Analysis of the impact of a diabetes education program on glycemic control and prevalence of chronic complications

ABSTRACT Objective: Diabetes mellitus (DM) is a chronic disease of increasing importance in public health, associated with chronic complications including retinopathy, neuropathy, and kidney, cardiovascular and cerebrovascular disease. This study assessed the impact of strategic DM education actions on glycemic control and prevalence of chronic complications in patients with DM. Subjects and methods: Retrospective, quantitative, cohort study at a diabetes patients association comprised of a multidisciplinary team. In all, 533 individuals with DM were included. Sociodemographic and clinical data were collected using questionnaire and medical records. Of these, 333 patients evaluated for 12 to 24 months, with type 2 DM (T2DM, n = 317) and other types of DM (n = 16), were selected to collect data on retinopathy and diabetes kidney disease (DKD). Results: There was a predominance of elderly individuals, low education level, women, high rate of overweight and obesity, physical inactivity, dietary errors, dyslipidemia, and T2DM. More patients with T2DM versus type 1 DM had optimal glycemic control (46.3% vs. 12.2%, respectively; p < 0.001). The impact of the educational processes was demonstrated by the analysis of the initial and final glycated hemoglobin (HBA1c) levels. There was an increased prevalence of individuals with well-controlled DM during follow-up (prevalence ratio [PR] 2.76, 95%, p = 0.001), along with a significant reduction in retinopathy (PR: 0.679, p = 0.001) and albuminuria (PR: 0.637, 95%, p = 0.002) when these variables were evaluated in well-controlled versus uncontrolled HbA1c groups. Conclusions: A multidisciplinary approach with integration and quality was associated with improvements in DM control and reduced occurrence of chronic DM complications.

Microsatellite instability detection in breast cancer using drop-off droplet digital PCR.

The use of conventional methods (immunohistochemistry, pentaplex PCR) for detecting microsatellite instability (MSI), a predictive biomarker of immunotherapy efficacy, is debated for cancers with low MSI prevalence, such as breast cancer (BC). We developed two multiplex drop-off droplet digital PCR (ddPCR) assays targeting four microsatellites, initially identified from public BC whole-genome sequencing dataset. Performances of the assays were investigated and 352 tumor DNA and 28 circulating cell-free DNA from BC patients, with unknown MSI status were blindly screened. Cross-validation of ddPCR MSI status with other MSI detection methods was performed. We then monitored circulating tumor DNA (ctDNA) dynamics before and during pembrolizumab immunotherapy in one patient with MSI-high (MSI-H) metastatic BC. The assays showed high analytical specificity and sensitivity (limit of detection = 0.16%). Among N = 380 samples, seven (1.8%) were found as MSI-H by ddPCR with six of them confirmed by next-generation sequencing (NGS). Specificity was 100% in N = 133 microsatellite stable BC submitted to NGS. In the patient with MSI-H metastatic BC, ctDNA monitoring revealed an early decrease of microsatellite mutant allelic frequencies during immunotherapy. These results demonstrated MSI detection by ddPCR, a non-invasive, fast and cost-effective approach, allowing for large pre-screening of BC patients who may benefit from immunotherapy.

Avaliação do aporte proteico e de indicadores antropométricos no desfecho clínico de pacientes críticos / Evaluation of protein support and anthropometric indicators in the clinical outcome of critical patients

A terapia nutricional é uma das intervenções terapêuticas mais utilizadas em cuidados intensivos, quando aplicada de forma correta auxilia na diminuição de complicações metabólicas, no equilíbrio imunológico, além de amenizar a perda de massa corporal do paciente gravemente enfermo. Objetivo: avaliar a associação dos indicadores antropométricos e o consumo proteico com o desfecho clínico de pacientes críticos em uso de terapia nutricional enteral (TNE) exclusiva. Materiais e Métodos: Trata-se de um estudo prospectivo de caráter observacional analítico, com a utilização de dados de pacientes adultos e idosos em uso exclusivo de TNE desenvolvido em uma Unidade de Terapia Intensiva (UTI). Realizado por meio da coleta de dados secundários registrados nos prontuários de pacientes ≥ 18 anos, que receberam terapia nutricional enteral exclusiva por pelo menos 72 horas. Utilizou-se os indicadores antropométricos índice de massa corporal (IMC) e circunferência do braço. Para a estimativa das necessidades proteicas, considerou-se a recomendação da American Society for Parenteral and Enteral Nutrition. A adequação nutricional foi realizada por meio da coleta diária do volume da formula enteral prescrita e administrada. Nas análises utilizaram-se testes paramétricos e não paramétricos e foi considerado significante p < 0,05. Resultado: Participaram do estudo 52 pacientes que estiveram em uso de nutrição enteral exclusiva internados na UTI no hospital por pelo menos de 72 horas durante a etapa de coleta de dados. Desses pacientes a maioria era do sexo masculino (76,9%), com idade média de 45,7 anos (DP=15,0, mínimo 20 e máximo 71). O tempo de internação médio foi de 12 dias. Os diagnósticos de AIDS (síndrome da imunodeficiência adquirida) (46,1%) e COVID-19 (13,4%) foram os mais prevalentes. Foram identificados que quase 60% da amostra não tinham comorbidades e o desfecho clínico mais frequente foi a alta hospitalar. Conclusão: Neste estudo não foi verificado associações entre os desfechos clínicos avaliados (alta ou óbito) com o aporte proteico ofertado e os indicadores antropométricos, assim também como não tiveram entre as variáveis demográficas e clínicas investigadas

Nutritional therapy is one of the most used therapeutic interventions in intensive care, when correctly applied, it helps to reduce metabolic complications, immune balance, in addition to mitigating the loss of body mass in seriously ill patients. Objective: to evaluate the association of anthropometric indicators and protein consumption with the clinical outcome of critically ill patients using exclusive enteral nutritional therapy (EN). Materials and Methods: This is a prospective, observational, analytical study, using data from adult and elderly patients exclusively using EN developed in an Intensive Care Unit (ICU). Performed by collecting secondary data recorded in the medical records of patients ≥ 18 years old, who received exclusive enteral nutritional therapy for at least 72 hours. Anthropometric indicators body mass index (BMI) and arm circumference were used. For the estimation of protein requirements, the recommendation of the American Society for Parenteral and Enteral Nutrition was considered. Nutritional adequacy was performed through the daily collection of the volume of the prescribed and administered enteral formula. Parametric and non-parametric tests were used in the analyses, and p < 0.05 was considered significant. Result: The study included 52 patients who had been using exclusive enteral nutrition and were hospitalized in the ICU for at least 72 hours during the data collection stage. Of these patients, the majority were male (76.9%), with a mean age of 45.7 years (SD=15.0, minimum 20 and maximum 71). The mean hospital stay was 12 days. The diagnoses of AIDS (acquired immunodeficiency syndrome) (46.1%) and COVID-19 (13.4%) were the most prevalent. It was identified that almost 60% of the sample had no comorbidities and the most frequent clinical outcome was hospital discharge. Conclusion: In this study, there were no associations between the evaluated clinical outcomes (discharge or death) with the protein intake offered and the anthropometric indicators, as well as they did not have between the demographic and clinical variables investigated

Multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer.

Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are two cancer-derived blood biomarkers that inform on patient prognosis and treatment efficacy in breast cancer. We prospectively evaluated the clinical validity of quantifying both CTCs (CellSearch) and ctDNA (targeted next-generation sequencing). Their combined value as prognostic and early monitoring markers was assessed in 198 HER2-negative metastatic breast cancer patients. All patients were included in the prospective multicenter UCBG study COMET (NCT01745757) and treated by first-line chemotherapy with weekly paclitaxel and bevacizumab. Blood samples were obtained at baseline and before the second cycle of chemotherapy. At baseline, CTCs and ctDNA were respectively detected in 72 and 74% of patients and were moderately correlated (Kendall's τ = 0.3). Only 26 (13%) patients had neither detectable ctDNA nor CTCs. Variants were most frequently observed in TP53 and PIK3CA genes. KMT2C/MLL3 variants detected in ctDNA were significantly associated with a lower CTC count, while the opposite trend was seen with GATA3 alterations. Both CTC and ctDNA levels at baseline and after four weeks of treatment were correlated with survival. For progression-free and overall survival, the best multivariate prognostic model included tumor subtype (triple negative vs other), grade (grade 3 vs other), ctDNA variant allele frequency (VAF) at baseline (per 10% increase), and CTC count at four weeks (≥5CTC/7.5 mL). Overall, this study demonstrates that CTCs and ctDNA have nonoverlapping detection profiles and complementary prognostic values in metastatic breast cancer patients. A comprehensive liquid-biopsy approach may involve simultaneous detection of ctDNA and CTCs.

Circulating tumor DNA as a dynamic biomarker of response to palbociclib and fulvestrant in metastatic breast cancer patients.

BACKGROUND: Following the PALOMA-3 study results, the combination of palbociclib, a CDK4/6 inhibitor, with fulvestrant, a selective estrogen receptor degrader, has become a standard therapy in women with estrogen receptor-positive (ER+) HER2-negative (HER2-) metastatic breast cancer (MBC). Palbociclib has been shown to increase the progression-free survival (PFS) overall but no predictive biomarker of palbociclib efficacy has been validated so far. We thus evaluated whether early changes of circulating tumor DNA (ctDNA) levels are associated with palbociclib plus fulvestrant efficiency. METHODS: ER+ HER2- MBC patients were included in a prospective observational cohort before treatment initiation. Tumor response was assessed by radiological evaluation (RECIST v1.1) every 3 months. Plasma samples were collected before treatment (baseline), at day 15 (D15), at day 30 (D30), and at disease progression. We searched for somatic mutations from archived tumor tissues by targeted deep sequencing. For patients with somatic mutations identified, circulating tumor DNA (ctDNA) was tracked using digital droplet PCR. Ratios of ctDNA levels ([D15/baseline] and [D30/baseline]) were then correlated with prospectively registered patient characteristics and outcomes. RESULTS: Twenty-five of the 61 patients enrolled had a somatic mutation testable in plasma (NPIK3CA = 21, NTP53 = 2, NAKT1 = 2). At baseline, 84% of patients had detectable ctDNA levels but ctDNA levels had no prognostic impact on PFS (p = 0.10). Among those patients, ctDNA was still detected in 82% at D15 and 68% at D30. ctDNA clearance observed at day 30 was associated with longer PFS (HR = 7.2, 95% CI = 1.5-32.6, p = 0.004). On the contrary, a [D30/baseline] ctDNA ratio > 1 was associated with a shorter PFS (HR = 5.1, 95% CI = 1.4-18.3, p = 0.02) and all 5 patients with increased ctDNA levels at D30 showed disease progression after 3 months under palbociclib-fulvestrant. Finally, at the time of radiological tumor progression, ctDNA was detected in all patients tested. CONCLUSION: Our study demonstrates that the efficiency of palbociclib and fulvestrant can be monitored by serial analyses of ctDNA before radiological evaluation and that early ctDNA variation is a prognostic factor of PFS.

High-Accuracy Determination of Microsatellite Instability Compatible with Liquid Biopsies.

BACKGROUND: Microsatellite instability (MSI) has recently emerged as a predictive pan-tumor biomarker of immunotherapy efficacy, stimulating the development of diagnostic tools compatible with large-scale screening of patients. In this context, noninvasive detection of MSI from circulating tumor DNA stands as a promising diagnostic and posttreatment monitoring tool. METHODS: We developed drop-off droplet-digital PCR (ddPCR) assays targeting BAT-26, activin A receptor type 2A (ACVR2A), and defensin beta 105A/B (DEFB105A/B) microsatellite markers. Performances of the assays were measured on reconstitution experiments of various mutant allelic fractions, on 185 tumor samples with known MSI status, and on 72 blood samples collected from 42 patients with advanced colorectal or endometrial cancers before and/or during therapy. RESULTS: The 3 ddPCR assays reached analytical sensitivity <0.1% variant allelic frequency and could reliably detect and quantify MSI in both tumor and body fluid samples. High concordance between MSI status determination by the three-marker ddPCR test and the reference pentaplex method were observed (100% for colorectal tumors and 93% for other tumor types). Moreover, the 3 assays showed correlations with r ≥ 0.99 with other circulating tumor DNA markers and their dynamic during treatment correlated well with clinical response. CONCLUSIONS: This innovative approach for MSI detection provides a noninvasive, cost-effective, and fast diagnostic tool, well suited for large-scale screening of patients that may benefit from immunotherapy agents, as well as for monitoring treatment responses.

Comparison of rRNA-based reverse transcription PCR and rDNA-based PCR for the detection of streptococci in root canal infections

Abstract Objective The rDNA-based method is unable to distinguish between alive and dead cells. Alternatively, bacterial viability can be assessed by molecular methods based on ribosomal RNA (rRNA). Therefore, this study aimed to detect viable streptococci in root canal samples using rRNA-based reverse transcription polymerase chain reaction (RT-PCR), compared to an rDNA-based PCR assay. Methodology Microbiological root canal samples were obtained from 32 teeth with primary endodontic infections before (S1) and after chemomechanical preparation (S2), and after removal of intracanal medication (S3). RNA and DNA were extracted, and complementary DNA (cDNA) was synthesized from RNA using RT reaction. cDNA and genomic DNA were subjected to PCR with primers complementary to the 16S rRNA sequences of Streptococcus spp. McNemar's test was used to compare the detection rate of both assays (P<0.05). Results Streptococci were detected in 28.12% (9/32) and 37.5% (12/32) of S1 samples using rRNA- and rDNA-based PCR assays, respectively. In contrast, they were detected in only 6.25% (2/32) of S2 samples using rRNA-based RT-PCR, compared to 15.62% (5/32) using rDNA-based PCR. Finally, in S3 samples, streptococci were not detected by rRNA, whereas rDNA-based PCR still detected the bacteria in 12.5% (4/32) of the samples. The total number of PCR-positive reactions in the rDNA-based PCR was higher than in the rRNA-based assay (P<0.05). Conclusions The rRNA-based RT-PCR showed a lower detection rate of streptococci when compared to the rDNA-based PCR, suggesting that the latter may have detected dead cells of streptococci in root canal samples.

Single Droplet Digital Polymerase Chain Reaction for Comprehensive and Simultaneous Detection of Mutations in Hotspot Regions.

Droplet digital polymerase chain reaction (ddPCR) is a highly sensitive quantitative polymerase chain reaction (PCR) method based on sample fractionation into thousands of nano-sized water-in-oil individual reactions. Recently, ddPCR has become one of the most accurate and sensitive tools for circulating tumor DNA (ctDNA) detection. One of the major limitations of the standard ddPCR technique is the restricted number of mutations that can be screened per reaction, as specific hydrolysis probes recognizing each possible allelic version are required. An alternative methodology, the drop-off ddPCR, increases throughput, since it requires only a single pair of probes to detect and quantify potentially all genetic alterations in the targeted region. Drop-off ddPCR displays comparable sensitivity to conventional ddPCR assays with the advantage of detecting a greater number of mutations in a single reaction. It is cost-effective, conserves precious sample material, and can also be used as a discovery tool when mutations are not known a priori.

Multiple Hotspot Mutations Scanning by Single Droplet Digital PCR.

BACKGROUND: Progress in the liquid biopsy field, combined with the development of droplet digital PCR (ddPCR), has enabled noninvasive monitoring of mutations with high detection accuracy. However, current assays detect a restricted number of mutations per reaction. ddPCR is a recognized method for detecting alterations previously characterized in tumor tissues, but its use as a discovery tool when the mutation is unknown a priori remains limited. METHODS: We established 2 ddPCR assays detecting all genomic alterations within KRAS exon 2 and EGFR exon 19 mutation hotspots, which are of clinical importance in colorectal and lung cancer, with use of a unique pair of TaqMan® oligoprobes. The KRAS assay scanned for the 7 most common mutations in codons 12/13 but also all other mutations found in that region. The EGFR assay screened for all in-frame deletions of exon 19, which are frequent EGFR-activating events. RESULTS: The KRAS and EGFR assays were highly specific and both reached a limit of detection of <0.1% in mutant allele frequency. We further validated their performance on multiple plasma and formalin-fixed and paraffin-embedded tumor samples harboring a panel of different KRAS or EGFR mutations. CONCLUSIONS: This method presents the advantage of detecting a higher number of mutations with single-reaction ddPCRs while consuming a minimum of patient sample. This is particularly useful in the context of liquid biopsy because the amount of circulating tumor DNA is often low. This method should be useful as a discovery tool when the tumor tissue is unavailable or to monitor disease during therapy.

Tannic extract potential as natural wood preservative of Acacia mearnsii

ABSTRACT High toxicity of the preservatives most frequently used in wood treatment and the resulting risks of handling pose a threat to small producers and to the environment. In an attempt to mitigate these problems, the present study was conducted with the objective of evaluating the preservative effect of tannic extract on biodeterioration of Acacia mearnsii wood. For this purpose, untreated and preserved specimens, some with tannin extract and some with a preservative mixture based on CCB (Chromated Copper Borate), were submitted to accelerated rotting trials with the fungus that causes white rot (Pycnoporus sanguineus) for 16 weeks. The evaluations were made with a basis on weight loss and chemical components analysis, and they showed that the natural resistance of Acacia wood is moderate when exposed to the white rot fungus. The tannin concentrations showed similar effects to those of the CBB mixture in all evaluations, i.e., they significantly increased the biological resistance of the material, which started to be classified as very resistant to the fungus. Overall, the results suggest that tannin can be considered as a potential natural preservative product.

The IL-10 polarized cytokine pattern in innate and adaptive immunity cells contribute to the development of FVIII inhibitors.

BACKGROUND: Hemophilia A (HA) is an X-linked inherited bleeding disorder, resulting from a qualitative or quantitative deficiency of clotting factor VIII (FVIII). Antibodies against FVIII, also called inhibitors, block the procoagulant activity of FVIII; thus, impairing hemostatic activity in patients with HA. The exact mechanism underlying the immunological events behind the development of inhibitors remains unknown. This study aimed to understand immune response to FVIII in patients with HA who were either positive [HAα-FVIII(+)] or negative [HAα-FVIII(-)] for inhibitors. METHODS: Cytokine profiles [interferon-γ (IFN - γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-5, and IL-10] of innate and adaptive immune cells present in the peripheral blood of participants were characterized. RESULTS: Presence of inhibitors was significantly associated with decreased frequencies of TNF-α-positive monocytes and neutrophils, IL-5-positive monocytes, IL-4-positive neutrophils, and increased frequencies of IL-10-positive neutrophils and T cells. T cells from HAα-FVIII(-) patients expressed increased levels of almost all cytokines. In contrast, HAα-FVIII(+) patients showed lower levels of all cytokines in CD4(+) and CD8(+) T cells, except IL-10. B cells from HAα-FVIII(-) patients expressed increased levels of IL-4 while those from HAα-FVIII(+) patients expressed increased levels of IL-10. CONCLUSIONS: The global cytokine profiles of innate and adaptive immune cells showed an anti-inflammatory/regulatory pattern in HAα-FVIII(+) patients and a mixed pattern, with a bias toward inflammatory cytokine profile, in HAα-FVIII(-) patients. The occurrence of these profiles seems to be associated with presence FVIII inhibitors.

Análise in vivo da redução bacteriana em dentes portadores de periodontite apical primária e sua correlação com o sucesso do tratamento endodôntico / In vivo analysis of bacterial reduction in teeth with apical periodontitis primary and its correlation with the success of endodontic treatment

O principal objetivo do tratamento endodôntico em dentes com infecções primárias é a cura da periodontite apical, o que ocorre geralmente após a máxima redução de micro-organismos do canal radicular. Métodos microbiológicos moleculares são os métodos de escolha para avaliar a redução de micro-organismos após o tratamento endodôntico por serem mais sensíveis, específicos e precisos do que os métodos baseados em cultura bacteriológica. Entretanto, poucos estudos clínicos avaliaram a eficácia antimicrobiana do tratamento endodôntico por métodos moleculares. Além disso, até o presente momento, não há nenhum estudo correlacionando esses dados com o sucesso do tratamento endodôntico. Portanto, os objetivos do presente estudo foram: (a) avaliar in vivo, por métodos moleculares quantitativos, a concentração de bactérias nos canais radiculares e sua, correlação com aspectos clínicos e radiográficos; (b) correlacionar a redução bacteriana após o tratamento endodôntico com reparo apical após controle radiográfico e tomográfico. Trinta e quatro pacientes portadores de dentes com necrose pulpar e periodontite apical foram selecionados para o estudo. O protocolo de antissepsia consistiu em realizar o Preparo Químico-Cirúrgico (PQC) com sistema Reciproc e NaOCl 2,5%; irrigação final com EDTA-T 17%; e medicação intracanal com pasta de hidróxido de cálcio por 14 dias antes da obturação dos canais radiculares. Foram realizadas coletas microbiológicas dos canais radiculares no início do tratamento e na segunda sessão, após a remoção da medicação intracanal antes da obturação.

As amostras microbiológicas foram analisadas por Reação em Cadeia da Polimerase quantitativa (qPCR) para detecção e quantificação de bactérias utilizando iniciadores universais para o domínio Bactéria. Para análise do sucesso do tratamento endodôntico, foram analisados aspectos clínicos, radiográficos e tomográficos após um período mínimo de controle de 1 ano. Os casos foram classificados em 4 categorias: ausência de rarefação óssea periapical, redução ou aumento e incerto. Bactérias foram observadas em 100% das amostras iniciais coletadas, com concentrações medianas de 1,68 x 106 cópias de DNA. A análise estatística de regressão logística não apresentou correlação entre concentrações de DNA bacteriano com dados clínicos. Após o tratamento endodôntico, as medianas das concentrações de bactérias foram de 8.72 x 102, os resultados mostraram que houve diminuição significativa na concentração de DNA bacteriano (p<0,05), correspondendo a porcentagem de redução de 99.98% nos canais radiculares após os procedimentos de antissepsia. Retornaram para o controle, 20 dos 34 pacientes (58,82%), entre 13 a 22 meses após o tratamento endodôntico. Dois dentes foram extraídos, restando um total de 18 dentes para análise clínica e radiográfica. O sucesso classificado por ausência ou redução da rarefação óssea na radiografia periapical foi observada em 16 dos 18 dentes (88,83%). Dos 2 casos de insucesso radiográfico, um apresentou elevada quantidade de bactérias (>104) persistentes após os procedimentos de antissepsia e um caso apresentou obturação deficiente. Entretanto, a análise estatística de regressão logística não identificou nenhum fator específico associado ao insucesso endodôntico. A análise tomográfica foi realizada em 12 dos 18 pacientes. Os achados tomográficos confirmaram ausência/ redução da rarefação periapical verificada na radiografia, com exceção de um caso onde não houve redução da área da rarefação. Conclui-se que dentes com necrose...

The objectives of the endodontic treatment of teeth with primary infections is the healing of apical periodontitis, which usually occurs after the maximum reduction of micro-organisms in the root canal. Molecular methods are the methods of choice for assessing the reduction of micro-organisms after endodontic treatment to be more sensitive, specific and accurate than methods based on bacteriological culture. The objectives of this study were to evaluate in vivo by molecular methods, the concentration of bacteria in root canals and correlation of bacterial reduction after endodontic treatment with apical repair after radiographic control and CBCT. Thirty four teeth with apical periodontitis, with radiographic evidence of periapical were selected for this study. The root canal preparation of all the teeth was carried out with reciprocating files and 2.5% NaOCl during preparation; and 17% EDTA for smear layer removal. The root canals were medicated with calcium hydroxide for 14 days. Microbiological sampling were performed before the preparation and after intracanal medication. The samples were analyzed by real time PCR, for the detection and quantification of bacteria,. Bacteria were observed in 100% of the initial samples. . Bacteria were observed in 100% of the initial samples, with median concentrations of 1.68 x 106 copies of the DNA. After endodontic treatment, the median bacterial concentrations were 8.72 x 102, the results showed a significant decrease in the concentration of bacterial DNA (p <0.05), corresponding to 99.98% reduction in the percentage of root canals after procedures of antisepsis.

13 to 19 months after treatment, the teeth were examined by using periapical radiography (PA) and cone-beam computed tomography (CBCT). Area and volume of the periapical lesions were measured, and the outcome was presented in 4 categories: absence, reduction or enlargement of the radiolucency, or uncertain. Lesions were classified as reduced or enlarged when the change in size of the radiolucency was 20% or more. The recall rate was 58,82%, and 18 teeth were analyzed. Success classified by the absence or reduction of bone thinning in periapical radiography was observed in 16 of the 18 teeth (88.83%). CT findings confirmed the absence / reduction of periapical rarefaction observed on radiographs, except for one case. Conclude that teeth with pulp...

Dissociação entre seres vivos e artefatos: investigação de efeito categoria específica no processamento de substantivos na bateria de memória semântica de cambridge / Dissociation between living and nonliving concepts: investigation of category specific effects in semantic processing using the cambridge battery of semantic memory tests

Este trabalho investigou a existência de dissociação entre seres vivos e artefatos em dois estudos: um com adultos típicos e outro com a descrição de dois pacientes que receberam diagnósticos de Demência Semântica (DS) ou de Doença de Alzheimer (DA). Para tanto, foram utilizadas as provas de fluência verbal, nomeação, compreensão e definição da Bateria de Memória Semântica de Cambridge. Entre os adultos típicos, o número de acertos em seres vivos foi maior na nomeação, definição e fluência verbal. Diante do controle das covariáveis sociodemográficas correlacionadas com as tarefas, não se encontraram diferenças significativas. Já a investigação dos dois casos identificou diferentes perfis de distúrbio nas provas. Sugere-se que o paciente com DS teve dupla-dissociação em relação aos controles e à paciente com DA. Os resultados foram discutidos com base em modelos de organização do conhecimento semântico e correlatos neuroanatômicos.

This study investigated dissociations between nouns representing living and nonliving entities in cognitively unimpaired adults and in two patients, one with Semantic Dementia (SD) and another with Alzheimer's disease (AD), using tests from the Cambridge Battery of Semantic Memory Tests. Among controls a higher number of correct responses in naming, definition and verbal fluency was observed in nouns representing living concepts but differences did not reach statistical significance when we controlled for sociodemographic variables correlated to the tasks. The description of the performance of two patients allowed for recognition of different profiles in the tasks. It is suggested that the patient with SD presented a double-dissociation compared to controls and to the patient with AD. Results are discussed in terms of models of semantic memory organization and neuroanatomical correlates.

Cytokines signatures in short and long-term stable renal transplanted patients.

Despite the evidences showing the relevance of regulatory immune-mediated mechanisms to guarantee the stable graft function in renal transplanted patients, studies focusing on the immune response observed over a long-term period after renal transplantation are still limited. Several efforts have been done to establish novel biomarkers with relevant predictive values that could be used as prognostic laboratorial tools to monitor the complex network triggered through time after kidney transplantation. In this study, we have evaluated the pro-inflammatory and regulatory patterns of plasma cytokines in a group of 120 renal transplanted patients with stable graft function ranging from 1 to 160 months. Our data demonstrated an overall predominance of regulatory cytokines short-term after renal transplantation (1-24 months) with peaks of IL-4, IL-5 and IL-10. Moreover, a slight peak of TNF-α was observed 25-60 months after renal transplantation. Following a gap of stable cytokine profile (61-120 months), peaks of pro-inflammatory cytokines IL-8, IL-6, IL1ß, TNF-α and IL-12 were observed later on (>120 months) after renal transplantation. Additionally, the categorical analysis of "low" or "high" cytokine producers re-enforce the occurrence of an overall regulatory status early-after stable renal graft function with a predominant pro-inflammatory pattern later on long-term renal transplantation. Taken together, our data suggest that IL-5 is a good biomarker associated with short-term stable renal function, whereas IL-12 seems to be a relevant pro-inflammatory element in long-term renal transplanted patients.

Nonpharmacological interventions for cognitive impairments following primary progressive aphasia: A systematic review of the literature / Intervenções não-farmacológicas para distúrbios cognitivos na Afasia Progressiva Primária: uma revisão sistemática da literatura

ABSTRACT This study provided a systematic review on nonpharmacological interventions applied to patients diagnosed with Primary Progressive Aphasia (PPA) and its variants: Semantic (SPPA), Nonfluent (NFPPA) and Logopenic (LPPA) to establish evidence-based recommendations for the clinical practice of cognitive rehabilitation for these patients. Methods: A PubMed and LILACS literature search with no time restriction was conducted with the keywords PPA (and its variants) AND rehabilitation OR training OR intervention OR therapy OR treatment OR effectiveness. To develop its evidence-based recommendations, a research committee identified questions to be addressed and determined the level of evidence for each study according to published criteria (Cicerone et al., 2000). Overall evidence for treatments was summarized and recommendations were derived. Results: Our search retrieved articles published from 1995 to 2013: 21 for SPPA, 8 for NFPPA, 3 for LPPA and 8 for PPA with no specification. Thirty-five studies were rated as Class III, consisting of studies with results obtained from one or more single-cases and that used appropriate single-subject methods with adequate quantification and analysis of results. The level of evidence of three functional interventions could not be established. One study was rated as Class II and consisted of a nonrandomized case-control investigation. Conclusion: Positive results were reported in all reviewed studies. However, in order to be recommended, some investigation regarding the intervention efficacy was required. Results of the present review allows for recommendation of some nonpharmacological interventions for cognitive deficits following PPA as Practice Options. Suggestions for further studies on PPA interventions and future research are discussed.

RESUMO Este estudo ofereceu uma revisão sistemática de intervenções não-farmacológicas aplicadas a pacientes com Afasia Progressiva Primária (APP) e suas variantes: Semântica (APPS), Não-fluente (APPNF) e Logopênica (APPL) com o objetivo de estabelecer recomendações baseadas em evidências para a prática clínica de reabilitação cognitiva para estes pacientes. Métodos: Conduziu-se busca por literatura, sem restrição de período, no PubMed e LILACS com as palavras-chave PPA (e variantes) AND rehabilitation OR training OR intervention OR therapy OR treatment OR effectiveness. Para desenvolver recomendações baseadas em evidências um comitê de pesquisadores identificou as questões relevantes para investigação e determinou o nível de evidência para cada estudo de acordo com critérios publicados (Cicerone et al., 2000). A evidência total para os tratamentos foi sumarizada e recomendações redigidas. Resultados: Foram encontrados artigos publicados de 1995 a 2013: 21 para APPS, 8 para APPNF, 3 para APPL e 8 para APP sem especificações. Trinta e cinco estudos foram classificados como Classe III, consistindo de resultados obtidos com um ou mais indivíduos e utilizando metodologia apropriada para estudo de casos. O nível de evidência de três intervenções funcionais não pôde ser estabelecido. Um estudo foi classificado como Classe II e consistiu de pesquisa caso-controle não-randomizada. Conclusão: Resultados positivos foram reportados em todos os trabalhos analisados mas, para serem recomendados, os tratamentos requerem investigação em relação a sua eficácia. Resultados da presente revisão permitiram recomendação de algumas intervenções como Opções Práticas. Ademais, apresentamos sugestões para futuros estudos de intervenção em APP.

Antitumor effectiveness and toxicity of cisplatin-loaded long-circulating and pH-sensitive liposomes against Ehrlich ascitic tumor.

Cisplatin (CDDP) is one of the most active cytotoxic agents commonly used in the treatment of peritoneal carcinomatosis. The disadvantages of its clinical use are systemic side-effects, such as nephrotoxicity and myelotoxicity. Long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP) were developed by our research group aiming to promote the release of CDDP near the tumor as well as decreasing toxicity. The aim of this study was to evaluate the antitumor efficacy and toxicity of SpHL-CDDP after intraperitoneal administration in initial or disseminated tumor-bearing mice, at a dose of 12 mg/kg. The survival was monitored and blood samples were collected for biochemical and hematological analysis. Kidneys, liver and spleen were removed for histopathological examination. Tumor cells were evaluated for cellular viability and cell cycle. The survival of animals treated with SpHL-CDDP was higher than those treated with free CDDP. The cell death caused by treatment with SpHL-CDDP occurred through induction of apoptosis, with a cell cycle arrest at the G0/G1 phase. The treatment of mice presenting initial cancer with both formulations provoked a suppression of granulocytes. Mice treated with free CDDP also showed a decrease in platelet count, which suggests a high myelotoxicity. In an advanced cancer model, SpHL-CDDP treatment allowed an improvement of the immune response. Mice affected by cancer at an early stage and treated with free CDDP or SpHL-CDDP showed a lower urea/creatinine index compared with the saline control group. These findings indicate that both treatments were able to reduce the renal damage caused by peritoneal carcinomatosis. Microscopic analysis of kidneys from mice treated with SpHL-CDDP showed a discrete morphological alteration, while tubular necrosis was observed for free CDDP-treated mice. Concerning hepatotoxicity, no alteration in clinical chemistry parameters was observed. These findings reveal that SpHL-CDDP can improve the antitumor efficacy and decrease renal and bone marrow toxicity.

Self: um conceito em desenvolvimento / Self: a concept in development / Self: un concepto en desarrollo

Diversas definições de self coexistem nas teorias e práticas psicológicas. Essa variedade é resultante de bases epistemológicas a partir das quais se adotam estratégias diferentes para abordar e demarcar os limites do objeto em questão e descrevê-lo. Este estudo teve como objetivo oferecer uma revisão dos conceitos de self e uma reflexão sobre como esse conceito se articula nas diferentes abordagens teóricas da psicologia. Destaca-se que dilemas centrais à psicologia do desenvolvimento atravessam o conceito de self. Por essa razão, apresenta-se a tese de que, ao analisar cada definição de self, deve-se buscar responder como cada teoria colocou-se diante das dicotomias estabilidade versus transformação, específico versus universal e mundo interno versus mundo externo.

Many definitions for the self coexist in the psychological theory and praxis. This diversity is a result of epistemological basis from which different strategies are selected in order to approach, describe and limit the target object. This paper aims to provide a review on concepts concerning the self and a reflection on how this concept is articulated in different Psychology theoretical approaches. The impact of the central dilemmas of developmental Psychology to the concept of self is also discussed. Thus, this paper suggests a systematic approach in order to analyze each self definition: One should seek to answer how each theory has positioned itself in relation to the dicotomies of stability versus transformation, specific versus universal, and inner world versus external world.

Diversas definiciones de self coexisten en las teorias y prácticas psicológicas. Esta diversidad resulta de bases epistemologícas donde diferentes estrategias son seleccionadas para aproximar, describir y limitar el objecto blanco. Este estudio tuvo como objetivo ofrecer una revisión de los conceptos de self y una reflexión sobre cómo este concepto se articula en diferentes enfoques teóricos de la psicología. El impacto de los dillemas centrales de la psicologia de desarrollo en el concepto del self tambien son discutidos. Así, este artículo sugiere una aproximación sistemática para analisar cada definiccion del self: se debe intentar responder como cada teoría se posicionó delante de las dicotomías estabilidad versus transformación, especifico versus universal y mundo interno versus mundo externo.

Adaptação e validação da Escala Filadélfia de Mindfulness para adultos brasileiros / Adaptation and validation of the Philadelphia Mindfulness Scale among Brazilian adults / Adaptación y validez de la Escala Filadélfia de Mindfulness para adultos brasileños

A literatura psicológica tem referido especial interesse ao processo psicológico de monitoramento contínuo da experiência individual, ou mindfulness. Neste estudo, buscou-se adaptar e apresentar evidências de validade convergente e divergente para uma escala de autorrelato que visa a mensurar mindfulness, a Escala Filadélfia de Mindfulness (EFM). Participaram da pesquisa 703 adultos brasileiros, que responderam EFM e outras três medidas relacionadas a conceitos como autoconsciência e insight. A análise fatorial indicou a presença de duas dimensões da EFM, relativas a dois componentes de mindfulness: Aceitação e Awareness. Essas dimensões apresentaram índices de consistência interna de 0,859 e 0,816, respectivamente. Os resultados também indicaram convergência entre o fator Awareness e os dados de autoconsciência enquanto autofoco, e divergência entre Aceitação e facetas mal-adaptativas da autoconsciência (ansiedade social e ruminação). Em consonância com a literatura que refere haver uma faceta de mindfulness voltada à meditação, Aceitação apresentou também correlação positiva com Insight.

Current psychological research has paid special attention to the psychological process of continuous monitoring of inner experience, i.e., mindfulness. This study aimed to adapt and to present convergent and divergent validity evidence of a mindfulness self-report measure, the Philadelphia Mindfulness Scale (PMS). Data was based on the answers of 703 Brazilian adults to the adapted version of PMS and three other measures related to self-consciousness and insight. Factorial analysis presented two principal dimensions among the items of PMS, which were related to two components of mindfulness: Acceptance and Awareness. These two dimensions presented internal consistency levels of 0,859 and 0,816, respectively. Convergences among Awareness and data related to self-consciousness taken as self-focus were observed, as well as divergences among Acceptance and maladaptive facets of self-consciousness (Social Anxiety and Rumination). In consonance to the literature on the meditating aspect of mindfulness, Acceptance also presented significant positive correlation with Insight.

La literatura psicológica ha tenido especial interés en el proceso psicológico de monitoreo continuo de la experiencia individual, o mindfulness. En este estudio, se buscó adaptar y presentar evidencias de validez convergente y divergente para una escala de autorrelato que tiene por objeto mensurar mindfulness, la Escala Filadelfia de Mindfulness (EFM). Participaron de la investigación 703 adultos brasileños, que respondieron la EFM y otras tres medidas relacionadas a conceptos como autoconsciencia e insight. El análisis factorial indicó la presencia de dos dimensiones de la EFM, relativos a dos componentes de mindfulness: Aceptación y Awareness. Esas dimensiones presentaron índices de consistencia interna de 0,859 y 0,816, respectivamente. Los resultados también indicaron convergencia entre el factor Awareness y los datos de autoconsciencia como autofoco, y divergencia entre Aceptación y facetas mal adaptativas de la autoconsciencia (ansiedad social y ruminación). En consonancia con la literatura que refiere haber una faceta de mindfulness vuelta a la meditación, Aceptación presentó también correlación positiva con Insight.

A study of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) serum levels in rats subjected to fecal peritonitis and treated with intraperitoneal ropivacaine.

PURPOSE: The objective of this study was to assess the cytokine serum levels of IL-6 and TNF-α in rats subjected to fecal peritonitis and treated with peritoneal lavage with 0.2% ropivacaine by peritoneal lavage. METHODS: We subjected 16 Wistar rats to laparotomy 6 hours after the induction of fecal peritonitis with autogenous stool and subsequently divided the rats randomly into 4 groups: I-control, no treatment; II- drying of the abdominal cavity; III- lavage of the abdominal cavity with 3 mL of 0.9% normal saline and drying; IV- lavage of the abdominal cavity with 3 mL of 0.2% ropivacaine and drying. Six hours following the laparotomy, the animals underwent cardiac puncture, and 1 mL of blood was collected for cytokine assessment before the animals were euthanized. RESULTS: The lavage with ropivacaine resulted in smaller TNF-α levels compared with those observed in the other treatment groups (p <0.05). Regarding IL-6, the ropivacaine group showed lower cytokine levels than those observed in groups I and II, but there was no significant difference (p> 0.05) between groups III and IV. CONCLUSION: Peritoneal lavage with 0.2% ropivacaine was shown to reduce plasma levels of IL-6 and TNF-α in the treatment of fecal peritonitis in rats.

A study of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) serum levels in rats subjected to fecal peritonitis and treated with intraperitoneal ropivacaine / Avaliação dos níveis séricos de interleucina 6 (IL-6) e fator de necrose tumoral (TNF-α) em ratos submetidos a peritonite fecal e tratado com ropivacaína intraperitoneal

PURPOSE: The objective of this study was to assess the cytokine serum levels of IL-6 and TNF-α in rats subjected to fecal peritonitis and treated with peritoneal lavage with 0.2% ropivacaine by peritoneal lavage. METHODS: We subjected 16 Wistar rats to laparotomy 6 hours after the induction of fecal peritonitis with autogenous stool and subsequently divided the rats randomly into 4 groups: I-control, no treatment; II- drying of the abdominal cavity; III- lavage of the abdominal cavity with 3 mL of 0.9% normal saline and drying; IV- lavage of the abdominal cavity with 3 mL of 0.2% ropivacaine and drying. Six hours following the laparotomy, the animals underwent cardiac puncture, and 1 mL of blood was collected for cytokine assessment before the animals were euthanized. RESULTS: The lavage with ropivacaine resulted in smaller TNF-α levels compared with those observed in the other treatment groups (p <0.05). Regarding IL-6, the ropivacaine group showed lower cytokine levels than those observed in groups I and II, but there was no significant difference (p> 0.05) between groups III and IV. CONCLUSION: Peritoneal lavage with 0.2% ropivacaine was shown to reduce plasma levels of IL-6 and TNF-α in the treatment of fecal peritonitis in rats.

OBJETIVO: O objetivo do presente estudo foi avaliar as dosagens séricas das citocinas Il-6 e TNF-α em ratos submetidos à peritonite fecal e tratados com lavagem peritoneal com ropivacaína a 0,2%. MÉTODOS: Utilizaram-se 16 ratos Wistar, submetidos à laparotomia 6 horas após a indução de peritonite fecal com fezes autógenas, distribuídos aleatoriamente em 4 grupos: I- Controle, nenhum tratamento; II- Enxugamento da cavidade abdominal; III- Lavagem da cavidade abdominal com 3 ml de solução salina 0,9% e enxugamento; IV- Lavagem da cavidade abdominal com 3 ml de ropivacaína a 0,2% e enxugamento. Seis horas após a laparotomia os animais foram submetidos à punção cardíaca com retirada de 1 mL de sangue para a dosagem das citocinas e, a seguir, eutanasiados. RESULTADOS: A lavagem com ropivacaína apresentou valores de TNF-α menores do que os observados com os outros tratamentos (p<0,05). Em relação aos valores da IL-6, o grupo da ropivacaína apresentou valores menores do que os observados com os grupos I e II, mas não houve diferença estatística (p>0,05) em relação ao grupo III. CONCLUSÃO: A lavagem peritoneal com ropivacaína a 0,2% no tratamento da peritonite fecal em ratos demonstrou reduzir os níveis plasmáticos de IL-6 e do TNF-α.