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Purpose Cerebral venous sinus thrombosis (CVST) is an unusual and potentially life-threatening condition with variable and nonspecific clinical symptoms and high morbimortality rates. Standard therapy consists of systemic anticoagulation; although there is no clear evidence about the best choice for treatment, intravenous heparin is used as the first-line treatment modality. Intravenous sinus thrombolysis can be an effective and relatively safe treatment for acutely deteriorating patients who have not responded to conventional therapy. This case report presents the possibility of endovascular treatment in multiple steps with mechanical thrombolysis with balloon, local pharmacological thrombolysis and stenting, in a patient with a severe form of CVST. Case summary A 67-year-old woman presented severe headache, agitation and confusion with diagnosis of venous sinus dural thrombosis in both lateral sinus and torcula. After 24 h there was neurological worsening evolving with seizures and numbness even after starting heparin, without sinus recanalization; CT scan showed left temporal intracerebral hemorrhage. We decided to take an endovascular approach in multiple steps. The first step was mechanical static thrombolysis with balloon; the second step was dynamic mechanical thrombolysis with a balloon partially deflated and “pulled”; the third step was local thrombolysis with Actilyse™; finally, the fourth step was angioplasty and reconstruction of the sinuses using multiple carotid stents and complete angiographic recanalization of both sinuses and torcula. After 24 h of endovascular treatment there was full clinical recovery and no tomographic complications. Conclusion This result shows that mechanical clot disruption, intrasinus thrombolysis and reconstruction of wall sinuses with stenting can be an endovascular option in the severe form of CVST with intracerebral hemorrhage and rapid worsening of neurological symptoms. Although this type of treatment can re-channel the occluded sinuses, further comparative and randomized studies are needed to clarify its efficacy versus other therapeutic modalities. [ABSTRACT FROM AUTHOR]

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It is shown that the structure of functionals and operators on a quaternionic Hilbert space is much richer than is generally appreciated, but one has to work simultaneously with the usual definition and an unusual one of multiplication by scalar for functionals—the different definitions, of course, give rise to different vector spaces. A generalized version of the Riesz representation theorem for quaternionic Hilbert spaces is proved along with the basic theorem on the algebra of additive operators on such a space. [ABSTRACT FROM AUTHOR]

Semilinear operators on a complex Hilbert space are studied in a part of a program that aims to develop the theories of additive operators on complex and quaternionic Hilbert spaces for application to problems in mathematical physics. The more notable among the new results proved on the eigenvalue problem for semilinear operators are the following: (i) if α is an eigenvalue of a semilinear operator then so also is any complex number which has the same modulus as α; (ii) if a normal semilinear operator has two eigenvectors belonging to different eigenvalues, then either the two eigenvectors are orthogonal or two eigenvalues have the same moduli; and (iii) a normal semilinear operator has a complete set of eigenvectors if and only if it is self-adjoint. Further, it is shown that there exists a norm-preserving semilinear isomorphism between the spaces of bounded linear and semilinear operators on a complex Hilbert space. Finally it is demonstrated how the theory of semilinear operators can be exploited to solve the problems of finding three involutive mutually anticommuting self-adjoint two-by-two matrices and four four-by-four matrices with the same properties: the unusual and remarkably easy solution of this old familiar exercise establishes the relevance of the theory being developed here to physics. [ABSTRACT FROM AUTHOR]

A Salmonella agona strain has caused a hospital outbreak of gastroenteritis in a pediatric unit in Rio de Janeiro. It bears two plasmids, a small (6·5 MDa molecular weight) plasmid coding for type B colicin production and a larger one (36 MDa molecular weight) determining resistance to ampicillin, gentamicin, kanamycin and trimethoprim-sulphamethoxazole. The R-plasmid, but not the Col-plasmid, is self-transferable to a Escherichia coli recipient strain. Curing for the R-plasmid was achieved by treatment with 0·05 % SDS followed by incubation at 44°C. It has not been possible to cure the S. agona strain for its Col-plasmid. [ABSTRACT FROM PUBLISHER]

Given sufficient training samples, statistical shape models can provide detailed population representations for use in anthropological and computational genetic studies, injury biomechanics, musculoskeletal disease models or implant design optimization. While the technique has become extremely popular for the description of isolated anatomical structures, it suffers from positional interference when applied to coupled or articulated input data. In the present manuscript we describe and validate a novel approach to extract positional noise from such coupled data. The technique was first validated and then implemented in a multicomponent model of the lower limb. The impact of noise on the model itself as well as on the description of sexual dimorphism was evaluated. The novelty of our methodology lies in the fact that no rigid transformations are calculated or imposed on the data by means of idealized joint definitions and by extension the models obtained from them., Competing Interests: The authors declare that they have no competing interests that could inappropriately influence this work., (© 2020 The Authors.)

Introduction: There has been a great improvement in transplantation medicine in Brazil in the last 2 decades. However, there remain several barriers regarding notification of brain and cardiac death as well as completion of the donation process., Methods: This retrospective study was performed between January 2008 and December 2010. We reviewed all deaths in a University Hospital, observing the causes of non-notification to the State Transplantation Authority and non-donations., Results: There were 41 notifications of brain death resulting in donation in only 19.5% of those cases. Cardiac death was diagnosed in 21 patients, resulting in 52.4% donations. The main cause for non-donation were family refusal (37.2%), infectious diseases (30.2%), and clinical contraindications (32.6%). Most of the missed possible donors occurred during the night (54.8%) and in the emergency room (80.9%)., Conclusion: There is an urgent need for better education of the Brazilian population about organ donation and brain death definitions. Other identified problems include lack of uniformity in brain death determinations among hospitals, rigid contraindications to donation in the State of Parana, physician unawareness or disbelief about brain death diagnostic criteria, and lack of structure of our Hospital., (Copyright © 2012. Published by Elsevier Inc.)

The CFA/I fimbria promotes the attachment of enterotoxigenic Escherichia coli (ETEC) to the surface of human enterocytes. The generation of a protective immune response requires the induction of antibodies able to block the CFA/I-mediated binding of ETEC to receptors located on the small intestine epithelium or on the surface of human red blood cells, in hemagglutination tests. An eukaryotic expression plasmid, pBLCFA, encoding the CFA/I gene under the control of the human cytomegalovirus major immediate-early promoter was constructed as a prototype DNA vaccine against ETEC. pBLCFA-tranfected BHK-21 cells secreted a peptide cross-reacting with a monoclonal antibody raised against CFA/I subunits. BALB/c mice immunized intramuscularly with one or two doses of purified pBLCFA developed CFA/I-specific serum antibodies for at least 52 weeks, composed predominantly of the IgG1 subclass. pBLCFA-induced antibodies bind mainly to epitopes exposed on the surface of intact CFA/I fimbriae and do not react with immune recessive epitopes found in other ETEC fimbra sharing amino acid homologies with CFA/I. Furthermore, pBLCFA-induced antibodies were able to block the adhesive properties of the CFA/I fimbriae, as evaluated by the ability to inhibit the hemagglutination promoted by CFA/I-expressing ETEC cells. These results suggest that secretion of CFA/I encoded by pBLCFA preserves important conformational epitopes required for the generation of protective antibodies against the adhesive properties of the CFA/I fimbriae and open new perspectives for the development of DNA vaccines against enteric bacterial pathogens.

The colonization factor antigen I (CFA/I) is one of the most epidemiologically relevant enterotoxigenic Escherichia coli (ETEC) fimbrial adhesins, which mediates the binding to human small intestine epithelium. A recombinant eukaryotic expression plasmid, pRECFA, encoding the CFA/I protein fused to the glycoprotein D of herpes simplex type 1 virus, was used to generate an antibody response in a murine model following intramuscular inoculation of purified DNA. Eukaryotic cells (BHK-21) transfected with pRECFA expressed the CFA/I protein in vitro, as revealed by Western blot and immunofluorescence microscopy. Administration of a single pRECFA 100-microg dose induced a long-term CFA/I-specific antibody response in BALB/c mice composed mainly of IgG and, to a lesser extent, IgA isotypes. The major CFA/I-specific IgG subclass was IgG2a, suggesting a Th-1-type immune response. A second dose with the same amount of purified DNA, given 2 weeks later, caused a booster effect on the immunoglobulin levels, but did not qualitatively alter the isotypes and subclasses of the induced antibody response. Immunization with different amounts of purified DNA and/or number of doses showed that maximal transient CFA/I-specific antibody levels could be obtained after two 100-microg doses of pRECFA given 2 weeks apart, but long-term antibody levels were similar.

The induction of systemic (IgG) and mucosal (IgA) antibody responses against the colonization factor I antigen (CFA/I) of enterotoxigenic Escherichia coli (ETEC) was evaluated in mice primed with an intramuscularly delivered CFA/I-encoding DNA vaccine followed by two oral immunizations with a live recombinant Salmonella typhimurium vaccine strain expressing the ETEC antigen. The booster effect induced by the oral immunization was detected two weeks and one year after the administration of the DNA vaccine. The DNA-primed/Salmonella-boosted vaccination regime showed a synergistic effect on the induced CFA/I-specific systemic and secreted antibody levels which could not be attained by either immunization strategy alone. These results suggest that the combined use of DNA vaccines and recombinant Salmonella vaccine strains can be a useful immunization strategy against enteric pathogens.

Stimulation of the mammalian immune system by administration of plasmid DNA has been shown to be an important approach for vaccine development against several pathogens. In the present study we investigated the use of DNA vaccines to induce immune responses against an enteric bacterial pathogen, enterotoxigenic Escherichia coli (ETEC). Three plasmid vectors encoding colonization factor antigen 1 (CFA/I), an ETEC fimbrial adhesin, were constructed. Eukaryotic cells transfected with each of these plasmids expressed the heterologous antigen in different compartments: bound to the cytoplasmic membrane (pRECFA), accumulated in the cytoplasm (pPolyCFA) or secreted to the outside medium (pBLCFA). BALB/c mice were intramuscularly (i.m.) inoculated with purified plasmid DNA and the systemic, cellular and secreted CFA/I-specific immune responses were analyzed. The results showed that all three DNA vaccine formulations could elicit CFA/I-specific immune responses. Moreover, cellular location of the plasmid-encoded CFA/I seems to have an important role in the induced immune response. Taken together, these results indicate that DNA vaccines also represent a promising approach against enteric bacterial pathogens.

The genetic relatedness among 29 enterotoxigenic Escherichia coli strains of serotype O6:H16 was investigated by randomly amplified polymorphic DNA (RAPD) analysis. The strains were isolated in different parts of the world, displayed CS1-CS3 or CS2-CS3 profiles, and expressed heat-labile toxin (LT) and heat-stable toxin; a single strain expressed only LT. Ten RAPD types were distinguished and showed significant similarity, having on average 82% of the amplified bands in common. These results indicated that, irrespective of the different geographical origin or virulence factors, these strains belonged to a widespread clonal group.

An expression plasmid (pCFA-1) carrying the cfaB gene that codes for the enterotoxigenic Escherichia coli (ETEC) fimbrial adhesin colonization factor antigen I (CFA/I) subunit was constructed and used to transform a derivative of the attenuated Salmonella typhimurium aroA vaccine strain SL3261 carrying an F'lacIq. Treatment of the transformed strain with isopropyl-beta-D-thiogalactopyranoside (IPTG) resulted in elevated in vitro expression of the CFA/I subunit. Although flagellar function and lipopolysaccharide (LPS) synthesis were similar in both the parental and the recombinant strains, spleen colonization was reduced in the recombinant strain. All BALB/c mice parenterally inoculated with the recombinant strain developed significant anti-CFA/I and anti-LPS serum antibody titers (P < 0.05). Moreover, 2 of 5 mice orally inoculated with the engineered Salmonella strain developed anti-CFA/I intestinal IgA (P > 0.05) while 4/5 of the same mice developed anti-LPS IgA (P < 0.05). The results indicate that the vaccine strain elicited an antibody response against the bacterial host both after oral and intravenous immunization while the response against the CFA/I antigen was significant only after inoculation by the intravenous route.

The cfaB gene, coding for the CFA/I fimbrial adhesin of enterotoxigenic Escherichia coli (ETEC), was cloned and expressed as a fusion peptide with the glycoprotein D (gD) from herpes simplex virus type 1 (HSV) in the pRE4 eukaryotic expression vector, resulting in the recombinant plasmid pRECFA. All BALB/c mice injected intramuscularly (i.m.) with a single dose (100 micrograms) of the purified plasmid developed antibodies against epitopes found on dissociated CFA/I subunits as well as other homologous ETEC fimbriae. Surface-exposed epitopes found on intact CFA/I fimbriae were also recognized by antibodies derived from DNA immunization, but they did not overlap with those generated with purified CFA/I fimbriae. None of the sera raised in mice immunizated with pRECFA were able to agglutinate bacterial cells or inhibit haemagglutination promoted by CFA/I bearing ETEC cells. These results show that pRECFA can elicit CFA/I-specific antibodies, which may have different epitope specificities and functional properties compared with those generated with purified bacterial protein.

A monoclonal antibody (MAb 84) raised against the dissociated CFA/I fimbriae of enterotoxigenic Escherichia coli was characterized with regard to antigen binding and epitope specificity. Enzyme-linked immunosorbent assay (ELISA) showed that MAb 84 had higher affinity to CFA/I subunits than to intact CFA/I fimbriae and recognized a Salmonella flagellin carrying an insert corresponding to amino acids 32 to 45 of the CFA/I subunit. Fine epitope mapping based on the Pepscan technique showed that the peptide 39TFESY43, derived from the sequence of the mature CFA/I subunit, was specifically recognized by MAb 84. The 39TFESY43 sequence is probably not accessible on the surface of the native CFA/I fimbriae since MAb 84 did not bind to intact fimbriae as evaluated in inhibition ELISA tests. Moreover, MAb 84 did not agglutinate fimbriated ETEC cells nor inhibit CFA/I-mediated hemagglutination or the adhesion to Caco-2 cells.