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Resumo: Relatase o caso de uma doente de 75 anos que em Out./2004 recorreu ao SU por queixas de tosse, febre e toracalgia esq. Com características pleuríticas. A semiologia pulmonar foi compatível com derrame pleural esq. E procedeu-se à respectiva investigação clínica. Existiam parâmetros de infecção elevados no contexto de um exsudado pleural. A tomografia computorizada evidenciou derrame pleural e espessamento no segmento anterior do LSD, cuja bronco-fibroscopia apenas visualizou alterações inflamatórias. Em Fev./2005 verifica-se recidiva do derrame pleural. A tomografia computorizada referia agora a existência de densificação nodular adjacente ao BLSE e língula. Em conjunto com a equipa de cirurgia torácica, foi decidido procederse a videoto-racoscopia. Durante a realização da técnica houve necessidade de conversão para toracotomia e o pós-operatório foi moroso. O exame histológico revelou um CPNPC â adenocarcinoma. A doente iniciou quimioterapia de primeira linha e em Mar./2006 sur-giu metastização óssea. Efectua quimioterapia de segunda linha, tendo-se mantido em doença estável, e em Jul./2007 inicia terapêutica com erlotinib que mantém actualmente, com boa tolerância, sem queixas álgicas e sem progressão da doença sob 13 meses de terapêutica. E até quando esta resposta?Rev Port Pneumol 2008; XIV (Supl 3): S71-S77 Abstract: A 75 year old woman was observed at the emergency department with cough, hyperthermia and thoracic pain in October 2004.A pleural effusion was identified and studied. Thorax CT scan evidenced a pleural effusion and thickening in the RSL anterior segment but bronchofibroscopy only identified inflammatory changes. In February 2005 the pleural effusion relapsed and the CT scan showed nodular densification adjacent to LSLB and lingual. VATS converted to thoracotomy was preformed and followed by a long recover period. Histology of surgical specimen revealed an adenocarcinoma. First line CT was administered until progression as bone metastasis, in March 2006. Second line CT was started, with disease stabilization. The administration of erlotinib was started in July 2007 and continues to the present with good tolerance. The patient has no pain and continues without progression of disease after 13 month of treatment. For how long will she maintain this response, is the question.Rev Port Pneumol 2008; XIV (Supl 3): S71-S77 Palavras-chave: Adenocarcinoma do pulmão, derrame pleural, quimioterapia, erlotinib, qualidade de vida, sobrevivência, Key-words: Lung adenocarcinoma, pleural effusion, chemotherapy, erlotinib, quality of life, survival

Over 60,500 dengue cases were reported in the state of Espírito Santo (ES), Brazil, between 1995 and 1998. The study's purpose was to identify whether Aedes albopictus was transmitting the dengue virus during an epidemic in the locality of Vila Bethânia (Viana County),Vitória, ES. From April 3 to 9, 1998, blood and serum samples were collected daily for virus isolation and serological testing. Four autochthonous cases were confirmed through DEN 1 virus isolation and two autochthonous cases through MAC ELISA testing. Of 37 Ae. aegypti and 200 Ae. albopictus adult mosquitoes collected and inoculated, DEN1 virus was isolated only from a pool of two Ae. aegypti female mosquitoes. The study results suggest that Ae. albopictus still cannot be considered an inter-human vector in dengue epidemics in Brazil.

Abstract In this article, we present an investigation of (Ge + SiO2)/SiO2 multilayers deposited by magnetron sputtering and subsequently annealed at different temperatures. The structural properties were investigated by transmission electron microscopy, grazing incidence small angles X-ray scattering, Rutherford backscattering spectrometry, Raman, and X-ray photoelectron spectroscopies. We show a formation of self-assembled Ge clusters during the deposition at 250°C. The clusters are ordered in a three-dimensional lattice, and they have very small sizes (about 3 nm) and narrow size distribution. The crystallization of the clusters was achieved at annealing temperature of 700°C.

Dengue is present in the Federal District since 1991 and virological studies of the vector began in 1998. Two strains of DEN1 were isolated from 9 pools of female Aedes aegypti (78 mosq.), collected in April in Gama county, where the Breteau index was 5.4, and 32 autochtonous human cases were notified.

To behave adaptively, animals must learn to predict future reward, or value. To do this, animals are thought to learn reward predictions using reinforcement learning. However, in contrast to classical models, animals must learn to estimate value using only incomplete state information. Previous work suggests that animals estimate value in partially observable tasks by first forming "beliefs"-optimal Bayesian estimates of the hidden states in the task. Although this is one way to solve the problem of partial observability, it is not the only way, nor is it the most computationally scalable solution in complex, real-world environments. Here we show that a recurrent neural network (RNN) can learn to estimate value directly from observations, generating reward prediction errors that resemble those observed experimentally, without any explicit objective of estimating beliefs. We integrate statistical, functional, and dynamical systems perspectives on beliefs to show that the RNN's learned representation encodes belief information, but only when the RNN's capacity is sufficiently large. These results illustrate how animals can estimate value in tasks without explicitly estimating beliefs, yielding a representation useful for systems with limited capacity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hennig et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Soil-transmitted helminth (STH) control programs currently lack evidence-based recommendations for cost-efficient survey designs for monitoring and evaluation. Here, we present a framework to provide evidence-based recommendations, using a case study of therapeutic drug efficacy monitoring based on the examination of helminth eggs in stool., Methods: We performed an in-depth analysis of the operational costs to process one stool sample for three diagnostic methods (Kato-Katz, Mini-FLOTAC and FECPAKG2). Next, we performed simulations to determine the probability of detecting a truly reduced therapeutic efficacy for different scenarios of STH species (Ascaris lumbricoides, Trichuris trichiura and hookworms), pre-treatment infection levels, survey design (screen and select (SS); screen, select and retest (SSR) and no selection (NS)) and number of subjects enrolled (100-5,000). Finally, we integrated the outcome of the cost assessment into the simulation study to estimate the total survey costs and determined the most cost-efficient survey design., Principal Findings: Kato-Katz allowed for both the highest sample throughput and the lowest cost per test, while FECPAKG2 required both the most laboratory time and was the most expensive. Counting of eggs accounted for 23% (FECPAKG2) or ≥80% (Kato-Katz and Mini-FLOTAC) of the total time-to-result. NS survey designs in combination with Kato-Katz were the most cost-efficient to assess therapeutic drug efficacy in all scenarios of STH species and endemicity., Conclusions/significance: We confirm that Kato-Katz is the fecal egg counting method of choice for monitoring therapeutic drug efficacy, but that the survey design currently recommended by WHO (SS) should be updated. Our generic framework, which captures laboratory time and material costs, can be used to further support cost-efficient choices for other important surveys informing STH control programs. In addition, it can be used to explore the value of alternative diagnostic techniques, like automated egg counting, which may further reduce operational costs., Trial Registration: ClinicalTrials.gov NCT03465488., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: the FECPAKG2 technology was produced and distributed by Techion Group Ltd, of which ET is an employee and GM is managing director. Both hold stocks in Techion Group Ltd. The Mini-FLOTAC device is a commercial product distributed by GC, LR and MPM through the University of Napoli Federico II. All other authors declared that they have no competing interests., (Copyright: © 2023 Coffeng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The combination of electrical stimulation (ES) and bone tissue engineering (BTE) has been successful in treatments of bone regeneration. This study evaluated the effects of ES combined with PCL + β-TCP 5% scaffolds obtained by rotary jet spinning (RJS) in the regeneration of bone defects in the calvaria of Wistar rats. We used 120 animals with induced bone defects divided into 4 groups (n = 30): (C) without treatment; (S) with PCL+ β-TCP 5% scaffold; (ES) treated with ES (10 μA/5 min); (ES + S) with PCL + β-TCP 5% scaffold. The ES occurred twice a week during the entire experimental period. Cell viability (in vitro: Days 3 and 7) and histomorphometric, histochemical, and immunohistochemical (in vivo; Days 30, 60, and 90) analysis were performed. In vitro, ES + S increased cell viability after Day 7 of incubation. In vivo, it was observed modulation of inflammatory cells in ES therapy, which also promoted blood vessels proliferation, and increase of collagen. Moreover, ES therapy played a role in osteogenesis by decreasing ligand kappa B nuclear factor-TNFSF11 (RANKL), increasing alkaline phosphatase (ALP), and decreasing the tartarate-resistant acid phosphatase. The combination of ES with RJS scaffolds may be a promising strategy for bone defects regeneration, since the therapy controlled inflammation, favored blood vessels proliferation, and osteogenesis, which are important processes in bone remodeling., (© 2022 American Association for Anatomy.)

For lesbian, gay, bisexual, and questioning (LGBQ) youth of color, the intersection of identifying as both LGBQ and a person of color results in not only managing racial stereotypes, but also heterosexism and genderism. Developing a critical understanding of oppressive social conditions and ways to engage in social action is a form of resistance for these youth. Research is needed among LGBQ youth of color that examines the range of predictors and outcomes related to civic engagement, development, and empowerment. Drawing on data derived from a sample of urban youth of color ( N = 383; 53.1% Female; 75% Hispanic; Age range = 14 to 18 years; 15% identify as LGBQ), this study will: (1) examine the relationship between community-based perceptions (e.g., psychological sense of community), ethnic identity, behaviors (e.g., community civic participation) and awareness of social justice concerns with dimensions of psychological empowerment; and (2) assess differences that these relationships have between LGBQ and non-LGBQ youth of color. Findings indicate that main predictors have a positive impact on intrapersonal and cognitive dimensions of psychological empowerment through social justice orientation, with noted variations between LGBQ and non-LGBQ youth of color.

This study aimed to evaluate in vitro and in vivo polymeric membranes obtained by a rotary jet-spinning process for the repair of critical bone defects in the calvaria of Wistar rats, for future use in tissue engineering. Experimental sample collections were performed on the 30, 60 and 90th postoperative days, and the analyses performed were histomorphometric, immunohistochemistry, and western blotting. Reducing inflammatory infiltrate in all groups and experimental periods, angiogenesis on the 30th day did not show any difference between the groups, on the 60th day, 5% polycaprolactone/beta-tricalcium phosphate(PCL/β-TCP) was high compared to control (C), and on the 90th day, the same group reduced when compared to C and 10% PCL/β-TCP. The fibroplasia presented oscillations in every segment; on the 30th and 60th day, there was an increase in 5% PCL/β-TCP, which decreased by the 90th day compared to group C. 10% PCL/β-TCP decreased compared to C on the 60th and 90th day. The percentage of the collagen area remained high in all groups and all experimental periods. Immunohistochemistry quantifications showed variations in bone metabolism suggesting new bone formation. The 5 and 10% PCL/β-TCP scaffold were promising for the bone regeneration process because they participated in the modulation of inflammation, angiogenesis, fibroplasia, and collagenosis., (© 2021 S. Karger AG, Basel.)

Coinfection with the human immunodeficiency virus (HIV) and Leishmania impairs immune responses, increases treatment failure and relapse rates in patients with American tegumentary leishmaniasis (ATL), as well as visceral leishmaniasis (VL). There is insufficient data on the treatment, relapse, and secondary prophylaxis in patients coinfected with HIV/Leishmania in Brazil. This study investigated patients with HIV/ATL and HIV/VL to describe the outcome of leishmaniasis in patients assisted at a referral hospital of Brazilian midwestern region. Patients with HIV/ATL (n = 21) mainly presented cutaneous diseases (76.2%) with an overall relapse rate of 28.57% after treatment, whereas HIV/VL (n = 28) patients accounted for 17.5% of the cases. The counts of CD4 + T cells and CD8 + T cells and the CD4 + /CD8 + cell ratios at diagnosis or relapses were not significantly different between relapsing and non-relapsing patients. Patients with HIV/ATL or HIV/VL showed high levels of activation markers in CD4 + and CD8 + T cells. The regular use of highly active antiretroviral therapy (HAART) and viral load at the time of diagnosis did not influence the relapse rates. Relapses occurred in 36.4% (4/11) of the patients with HIV/VL receiving secondary prophylaxis and in 5.9% (1/17) of the patients who did not receive secondary prophylaxis (p = 0.06). These data are relevant for the therapeutic management of the patients coinfected with HIV/Leishmania., (Copyright © 2021. Published by Elsevier B.V.)

Background: Albendazole (ALB) is administered annually to millions of children through global deworming programs targeting soil-transmitted helminths (STHs: Ascaris lumbricoides, Trichuris trichiura and hookworms, Necator americanus and Ancylostoma duodenale). However, due to the lack of large individual patient datasets collected using standardized protocols and the application of population-based statistical methods, little is known about factors that may affect individual responses to treatment., Methodology/principal Findings: We re-analyzed 645 individual patient data from three standardized clinical trials designed to assess the efficacy of a single 400 mg oral dose of ALB against STHs in schoolchildren from different study sites, each with varying history of drug pressure based on duration of mass drug administration programs: Ethiopia, low; Lao People's Democratic Republic (PDR), moderate; Pemba Island (Tanzania), high. Using a Bayesian statistical modelling approach to estimate individual responses (individual egg reduction rates, ERRi), we found that efficacy was lower in Pemba Island, particularly for T. trichiura. For this STH, the proportion of participants with a satisfactory response (ERRi ≥50%), was 65% in Ethiopia, 61% in Lao PDR but only 29% in Pemba Island. There was a significant correlation between ERRi and infection intensity prior to drug administration (ERRi decreasing as a function of increasing infection intensity). Individual age and sex also affected the drug response, but these were of negligible clinical significance and not consistent across STHs and study sites., Conclusions/significance: We found decreased efficacy of ALB against all the STHs analyzed in Pemba Island (Tanzania), an area with high drug pressure. This does not indicate causality, as this association may also be partially explained by differences in infection intensity prior to drug administration. Notwithstanding, our results indicate that without alternative treatment regimens, program targets will not be achievable on Pemba Island because of inadequate efficacy of ALB., Trial Registration: The study was registered on Clinicaltrials.gov (ID: NCT03465488) on March 7, 2018., Competing Interests: The authors have declared that no competing interests exist.

Background: Cells of the innate immune system undergo long-term functional reprogramming in response to Bacillus Calmette-Guérin (BCG) exposure via a process called trained immunity, conferring nonspecific protection to unrelated infections. Here, we investigate whether BCG-induced trained immunity is able to protect against infections caused by different Leishmania spp., protozoa that cause cutaneous and mucosal or visceral lesions., Methods: We used training models of human monocytes with BCG and subsequent infection by L. braziliensis, L. amazonensis and L. infantum, and the vaccination of wild-type and transgenic mice for IL-32γ before in vivo challenge with parasites., Results: We demonstrated that monocytes trained with BCG presented enhanced ability to kill L. braziliensis, L. amazonensis and L. infantum through increased production of reactive oxygen species. Interleukin (IL)-32 appears to play an essential role in the development of trained immunity. Indeed, BCG exposure induced IL-32 production in human primary monocytes, both mRNA and protein. We have used a human IL-32γ transgenic mouse model (IL-32γTg) to study the effect of BCG vaccination in different Leishmania infection models. BCG vaccination decreased lesion size and parasite load in infections caused by L. braziliensis and reduced the spread of L. amazonensis to other organs in both infected wild-type (WT) and IL-32γTg mice. In addition, BCG reduced the parasite load in the spleen, liver and bone marrow of both WT and IL-32γTg mice infected with L. infantum. BCG vaccination increased inflammatory infiltrate in infected tissues caused by different Leishmania spp. In all infections, the presence of IL-32γ was not mandatory, but it increased the protective and inflammatory effects of BCG-induced training., Conclusions: BCG's ability to train innate immune cells, providing protection against leishmaniasis, as well as the participation of IL-32γ in this process, pave the way for new treatment strategies for this neglected infectious disease., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Inhibitors of the epidermal growth factor (EGFR) represent an effective therapeutic option for patients with metastatic colorectal carcinoma, free of activating mutations in KRAS and NRAS. However, the research of mutations is of high cost and scarcely accessible. The expression of the EGFR by immunohistochemistry predicting the mutation status of the expanded RAS (KRAS and NRAS), may allow treatment by a diagnostic method less costly and more accessible., Aim: Investigate the correlation between the clinical-pathological data, the cytoplasmic-membrane expression of the EGFR and the mutational status of the expanded RAS., Method: A total of 139 patients with colorectal carcinoma from the archives of Instituto Goiano de Oncologia e Hematologia were evaluated., Results: Mutation of the expanded RAS was detected in 78 (56.1%) cases. The EGFR expression was stratified in 23 (16.5%) "positive", 49 (35.2%) "negative" and 67 (48.2%) "uncertain". No significant correlation was found between the mutational status of the RAS and the EGFR expression in comparison to age, gender, location, histological type, histological grade and stage. From 23 "positive" cases, 21 (91.3%) showed wild-type RAS gene, and 49 "negative", 41 (83.7%) presented mutation, resulting in a strong association between EGFR "positive", "negative" groups and the mutational status of the RAS (p<0.001), with 86.1% of accuracy., Conclusions: The cytoplasmic-membrane analysis of the EGFR expression stratified into "positive", "negative" and "uncertain" predicts mutational status of the RAS in 51.7% of the cases (p<0.001), with 86.1% of accuracy.

Background: Efforts to control soil-transmitted helminth (STH) infections have intensified over the past decade. Field-survey data on STH prevalence, infection intensity and drug efficacy is necessary to guide the implementation of control programs and should be of the best possible quality., Methodology: During four clinical trials designed to evaluate the efficacy of albendazole against STHs in Brazil, Ethiopia, Lao PDR and Tanzania, quality control (QC) was performed on the duplicate Kato-Katz thick smears and the data entry. We analyzed datasets following QC on both fecal egg counts (FECs) and data entry, and compared the prevalence of any STH infection and moderate-to-heavy intensity (MHI) infections and the drug efficacy against STH infections., Results: Across the four study sites, a total of 450 out of 4,830 (9.3%) Kato-Katz thick smears were re-examined. Discrepancies in FECs varied from ~3% (hookworms) to ~6.5% (Ascaris lumbricoides and Trichuris trichiura). The difference in STH prevalence and prevalence of MHI infections using the datasets with and without QC of the FECs did not exceed 0.3%, except for hookworm infections in Tanzania, where we noted a 2.2 percentage point increase in MHI infections (pre-QC: 1.6% vs. post-QC: 3.8%). There was a 100% agreement in the classification of drug efficacy of albendazole against STH between the two datasets. In total, 201 of the 28,980 (0.65%) data entries that were made to digitize the FECs were different between both data-entry clerks. Nevertheless, the overall prevalence of STH, the prevalence of MHI infections and the classification of drug efficacy remained largely unaffected., Conclusion/significance: In these trials, where staff was informed that QC would take place, minimal changes in study outcomes were reported following QC on FECs or data entry. Nevertheless, imposing QC did reduce the number of errors. Therefore, application of QC together with proper training of the personnel and the availability of clear standard operating procedures is expected to support higher data quality., Competing Interests: The authors have declared that no competing interests exist.

The World Health Organization (WHO) has defined moderate-to-heavy intensity (M&HI) infections with soil-transmitted helminths (Ascaris lumbricoides, Trichuris trichiura and the two hookworms, Ancylostoma duodenale and Necator americanus) based on specific values of eggs per gram of stool, as measured by the Kato-Katz method. There are a variety of novel microscopy and DNA-based methods but it remains unclear whether applying current WHO thresholds on to these methods allows for a reliable classification of M&HI infections. We evaluated both WHO and method-specific thresholds for classifying the M&HI infections for novel microscopic (FECPAKG2, McMaster and Mini-FLOTAC) and DNA-based (qPCR) diagnostic methods. For this, we determined method-specific thresholds that best classified M&HI infections (defined by Kato-Katz and WHO thresholds; reference method) in two multi-country drug efficacy studies. Subsequently, we verified whether applying these method-specific thresholds improved the agreement in classifying M&HI infections compared to the reference method. When we applied the WHO thresholds, the new microscopic methods mainly misclassified M&HI as low intensity, and to a lesser extent low intensity infection as M&HI. For FECPAKG2, applying the method-specific thresholds significantly improved the agreement for Ascaris (moderate → substantial), Trichuris and hookworms (fair → moderate). For Mini-FLOTAC, a significantly improved agreement was observed for hookworms only (fair → moderate). For the other STHs, the agreement was almost perfect and remained unchanged. For McMaster, the method-specific thresholds revealed a fair to a substantial agreement but did not significantly improve the agreement. For qPCR, the method-specific thresholds based on genome equivalents per ml of DNA moderately agreed with the reference method for hookworm and Trichuris infections. For Ascaris, there was a substantial agreement. We defined method-specific thresholds that improved the classification of M&HI infections. Validation studies are required before they can be recommended for general use in assessing M&HI infections in programmatic settings., Competing Interests: The FECPAKG2 technology was produced and distributed by Techion Group Ltd, of which ET is an employee and GM is managing director. Both hold stocks in Techion Group Ltd. The Mini-FLOTAC device is a commercial product distributed by GC, LR and MPM through the University of Napoli Federico II. However, their affiliations did not play any role in the preparation and submission of this manuscript. All other authors declared that they have no competing interests.

Background: Porphyrias are a group of metabolic diseases, individually rare but with an important combined prevalence. Because of their pathological complexity and clinical heterogeneity, they present a challenging diagnosis. The present review aims to provide a clinically based approach to the recognition and treatment of these disorders., Methods: We carried out a search in PubMed, with the keyword "porphyria", for reviews published in English from 2010 until 2017., Results: The research yielded 196 papers, of which 64 were included in the final narrative review., Conclusions: Porphyrias can be divided based on clinical presentation in acute neurovisceral, chronic cutaneous bullous, chronic cutaneous non-bullous and acute neurovisceral/chronic cutaneous bullous. Each individual porphyria presents a characteristic pattern of porphyrins in plasma, urine, stool and red blood cells. As such, diagnosis is easily obtained by following a simple diagnostic algorithm. Early recognition is key in managing these diseases. Neurovisceral porphyrias require acute support therapy and chronic eviction of precipitating factors. Cutaneous prophyrias, as photosensitivity disorders, rely on sunlight avoidance and, in some cases, specific therapeutic interventions. Given the rarity of these conditions, physician awareness is crucial., (Copyright © 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Preventive chemotherapy (PC) with benzimidazole drugs is the backbone of soil-transmitted helminth (STH) control programs. Over the past decade, drug coverage has increased and with it, the possibility of developing anthelmintic resistance. It is therefore of utmost importance to monitor drug efficacy. Currently, a variety of novel diagnostic methods are available, but it remains unclear whether they can be used to monitor drug efficacy. In this study, we compared the efficacy of albendazole (ALB) measured by different diagnostic methods in a head-to-head comparison to the recommended single Kato-Katz., Methods: An ALB efficacy trial was performed in 3 different STH-endemic countries (Ethiopia, Lao PDR and Tanzania), each with a different PC-history. During these trials, stool samples were evaluated with Kato-Katz (single and duplicate), Mini-FLOTAC, FECPAKG2, and qPCR. The reduction rate in mean eggs per gram of stool (ERR) and mean genome equivalents / ml of DNA extract (GERR) were calculated to estimate drug efficacy., Principal Findings and Conclusions: The results of the efficacy trials showed that none of the evaluated diagnostic methods could provide reduction rates that were equivalent to a single Kato-Katz for all STH. However, despite differences in clinical sensitivity and egg counts, they agreed in classifying efficacy according to World Health Organization (WHO) guidelines. This demonstrates that diagnostic methods for assessing drug efficacy should be validated with their intended-use in mind and that other factors like user-friendliness and costs will likely be important factors in driving the choice of diagnostics. In addition, ALB efficacy against STH infections was lower in sites with a longer history of PC. Yet, further research is needed to identify factors that contribute to this finding and to verify whether reduced efficacy can be associated with mutations in the β-tubulin gene that have previously been linked to anthelmintic resistance., Trial Registration: ClinicalTrials.gov NCT03465488., Competing Interests: The FECPAKG2 technology was produced and distributed by Techion Group Ltd, of which ET is an employee and GM is managing director. Both hold stocks in Techion Group Ltd. The Mini-FLOTAC device is a commercial product distributed by GC, LR and MPM through the University of Napoli Federico II. However, their affiliations did not play any role in the preparation and submission of this manuscript. All other authors declared that they have no competing interests.

Background: Because the success of deworming programs targeting soil-transmitted helminths (STHs) is evaluated through the periodically assessment of prevalence and infection intensities, the use of the correct diagnostic method is of utmost importance. The STH community has recently published for each phase of a deworming program the minimal criteria that a potential diagnostic method needs to meet, the so-called target product profiles (TPPs)., Methodology: We compared the diagnostic performance of a single Kato-Katz (reference method) with that of other microscopy-based methods (duplicate Kato-Katz, Mini-FLOTAC and FECPAKG2) and one DNA-based method (qPCR) for the detection and quantification of STH infections in three drug efficacy trials in Ethiopia, Lao PDR, and Tanzania. Furthermore, we evaluated a selection of minimal diagnostic criteria of the TPPs., Principal Findings: All diagnostic methods showed a clinical sensitivity of ≥90% for all STH infections of moderate-to-heavy intensities. For infections of very low intensity, only qPCR resulted in a sensitivity that was superior to a single Kato-Katz for all STHs. Compared to the reference method, both Mini-FLOTAC and FECPAKG2 resulted in significantly lower fecal egg counts for some STHs, leading to a substantial underestimation of the infection intensity. For qPCR, there was a positive significant correlation between the egg counts of a single Kato-Katz and the DNA concentration., Conclusions/significance: Our results indicate that the diagnostic performance of a single Kato-Katz is underestimated by the community and that diagnostic specific thresholds to classify intensity of infection are warranted for Mini-FLOTAC, FECPAKG2 and qPCR. When we strictly apply the TPPs, Kato-Katz is the only microscopy-based method that meets the minimal diagnostic criteria for application in the planning, monitoring and evaluation phase of an STH program. qPCR is the only method that could be considered in the phase that aims to seek confirmation for cessation of program., Trial Registration: ClinicalTrials.gov NCT03465488., Competing Interests: The FECPAKG2 technology was produced and distributed by Techion Group Ltd, of which ET is an employee and GM is managing director. Both hold stocks in Techion Group Ltd. The Mini-FLOTAC device is a commercial product distributed by GC, LR and MPM through the University of Napoli Federico II. However, the affiliations of ET, GM, GC, LR and MPM did not play any role in the preparation and submission of this manuscript. All other authors declared that they have no competing interests.

Phenotypic and functional aspects of monocytes from Localized Cutaneous Leishmaniasis (LCL) patients were evaluated. The frequencies of monocyte subsets and TLR2/TLR4 expression were evaluated in fresh peripheral blood whereas cytokine production was evaluated in whole blood cell cultures stimulated with TLR agonists or Leishmania braziliensis antigen (Ag). CD16 + monocytes frequency was increased in patients compared with controls. A TLR4 agonist (LPS) induced expression of TNF and IL-10 in monocyte subsets of patients and controls. The CD14 + CD16 + monocytes expressed higher levels of these cytokines than CD14 + CD16 - cells. The levels of secreted TNF were higher in whole blood cell cultures from patients than controls after LPS/TLR4 or Ag stimulation. Whereas in controls there was a positive correlation between TNF and IL-10 levels, this was not observed in stimulated cell cultures from patients. The high levels of LPS-induced TNF were associated with the number of lesions and the percentages of CD14 hi CD16 + monocytes. The levels of TLR2-induced TNF were also associated with number of lesions. All monocyte subsets from patients expressed higher levels of TLR2 and TLR4 than controls. Data suggest that systemically activated monocytes contribute for an imbalance in pro- and anti-inflammatory cytokine production during LCL, participating in the immunopathogenesis of the disease., (© 2019 John Wiley & Sons Ltd.)

Background: Sun exposure may lead to actinic keratoses (AKs), field cancerization, and skin cancer. Effective treatment of AKs and field cancerization is important. Oral and topical retinoids can be used for this purpose. To compare clinical, histological, and immunohistochemical effects of oral and topical retinoid for AKs and field cancerization on face and upper limbs of immunocompetent patients, as well as the impact on quality of life, safety, and tolerability., Methods: This study compared 10 mg/day oral isotretinoin (ISO) to 0.05% tretinoin cream (TRE) every other night, associated with sunscreen (SPF 60). Patients of both genders, aged 50-75 years, underwent cryotherapy with liquid nitrogen for AKs at baseline and after 120 days when they were randomized into two groups, TRE (n = 31) and ISO (n = 30), for 6 months. Outcome measures were: number of AKs, histological (thickness of stratum corneum and epithelium) and immunohistochemical parameters (p53, Bcl-2 and Bax), dermatology life quality index (DLQI), and adverse events., Results: Both treatments reduced the number of AKs (around 28%), the thickness of stratum corneum, and expression of p53 and Bax. By contrast, the epithelium thickness and Bcl-2 expression increased. There was no difference in the outcomes between TRE and ISO. Both treatments improved quality of life and were well tolerated with minimal side effects., Conclusions: Retinoids are effective and safe for field cancerization. Classical treatments for field cancerization (imiquimod and ingenol mebutate) are used for a short period; retinoids may be a good choice to intercalate with them and can be used continuously., (© 2019 The International Society of Dermatology.)

The disseminated form of leishmaniasis is a serious and rare disease, being diagnosed in 2% of the cutaneous cases registered per year in Brazil. The main characteristic is the appearance of multiple pleomorphic lesions on the cutaneous surface. A 68-year-old male from the rural area of Tocantins, Brazil, presented atypical disseminated cutaneous leishmaniasis (ACL). The clinical course and histopathological and immunological findings presented a mixed pattern that hindered diagnosis and therapeutic management. Molecular typing revealed a mixed infection with Leishmania (V.) guyanensis and Leishmania (L.) amazonensis . Molecular identification of the agents responsible for ACL is important for adequate therapeutic planning, minimizing the possibility of sequellae that impact the quality of life of the patient.

Visceral leishmaniasis (VL) is a chronic parasitic disease caused by Leishmania infantum in the Americas. During VL, several proinflammatory cytokines are produced in spleen, liver, and bone marrow. However, the role of interleukin-32 (IL-32) has not been explored in this disease. IL-32 can induce production of proinflammatory cytokines in innate immune cells and polarize the adaptive immune response. Herein, we discovered that L. infantum antigens induced expression of mRNA mainly for the IL-32γ isoform but also induced low levels of the IL-32β transcript in human peripheral blood mononuclear cells. Furthermore, infection of human IL-32γ transgenic mice (IL-32γTg mice) with L. infantum promastigote forms increased IL-32γ expression in the spleen and liver. Interestingly, IL-32γTg mice harbored less parasitism in the spleen and liver than wild-type (WT) mice. In addition, IL-32γTg mice showed increased granuloma formation in the liver compared to WT mice. The protection against VL was associated with increased production of nitric oxide (NO), interferon gamma (IFN-γ), IL-17A, and tumor necrosis factor alpha by splenic cells restimulated ex vivo with L. infantum antigens. In parallel, there was an increase in the number of Th1 and Th17 T cells in the spleens of IL-32γTg mice infected with L. infantum IL-32γ induction of IFN-γ and IL-17A expression was found to be essential for NO production by splenic cells of infected animals. These data indicate that IL-32γ potentiates the Th1/Th17 immune response during experimental VL, thus contributing to the control of L. infantum infection., (Copyright © 2018 American Society for Microbiology.)

Objective: To investigate the perception and attitude of health professionals (HPs) about the patient participation in hand hygiene (HH)., Method: A cross-sectional study with 150 HPs from a university hospital in Brazil. A descriptive analysis was conducted., Results: Simple hand hygiene was the preferred method of HPs, rather than hand rubbing with alcohol-based solutions. A total of 83.3% of the HPs supported the patient participation in reminding them about HH, but 48% reported that they would feel uncomfortable; 45.3%, comfortable; and 20.7% were familiar with the "Patients for Patient Safety" program., Conclusion: HPs showed limited knowledge about HH, opposing recommendations on the topic. The contradiction between the HPs acceptance and attitude when questioned by the patient regarding HH was revealed, reflecting a lack of knowledge about the WHO program and the need to implement educational practices in health.

American tegumentary leishmaniasis (ATL) is a neglected disease widely distributed in Latin America. In Brazil, it is caused by different Leishmania species belonging to the Subgenera Viannia and Leishmania. ATL diagnosis is routinely based on clinical, epidemiological, parasitological and immunological (delayed-type hypersensitivity skin test-DTH) evidences. The main objective of this work was to determine the efficacy of a previous immunohistochemical (IHC) method developed by our group. Seventy eight skin biopsies from patients with different ATL clinical forms and origins were evaluated. The method was previously standardized in ATL patients from the municipality of Caratinga, Minas Gerais, Brazil, all infected with Leishmania (V.) braziliensis. Here, it is evaluated in patients from the North, Southeast and Midwest regions of Brazil. Clinical, parasitological (biopsy PCR) and immunological (Montenegro skin test-MST) diagnosis were performed prior to IHC procedure. The IHC procedure detected 70.5% of the cases having a high agreement with MST diagnosis (kappa=0.84). A distinguished contribution of this work is that IHC succeed in diagnosing some negative DTH patients. Those were infected with Leishmania (L.) amazonensis, commonly causing the anergic form of the disease. In conclusion, IHC succeed in detecting ATL caused by different Leishmania species from various geographic regions and clinical status. Although it was not able to detect ATL in all patients, it was better than MST providing an additional tool for the diagnosis of ATL patients. There was no significant correlation between clinical forms and histological features including the presence of necrosis., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Primary osteosarcoma of the breast (POB) is an extremely rare and aggressive tumor. Differential diagnosis of POB includes osteosarcoma of the chest wall and metaplastic breast carcinoma. Imaging tests that exclude the existence of a direct connection between the tumor and chest wall, as well as histopathological and immunohistochemical studies that rule out the presence of an epithelial component are required for the diagnosis of POB. We report a case of a 69-year old woman with POB. Imaging and pathological findings are presented. Therapeutic approach is discussed in the light of current knowledge, including potential complications.

Background: Due to the recent increased use of the McMaster (MM) fecal egg counting method for assessing benzimidazole drug efficacy for treating soil-transmitted helminth (STH) infections, the aim of the current study was to determine the operational value of including the MM method alongside the Kato-Katz (KK) fecal thick smear to increase the diagnostic sensitivity when STHs are co-endemic with trematode helminths (e.g., Schistosoma mansoni)., Methods: A cross-sectional study was conducted in school-aged children aged 4-18 years in the northeastern region of the State of Minas Gerais (Brazil), where Necator americanus, Ascaris lumbricoides, Trichuris trichiura, and S. mansoni are co-endemic. One fecal sample from each participant was collected and transported to the field laboratory for analysis. Coprological diagnosis was performed on each fecal sample by three different methods: Formalin-Ether Sedimentation (FES), KK and the MM technique. The diagnostic sensitivity and negative predictive value (NPV) of each technique was calculated using the combination of all three techniques as the composite standard. In order to determine the agreement between the three techniques Fleiss´ kappa was used. Both the Cure Rate (CR) and the Fecal Egg Count Reduction (FECR) were calculated using the two quantification techniques (i.e., the MM and KK)., Results: Fecal samples from 1260 children were analyzed. The KK had higher diagnostic sensitivity than the MM for the detection of both A. lumbricoides (KK 97.3%, MM 69.5%) and hookworm (KK 95.1%, MM 80.8%). The CR of a single dose of mebendazole varied significantly between the KK and MM for both A. lumbricoides (p = 0.016) and hookworm (p = 0.000), with lower rates obtained with the KK. On the other hand, the FECR was very similar between both techniques for both A. lumbricoides and hookworm., Conclusion: The MM did not add any diagnostic value over the KK in areas where both STHs and trematodes were co-endemic. The lower sensitivity of the MM would have an important impact on the administration of selective school-based treatment in this area since if only the MM were used, 36 (13.9%) children diagnosed with A. lumbricoides would have gone untreated.

Objectives: To compare the effects of tamoxifen and raloxifene on the proliferative activity of normal breast tissue in premenopausal women as measured by Ki-67/MIB-1 expression., Study Design: A total of 48 women with benign breast nodules and a recommendation for surgical removal of the lesion took part in this study. They were randomized to use tamoxifen or raloxifene for 22 days, after which they were submitted to surgery. During the surgical procedure, a 1-cm fragment of normal breast tissue was removed to study Ki-67 expression., Results: The mean percentage ratios between immunolabeled and non-labeled cells were 2.02 ± 1.09 and 3.13 ± 3.23 for the tamoxifen and raloxifene groups, respectively. There was no statistically significant difference between the tamoxifen (n = 16) and raloxifene (n = 14) groups in relation to the immunohistochemical analysis of Ki-67 (P = 0.205)., Conclusion: The results of this study showed no difference between tamoxifen and raloxifene with respect to the potential of these drugs to reduce the proliferative activity of the normal breast epithelium in premenopausal women.

The aim of this study was to characterize clinical field isolates of Leishmania spp. obtained from patients with American Tegumentary Leishmaniasis (ATL) who live in Goiás state, Brazil. The presumed areas of infection were in Goiás, Tocantins, and Pará states. Three isolates of parasites were identified as L. (Viannia) braziliensis and one as L. (V.) guyanensis. The in vitro growth profiles were found to be similar for all parasites. Nevertheless, in C57BL/6 mice, L. (V.) guyanensis infection was better controlled than L. (V.) braziliensis. Yet in C57BL/6 mice deficient in interferon gamma, L. (V.) guyanensis lesions developed faster than those caused by L. (V.) braziliensis isolates. In BALB/c mice, the development of lesions was similar for isolates from both species; however, on the 11th week of infection, amastigotes could not be observed in macrophages from L. (V.) guyanensis-infected mice. Thus, L. (V.) guyanensis can be circulating in Goiás, a state where autochthonous cases of this species had not yet been reported. Considering the difficulties to differentiate L. (V.) guyanensis from L. (V.) braziliensis at the molecular, morphological, and clinical (human and murine models) levels, the presence of L. (V.) guyanensis infections is possibly underestimated in several regions of Brazil.

Background: The interleukin 32 (IL-32) is a proinflammatory cytokine produced by immune and non-immune cells. It can be induced during bacterial and viral infections, but its production was never investigated in protozoan infections. American Tegumentary Leishmaniasis (ATL) is caused by Leishmania protozoan leading to cutaneous, nasal or oral lesions. The aim of this study was to evaluate the expression of IL-32 in cutaneous and mucosal lesions as well as in peripheral blood mononuclear cells (PBMC) exposed to Leishmania (Viannia) braziliensis., Methods: IL-32, tumour necrosis factor (TNF) and IL-10 protein expression was evaluated by immunohistochemistry in cutaneous, mucosal lesions and compared to healthy specimens. The isoforms of IL-32α, β, δ, γ mRNA, TNF mRNA and IL-10 mRNA were assessed by qPCR in tissue biopsies of lesions and healthy skin and mucosa. In addition, PBMC from healthy donors were cultured with amastigotes of L. (V.) braziliensis. In lesions, the parasite subgenus was identified by PCR-RFLP., Results: We showed that the mRNA expression of IL-32, in particular IL-32γ was similarly up-regulated in lesions of cutaneous (CL) or mucosal (ML) leishmaniasis patients. IL-32 protein was produced by epithelial, endothelial, mononuclear cells and giant cells. The IL-32 protein expression was associated with TNF in ML but not in CL. IL-32 was not associated with IL-10 in both CL and ML. Expression of TNF mRNA was higher in ML than in CL lesions, however levels of IL-10 mRNA were similar in both clinical forms. In all lesions in which the parasite was detected, L. (Viannia) subgenus was identified. Interestingly, L. (V.) braziliensis induced only IL-32γ mRNA expression in PBMC from healthy individuals., Conclusions: These data suggest that IL-32 plays a major role in the inflammatory process caused by L. (Viannia) sp or that IL-32 is crucial for controlling the L. (Viannia) sp infection.

Leishmania (Viannia) braziliensis causes cutaneous and mucosal leishmaniasis in several countries in Latin America. In mammals, the parasites live as amastigotes, interacting with host immune cells and stimulating cytokine production that will drive the type of the specific immune responses. Generation of Th17 lymphocytes is associated with tissue destruction and depends on IL-1β, IL-6, TGF-β and IL-23 production, whereas IL-10 and TGF-β are associated with tissue protection. Here, we evaluate whether amastigotes stimulate peripheral blood mononuclear cells (PBMCs) from healthy donors to produce the major cytokines responsible for the generation of Th17. Seven L. (V.) braziliensis isolates from patients with different clinical forms of leishmaniasis were expanded in interferon-γ knockout mice to obtain amastigotes and in culture to get promastigotes. The parasites were used to stimulate PBMCs from healthy donors, and cytokine production was evaluated by ELISA or qPCR. Amastigotes and promastigotes induced IL-10 production in PBMCs; however, only amastigotes induced IL-1β, IL-6 and TGF-β. These data demonstrate for the first time that L. (V.) braziliensis amastigotes directly stimulate production of a unique pattern of cytokines that could contribute to the generation of Th17., (© 2014 John Wiley & Sons Ltd.)

A 6 year-old patient began to experience localized hairloss in the right temporal region three years ago. During the first appointment, diagnoses of alopecia areata and congenital triangular alopecia were made. After one year, there was no change. Upon dermatological examination, non-scarring alopecia was noted in the right temporal region, revealing extremely fine and fair hair follicles. A dermoscopy revealed only thin vellus-type hairs. Congenital triangular alopecia is a condition commonly confused with alopecia areata and is thus underdiagnosed. However, well-established clinical parameters and dermoscopic criteria can be used to distinguish skin diseases that affect hair and define the diagnosis.

Esophagitis caused by herpes simplex virus (HSV) is often documented during periods of immunosuppression in patients infected with human immunodeficiency virus (HIV); it is rare in immunocompetent diagnosed patients. Case reports of herpetic esophagitis in students of health sciences are extremely rare. The disease presents with a clinical picture characterized by acute odynophagia and retrosternal pain without obvious causes and ulcers, evidenced endoscopically in the middistal esophagus. Diagnosis depends on endoscopy, biopsies for pathology studies, and immunohistochemistry techniques. The disease course is often benign; however, treatment with acyclovir speeds the disappearance of symptoms and limits the severity of infection. In this report, we present a case of herpetic esophagitis in an immunocompetent medical student, with reference to its clinical features, diagnosis, and treatment. The disease may have manifested as a result of emotional stress experienced by the patient.

Objective: The purpose of this study was to investigate the effect of vitamin E on alveolar bone loss (ABL) and anxiety in rats with ligature-induced experimental periodontitis (EP)., Material and Methods: Wistar rats were subjected to ligature-induced EP and treated with vitamin E (500mg/kg, orally) for 9 days. Then anxiety was tested using the elevated plus-maze (EPM) test. All of the animals were euthanised by cervical dislocation on day 11. ABL was analysed morphometrically and histopathologically. Lipid peroxidation quantification, activity of the enzyme superoxide dismutase and immunohistochemistry to tumour necrosis factor-alpha (TNF-α) and inducible isoform of nitric oxide synthases (iNOS) were also tested., Results: EP induced a marked inflammatory process and intense ABL. Treatment with vitamin E decreased inflammatory reaction, prevented malondialdehyde formation and reduced the immunoreactivity to iNOS, but did not decrease ABL. Vitamin E had an anxiogenic effect on rats with or without EP., Conclusions: Vitamin E may have potential to reduce oxidative damage and inflammatory response in EP but does not prevent ABL. Attention should be given to indiscriminate use of vitamin E due to the risk of causing anxiety in patients., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Tegumentary leishmaniasis is an endemic protozoan disease that, in Brazil, is caused by parasites from Viannia or Leishmania complex. The clinical forms of cutaneous disease comprise localized, disseminated, mucosal or mucocutaneous, and diffuse leishmaniasis. Viannia complex parasites are not easy to isolate from patient lesions, especially from mucosal lesions, and they are difficult to culture. The aim of the present study was to compare the efficiency of ex vivo (culture) and in vivo (IFNγ-deficient mice) parasite isolation methods to improve the isolation rate and storage of stocks of New World Leishmania sp that cause cutaneous leishmaniasis (CL) or mucosal leishmaniasis (ML). Biopsy fragments from cutaneous or mucosal lesions were inoculated into culture medium or mouse footpads. We evaluated 114 samples (86 CL, 28 ML) using both methods independently. Samples from CL patients had a higher isolation rate in ex vivo cultures than in mice (34.1% vs. 18.7%, P<0.05). Nevertheless, almost twice the number of isolates from ML lesions was isolated using the mouse model compared to ex vivo cultures (mouse, 6/25; culture, 3/27). The overall rates of isolation were 40.2% for CL samples and 29.6% for ML samples. Of the 43 isolations, we successfully stocked 35 isolates (81.4%; 27 CL, 8 ML). Contaminations were more frequently detected in cultures of ML than CL lesions. For comparison, the use of both methods simultaneously was performed in 74 samples of CL and 25 samples of ML, and similar results were obtained. Of the eight ML isolates, five were isolated only in mice, indicating the advantage of using the in vivo method to obtain ML parasites. All parasites obtained from in vivo isolation were cryopreserved, whereas only 68% of ex vivo isolations from CL lesions were stocked. In conclusion, the use of genetically modified mice can improve the isolation of parasites from ML. Isolation and stocking of New World Leishmania parasites, especially those from ML that are almost absent in laboratory stocks, are critical for evaluating parasite genetic diversity as well as studying host-parasite interactions to identify biological markers of Leishmania. In this paper, we also discuss some of the difficulties associated with isolating and stocking parasites., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To compile fiberoptic bronchoscopy findings in patients diagnosed with lung cancer and to correlate those with histopathological findings., Methods: This was a retrospective study involving 212 patients with a confirmed diagnosis of lung cancer by cytological evaluation of BAL specimens or by histopathological evaluation of endobronchial or transbronchial biopsy specimens. The data were collected at the Respiratory Endoscopy Sector of Hospital São Salvador, located in the city of Goiânia, Brazil, between 2005 and 2010. The endoscopic findings were classified as endoscopically visible tumor, endoscopically invisible tumor, mucosal injury, as well as being classified by the presence/type of secretion. The visible tumors were also classified according to their location in the tracheobronchial tree., Results: Endobronchial mass (64%) and mucosal infiltration (35%) were the main endoscopic findings. The histological type was determined in 199 cases, the most prevalent types being squamous carcinoma, in 78 (39%), adenocarcinoma, in 42 (21%) small cell carcinoma, in 24 (12%), and large cell carcinoma, in 2 (1%). More than 45% of the visible tumors were at the upper bronchi. Squamous carcinoma (n = 78) was most commonly visualized as an endobronchial mass (in 74%), mucosal infiltration (in 36%), luminal narrowing (in 10%), or external compression (in 6%)., Conclusions: Our results show that the endobronchial mass is the most common bronchoscopic finding that is suggestive of malignancy. Proportionally, mucosal infiltration is the most common finding in small cell carcinoma. In adenocarcinoma, luminal narrowing, external compression, mucosal injury, and endobronchial secretion prevail.

In the present case we deal with a medial eyelid necrosis and injury of the canalicular system in a patient in treatment for lepromatous leprosy. Histology of the necrotic lesion showed granulomatous inflammatory reaction with accumulation of histiocytes and presence of alcohol-acid resistant bacilli. After medical treatment, the patient had a spontaneous recovery of the medial canthus architecture but with complete destruction of the canalicular system.

Lipoid pneumonia is an underdiagnosed disease that is caused by the aspiration of lipid particles into the lungs. Although most of the reported cases have been associated with the use of mineral oil as a laxative, other lipid substances can also cause the disease. We report the case of a 50-year-old female patient with a complaint of productive cough who was initially diagnosed with bronchial hyperresponsiveness and gastroesophageal reflux disease (GERD). The patient was treated for GERD. Because the productive cough persisted, the patient underwent chest CT, fiberoptic bronchoscopy, and open lung biopsy. She was diagnosed with lipoid pneumonia. The patient was questioned regarding the use of lipid substances, and she reported the chronic use of evening primrose oil. After the discontinuation of the substance and the maintenance of GERD treatment, her condition improved.

Background: The present study investigated the effects of venlafaxine, an antidepressant drug with immunoregulatory properties on the inflammatory response and bone loss associated with experimental periodontal disease (EPD)., Materials and Methods: Wistar rats were subjected to a ligature placement around the second upper left molar. The treated groups received orally venlafaxine (10 or 50 mg/kg) one hour before the experimental periodontal disease induction and daily for 10 days. Vehicle-treated experimental periodontal disease and a sham-operated (SO) controls were included. Bone loss was analyzed morphometrically and histopathological analysis was based on cell influx, alveolar bone, and cementum integrity. Lipid peroxidation quantification and immunohistochemistry to TNF-alpha and iNOS were performed., Results: Experimental periodontal disease rats showed an intense bone loss compared to SO ones (SO = 1.61 +/- 1.36; EPD = 4.47 +/- 1.98 mm, p < 0.001) and evidenced increased cellular infiltration and immunoreactivity for TNF-alpha and iNOS. Venlafaxine treatment while at low dose (10 mg/kg) afforded no significant protection against bone loss (3.25 +/- 1.26 mm), a high dose (50 mg/kg) caused significantly enhanced bone loss (6.81 +/- 3.31 mm, p < 0.05). Venlafaxine effectively decreased the lipid peroxidation but showed no significant change in TNF-alpha or iNOS immunoreactivity., Conclusion: The increased bone loss associated with high dose venlafaxine may possibly be a result of synaptic inhibition of serotonin uptake.

Isolation of Leishmania parasite and species identification are important for confirmation and to help define the epidemiology of the leishmaniasis. Mice are often used to isolate pathogens, but the most common mouse strains are resistant to infection with parasites from the Leishmania (Viannia) subgenus. In this study we tested the inoculation of interferon gamma knockout (IFNgamma KO) mice with biopsy macerates from Leishmania-infected patients to increase the possibility of isolating parasites. Biopsies from twenty five patients with clinical signs of leishmaniasis were taken and tested for the presence of parasites. Immunohistochemical assay (IHC) and conventional histopathology detected the parasite in 88% and 83% of the patients, respectively. Leishmania sp. were isolated in biopsy macerates from 52% of the patients by culture in Grace's insect medium, but 13% of isolates were lost due to contamination. Inoculation of macerates in IFNgamma KO mice provides isolation of parasites in 31.8% of the biopsies. Most isolates belong to L. (Viannia) subgenus, as confirmed by PCR, except one that belongs to L. (Leishmania) subgenus. Our preliminary results support the use of IFNgamma KO mice to improve the possibility to isolate New World Leishmania species.

Diffuse cutaneous leishmaniasis (DCL) is characterized by disseminated lesions and the absence of a specific cellular immune response. Here, the immunochemotherapy outcome of a patient with DCL from Amazonian Brazil infected with Leishmania (Leishmania) amazonensis is presented. After several unsuccessful chemotherapy treatment regimens and many relapses, a monthly immunotherapy scheme of L. amazonensis PH8 plus L. (Viannia) braziliensis M2903 monovalent vaccines associated with Bacillus Calmette-Guerin (BCG) was established, one round of which also included an M2903 vaccine associated with intermittent antimonial treatment. Temporary healing of all lesions was achieved, although Leishmania skin tests were negative and interferon gamma was not detected in mononuclear cell cultures stimulated with Leishmania antigens. The frequencies of CD16 (+)CD56(+) NK cells (approximately 2x) and CD14 (+)CD16(+) proinflammatory monocytes (approximately 8x) increased in peripheral blood, and CD56 (+) lymphocytes were found infiltrating the lesions. An association between the increase of the frequency of innate immune system cells and the healing of lesions is shown, suggesting that this protocol of immunotherapy reduced the parasite load and activated NK cells and monocytes.

Following sequence alignment, clustering algorithms are among the most utilized techniques in gene expression data analysis. Clustering gene expression patterns allows researchers to determine which gene expression patterns are alike and most likely to participate in the same biological process being investigated. Gene expression data also allow the clustering of whole samples of data, which makes it possible to find which samples are similar and, consequently, which sampled biological conditions are alike. Here, a novel similarity measure calculation and the resulting rank-based clustering algorithm are presented. The clustering was applied in 418 gene expression samples from 13 data series spanning three model organisms: Homo sapiens, Mus musculus, and Arabidopsis thaliana. The initial results are striking: more than 91% of the samples were clustered as expected. The MESs (most expressed sequences) approach outperformed some of the most used clustering algorithms applied to this kind of data such as hierarchical clustering and K-means. The clustering performance suggests that the new similarity measure is an alternative to the traditional correlation/distance measures typically used in clustering algorithms.

The effects of alpha,beta-amyrin, a pentacyclic triterpene isolated from Protium heptaphylum was investigated on rat model of orofacial pain induced by formalin or capsaicin. Rats were pretreated with alpha,beta-amyrin (10, 30, and 100mg/kg, i.p.), morphine (5mg/kg, s.c.) or vehicle (3% Tween 80), before formalin (20 microl, 1.5%) or capsaicin (20 microl, 1.5 microg) injection into the right vibrissa. In vehicle-treated controls, formalin induced a biphasic nociceptive face-rubbing behavioral response with an early first phase (0-5 min) and a late second phase (10-20 min) appearance, whereas capsaicin produced an immediate face-rubbing (grooming) behavior that was maximal at 10-20 min. Treatment with alpha,beta-amyrin or morphine significantly inhibited the face-rubbing response in both test models. While morphine produced significant antinociception in both phases of formalin test, alpha,beta-amyrin inhibited only the second phase response, more prominently at 30 mg/kg, in a naloxone-sensitive manner. In contrast, alpha,beta-amyrin produced much greater antinociceptive effect at 100mg/kg in the capsaicin test, which was also naloxone-sensitive. These results provide first time evidence to show that alpha,beta-amyrin attenuates orofacial pain at least, in part, through a peripheral opioid mechanism but warrants further detailed study for its utility in painful orofacial pathologies.