Renin-angiotensin-aldosterone system blockers effect in chronic kidney disease progression in hypertensive elderly patients without proteinuria: PROERCAN trial.

INTRODUCTION: Evidence about nefroprotective effect with RAAS blockers in elderly patients with chronic kidney disease (CKD) without proteinuria is lacking. The primary outcome of our study is to evaluate the impact of RAAS blockers in CKD progression in elderly patients without proteinuria. MATERIALS AND METHODS: Multicenter open-label, randomized controlled clinical trial including patients over 65 year-old with hypertension and CKD stages 3-4 without proteinuria. Patients were randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs and were followed up for three years. Primary outcome is estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcome measures include BP control, renal and cardiovascular events and mortality. RESULTS: 88 patients were included with a mean age of 77.9±6.1 years and a follow up period of 3 years: 40 were randomized to RAAS group and 48 to standard treatment. Ethiology of CKD was: 53 vascular, 16 interstitial and 19 of unknown ethiology. In the RAAS group eGFR slope during follow up was -4.3±1.1ml/min, whereas in the standard treatment group an increase on eGFR was observed after 3 years (+4.6±0.4ml/min), p=0.024. We found no differences in blood pressure control, number of antihypertensive drugs, albuminuria, potassium serum levels, incidence of cardiovascular events nor mortality during the follow up period. CONCLUSIONS: In elderly patients without diabetes nor cardiopathy and with non proteinuric CKD the use of RAAS blockers does not show a reduction in CKD progression. The PROERCAN (PROgresión de Enfermedad Renal Crónica en ANcianos) trial (trial registration: NCT03195023).

Obesity related risk for chronic kidney disease progression and cardiovascular disease after propensity score matching.

INTRODUCTION: Obesity is a major health problem worldwide. It carries a markedly increased risk for multiple diseases such as type 2 diabetes mellitus, hypertension, cardiovascular disease (CVD) and chronic kidney disease (CKD). To complicate an already difficult topic a new subtype of obesity has been defined lately, the metabolically healthy obese. Our study aimed to clarify the association between obesity, metabolic syndrome and kidney disease progression. METHODS: Observational retrospective single centre study including 212 patients with stage 3-4 CKD with no previous history of rapid kidney disease progression. Patients were divided according to BMI status and presence of metabolic syndrome. Anthropometric, clinical and laboratory data were collected to follow-up. Propensity score matching was performed for age, albuminuria and baseline renal function. During follow-up renal and cardiovascular events were recorded. RESULTS: After a mean follow-up of 88.44±36.07 months a total of 18 patients reached the renal outcome in the non-obese group and 21 in the obese group. Differences were not statistically significant (log rank=0.21: p=0.64). Multiple Cox regression analysis showed that obesity was not predictor for worse renal outcomes [HR 1.01, 95% CI 0.45-2.24; p=0.97]. When stratifying the sample according to baseline metabolic syndrome and obesity presence there was no difference in renal survival (log rank=0.852; p=0.35) A total of 48 cardiovascular events were registered: seventeen in the non-obese group and thirty-one in the obese group. Differences in event-free time between both groups were statistically significant (log rank=4.44;p=0.035), especially after four years of follow-up. After stratifying for MS and obesity presence at baseline the event-free time differences where again statistically significant (log rank=16.86;p=0.001), specially for the obese patients with metabolic syndrome. CONCLUSIONS: Obesity has little impact on chronic kidney disease progression despite the presence or absence of metabolic syndrome in a cohort matched for age, baseline renal function and albuminuria. Obesity conferred greater cardiovascular risk when combined with metabolic syndrome.

Life cycle assessment of roads: Exploring research trends and harmonization challenges.

The transparency, heterogeneity and hypotheses considered in the calculation of the environmental impacts of roads are still barriers to the identification of low-carbon solutions. To overcome this problem, this study presents an analysis of 94 papers obtained in a systematic literature review of the Scopus, Science Direct, Mendeley, Springer Link, and Web of Science databases. From a total of 417 road case studies, only 18% were found to be fully transparent, reproducible, and likely to present reliable results. The road design parameters of the speed limit were provided in 11% of the cases, and the average annual daily traffic data were provided in 42%. Limited data were found for the dimensions of road elements such as the number (77%) and width of lanes (33%), shoulders (15%), footpaths (5%), berms (1%) and foreslope (4%). The source of the life cycle inventory was presented in 57% of the case studies, impact assessment method was indicated in 22%, and the software utilized was listed in 50%. A lack of information was noted in the description of the types of materials employed in road projects. In addition, the large heterogeneity in the definitions of the functional unit, system boundary and in the reference study period of repair, replacement, rehabilitation or end-of-life for both flexible and rigid pavement does not support the identification of the most environmentally friendly solutions. Based on the results of the analysis, several recommendations for design parameters and life cycle assessment aspects are proposed to support a harmonized calculation of the environmental impacts of road projects.

The effect of renin-angiotensin-aldosterone system blockers on the progression of chronic kidney disease in hypertensive elderly patients without proteinuria: PROERCAN study. Rationale and design.

INTRODUCTION: Blood pressure (BP) control is fundamental to the care of patients with chronic kidney disease (CKD), and is relevant at all stages of CKD. Renin-angiotensin-aldosterone system (RAAS) blockers have shown to be effective, not only in BP control but also in reducing proteinuria and slowing CKD progression. However, there is a lack of evidence for recommending RAAS blockers in elderly patients with CKD without proteinuria. The primary outcome of the present study is to evaluate the impact of RAAS blockers on CKD progression in elderly patients without proteinuria. MATERIALS AND METHODS: The PROERCAN trial (trial registration, NCT03195023) is a multicentre open-label, randomized controlled clinical trial with 110 participants over 65 years-old with hypertension and CKD stages 3-4 without proteinuria. Patients will be randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs, and will be followed up for three years. Primary outcome is the estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcomes include BP control, renal and cardiovascular events, and mortality. RESULTS AND CONCLUSIONS: The design of this trial is presented here. The results will show if antihypertensive treatment with RAAS blockers has an impact on CKD progression in elderly patients without proteinuria. Any differences in BP control, cardiovascular events, and mortality with each antihypertensive treatment will be also clarified.

Accelerated bone formation by biphasic calcium phosphate with a novel sub-micron surface topography.

Osteoinductive calcium phosphate (CaP) bone grafts have equivalent performance to autografts in repairing critical-size bone defects. The osteoinductive potential of CaP is linked to the size of the surface topographical features. In the present study, two novel biphasic calcium phosphate (BCP) bone grafts were synthesised with either sub-micron- (BCP<µm) or micron-scale (BCPµm) needle-shaped surface topography and compared to dimensionally similar tricalcium phosphate (TCP) with grain-shaped surface structures (TCP<µm and TCPµm). To clarify the possible function of the surface morphology (needle-like vs. grain-like) in initiating bone formation, the four CaP test materials were physicochemically characterised and implanted for 12 weeks in the dorsal muscle of beagles. The sub-micron needle-shaped topography of BCP<µm triggered earlier bone formation (3-6 weeks) as compared to the grain-shaped surface topography of TCP<µm, which formed bone at 6-9 weeks. After 12 weeks, the amount of induced bone formation in both materials was equivalent, based on histomorphometry. The micron-sized needle-shaped surface topography of BCPµm led to limited formation of new bone tissue, whereas its counterpart, TCPµm with grain-shaped surface topography, failed to trigger de novo bone formation. The relative strength of the parameters affecting CaP-driven bone induction was as follows: surface feature size > surface feature morphology > substrate chemistry. BCP materials with needle-shaped sub-micron surface topography gave rise to accelerated bone formation and slower rate of resorption than a comparable TCP. These characteristics may be translated to improve bone healing in orthotopic defects.

Whole genome sequence and phenotypic characterization of a Cbm+ serotype e strain of Streptococcus mutans.

We report the whole genome sequence of the serotype e Cbm+ strain LAR01 of Streptococcus mutans, a dental pathogen frequently associated with extra-oral infections. The LAR01 genome is a single circular chromosome of 2.1 Mb with a GC content of 36.96%. The genome contains 15 phosphotransferase system gene clusters, seven cell wall-anchored (LPxTG) proteins, all genes required for the development of natural competence and genes coding for mutacins VI and K8. Interestingly, the cbm gene is genetically linked to a putative type VII secretion system that has been found in Mycobacteria and few other Gram-positive bacteria. When compared with the UA159 type strain, phenotypic characterization of LAR01 revealed increased biofilm formation in the presence of either glucose or sucrose but similar abilities to withstand acid and oxidative stresses. LAR01 was unable to inhibit the growth of Strpetococcus gordonii, which is consistent with the genomic data that indicate absence of mutacins that can kill mitis streptococci. On the other hand, LAR01 effectively inhibited growth of other S. mutans strains, suggesting that it may be specialized to outcompete strains from its own species. In vitro and in vivo studies using mutational and heterologous expression approaches revealed that Cbm is a virulence factor of S. mutans by mediating binding to extracellular matrix proteins and intracellular invasion. Collectively, the whole genome sequence analysis and phenotypic characterization of LAR01 provides new insights on the virulence properties of S. mutans and grants further opportunities to understand the genomic fluidity of this important human pathogen.

Influence of fluoride in poly(d,l-lactide)/apatite composites on bone formation.

The influence of fluoride in poly(d,l-lactide)/apatite composites on ectopic bone formation was evaluated in sheep. Nano-apatite powders with different replacement levels of OH groups by fluoride (F) (0% (F0), 50% (F50), 100% (F100), and excessive (F200)) were co-extruded with poly (d,l-lactide) at a weight ratio of 1:1. Fluoride release from the composites (CF0, CF50, CF100, and CF200) was evaluated in vitro and bone formation was assessed after intramuscular implantation in sheep. After 24 weeks in simulated physiological solution, CF0 and CF50 showed negligible fluoride release, whereas it was considerable from the CF100 and CF200 composites. Histology showed that the incidence of de novo bone formation decreased in implants with increasing fluoride content indicating a negative influence of fluoride on ectopic bone formation. Furthermore, a significant decrease in resorption of the high fluoride-content composites and a reduction in the number of multinucleated giant cells were seen. These results show that instead of promoting, the presence of fluoride in poly(d,l-lactide)/apatite composites seemed to suppresses their resorption and osteoinductive potential in non-osseous sites.

How uncertainty bounds the shape index of simple cells.

We propose a theoretical motivation to quantify actual physiological features, such as the shape index distributions measured by Jones and Palmer in cats and by Ringach in macaque monkeys. We will adopt the uncertainty principle associated to the task of detection of position and orientation as the main tool to provide quantitative bounds on the family of simple cells concretely implemented in primary visual cortex.Mathematics Subject Classification (2000)2010: 62P10, 43A32, 81R15.

Toxic effects of glibenclamide in fetuses of normoglycemic rats: an alternative therapy for gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is defined as glucose intolerance first diagnosed during the second or third trimester of pregnancy. The treatment aims at glycemic control through changes in the patient's diet with or without exercise, but some patients need insulin therapy. An alternative would be to use oral hypoglycemic agents such as glibenclamide (GLIB). The present study aims to analyze the toxic effects of GLIB in fetuses of pregnant rats which received 5 or 20mg/kg doses of GLIB. Glycemic dosage reveals no significant difference between control (deionized water) and treated groups, showing that these concentrations of GLIB were not effective to cause hypoglycemia in rats. The vitality of the fetuses in all groups was 100%. GLIB administration promoted increase in weight and significant changes in measures of external morphological parameters of treated fetuses. Histological analysis revealed that liver lobes, lobules and central lobular veins were well defined for all treatments. However, GLIB animals presented a light brownish precipitate into the center-lobular veins and in the liver parenchyma among the hepatocytes. These results indicated a possible passage of the drug through the blood-placental membrane, without serious changes that impair the development of neither bone tissue, nor the liver of these animals.

Primary cutaneous cryptococcosis in Brazil: report of 11 cases in immunocompetent and immunosuppressed patients.

BACKGROUND: Primary cutaneous cryptococcosis is an uncommon infectious disease caused by Cryptococcus neoformans or Cryptococcus gattii affecting immunosuppressed as well as immunocompetent patients. It is often misdiagnosed as it may mimic other cutaneous diseases. MATERIALS AND METHODS: We report a series of cases diagnosed from 2005 to 2010 in two general hospitals. The diagnosis in all patients was made on the basis of histopathology and culture. Phenoloxidase and canavanine-glycine-bromothymol blue tests were used in order to identify the Cryptococcus species. Systematic investigation ruled out the systemic involvement in every case. RESULTS: Eleven patients, 81.8% male, were diagnosed during this study. The immunosuppression status was identified in 54.5% of patients, and all of them were under corticosteroid therapy due to a variable set of diseases. All patients presented with circumscribed lesions on their upper limbs. Most lesions showed an infiltrative or tumoral aspect with up to 40 cm diameter. Fluconazole, up to 400 mg/daily, was the main therapeutic regimen and proved to be efficient. CONCLUSIONS: Primary cutaneous cryptococcosis has been diagnosed in both immunosuppressed and immunocompetent patients. Its peculiar clinical aspect could facilitate early diagnosis. Culture and biochemical tests should be performed in order to define the species involved.

Psychosocial indicators among aircraft maintenance workers with and without neck and shoulder musculoskeletal symptoms.

In the aircraft maintenance industry, most of workers performs manual handling tasks of different materials, varying from small objects up to large pieces of the aircraft. It can increase the occurrence of work-related musculoskeletal disorders (WMSDs), which are strongly associated with high physical demands required by the task. Moreover, psychosocial demands are considered as risk factors for musculoskeletal disorders in both the upper limbs and lumbar spine. Thus, the objective of this study was to assess psychosocial indicators among aircraft maintenance workers according to the presence of neck and shoulder musculoskeletal symptoms. Eighty workers of an aircraft maintenance company were evaluated (32.69 ± 8.25 years, 79.8 ± 13.4 kg, 175 ± 7 cm). According to physical examination, 50 workers were classified as asymptomatic (AS - 4.1 ± 3.17 positive signs) whilst 30 workers were classified as symptomatic (SS - 26.72 ± 11.44 positive signs). AS and SS have shown similar profile of demand (p = 0.62), control (p = 0.66) and social support (p = 0.74) according to the Job Content Questionnaire. However, the groups are different when considering work engagement variables. In general, SS have higher scores than AS (p < 0.05).

A benchmark study on 883 nasopharyngeal cancer patients treated in two Italian centres from 1977 to 2000. Part I: Evolving technical choices and survival.

PURPOSE: The authors sought to define treatment results according to the different accrual periods and clinical-therapeutic features in a large series of nasopharyngeal cancer (NPC) patients treated in two Italian centres over more than two decades. MATERIALS AND METHODS: A total of 883 patients consecutively treated with radiotherapy between 1977 and 2000 at the Florence (FLO) and Brescia (IRA) Radiation Oncology centres were studied. Five-year overall (OS) and disease-specific (DSS) actuarial survival rates in the different pathological, clinical and therapeutic subgroups were calculated, along with the actuarial local-regional control (LRC) probability. RESULTS: At univariate analysis, survival and local control rates were significantly better in the more recent accrual periods and in the more favourable disease presentations; treatment-related parameters mainly affect LRC. At multivariate analysis, patient- and disease-related factors had a more evident prognostic effect than did therapeutic factors, although dose to the nasopharynx and treatment technique had a marginally significant impact on DSS and OS. CONCLUSIONS: Results of this benchmark study may be useful for understanding the development of new radio-therapy techniques for NPC, such as three-dimensional conformal radiotherapy (3D-CRT) and particularly intensity-modulated radiotherapy (IMRT).

Análise de crescimento de Bixa orellana L. sob efeito da inoculação micorrízica e adubação fosfatada / Analyses of Bixa orellana L. growth under the effects of mycorrhizal inoculation and phosphate fertilization

Este estudo objetivou avaliar o desenvolvimento de Bixa orellana L. em condições de viveiro sob efeito da inoculação micorrízica e adubação fosfatada. As plantas foram cultivadas em sacos de polietileno com 0,18 X 0,30 m e capacidade de 1,3 kg de substrato. O delineamento experimental utilizado foi inteiramente casualizado com seis tratamentos e trinta repetições. As dosagens de fósforo utilizadas foram 0, 4.200 e 8.400 g m-3 de substrato. O fungo micorrízico arbuscular (FMA) da espécie Glomus clarum, foi utilizado em metade dos tratamentos (com e sem micorrizas) com inoculação de 2 g do fungo. As avaliações ocorreram 30, 60, 90 e 120 dias após a emergência das plântulas. Determinou-se a massa seca de folhas, área foliar, massa seca total, razão de área foliar, área foliar específica, taxa assimilatória líquida, taxa de crescimento relativo e taxa de crescimento absoluto. O fungo micorrízico facilita a absorção de fósforo pelo urucum, atendendo a sua exigência em relação ao nutriente. A dose de fósforo de 4.200 g m-3 em associação com FMA Glomus clarum ou 8.400 g m-3, com ou sem essa associação, são indicadas para o crescimento de plantas de urucum em viveiro, por promoverem adequadas respostas dos índices fisiológicos, contribuindo com seu desenvolvimento.

This study aimed to evaluate the development of Bixa orellana L. under nursery conditions and subjected to the effects of mycorrhizal inoculation and phosphate fertilization. The plants were grown in polyethylene bags with dimensions of 0.18 x 0.30 m and capacity of 1.3 kg substrate. The adopted experimental design was completely randomized with six treatments and thirty replicates. The used phosphorus levels were 0, 4.200 and 8.400 g m-3 substrate. The arbuscular mycorrhizal fungus (AMF) of the species Glomus clarum was used in half of the treatments (with and without mycorrhizae) with inoculation of 2 g of the fungus. Evaluations occurred at 30, 60, 90 and 120 days after the emergence of seedlings. Leaf dry mass, leaf area, total dry mass, leaf area ratio, specific leaf area, net assimilation rate, relative growth rate and absolute growth rate were determined. The mycorrhizal fungus facilitates phosphorus uptake by annatto, fulfilling its requirement for the nutrient. The phosphorus level of 4.200 g m-3 in association with Glomus clarum or 8.400 g m-3, with or without this association, are indicated for annatto plant growth in nurseries since they promote appropriate responses of physiological indexes, contributing to the plant development.

Heterotopic bone formation by nano-apatite containing poly(D,L-lactide) composites.

To render polymeric materials osteoinductive, nano-sized calcium phosphate apatite particles (CaP) were introduced into a low molecular weight poly(D,L-lactide). Homogenous composites were made with 10%, 20% and 40% by weight of apatite content while pure polylactide was used as control. Thereafter porous samples (pore size 300-400 microm, 60% porosity) were fabricated and sterilized. In vitro studies showed that calcium ions were released from the composites depending on the apatite content, while surface mineral deposition was observed only on the 40% CaP composites in simulated body fluid (SBF) within 14 days. After 12 weeks of intramuscular implantation in dogs, only the 40% CaP composite implant retained its shape and showed ectopic bone formation within the pores. In conclusion, adding a content of 40% apatite into poly(D,L-lactide) could lead to an osteoinductive material. Future studies will focus on understanding this phenomenon of material-directed osteoinduction in order to develop a promising bone graft substitute.

A experiencia do Centro de Referencia e Treinamento DST/AIDS na implantacao do Projeto Leia Comigo: Uma proposta de estimulo a leitura / Experience of the STD/AIDS Reference and Training Center (CRT-DST/AIDS) on the implementation of the

O Projeto Leia Comigo e uma atividade piloto proposta pela Secretaria de Estado da Cultura em parceria com a Secretaria de Estado da Saude para hospitais e centros de referencia. O Centro de Referencia e Treinamento DST/AIDS (CRT-DST/AIDS) encampou esta ideia por se tratar de uma acao humanizadora e de inclusao social. O Projeto Leia Comigo tem como objetivo promover entre os usuarios, funcionarios, familiares e comunidade local o habito de leitura, no sentido de trazer conforto, entretenimento, cultura e a oportunidade de adquirir novos conhecimentos. O CRT-DST/AIDS recebeu da Secretaria da Saude e da Cultura a supervisao e orientacao basica para a sua implantacao. Procuramos adapta-lo a realidade vivenciada pela Instituicao, pelo fato de nao dispormos de uma sala de leitura especifica para tal atividade. Profissionais de diversas areas foram sensibilizados no sentido de colaborar e efetivar seu desenvolvimento. O processo de implantacao aconteceu apos reunios semanais onde as tarefas criadas pelo grupo eram divididas entre os profissionais visando atingir todas as pessoas que participam direta ou indiretamente da Instituicao. Estao sendo utilizadas as seguintes ferramentas para a divulgacao das publicacoes disponiveis: um carrinho volante contendo diversos tipos de literaturas infanto-juvenis e de adultos e dois armarios localizados em pontos estrategicos de circulacao de pessoas, com visores de vidro temperado que permitem a visualizacao do acervo disponivel. Estao sendo desenvolvidas por profissionais e colaboradores diversas atividades em varios espacos da Instituicao, tais como: declamacoes de poemas, conto de historias, apresentacoes artisticas, dramatizacoes, saraus, dentre outras. A implantacao do Projeto resultou no aumento significativo de pessoas interessadas em ler. O Projeto tem sensibilizado amplamente seus participantes, de modo que foi iniciado um processo de sele‡ao e recrutamento de voluntarios e de novos talentos que irao auxiliar no desenvolvimento de atividades e eventos culturais relacionados aos Projeto Leia Comigo

Sindrome platipnea-ortodeoxia por foramen oval permeable, aneurisma del septum interauricular y paralisis del hemidiafragma derecho / Platypnea-orthodeoxia syndrome, atrial septal aneurysm and right hemidiaphragmatic elevation with a right-to-left shunt through a patent foramen ovale

El síndrome platipnea-ortodeoxia (SPO) está caracterizado por disnea e hipoxemia en posición erecta que mejoran con el decúbito supino. Se presenta un paciente de 75 años sin antecedentesremarcables, con cuadro de disnea de 7 días de evolución. La radiografía y tomografía de tórax mostraron una elevación del hemidiafragma derecho (confirmándose su parálisis por radioscopia) sin alteraciones en el parénquima pulmonar y mediastino. El ecocardiograma contrastado evidenció un foramen oval permeable y un aneurisma del septum interauricular. La angiografía pulmonar descartó tromboembolismo o malformación vascular y las presiones en la arteria pulmonar fueron normales, sin evidencia de shunt. Al momento de ambos estudios, realizados en decúbito supino, el paciente no tenía síntomas. En la evolución, la disnea también se manifestó en esa postura y el paciente espontáneamente adoptó el decúbito lateral derecho donde la oxemia era normal. Se realizó un ecocardiograma transesofágico contrastado que mostró un shunt derecha-izquierda intracardíaco y se colocó un dispositivo de Alplatzer para el cierre de la comunicación interauricular. Los gases arteriales post-procedimiento fueron normales. Se resalta la particularidad del SPO secundario a shunt intracardíaco sin gradiente de presión entre las cavidades.

Helicobacter pylori and cagA and vacA gene status in children from Brazil with chronic gastritis.

Helicobacter pylori has been shown to be strongly associated with chronic gastritis, gastric and duodenal ulceration, and is a risk factor for gastric carcinoma. Histology, urease, culture, and polymerase chain reaction have been employed as for H. pylori diagnostic methods, pre and post treatment or during follow-up of dyspeptic adult individuals referred for endoscopy. In order to obtain a more-sensitive and specific method for H. pylori detection, we evaluated gastric body and antrum biopsies of 134 consecutive Brazilian consecutive dyspeptic children aged 1-16 years by rapid urease test, histology and polymerase chain reaction using two pairs of oligonucleotides. Our results indicated that polymerase chain reaction with Southern blotting and hybridization with specific chemiluminescent probes increased the number of positive H. pylori patients by 35%. The genotyping of H. pylori strains directly from gastric biopsy using the same nucleic acid methodology revealed that there is no association of chronic gastritis in our infant patients with vacA s1 and the presence of the cagA gene. These data suggest an initial infection of children with normal mucosa and probably others factors than vacA s1 genotype or the presence of the cagA gene are associated with the onset of gastric disease. Altogether, our results reinforce the need for using more sensitive diagnostic methods in order to understand the role of H. pylori in the genesis of gastric disease in children and its progression in adults.