Pathogens and microorganisms in the mangrove oyster Crassostrea gasar cultivated in an estuarine environment in Northeast Brazil.

Estuaries are important ecosystems due to the ecological services they provide, acting as nurseries for many species of fish and invertebrates, and are also used as environments for the extraction and cultivation of mollusks. Oysters are animals that filter water to obtain oxygen and nutrients. In this process, they can bioaccumulate microorganisms and chemical substances in their tissues. The growth of mollusk culture in Northeastern Brazil requires the health identification of cultivated oysters through the quantification of the potentially harmful microbiota accumulated in the animals. Therefore, the present work aims to quantify and identify bacteria and possible pathogens found in the tissues of cultivated oysters and their culture waters. The Most Probable Number of Coliforms (MPN) in oysters and water were considered suitable according to the Brazilian current legislation, Vibrio sp. obtained low colonization and Salmonella sp. was not observed. The prevalence of microorganisms potentially pathogenic to oysters was 33.7%, highlighting metazoans and Nematopsis sp., however, the intensity of the infestation of these organisms was moderate. The low contamination of oysters demonstrates that this culture environment is promising for this activity. However, continuous environmental and sanitary monitoring is fundamental to guarantee the safety of the culture waters and the sustainability of aquaculture activities.

Trypanosoma cruzi infection changes the chromatin proteome profile of infected human cells.

Chagas disease is endemic in 22 Latin American countries, with approximately 8 million individuals infected worldwide and 10,000 deaths yearly. Trypanosoma cruzi presents an intracellular life cycle in mammalian hosts to sustain infection. Parasite infection activates host cell responses, promoting an unbalance in reactive oxygen species (ROS) in the intracellular environment inducing genomic DNA lesions in the host cell during infection. To further understand changes in host cell chromatin induced by parasite infection, we investigated alterations in chromatin caused by infection by performing quantitative proteomic analysis. DNA Damage Repair proteins, such as Poly-ADP-ribose Polymerase 1 (PARP-1) and X-Ray Repair Cross Complementing 6 (XRRC6), were recruited to the chromatin during infection. Also, changes in chromatin remodeling enzymes suggest that parasite infection may shape the epigenome of the host cells. Interestingly, the abundance of oxidative phosphorylation mitochondrial and vesicle-mediated transport proteins increased in the host chromatin at the final stages of infection. In addition, Apoptosis-inducing Factor (AIF) is translocated to the host cell nucleus upon infection, suggesting that cells enter parthanatos type of death. Altogether, this study reveals how parasites interfere with the host cells' responses at the chromatin level leading to significant crosstalk that support and disseminate infection. SIGNIFICANCE: The present study provides novel insights into the effects of Trypanosoma cruzi on the chromatin from the host cell. This manuscript investigated proteomic alterations in chromatin caused by parasite infection at early and late infection phases by performing a quantitative proteomic analysis. In this study, we revealed that parasites interfere with DNA metabolism in the early and late stages of infection. We identified that proteins related to DNA damage repair, oxidative phosphorylation, and vesicle-mediated transport have increased abundance at the host chromatin. Additionally, we have observed that Apoptosis-inducing Factor is translocated to the host cell nucleus upon infection, suggesting that the parasites could lead the cells to enter Parthanatos as a form of programmed cell death. The findings improve our understanding on how the parasites modulate the host cell chromatin to disseminate infection. In this study, we suggest a mechanistic parasite action towards host nucleus that could be used to indicate targets for future treatments.

Trypanosoma cruzi infection changes the chromatin proteome profile of infected human cells

Chagas disease is endemic in 22 Latin American countries, with approximately 8 million individuals infected worldwide and 10,000 deaths yearly. Trypanosoma cruzi presents an intracellular life cycle in mammalian hosts to sustain infection. Parasite infection activates host cell responses, promoting an unbalance in reactive oxygen species (ROS) in the intracellular environment inducing genomic DNA lesions in the host cell during infection. To further understand changes in host cell chromatin induced by parasite infection, we investigated alterations in chromatin caused by infection by performing quantitative proteomic analysis. DNA Damage Repair proteins, such as Poly-ADP-ribose Polymerase 1 (PARP-1) and X-Ray Repair Cross Complementing 6 (XRRC6), were recruited to the chromatin during infection. Also, changes in chromatin remodeling enzymes suggest that parasite infection may shape the epigenome of the host cells. Interestingly, the abundance of oxidative phosphorylation mitochondrial and vesicle-mediated transport proteins increased in the host chromatin at the final stages of infection. In addition, Apoptosis-inducing Factor (AIF) is translocated to the host cell nucleus upon infection, suggesting that cells enter parthanatos type of death. Altogether, this study reveals how parasites interfere with the host cells' responses at the chromatin level leading to significant crosstalk that support and disseminate infection.

Aquatic pollutants are associated with reproductive alterations and genotoxicity in estuarine fish (Sciades herzbergii - Bloch, 1794) from the Amazon Equatorial Coast.

Estuaries are constantly subject to continuous environmental impacts of human activities, such as fisheries, port or industry, and domestic sewage, with fish being one of the most affected aquatic animals, reflecting the impacts directly on their bodies. Thus, the aim of this study was to carry out the biomonitoring of an estuary located on the Amazonian Equatorial Coast through analysis of PAHs (Polycyclic Aromatic Hydrocarbons) in the water, in addition to trace metals, histopathological alterations and analysis of erythrocyte micronuclei in Sciades herzbergii. S. herzbergii was used as a model species, due to its estuarine-resident behavior. Gonad and gill samples were subjected to histopathological evaluations. The quantification of trace metals was performed in samples of skeletal muscles of the animals collected, where concentrations of Lead (Pb), Copper (Cu), Zinc (Zn), Cadmium (Cd), Magnesium (Mg), Iron (Fe) and Aluminum (Al) were found. Except for Cadmium (Cd), all the concentrations were above the recommended limits. The PAHs analysis revealed the presence of Naphthalene and Acenaphthene in the water samples Histopathological and genotoxic analyses revealed of lesions in 100% of the study specimens. Thus, the histological and genotoxic alterations found in 100% of S. herzbergii specimens captured in São José Bay-MA are potentially associated with PAH concentrations present in the water. These results are potentially associated with the presence of PAH and trace metals, both in water and in animal tissues, inferring a general scenario of environmental contamination which directly implies a risk to the health and survival of the local biota. This study shows the relevance of continuous biomonitoring of estuarine ecosystems, in order to guide authorities regarding sewage management and ensure the evolutionary development of estuarine species, especially fishes of importance in the local cuisine, therefore related to human food security.

High levels of NRF2 sensitize temozolomide-resistant glioblastoma cells to ferroptosis via ABCC1/MRP1 upregulation.

Glioblastoma patients have a poor prognosis mainly due to temozolomide (TMZ) resistance. NRF2 is an important transcript factor involved in chemotherapy resistance due to its protective role in the transcription of genes involved in cellular detoxification and prevention of cell death processes, such as ferroptosis. However, the relation between NRF2 and iron-dependent cell death in glioma is still poorly understood. Therefore, in this study, we analyzed the role of NRF2 in ferroptosis modulation in glioblastoma cells. Two human glioblastoma cell lines (U251MG and T98G) were examined after treatment with TMZ, ferroptosis inducers (Erastin, RSL3), and ferroptosis inhibitor (Ferrostatin-1). Our results demonstrated that T98G was more resistant to chemotherapy compared to U251MG and showed elevated levels of NRF2 expression. Interestingly, T98G revealed higher sensitivity to ferroptosis, and significant GSH depletion upon system xc- blockage. NRF2 silencing in T98G cells (T98G-shNRF2) significantly reduced the viability upon TMZ treatment. On the other hand, T98G-shNRF2 was resistant to ferroptosis and reverted intracellular GSH levels, indicating that NRF2 plays a key role in ferroptosis induction through GSH modulation. Moreover, silencing of ABCC1, a well-known NRF2 target that diminishes GSH levels, has demonstrated a similar collateral sensitivity. T98G-siABCC1 cells were more sensitive to TMZ and resistant to Erastin. Furthermore, we found that NRF2 positively correlates with ABCC1 expression in tumor tissues of glioma patients, which can be associated with tumor aggressiveness, drug resistance, and poor overall survival. Altogether, our data indicate that high levels of NRF2 result in collateral sensitivity on glioblastoma via the expression of its pro-ferroptotic target ABCC1, which contributes to GSH depletion when the system xc- is blocked by Erastin. Thus, ferroptosis induction could be an important therapeutic strategy to reverse drug resistance in gliomas with high NRF2 and ABCC1 expression.

Preclinical assessment of dual CYP26[A1/B1] inhibitor, DX308, as an improved treatment for keratinization disorders.

Background: Retinoid-based therapies are commonly used in the treatment of disorders of keratinization and other skin disorders but can result in non-specific effects and adverse reactions. Use of retinoic acid metabolism blocking agents (RAMBAs) such as DX308 may address these shortcomings. Objectives: Characterize the therapeutic potential of recently discovered, CYP26-selective RAMBA, DX308. Materials and Methods: Preliminary in vitro assessment of potential off-target activity, metabolic and toxicologic profiling. Studies to assess safety and efficacy of topical treatment in correcting abnormal skin morphology in rhino mice. Extensive gene expression profiling by RNA sequencing and qPCR in 3D epidermis grown with keratinocytes (KCs) from keratinization disorders and healthy controls, to investigate modulation of retinoid biopathways. Results: In vitro, DX308 does not interact with off-target nuclear receptors or CYP450s, is not genotoxic, and is stable in skin, despite vigorous hepatic metabolism. In vivo, topical DX308 induces comedolysis and epidermal thickening without apparent adverse effects. Gene expression profiling shows potent modulation of retinoid-responsive genes by DX308 in both healthy and keratinization disorder KCs. Pathway analysis suggests DX308 may inhibit inflammatory and immune responses in KCs. Conclusions: These preliminary studies suggest that DX308 is an efficacious topical therapeutic with a favourable metabolic and safety profiles. DX308 may present an improved therapeutic alternative for the treatment of keratinization disorders and other retinoid-responsive skin ailments.

Lipolytic Enzymes with Hydrolytic and Esterification Activities Produced by Filamentous Fungi Isolated from Decomposition Leaves in an Aquatic Environment.

Microbial lipases are prominent biocatalysts able to catalyze a wide variety of reactions in aqueous and nonaqueous media. In this work, filamentous fungi isolated from leaves decomposed in an aquatic environment were screened for lipase production with hydrolytic activity and esterification. Agar plates with Tween 20 and Rhodamine B were used for selection, while submerged cultures with olive oil were subsequently used to select 38 filamentous fungi. Trichoderma harzianum, Fusarium solani, Trichoderma harzianum F5, and Penicillium sp. F36 were grown in six different culture media. F. solani presented the highest lipase production (2.37 U/mL) with esterification activity of 0.07 U/mL using medium composed of (g.L-1) KH2PO4 1.00, MgSO4 H2O 1.123, and CuSO4 0.06. Supplementation of this culture medium with organic nitrogen sources increased lipase production by 461.3% using tryptone and by 419.4% using yeast extract. Among the vegetable oils from the Amazon region, degummed cotton oil induced lipase production up to 8.14 U/mL. The lipase produced by F. solani F61 has great potential to application in conventional processes and biodiesel production by transesterification of vegetable oils, as well as food industries in the production of fatty acid esters by hydrolysis and esterification.

Quality of life in climacteric women assisted by primary health care.

This cross-sectional study evaluated the quality of life and associated factors of climacteric women in Brazil using a random and representative sample of women assisted by primary care professionals. We investigated the variables using the Menopause-Specific Quality of Life Questionnaire, MENQOL, whose mean scores were compared using Mann-Whitney and Kruskal-Wallis tests according to the sample characteristics. The variables associated with the outcomes in univariate analyses with a p≤0.2 were jointly evaluated using multiple linear regression. In this study, 849 women ranging in age from 40 to 65 years were evaluated. The predictors of poor quality of life in the vasomotor domain were women with severe climacteric symptoms (p<0.001), increased Body Mass Index (BMI) (p = 0.006), sleep (p = 0.022), and postmenopausal (p<0.001) alterations. For the psychosocial domain, the associated variables were severe climacteric symptoms (p<0.001) and sleep alterations (p<0.001); for the physical domain, the associated variables were severe climacteric symptoms (p<0.001), increased BMI (p<0.001), sleep (p<0.001), and postmenopausal (p<0.001) alterations. Severe climacteric symptoms, low sleep quality, increased BMI, and postmenopausal status were factors that were more associated with impairments in quality of life. With the increase in life expectancy, we suggest that greater attention should be paid to women's quality of life associated with climacteric symptoms.

A Clinical Interpretable Approach Applied to Cardiovascular Risk Assessment.

The effectiveness of predictive models in supporting the Clinical Decision is closely related with their clinical interpretability, i.e.the model should provide clear information on how to reach a specific classification/decision. In fact, the development of interpretable and accurate predictive models assumes a key importance as these tools can be very useful in Clinical Decision Support Systems (CDSS). The development of those models may comprise two main perspectives; existent clinical knowledge (clinical expert knowledge, clinical guidelines, current models, etc.) as well as data driven approaches able to extract (new) knowledge from recent clinical datasets. This work focuses in knowledge extraction from recent datasets (data driven) based on computational intelligence techniques. The main hypothesis that supports this work is that individuals with similar characteristics present a similar risk prof ile. Thus, this work addresses the development of stratification models able to learn distinct groups (or classes) of subjects assessing the similarity between characterizing variables. In particular, in the current study a data-driven supervised cluster approach is proposed aiming the derivation of meaningful rules directly from the dataset. The validation was performed based on the largest Portuguese coronary artery disease patient's dataset, provided by the Portuguese Society of Cardiology and comprising 13902 acute coronary syndrome patients. The goal was to assess the risk of death 30 days after admission. The models' performance was assessed through the sensitivity, specificity and geometric mean values. The obtained results show the potential of this approach, as they represent an acceptable performance (GM= 72%) while the clinical interpretability of the model is assured through the derived rules. Despite the achieved results, there are several research directions to be followed in order to enhance this work.

Influence of dressing application time after breast augmentation on cutaneous colonization: A randomized clinical trial.

Concepts regarding the best way to treat a surgical wound vary, in literature, ranging from no dressing use to dressing maintenance for 24 to 48 hours or until suture removal. This study aimed to evaluate the influence of the length of dressing maintenance after breast augmentation with implants on cutaneous colonization and surgical site infection. This is a two-arm, parallel group, randomized clinical trial. Eighty patients who were candidates for augmentation mammoplasty with silicone implants were randomly allocated to two groups, in which the dressing was removed on postoperative day 1 (group A, n = 40) or postoperative day 6 (group B, n = 40). Cutaneous colonization was examined by culturing samples collected before and after dressing removal. The criteria defined by the Centers for Disease Control and Prevention were used to assess surgical site infection. No significant difference regarding cutaneous colonization was observed between groups before dressing application. On postoperative day 6, significantly more bacterial growth was observed in group A (p = 0.01). No surgical site infection occurred. We concluded that maintaining the dressing for 6 days led to a lower cutaneous colonization but did not influence surgical site infection rates.

Feasibility and Effectiveness of Tuberculosis Active Case-Finding among Children Living with Tuberculosis Relatives: a Cross-Sectional Study in Guinea-Bissau.

BACKGROUND AND OBJECTIVES: The World Health Organization End tuberculosis (TB) Strategy, approved in 2014, aims at a 90% reduction in TB deaths and an 80% reduction in TB incidence rate by 2030. One of the suggested interventions is the systematic screening of people with suspected TB, belonging to specific risk groups. The Hospital Raoul Follereau (HRF) in Bissau, Guinea-Bissau, is the National Reference Hospital for Tuberculosis and Lung Disease of the country. We performed an active case-finding program among pediatric age family members and cohabitants of admitted adult TB patients, from January to December 2013. METHODS: Newly admitted adult patients with a diagnosis of TB were invited to bring their family members or cohabitants in childhood age for clinical evaluation in a dedicated outpatient setting within the hospital compound. All the children brought to our attention underwent a medical examination and chest x-ray. In children with clinical and/or radiologic finding consistent with pulmonary TB, a sputum-smear was requested. RESULTS: All admitted adult patients accepted to bring their children cohabitants. In total, 287 children were examined in 2013. Forty-four patients (15%) were diagnosed with TB. The number needed to screen (NNS) to detect one case of TB was 7. 35 patients (80%) had pulmonary TB; 2 of them were sputum smear-positive. No adjunctive personnel cost was necessary for the intervention. CONCLUSIONS: A hospital-based TB active case-finding program targeted to high-risk groups like children households of severely ill admitted patients with TB can successfully be implemented in a country with limited resources.

An interpretable data-driven approach for rules construction: Application to cardiovascular risk assessment.

The development of models able to produce an understandable decision by the clinicians is of great importance to support their decision. Therefore, the research of methodologies able to extract useful knowledge from existing datasets, as well as to integrate this knowledge into the current clinical evidence, is a key aspect in the enhancement of the clinical decision. This work focuses on the development of interpretable models to assess the patient's condition based on supervised clustering theories, enabling the discovery of a set of features that best represents that condition. At the same time, the technique is supported on a structure that enables the formulation of simple and interpretable rules. Despite its general applicability, the proposed methodology is applied to coronary artery disease (CAD), particularly, in the risk of death assessment (30 days after the admission) of patients that have been admitted to the emergency unit. The validation is performed using a real dataset with Acute Coronary Syndromes, provided by the Portuguese Society of Cardiology. While the methodology produces simple and interpretable rules, the performance achieves an improvement of 7% in relation to geometric mean, when compared with GRACE model (commonly used in Portugal).

Improving clinical models based on knowledge extracted from current datasets: a new approach.

The Cardiovascular Diseases (CVD) are the leading cause of death in the world, being prevention recognized to be a key intervention able to contradict this reality. In this context, although there are several models and scores currently used in clinical practice to assess the risk of a new cardiovascular event, they present some limitations. The goal of this paper is to improve the CVD risk prediction taking into account the current models as well as information extracted from real and recent datasets. This approach is based on a decision tree scheme in order to assure the clinical interpretability of the model. An innovative optimization strategy is developed in order to adjust the decision tree thresholds (rule structure is fixed) based on recent clinical datasets. A real dataset collected in the ambit of the National Registry on Acute Coronary Syndromes, Portuguese Society of Cardiology is applied to validate this work. In order to assess the performance of the new approach, the metrics sensitivity, specificity and accuracy are used. This new approach achieves sensitivity, a specificity and an accuracy values of, 80.52%, 74.19% and 77.27% respectively, which represents an improvement of about 26% in relation to the accuracy of the original score.

Expert knowledge integration in the data mining process with application to cardiovascular risk assessment.

The data mining process, when applied to clinical databases, suffers from critical data problems, from noisy acquisitions to missing or incomplete data points. Expert knowledge, in the form of practitioners' experience and clinical guidelines, is already used to manually correct some of these problems, while enhancing expert's confidence in such systems. In this work, we propose the Knowledge-Biased Tree (KB3), a knowledge biased decision tree inducer that is able to exploit IF THEN rules to guide the tree inducing process. The KB3 approach was tested against its unbiased counterpart, the C5.0 algorithm in the cardiovascular risk assessment task. Using a clinical dataset provided by the hospital of Sta Cruz (Lisbon, Portugal) the performance of the proposed algorithm is compared against the unbiased C5.0 and the state of the art risk score used in clinical practice (GRACE risk score).

Assessment of cardiovascular risk based on a data-driven knowledge discovery approach.

The cardioRisk project addresses the development of personalized risk assessment tools for patients who have been admitted to the hospital with acute myocardial infarction. Although there are models available that assess the short-term risk of death/new events for such patients, these models were established in circumstances that do not take into account the present clinical interventions and, in some cases, the risk factors used by such models are not easily available in clinical practice. The integration of the existing risk tools (applied in the clinician's daily practice) with data-driven knowledge discovery mechanisms based on data routinely collected during hospitalizations, will be a breakthrough in overcoming some of these difficulties. In this context, the development of simple and interpretable models (based on recent datasets), unquestionably will facilitate and will introduce confidence in this integration process. In this work, a simple and interpretable model based on a real dataset is proposed. It consists of a decision tree model structure that uses a reduced set of six binary risk factors. The validation is performed using a recent dataset provided by the Portuguese Society of Cardiology (11113 patients), which originally comprised 77 risk factors. A sensitivity, specificity and accuracy of, respectively, 80.42%, 77.25% and 78.80% were achieved showing the effectiveness of the approach.

Ensino farmacêutico no Brasil na perspectiva de uma formação clínica / Pharmacist education in brazil from a clinical perspective

O objetivo deste estudo foi discutir a interação entre ensino e prática farmacêutica voltada para a formação clínica. A metodologia consistiu na busca, leitura e discussão de materiais impressos ou em formato eletrônico relacionados à temática. Os resultados apresentam uma pequena introdução sobre a evolução da profissão farmacêutica, que foi acompanhada pelo ensino, para, então, discutir as propostas que vêm sendo empregadas para garantir o desenvolvimento das diversas habilidades necessárias à práxis farmacêutica, sobretudo no âmbito clínico. Por muito tempo, o ofício farmacêutico esteve relacionado com a manipulação dos medicamentos, mas, com a ascensão da indústria farmacêutica, o profissional perdeu esse papel, indo atuar nas análises clínicas e na indústria. Na tentativa de reaproximar o farmacêutico da farmácia, resgatando o seu papel social, surgiram diversas propostas, como a Farmácia Clínica e a Atenção Farmacêutica. Entretanto, a incorporação da dimensão clínica na prática profissional exige uma adequação dos cursos de formação. Algumas experiências foram adotadas e são praticadas há muito tempo, como projetos de extensão e Farmácia-Escola. Entretanto, nos últimos anos, tem se difundido o uso de metodologias ativas, como as estratégias de ensino e aprendizagem baseadas na problematização, uso de realidade virtual, jogos e outros tipos de simulação. Todas essas práticas pedagógicas, inovadoras ou não, são úteis no processo ensino-aprendizagem, mas apenas se forem utilizadas na perspectiva de otimizar os resultados da farmacoterapia, melhorando a qualidade de vida dos usuários de medicamentos...

The aim of this study was to discuss the interaction between education and the practice of pharmacy, with a focus on clinical training. The methodology consisted in the discussion of papers and books related to the theme. The findings constitute a short introduction to the development of the pharmaceutical profession, which evolved side-by-side with teaching, and then discuss the measures that have been proposed to ensure the development of the various skills necessary for pharmaceutical practice, above all in the clinical setting. For a long time, the pharmacist was related to the handling of medicines, but the rise of the pharmaceutical industry led to the loss of this role, so that the pharmacist went to work in the industry and clinical analysis. In an attempt to bring pharmacists back to the pharmacy, rescuing their social role, several proposals were put forward, such as Clinical Pharmacy and Pharmaceutical Care. However, the incorporation of the clinical dimension into professional practice requires adjustments in the training courses. Some experiments were put into practice long ago, such as Faculty extension and Faculty-Pharmacy projects. In recent years, the use of active methods has been spreading, such as strategies for teaching and learning based on the use of problems, virtual reality, games and other types of simulation. All these teaching practices, innovative or not, are useful in the teaching-learning process, but only if used with a view to enhancing the results of pharmacotherapy, thus improving the quality of life of patients...

Quality of fermented milks produced with Lactobacillus rhamnosus and Lactobacillus fermentum isolated from artisanal cheeses / Qualidade de leites fermentados produzidos com Lactobacillus rhamnosus e Lactobacillus fermentum isolados de queijos artesanais

Leites fermentados por Lactobacillus rhamnosus e Lactobacillus fermentum, isolados de queijos artesanais, foram produzidos e avaliados quanto às características físico-químicas e microbiológicas durante 45 dias de estocagem a 8-10ºC. Análises sensoriais foram realizadas aos 15 e 60 dias. Ambos os leites fermentados apresentaram contagens adequadas das bactérias láticas, superiores a 108 UFC/g, durante toda a estocagem. As médias das análises físico-químicas e microbiológicas dos produtos durante a estocagem foram iguais e todos atenderam às especificações da legislação brasileira. Melhores resultados de avaliações sensoriais (P<0.05) foram aos 15 dias de estocagem. Leites fermentados por L. fermentum obtiveram melhor aceitação sensorial aos 60 dias de estocagem, quando apresentavam acidez titulável inferior à encontrada no leite fermentado por L. rhamnosus. Portanto, a utilização dessas culturas pode ser viável para a elaboração de novos leites fermentados, que apresentariam prazo de validade de 45 dias de estocagem sob refrigeração.(AU)

Safety profiles of adalimumab, etanercept and infliximab: a pharmacovigilance study using a measure of disproportionality in a database of spontaneously reported adverse events.

WHAT IS KNOWN AND OBJECTIVE: Despite being effective, the biologics approved for treating rheumatoid arthritis have been associated with serious adverse events. This study is aimed at comparing the safety profiles of adalimumab, etanercept and infliximab by analysing the disproportionalities of the associations between the different adverse events and the different biologics in the Portuguese spontaneous reporting database. METHODS: Adverse events spontaneously reported to the Portuguese pharmacovigilance system (PPS) between 2009 and 2011 were included. Adverse events were classified according to MedDRA in the primary system organ class. The reporting odds ratio (ROR) and its 95% confidence intervals (CI) were calculated for each biologic regarding the various categories of adverse events. Microsoft Excel was used to perform all the calculations. RESULTS AND DISCUSSION: The PPS received 12167 adverse events reported for all drugs, of which 741 were reported for biologics: 157 for adalimumab, 132 for etanercept and 452 for infliximab. Compared with the all other drugs, adalimumab, etanercept and infliximab were all disproportionately associated with 'infections and infestations' (ROR: 6·65, 95% CI: 4·50-9·83; ROR: 2·74, 95% CI: 1·56-4·81; ROR: 2·95, CI 95%: 2·16-4·02, respectively) and with 'neoplasms benign, malignant and unspecified' (ROR: 7·23, 95% CI: 3·92-13·33; ROR: 6·26, 95% IC: 3·12-12·57; ROR: 3·94, 95% CI: 2·41-6·44, respectively), etanercept with 'general disorders and administration site conditions' (ROR: 2·08, 95% CI: 1·44-3·02) and infliximab with 'immune system disorders' (ROR: 5·17, 95% CI: 3·50-7·64), 'respiratory, thoracic and mediastinal disorders' (ROR: 1·80, 95% CI: 1·31-2·48) and 'investigations' (ROR: 1·82, 95% CI: 1·19-2·78). When interpreting the results one should take into consideration the number of patients exposed and should not only rely on the number of adverse events reported. WHAT IS NEW AND CONCLUSION: Although the disproportionalities found for adalimumab and etanercept may suggest strong associations with particular adverse events, caution is needed when drawing conclusions on the association between infliximab and the adverse events analysed. In the light of the present findings, these results deserve further evaluation.

Classification systems for lower extremity amputation prediction in subjects with active diabetic foot ulcer: a systematic review and meta-analysis.

AIM: We systematically review the available systems used to classify diabetic foot ulcers in order to synthesize their methodological qualitative issues and accuracy to predict lower extremity amputation, as this may represent a critical point in these patients' care. MATERIAL AND METHODS: Two investigators searched, in EBSCO, ISI, PubMed and SCOPUS databases, and independently selected studies published until May 2013 and reporting prognostic accuracy and/or reliability of specific systems for patients with diabetic foot ulcer in order to predict lower extremity amputation. RESULTS: We included 25 studies reporting a prevalence of lower extremity amputation between 6% and 78%. Eight different diabetic foot ulcer descriptions and seven prognostic stratification classification systems were addressed with a variable (1-9) number of factors included, specially peripheral arterial disease (n = 12) or infection at the ulcer site (n = 10) or ulcer depth (n = 10). The Meggitt-Wagner, S(AD)SAD and Texas University Classification systems were the most extensively validated, whereas ten classifications were derived or validated only once. Reliability was reported in a single study, and accuracy measures were reported in five studies with another eight allowing their calculation. Pooled accuracy ranged from 0.65 (for gangrene) to 0.74 (for infection). CONCLUSION: There are numerous classification systems for diabetic foot ulcer outcome prediction, but only few studies evaluated their reliability or external validity. Studies rarely validated several systems simultaneously and only a few reported accuracy measures. Further studies assessing reliability and accuracy of the available systems and their composing variables are needed.

Reimplante dentário na dentição decídua: uma alternativa de sucesso – relato de caso / Tooth replantation in primary dentition: a successful choice - case report

A literatura ‚ muito controversa ao descrever os reimplantes de dentes decíduos.  um procedimento desencorajado pela maioria por poder causar danos ao sucessor permanente. O presente trabalho apresenta e discute relatos de sucesso de reimplantes na dentição decídua, bem como aborda sua técnica, suas indicações, contraindicações e possíveis sequelas. Frentes diversas condutas em relação … avulso de um dente decíduo, observa-se que são necessários mais estudos para que se possa obter êxito em um número maior de casos

Literature is very controversial while describing the replantation of primary teeth. This procedure is commonly discouraged due to the possibility of causing damage to its permanent successor. This article presents and discusses reports of successful replantation in primary dentition, and also discusses the technique, its indications and contraindications as well as possible sequels. Considering the different approaches after a deciduous tooth avulsion, it was observed that further researches are required to ensure successful procedures