of 2B actively insert as transmembrane helices. Using reverse genetics, a panel of 13 FMD recombinant mutant viruses was designed, which harbored nonconservative as well as alanine substitutions in critical amino acid residues in the area between amino acid residues 28 and 147. Alterations to any of these structures interfered with pore channel activity and the capacity of the protein to permeabilize the endoplasmic reticulum (ER) to calcium and were lethal for virus replication. Thus, FMDV 2B emerges as the first member of the viroporin family containing two distinct pore domains

One-Way Traffic of a Viral Motor Channel for Double-Stranded DNA Translocation

ABSTRACT Linear double-stranded DNA (dsDNA) viruses package their genome into a procapsid using an ATP-driven nanomotor. Here we report that bacteriophage phi29 DNA packaging motor exercises a one-way traffic property for dsDNA translocation from N-terminal entrance to C-terminal exit with a valve mechanism in DNA packaging, as demonstrated by voltage ramping, electrode polarity switching, and sedimentation force assessment. Without the use of gating control as found in other biological channels, the observed single direction dsDNA transportation provides a novel system with a natural valve to control dsDNA loading and gene delivery in bioreactors, liposomes, or high throughput DNA sequencing apparatus

The TGF-β/Smad Repressor TG-Interacting Factor 1 (TGIF1) Plays a Role in Radiation-Induced Intestinal Injury Independently of a Smad Signaling Pathway

Despite advances in radiation delivery protocols, exposure of normal tissues during the course of radiation therapy remains a limiting factor of cancer treatment. If the canonical TGF-β/Smad pathway has been extensively studied and implicated in the development of radiation damage in various organs, the precise modalities of its activation following radiation exposure remain elusive. In the present study, we hypothesized that TGF-β1 signaling and target genes expression may depend on radiation-induced modifications in Smad transcriptional co-repressors/inhibitors expressions (TGIF1, SnoN, Ski and Smad7). In endothelial cells (HUVECs) and in a model of experimental radiation enteropathy in mice, radiation exposure increases expression of TGF-β/Smad pathway and of its target gene PAI-1, together with the overexpression of Smad co-repressor TGIF1. In mice, TGIF1 deficiency is not associated with changes in the expression of radiation-induced TGF-β pathway-related transcripts following localized small intestinal irradiation. In HUVECs, TGIF1 overexpression or silencing has no influence either on the radiation-induced Smad activation or the Smad3-dependent PAI-1 overexpression. However, TGIF1 genetic deficiency sensitizes mice to radiation-induced intestinal damage after total body or localized small intestinal radiation exposure, demonstrating that TGIF1 plays a role in radiation-induced intestinal injury. In conclusion, the TGF-β/Smad co-repressor TGIF1 plays a role in radiation-induced normal tissue damage by a Smad-independent mechanism

Holoprosencephaly

Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the face. It is estimated to occur in 1/16,000 live births and 1/250 conceptuses. Three ranges of increasing severity are described: lobar, semi-lobar and alobar HPE. Another milder subtype of HPE called middle interhemispheric variant (MIHF) or syntelencephaly is also reported. In most of the cases, facial anomalies are observed in HPE, like cyclopia, proboscis, median or bilateral cleft lip/palate in severe forms, ocular hypotelorism or solitary median maxillary central incisor in minor forms. These latter midline defects can occur without the cerebral malformations and then are called microforms. Children with HPE have many medical problems: developmental delay and feeding difficulties, epilepsy, instability of temperature, heart rate and respiration. Endocrine disorders like diabetes insipidus, adrenal hypoplasia, hypogonadism, thyroid hypoplasia and growth hormone deficiency are frequent. To date, seven genes have been positively implicated in HPE: Sonic hedgehog (SHH), ZIC2, SIX3, TGIF, PTCH, GLI2 and TDGF1. A molecular diagnosis can be performed by gene sequencing and allele quantification for the four main genes SHH, ZIC2, SIX3 and TGIF. Major rearrangements of the subtelomeres can also be identified by multiplex ligation-dependent probe amplification (MLPA). Nevertheless, in about 70% of cases, the molecular basis of the disease remains unknown, suggesting the existence of several other candidate genes or environmental factors. Consequently, a "multiple-hit hypothesis" of genetic and/or environmental factors (like maternal diabetes) has been proposed to account for the extreme clinical variability. In a practical approach, prenatal diagnosis is based on ultrasound and magnetic resonance imaging (MRI) rather than on molecular diagnosis. Treatment is symptomatic and supportive, and requires a multidisciplinary management. Child outcome depends on the HPE severity and the medical and neurological complications associated. Severely affected children have a very poor prognosis. Mildly affected children may exhibit few symptoms and may live a normal life

Selectivity of Protein Ion Channels and the Role of Buried Charges. Analytical Solutions, Numerical Calculations, and MD Simulations

The preference of large protein ion channels for cations or anions is mainly determined by the electrostatic interactions of mobile ions with charged residues of the protein. Here we discuss the widely spread paradigm that the charges determining the channel selectivity are only those that can be considered solvent-accessible because of their location near the permeation pathways of ions and water molecules. Theoretical predictions for the electric potential and average ion densities inside the pore are presented using several approaches of increasing resolution: from analytical and numerical solutions of electrostatic equations in a model channel up to all-atom molecular dynamics simulations and continuum electrostatic calculations performed in a particular biological channel, the bacterial porin OmpF. The results highlight the role of protein dieletric properties and the importance of the initial choice of the residue ionization states in the understanding of the molecular basis of large channel selectivity irrespective of the level of resolution of the computational approach used.We acknowledge support from the Spanish Ministry of Economy and Competitiveness (MINECO Project FIS2013- 40473-P), Generalitat Valenciana (Prometeo 2012/069), and Fundacio ́ Caixa Castello ́ -Bancaixa (Projects No. P1-1B2012-03 and P1-1B2012-16)