De Novo Thrombotic Microangiopathy After Kidney Transplantation: Clinical Features, Treatment, and Long-Term Patient and Graft Survival

Introduction. Posttransplant thrombotic microangiopathy (TMA)/hemolytic uremic syndrome (HUS) can occur as a recurrent or de novo disease. Methods. A retrospective single-center observational study was applied in order to examine the incidence and outcomes of de novo TMA/HUS among transplantations performed between 2000 and 2010. Recurrent HUS or antibody-mediated rejections were excluded. Results. Seventeen (1.1%) among 1549 kidney transplant recipients fulfilled criteria for de novo TMA. The mean follow-up was 572 days (range, 69-1769). Maintenance immunosuppression was prednisone, tacrolimus (TAC), and mycophenolic acid in 14 (82%) patients. Mean age at onset was 40 +/- 15 years, and serum creatinine was 6.1 +/- 4.1 mg/dL. TMA occurred at a median of 25 days (range, 1-1755) after transplantation. Nine (53%) patients developed TMA within 1 month of transplantation and only 12% after 1 year. Clinical features were anemia (hemoglobin < 10 g/dL) in 9 (53%) patients, thrombocytopenia in 7 (41%), and increased lactate dehydrogenase in 12 (70%). Decreased haptoglobin was observed in 64% and schistocytes in 35%. Calcineurin inhibitor (CM) withdrawal or reduction was the first step in the management of 10/15 (66%) patients, and 6 (35%) received fresh frozen plasma (FFP) and/or plasmapheresis. TAC was successfully reintroduced in six patients after a median of 17 days. Eight (47%) patients needed dialytic support after TMA diagnosis and 75% remained on dialysis. At 4 years of follow-up, death-censored graft survival was worse for TMA group (43.0% versus 85.6%, log-rank = 0.001; hazard ratio = 3.74) and there was no difference in patient survival (53.1% versus 82.2%, log-rank = 0.24). Conclusion. De novo TMA after kidney transplantation is a rare but severe condition with poor graft outcomes. This syndrome may not be fully manifested, and clinical suspicion is essential for early diagnosis and treatment, based mainly in CM withdrawal and FFP infusions and/or plasmapheresis.

Clinical, epidemiological and molecular features of the HIV-1 subtype C and recombinant forms that are circulating in the city of Sao Paulo, Brazil

Background: The city of Sao Paulo has the highest AIDS case rate, with nearly 60% in Brazil. Despite, several studies involving molecular epidemiology, lack of data regarding a large cohort study has not been published from this city. Objectives: This study aimed to describe the HIV-1 subtypes, recombinant forms and drug resistance mutations, according to subtype, with emphasis on subtype C and BC recombinants in the city of Sao Paulo, Brazil. Study design: RNA was extracted from the plasma samples of 302 HIV-1-seropositive subjects, of which 211 were drug-naive and 82 were exposed to ART. HIV-1 partial pol region sequences were used in phylogenetic analyses for subtyping and identification of drug resistance mutations. The envelope gene of subtype C and BC samples was also sequenced. Results: From partial pol gene analyses, 239 samples (79.1%) were assigned as subtype B, 23 (7.6%) were F1, 16 (5.3%) were subtype C and 24 (8%) were mosaics (3 CRF28/CRF29-like). The subtype C and BC recombinants were mainly identified in drug-naive patients (72.7%) and the heterosexual risk exposure category (86.3%), whereas for subtype B, these values were 69.9% and 57.3%, respectively (p = 0.97 and p = 0.015, respectively). An increasing trend of subtype C and BC recombinants was observed (p < 0.01). Conclusion: The HIV-1 subtype C and CRFs seem to have emerged over the last few years in the city of Sao Paulo, principally among the heterosexual population. These findings may have an impact on preventive measures and vaccine development in Brazil.

Features of two proteins of Leptospira interrogans with potential role in host-pathogen interactions

Background: Leptospirosis is considered a re-emerging infectious disease caused by pathogenic spirochaetes of the genus Leptospira. Pathogenic leptospires have the ability to survive and disseminate to multiple organs after penetrating the host. Leptospires were shown to express surface proteins that interact with the extracellular matrix (ECM) and to plasminogen (PLG). This study examined the interaction of two putative leptospiral proteins with laminin, collagen Type I, collagen Type IV, cellular fibronectin, plasma fibronectin, PLG, factor H and C4bp. Results: We show that two leptospiral proteins encoded by LIC11834 and LIC12253 genes interact with laminin in a dose - dependent and saturable mode, with dissociation equilibrium constants (K-D) of 367.5 and 415.4 nM, respectively. These proteins were named Lsa33 and Lsa25 (Leptospiral surface adhesin) for LIC11834 and LIC12253, respectively. Metaperiodate - treated laminin reduced Lsa25 - laminin interaction, suggesting that sugar moieties of this ligand participate in this interaction. The Lsa33 is also PLG - binding receptor, with a K-D of 23.53 nM, capable of generating plasmin in the presence of an activator. Although in a weak manner, both proteins interact with C4bp, a regulator of complement classical route. In silico analysis together with proteinase K and immunoflorescence data suggest that these proteins might be surface exposed. Moreover, the recombinant proteins partially inhibited leptospiral adherence to immobilized laminin and PLG. Conclusions: We believe that these multifunctional proteins have the potential to participate in the interaction of leptospires to hosts by mediating adhesion and by helping the bacteria to escape the immune system and to overcome tissue barriers. To our knowledge, Lsa33 is the first leptospiral protein described to date with the capability of binding laminin, PLG and C4bp in vitro.

Flexible and conservative features of social systems in tufted capuchin monkeys: comparing the socioecology of Sapajus libidinosus and Sapajus nigritus

Socioecological models assume that primates adapt their social behavior to ecological conditions, and predict that food availability and distribution, predation risk and risk of infanticide by males affect patterns of social organization, social structure and mating system of primates. However, adaptability and variation of social behavior may be constrained by conservative adaptations and by phylogenetic inertia. The comparative study of closely related species can help to identify the relative contribution of ecological and of genetic determinants to primate social systems. We compared ecological features and social behavior of two species of the genus Sapajus, S. nigritus in Carlos Botelho State Park, an area of Atlantic Forest in Sao Paulo state, and S. libidinosus in Fazenda Boa Vista, a semi-arid habitat in Piaui state, Brazil. S. libidinosus perceived higher predation risk and fed on clumped, high quality, and usurpable resources (fruits) all year round, whereas S. nigritus perceived lower predation risk and relied on evenly distributed, low-quality food sources (leaves) during periods of fruit shortage. As predicted by socioecology models, S. libidinosus females were philopatric and established linear and stable dominance hierarchies, coalitions, and grooming relationships. S. nigritus females competed less often, and could transfer between groups, which might explain the lack of coalitions and grooming bonds among them. Both populations presented similar group size and composition and the same polygynous mating system. The species differed from each other in accordance with differences in the characteristics of their main food sources, as predicted by socioecological models, suggesting that phylogenetic inertia does not constrain social relationships established among female Sapajus. The similarity in mating systems indicates that this element of the social system is not affected by ecological variables and thus, is a more conservative behavioral feature of the genus Sapajus. Am. J. Primatol. 74:315331, 2012. (c) 2011 Wiley Periodicals, Inc.

Emission features of microstructures fabricated by two-photon polymerization containing three organic dyes

Fabrication of microstructures containing active compounds, such as fluorescent dyes and nanoparticles have been exploited in the last few years, aiming at applications from photonics to biology. Here we fabricate, using two-photon polymerization, microstructures containing the fluorescent dyes Stilbene 420, Disodium Fluorescein and Rhodamine B. The produced microstructures, containing dyes at specific sites, present good structural integrity and a broad fluorescence spectrum, from about 350 nm until 700 nm. Such spectrum can be tuned by using different excitation wavelengths and selecting the excitation position in the microstructure. These results are interesting for designing multi-doped structures, presenting tunable and broad fluorescence spectrum. (C)2012 Optical Society of America

A novel microdeletion syndrome at 3q13.31 characterised by developmental delay, postnatal overgrowth, hypoplastic male genitals, and characteristic facial features

Background Congenital deletions affecting 3q11q23 have rarely been reported and only five cases have been molecularly characterised. Genotype. phenotype correlation has been hampered by the variable sizes and breakpoints of the deletions. In this study, 14 novel patients with deletions in 3q11q23 were investigated and compared with 13 previously reported patients. Methods Clinical data were collected from 14 novel patients that had been investigated by high resolution microarray techniques. Molecular investigation and updated clinical information of one cytogenetically previously reported patient were also included. Results The molecular investigation identified deletions in the region 3q12.3q21.3 with different boundaries and variable sizes. The smallest studied deletion was 580 kb, located in 3q13.31. Genotype. phenotype comparison in 24 patients sharing this shortest region of overlapping deletion revealed several common major characteristics including significant developmental delay, muscular hypotonia, a high arched palate, and recognisable facial features including a short philtrum and protruding lips. Abnormal genitalia were found in the majority of males, several having micropenis. Finally, a postnatal growth pattern above the mean was apparent. The 580 kb deleted region includes five RefSeq genes and two of them are strong candidate genes for the developmental delay: DRD3 and ZBTB20. Conclusion A newly recognised 3q13.31 microdeletion syndrome is delineated which is of diagnostic and prognostic value. Furthermore, two genes are suggested to be responsible for the main phenotype.

A new species of Schizotetranychus (Acari, Prostigmata, Tetranychidae) from the Chilean fauna, with a few remarkable morphological features

Schizotetranychus tegophallos sp. nov., from papyrus sedge (Cyperus involucratus Rottb., Cyperaceae) from Santiago, Chile, is described and figured. The genital stylets of the male, palpal tarsus tactile setae and chaetotaxy of leg IV trochanter in deutonymphs are discussed.

Sulcus anatomy and diameter in pseudophakic eyes and correlation with biometric data: Evaluation with a 50 MHz ultrasound biomicroscope

PURPOSE: To evaluate the sulcus anatomy and possible correlations between sulcus diameter and white-to-white (WTW) diameter in pseudophakic eyes, data that may be important in the stability of add-on intraocular lenses (IOLs). SETTING: University Eye Hospital, Tuebingen, Germany. DESIGN: Case series. METHODS: In pseudophakic eyes, the axial length (AL) and horizontal WTW were measured by the IOLMaster device. Cross-sectional images were obtained with a 50 MHz ultrasound biomicroscope on the 4 meridians: vertical, horizontal (180 degrees), temporal oblique, and nasal oblique. Sulcus-to-sulcus (STS), angle-to-angle (ATA), and sclera-to-sclera (ScTSc) diameters were measured. The IOL optic diameter (6.0 mm) served as a control. To test reliability, optic measurements were repeated 5 times in a subset of eyes. RESULTS: The vertical ATA and STS diameters were statistically significantly larger than the horizontal diameter (P=.0328 and P=.0216, respectively). There was no statistically significant difference in ScTSc diameters. A weak correlation was found between WTW and horizontal ATA (r = 0.5766, P<.0001) and between WTW and horizontal STS (r = 0.5040, P=.0002). No correlation was found between WTW and horizontal ScTSc (r = 0.2217, P=.1217). CONCLUSIONS: The sulcus anatomy had a vertical oval shape with the vertical meridian being the largest, but it also had variation in the direction of the largest meridian. The WTW measurements showed a weak correlation with STS. In pseudophakic eyes, Soemmerring ring or a bulky haptic may affect the ciliary sulcus anatomy.

Xylella fastidiosa comparative genomic database is an information resource to explore the annotation, genomic features, and biology of different strains

The Xylella fastidiosa comparative genomic database is a scientific resource with the aim to provide a user-friendly interface for accessing high-quality manually curated genomic annotation and comparative sequence analysis, as well as for identifying and mapping prophage-like elements, a marked feature of Xylella genomes. Here we describe a database and tools for exploring the biology of this important plant pathogen. The hallmarks of this database are the high quality genomic annotation, the functional and comparative genomic analysis and the identification and mapping of prophage-like elements. It is available from web site http://www.xylella.lncc.br.

Genetic features and molecular epidemiology of Enterococcus faecium isolated in two university hospitals in Brazil

The global emergence of vancomycin-resistant Enterococcus faecium (VREfm) has been characterized by a clonal spread of strains belonging to clonal complex 17 (CC17). Genetic features and clonal relationships of 53 VREfm isolated from patients in 2 hospitals in Ribeirao Preto, Sao Paulo, Brazil, during 2005-2010 were determined as a contribution to the Brazilian evolutionary history of these nosocomial pathogens. All isolates were daptomycin susceptible, vancomycin-resistant, and had the vanA gene. The predominant virulence genes were acm and esp. Only 5 VREfm isolated in 2005-2006 had intact Tn1546, while 81% showed Tn1546 with deleted left extremity and insertion of IS1251 between the vanS and vanH genes. Multilocus sequence typing analysis permitted the identification of 9 different sequence types (STs), with 5 being new ones (656, 657, 658, 659, and 660). Predominant STs were ST412 and ST478, all belonging to CC17, except ST658. This is the first report of the ST78 in Brazil. (c) 2012 Elsevier Inc. All rights reserved.

Sequence features responsible for intron retention in human

Abstract Background One of the least common types of alternative splicing is the complete retention of an intron in a mature transcript. Intron retention (IR) is believed to be the result of intron, rather than exon, definition associated with failure of the recognition of weak splice sites flanking short introns. Although studies on individual retained introns have been published, few systematic surveys of large amounts of data have been conducted on the mechanisms that lead to IR. Results TTo understand how sequence features are associated with or control IR, and to produce a generalized model that could reveal previously unknown signals that regulate this type of alternative splicing, we partitioned intron retention events observed in human cDNAs into two groups based on the relative abundance of both isoforms and compared relevant features. We found that a higher frequency of IR in human is associated with individual introns that have weaker splice sites, genes with shorter intron lengths, higher expression levels and lower density of both a set of exon splicing silencers (ESSs) and the intronic splicing enhancer GGG. Both groups of retained introns presented events conserved in mouse, in which the retained introns were also short and presented weaker splice sites. Conclusion Although our results confirmed that weaker splice sites are associated with IR, they showed that this feature alone cannot explain a non-negligible fraction of events. Our analysis suggests that cis-regulatory elements are likely to play a crucial role in regulating IR and also reveals previously unknown features that seem to influence its occurrence. These results highlight the importance of considering the interplay among these features in the regulation of the relative frequency of IR.

Structural features beneath neuronal avalanches

The authors thank support from CAPES, FAPESP and USP.

Immunohistochemical features of a papillary squamous cell carcinoma of the endometrium with transitional cell differentiation

An 84-year-old woman underwent hysterectomy due to a friable endometrial mass infiltrating almost half way through the myometrial wall. The tumor consisted of papillary structures with thin fibrovascular cores covered by several layers of pleomorphic cells. The deeply located neoplastic cells were ovoid with a pale eosinophilic cytoplasm resembling urothelial cells. A diagnosis of papillary squamous cell carcinoma of the endometrium with transitional cell differentiation was made. Although she recovered well after surgery, she died one year later because of disseminated disease. In an attempt to obtain new insights into the physiopathology of this very rare tumor, an immunohistochemical panel with 32 markers was performed. The neoplastic cells were positive for cytokeratin 5, vimentin, p63, p21, VEGF, Ki67, BAG1, and bcl-2. The expression of BAG-1 and bcl-2 may suggest that anti-apoptotic stimuli are preponderant in this neoplasm.

“Features of two proteins of Leptospira interrogans with potential role in host-pathogen interactions”

Abstract Background Leptospirosis is considered a re-emerging infectious disease caused by pathogenic spirochaetes of the genus Leptospira. Pathogenic leptospires have the ability to survive and disseminate to multiple organs after penetrating the host. Leptospires were shown to express surface proteins that interact with the extracellular matrix (ECM) and to plasminogen (PLG). This study examined the interaction of two putative leptospiral proteins with laminin, collagen Type I, collagen Type IV, cellular fibronectin, plasma fibronectin, PLG, factor H and C4bp. Results We show that two leptospiral proteins encoded by LIC11834 and LIC12253 genes interact with laminin in a dose - dependent and saturable mode, with dissociation equilibrium constants (KD) of 367.5 and 415.4 nM, respectively. These proteins were named Lsa33 and Lsa25 (Leptospiral surface adhesin) for LIC11834 and LIC12253, respectively. Metaperiodate - treated laminin reduced Lsa25 - laminin interaction, suggesting that sugar moieties of this ligand participate in this interaction. The Lsa33 is also PLG - binding receptor, with a KD of 23.53 nM, capable of generating plasmin in the presence of an activator. Although in a weak manner, both proteins interact with C4bp, a regulator of complement classical route. In silico analysis together with proteinase K and immunoflorescence data suggest that these proteins might be surface exposed. Moreover, the recombinant proteins partially inhibited leptospiral adherence to immobilized laminin and PLG. Conclusions We believe that these multifunctional proteins have the potential to participate in the interaction of leptospires to hosts by mediating adhesion and by helping the bacteria to escape the immune system and to overcome tissue barriers. To our knowledge, Lsa33 is the first leptospiral protein described to date with the capability of binding laminin, PLG and C4bp in vitro.

The imaging and pathological features of a mucinous tubular and spindle cell carcinoma of the kidney: a case report

A mucinous tubular and spindle cell carcinoma (MTSCC) is a rare and recently described kidney neoplasm with distal nephron differentiation. It can affect patients of all ages and is more prevalent among women. In this case report, we present a 50-year-old woman who had a renal mass, which was accidently discovered during an investigation for chronic anemia. The final diagnosis of MTSCC was made after the lesion was removed and a pathology work-up was performed. The clinical, pathological and imaging findings of this rare neoplasm are described in this report.