Two highly homologous ribonuclease genes expressed in mouse eosinophils identify a larger subgroup of the mammalian ribonuclease superfamily.

Two putative ribonucleases have been isolated from the secondary granules of mouse eosinophils. Degenerate oligonucleotide primers inferred from peptide sequence data were used in reverse transcriptase-PCR reactions of bone marrow-derived cDNA. The resulting PCR product was used to screen a C57BL/6J bone marrow cDNA library, and comparisons of representative clones showed that these genes and encoded proteins are highly homologous (96% identity at the nucleotide level; 92/94% identical/similar at the amino acid level). The mouse proteins are only weakly homologous (approximately 50% amino acid identity) with the human eosinophil-associated ribonucleases (i.e., eosinophil-derived neurotoxin and eosinophil cationic protein) and show no sequence bias toward either human protein. Phylogenetic analyses established that the human and mouse loci shared an ancestral gene, but that independent duplication events have occurred since the divergence of primates and rodents. The duplication event generating the mouse genes was estimated to have occurred < 5 x 10(6) years ago (versus 30 to 40 x 10(6) years ago in primates). The identification of independent duplication events in two extant mammalian orders suggests a selective advantage to having multiple eosinophil granule ribonucleases. Southern blot analyses in the mouse demonstrated the existence of three additional highly homologous genes (i.e., five genes total) as well as several more divergent family members. The potential significance of this observation is the implication of a larger gene subfamily in primates (i.e., humans).

Efficacy and safety of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis homozygous for Phe508del CFTR by pulmonary function subgroup

Background Lumacaftor/ivacaftor combination therapy demonstrated clinical benefits inpatients with cystic fibrosis homozygous for the Phe508del CFTR mutation.Pretreatment lung function is a confounding factor that potentially impacts the efficacyand safety of lumacaftor/ivacaftor therapy. Methods Two multinational, randomised, double-blind, placebo-controlled, parallelgroupPhase 3 studies randomised patients to receive placebo or lumacaftor (600 mgonce daily [qd] or 400 mg every 12 hours [q12h]) in combination with ivacaftor (250 mgq12h) for 24 weeks. Prespecified analyses of pooled efficacy and safety data by lungfunction, as measured by percent predicted forced expiratory volume in 1 second(ppFEV1), were performed for patients with baseline ppFEV1 <40 (n=81) and ≥40(n=1016) and screening ppFEV1 <70 (n=730) and ≥70 (n=342). These studies wereregistered with ClinicalTrials.gov (NCT01807923 and NCT01807949). Findings The studies were conducted from April 2013 through April 2014.Improvements in the primary endpoint, absolute change from baseline at week 24 inppFEV1, were observed with both lumacaftor/ivacaftor doses in the subgroup withbaseline ppFEV1 <40 (least-squares mean difference versus placebo was 3∙7 and 3.3percentage points for lumacaftor 600 mg qd/ivacaftor 250 mg q12h and lumacaftor 400mg q12h/ivacaftor 250 mg q12h, respectively [p<0∙05] and in the subgroup with baselineppFEV1 ≥40 (3∙3 and 2∙8 percentage points, respectively [p<0∙001]). Similar absoluteimprovements versus placebo in ppFEV1 were observed in subgroups with screening 4ppFEV1 <70 (3∙3 and 3∙3 percentage points for lumacaftor 600 mg qd/ivacaftor 250 mgq12h and lumacaftor 400 mg q12h/ivacaftor 250 mg q12h, respectively [p<0∙001]) and≥70 (3∙3 and 1∙9 percentage points, respectively [p=0.002] and [p=0∙079]). Increases inBMI and reduction in number of pulmonary exacerbation events were observed in bothLUM/IVA dose groups vs placebo across all lung function subgroups. Treatment wasgenerally well tolerated, although the incidence of some respiratory adverse events washigher with active treatment than with placebo. Interpretation Lumacaftor/ivacaftor combination therapy benefits patients homozygousfor Phe508del CFTR who have varying degrees of lung function impairment. Funding Vertex Pharmaceuticals Incorporated.

Effect of telmisartan on functional outcome, recurrence, and blood pressure in patients with acute mild ischemic stroke: a PRoFESS subgroup analysis

Background and Purpose—High blood pressure (BP) is common in acute ischemic stroke and associated independently with a poor functional outcome. However, the management of BP acutely remains unclear because no large trials have been completed. Methods—The factorial PRoFESS secondary stroke prevention trial assessed BP-lowering and antiplatelet strategies in 20 332 patients; 1360 were enrolled within 72 hours of ischemic stroke, with telmisartan (angiotensin receptor antagonist, 80 mg/d, n647) vs placebo (n713). For this nonprespecified subgroup analysis, the primary outcome was functional outcome at 30 days; secondary outcomes included death, recurrence, and hemodynamic measures at up to 90 days. Analyses were adjusted for baseline prognostic variables and antiplatelet assignment. Results—Patients were representative of the whole trial (age 67 years, male 65%, baseline BP 147/84 mm Hg, small artery disease 60%, NIHSS 3) and baseline variables were similar between treatment groups. The mean time from stroke to recruitment was 58 hours. Combined death or dependency (modified Rankin scale: OR, 1.03; 95% CI, 0.84–1.26; P0.81; death: OR, 1.05; 95% CI, 0.27–4.04; and stroke recurrence: OR, 1.40; 95% CI, 0.68–2.89; P0.36) did not differ between the treatment groups. In comparison with placebo, telmisartan lowered BP (141/82 vs 135/78 mmHg, difference 6 to 7 mmHg and 2 to 4 mmHg; P0.001), pulse pressure (3 to 4 mmHg; P0.002), and rate-pressure product (466 mmHg.bpm; P0.0004). Conclusion—Treatment with telmisartan in 1360 patients with acute mild ischemic stroke and mildly elevated BP appeared to be safe with no excess in adverse events, was not associated with a significant effect on functional dependency, death, or recurrence, and modestly lowered BP.

Photoelastic And Finite Element Analyses Of Occlusal Loads In Mandibular Body.

This study proposed to evaluate the mandibular biomechanics in the posterior dentition based on experimental and computational analyses. The analyses were performed on a model of human mandible, which was modeled by epoxy resin for photoelastic analysis and by computer-aided design for finite element analysis. To standardize the evaluation, specific areas were determined at the lateral surface of mandibular body. The photoelastic analysis was configured through a vertical load on the first upper molar and fixed support at the ramus of mandible. The same configuration was used in the computer simulation. Force magnitudes of 50, 100, 150, and 200 N were applied to evaluate the bone stress. The stress results presented similar distribution in both analyses, with the more intense stress being at retromolar area and oblique line and alveolar process at molar level. This study presented the similarity of results in the experimental and computational analyses and, thus, showed the high importance of morphology biomechanical characterization at posterior dentition.

Chemical And Structural Analyses Of Titanium Plates Retrieved From Patients.

The aim of this study was to evaluate the microscopic structure and chemical composition of titanium bone plates and screws retrieved from patients with a clinical indication and to relate the results to the clinical conditions associated with the removal of these devices. Osteosynthesis plates and screws retrieved from 30 patients between January 2010 and September 2013 were studied by metallographic, gas, and energy dispersive X-ray (EDX) analyses and the medical records of these patients were reviewed. Forty-eight plates and 238 screws were retrieved. The time elapsed between plate and screw insertion and removal ranged between 11 days and 10 years. Metallographic analysis revealed that all the plates were manufactured from commercially pure titanium (CP-Ti). The screw samples analyzed consisted of Ti-6Al-4V alloy, except four samples, which consisted of CP-Ti. Titanium plates studied by EDX analysis presented greater than 99.7% titanium by mass. On gas analysis of Ti-6Al-4V screws, three samples were outside the standard values. One CP-Ti screw sample and one plate sample also presented an oxygen analysis value above the standard. The results indicated that the physical properties and chemical compositions of the plates and screws did not correspond with the need to remove these devices or the time of retention.

Comparative Study Of Transgenic And Non-transgenic Maize (zea Mays) Flours Commercialized In Brazil, Focussing On Proteomic Analyses.

Genetically modified foods are a major concern around the world due to the lack of information concerning their safety and health effects. This work evaluates differences, at the proteomic level, between two types of crop samples: transgenic (MON810 event with the Cry1Ab gene, which confers resistance to insects) and non-transgenic maize flour commercialized in Brazil. The 2-D DIGE technique revealed 99 differentially expressed spots, which were collected in 2-D PAGE gels and identified via mass spectrometry (nESI-QTOF MS/MS). The abundance of protein differences between the transgenic and non-transgenic samples could arise from genetic modification or as a result of an environmental influence pertaining to the commercial sample. The major functional category of proteins identified was related to disease/defense and, although differences were observed between samples, no toxins or allergenic proteins were found.

Micromorphological and hardness analyses of human and bovine sclerotic dentin: a comparative study

The purpose of this study was to test the hypothesis that both human and bovine sclerotic dentin have similar hardness properties, in addition to similar micromorphological characteristics. Sixteen teeth (8 human and 8 bovine) exhibiting exposed dentin in the incisal edge and showing characteristics typical of sclerosis were used. Vickers surface microhardness testing was conducted. Three areas of the dentin surface of each specimen were selected. All teeth were processed for scanning electron microscopy in order to estimate the amount (in percentage) of solid dentin on the sclerotic dentin surface. The data were compared by Student's t test (α = 0.05). The micromorphological and microhardness data were compared by Pearson's linear correlation test (α = 0.05). The mean percentages of solid dentin of human and bovine sclerotic dentin were similar (human 90.71 ± 0.83 and bovine 89.08 ± 0.81, p = 0.18). The mean microhardness value (VHN) of human sclerotic dentin was significantly higher than that of bovine sclerotic dentin (human 45.26 ± 2.92 and bovine 29.93 ± 3.83, p = 0.006). No correlation was found between the microhardness values and the amount of solid dentin in the sclerotic dentin, irrespective of the species considered (human R² = 0.0240, p = 0.714; bovine R² = 0.0017, p = 0.923; and combined R² = 0.038, p = 0.46). We concluded that although both bovine and human sclerotic dentin present a similar amount of solid tissue, human sclerotic dentin presents higher microhardness than bovine sclerotic dentin.

Phylogenetic analyses of Cladophora vagabunda (L.) C. Hoek (Cladophorales, Chlorophyta) from Brazil based on SSU rDNA sequences

The complete SSU rDNA was sequenced for 10 individuals of Cladophora vagabunda collected along the coast of Brazil. For C. rupestris (L.) Kütz. a partial SSU rDNA sequence (1634 bp) was obtained. Phylogenetic trees indicate that Cladophora is paraphyletic, but the section Glomeratae sensu lato including C. vagabunda from Brazil, Japan and France, C. albida (Nees) Kütz., C. sericea (Hudson) Kütz., and C. glomerata (L.) Kütz. is monophyletic. Within this group C. vagabunda is paraphyletic. The sequence identity for the SSU rDNA varied from 98.9% to 100% for the Brazilian C. vagabunda, and from 98.3% to 99.7% comparing the Brazilian individuals to the ones from France and Japan. Sequence identity of the Brazilian C. vagabunda to C. albida and C. sericea vary from 98.0% to 98.6%. The SSU rDNA phylogeny support partially the morphological characteristics presented by Brazilian populations of C. vagabunda. On the other hand, C. rupestris from Brazil does not group with C. rupestris from France, both sequences presenting only 96.9% of identity. The inclusion of sequences of individuals from Brazil reinforces the need of taxonomical revision for the genus Cladophora and for the complex C. vagabunda.

Karyotypic analyses and morphological comments on the endemic and endangered Brazilian painted tree rat Callistomys pictus (Rodentia, Echimyidae)

The genus Callistomys belongs to the rodent family Echimyidae, subfamily Echimyinae, and its only living representative is Callistomys pictus, a rare and vulnerable endemic species of the state of Bahia, Brazil. Callistomys has been previously classified as Nelomys, Loncheres, Isothrix and Echimys. In this paper we present the karyotype of Callistomys pictus, including CBG and GTG-banding patterns and silver staining of the nucleolus organizer regions (Ag-NORs). Comments on Callistomys pictus morphological traits and a compilation of Echimyinae chromosomal data are also included. Our analyses revealed that Callistomys can be recognized both by its distintinctive morphology and by its karyotype.

Envelhecimento e deficiência auditiva referida: um estudo de base populacional

O objetivo do estudo foi estimar a prevalência da deficiência auditiva referida por idosos do Município de São Paulo, Brasil, segundo características sociodemográficas e descrever características atribuídas a esta deficiência. Os dados são provenientes do Inquérito de Saúde do Município de São Paulo (ISA-Capital/2003), com análise do subgrupo dos idosos (n = 872). Realizaram-se o teste do χ2 e a análise de regressão de Poisson. A prevalência da deficiência auditiva referida pelos idosos foi 11,2% e foi maior entre os homens (RP = 1,86; IC95%: 1,19-2,92). Observou-se grande desconhecimento dos idosos quanto às causas da deficiência auditiva referida (42,5%), 25,5% relataram ter dificuldades em atividades de lazer, 11,4% necessitavam de ajuda para atividades cotidianas e 63,3% relataram não necessitar de assistência em decorrência deste déficit. A alta prevalência de deficiência auditiva referida pelos idosos, principalmente do sexo masculino, remete à relevância deste problema para a saúde pública, já que o envelhecimento populacional é uma realidade nova e vem acompanhada de exigências ainda desconhecidas por profissionais e pelo poder público.

The C242T polymorphism of the p22-phox gene (CYBA) is associated with higher left ventricular mass in Brazilian hypertensive patients

Background: Reactive oxygen species have been implicated in the physiopathogenesis of hypertensive end-organ damage. This study investigated the impact of the C242T polymorphism of the p22-phox gene (CYBA) on left ventricular structure in Brazilian hypertensive subjects. Methods: We cross-sectionally evaluated 561 patients from 2 independent centers [Campinas (n = 441) and Vitoria (n = 120)] by clinical history, physical examination, anthropometry, analysis of metabolic and echocardiography parameters as well as p22-phox C242T polymorphism genotyping. In addition, NADPH-oxidase activity was quantified in peripheral mononuclear cells from a subgroup of Campinas sample. Results: Genotype frequencies in both samples were consistent with the Hardy-Weinberg equilibrium. Subjects with the T allele presented higher left ventricular mass/height(2.7) than those carrying the CC genotype in Campinas (76.8 +/- 1.6 vs 70.9 +/- 1.4 g/m(2.7); p = 0.009), and in Vitoria (45.6 +/- 1.9 vs 39.9 +/- 1.4 g/m(2.7); p = 0.023) samples. These results were confirmed by stepwise regression analyses adjusted for age, gender, blood pressure, metabolic variables and use of anti-hypertensive medications. In addition, increased NADPH-oxidase activity was detected in peripheral mononuclear cells from T allele carriers compared with CC genotype carriers (p = 0.03). Conclusions: The T allele of the p22-phox C242T polymorphism is associated with higher left ventricular mass/height(2.7) and increased NADPH-oxidase activity in Brazilian hypertensive patients. These data suggest that genetic variation within NADPH-oxidase components may modulate left ventricular remodeling in subjects with systemic hypertension.

Molecular and geographic analyses of vampire bat-transmitted cattle rabies in central Brazil

Background: Vampire bats are important rabies virus vectors, causing critical problems in both the livestock industry and public health sector in Latin America. In order to assess the epidemiological characteristics of vampire bat-transmitted rabies, the authors conducted phylogenetic and geographical analyses using sequence data of a large number of cattle rabies isolates collected from a wide geographical area in Brazil. Methods: Partial nucleoprotein genes of rabies viruses isolated from 666 cattle and 18 vampire bats between 1987 and 2006 were sequenced and used for phylogenetic analysis. The genetic variants were plotted on topographical maps of Brazil. Results: In this study, 593 samples consisting of 24 genetic variants were analyzed. Regional localization of variants was observed, with the distribution of several variants found to be delimited by mountain ranges which served as geographic boundaries. The geographical distributions of vampire-bat and cattle isolates that were classified as the identical phylogenetic group were found to overlap with high certainty. Most of the samples analyzed in this study were isolated from adjacent areas linked by rivers. Conclusion: This study revealed the existence of several dozen regional variants associated with vampire bats in Brazil, with the distribution patterns of these variants found to be affected by mountain ranges and rivers. These results suggest that epidemiological characteristics of vampire bat-related rabies appear to be associated with the topographical and geographical characteristics of areas where cattle are maintained, and the factors affecting vampire bat ecology.

Chemical analyses confirm a rare case of seed dispersal by bees

It has been suggested that dispersal of seeds of Coussapoa asperifolia magnifolia could have endozoochoric dispersal by frugivorous birds and monkeys because the fruits are red when ripe, or exozoochoric dispersal, because the exocarp is mucilaginous and sticky. However, our field observations showed only stingless bees collecting the exocarp with seeds of C. asperifolia magnifolia, which are used for building and repairing their nests, from which the plants sprout. This paper aimed to determine the fruit chemical composition, since we postulated that C. asperifolia magnifolia is neither consumed by birds nor monkeys due to being very sticky and apparently resinous. Apolar extract analyses revealed the fruits are not resinous but extremely rich in waxes ( mainly esterified triglycerides), and polar extract analyses revealed the sugar content to be close to the sensorial minimum level. This probably accounts for why only stingless bees are seen visiting fruits and dispersing seeds.

Facies, delta(13)C, delta(15)N and C/N analyses in a late Quaternary compound estuarine fill, northern Brazil and relation to sea level

The present work integrates sedimentary facies, (14)C dating, delta(13)C, delta(15)N, and C/N with geologic and geomorphologic data available from literature. The aim was to characterize the depositional settings of a late Quaternary estuary in northeastern Marajo Island and analyze its evolution within the context of relative sea level fluctuations. The data derive from four continuous cores along a proximal-to-distal transect of a paleoestuary, previously recognized using remote sensing information. Fifteen sediment samples recorded ages ranging from 42,580 +/- 1430 to 3184 +/- 37 (14)C yr B.P. Fades analysis indicated fine- to coarse-grained sands with parallel lamination or cross stratification, massive or laminated muds and heterolithic deposits. delta(13)C (-28.1 parts per thousand to -19.7 parts per thousand, mean = -23.0 parts per thousand), delta(15)N (+ 14.8 parts per thousand to + 4.7 parts per thousand, mean = + 9.2 parts per thousand) and C/N (14.5 to 1.5, mean = 7.9) indicate mostly marine and freshwater phytoplankton sources for the organic matter. The results confirm a large late Quaternary paleoestuary in northeastern Marajo Island. The distribution of delta(13)C, delta(15)N, and C/N, together with fades associations, led to identify depositional settings related to fluvial channel, floodplain, tidal channel/tidal flat, central basin, tidal delta, and tidal inlet/sand barrier. These deposits are consistent with a wave-dominated estuary. Variations in stratigraphy and geochemistry are controlled by changes in relative sea level, revealing a main transgression from an undetermined time around 42,000 (14)C yr B.P. and 29,340 (+/- 200) (14)C yr B.P., which is synchronous to the overall drop in sea level after the last interglacial. Following this period, and probably until 9110 +/- 37 (14)C yr B.P., i.e., during a time interval encompassing two glacial episodes including the Last Glacial and the Younger Dryas, there was a pronounced drop in sea level, recorded by the development of a major erosional discontinuity due to valley re-incision. Sea level rose again until 5464 +/- 40 (14)C yr B.P, just before the main worldwide mid-Holocene transgressive peak. Mid to late Holocene coastal progradation ended the Marajo paleoestuarine history, and promoted the establishment of continental conditions throughout the island. The divergence comparing the Marajo sea level behavior with the eustatic curve allows hypothesizing that post-rifting tectonics along the Brazilian Equatorial margin influenced the sedimentary evolution of the studied paleoestuary. Considering that sedimentary facies in estuarine settings are highly variable both laterally and vertically, the present integration of facies with isotope and elemental analyses was crucial to provide a more precise interpretation of the Late Pleistocene and Holocene Marajo paleoestuary, and analyze its sea level history within the eustatic and tectonic context. (C) 2010 Elsevier B.V. All rights reserved.

Impact of cancer-related symptom synergisms on health-related quality of life and performance status

To identify the impact of multiple symptoms and their co-occurrence on health-related quality of life (HRQOL) dimensions and performance status (PS), 115 outpatients with cancer, who were not receiving active cancer treatment and were recruited from, a university hospital in Sao Paulo, Brazil completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, the Beck Depression Inventory, and the Brief Pain Inventory. Karnofsky Performance Status scores also were completed. Application of TwoStep Cluster analysis resulted in two distinct patient subgroups based on 113 patient experiences with pain, depression, fatigue, insomnia, constipation, lack of appetite, dyspnea, nausea, vomiting, and diarrhea. One group had multiple and severe symptom subgroup and another had Less symptoms and with lower severity. Multiple and severe symptoms had worse PS, role functioning, and physical, emotional, cognitive, social, and overall HRQOL. Multiple and severe symptom subgroup was also six times as likely as lower severity to have poor role functioning;five times more likely to have poor emotional;four times more likely to have poor PS, physical, and overall HRQOL, and three times as likely to have poor cognitive and social HRQOL, independent of gender, age, level of education, and economic condition. Classification and Regression Tree analyses were undertaken to identify which co-occurring symptoms would best determine reduction in HRQOL and PS. Pain and fatigue were identified as indicators of reduction on physical HRQOL and PS. Fatigue and insomnia were associated with reduction in cognitive; depression and pain in social; and fatigue and constipation in role functioning. Only depression was associated with reduction in overall HRQOL. These data demonstrate that there is a synergic effect among distinct cancer symptoms that result in reduction in HRQOL dimensions and PS.