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O artigo faz parte de uma pesquisa que tem como um dos elementos centrais a educação freiriana. O objetivo do artigo, de caráter teórico, é refletir sobre as possibilidades de processos educativos humanizadores na educação superior, que tenham como propósito a construção da dignidade e da liberdade humana. Em um primeiro momento, tem-se o foco no que significa ser, hoje, um professor comprometido com o processo de humanização, de liberdade e de dignidade dos indivíduos. Em seguida, apresenta-se a contribuição que o processo educativo pode propiciar às pessoas, a fim de fortalecer a humanização e, com isso, ajudar na construção de uma vida mais digna. Na conclusão, ressalta-se a importância de Paulo Freire para o processo educativo e a atuação dos professores da educação superior no desenvolvimento da dignidade e humanização das pessoas.

This double-blind randomized clinical trial compared the effectiveness and bleaching sensitivity (BS) of at-home dental bleaching performed on the buccal surface and on the lingual surface. Using a split-mouth design, 25 patients were assigned to two bleaching groups: 10% hydrogen peroxide (White Class 10%, FGM) applied once daily for 60 min to the buccal surface (BSB) and 10% hydrogen peroxide (White Class 10%, FGM) applied once daily for 60 min to the lingual surface (LSB), both for 14 days. The color was evaluated before bleaching, after the first and second weeks, and 1 month after the bleaching using Vita Classical and Vita Bleachedguide scales and a Vita Easyshade spectrophotometer. BS was recorded daily using a 0–4 numerical rating scale and a 0–10 visual analogue scale. The following statistical tests were used: color changes (Mann–Whitney), absolute risk of BS (McNemar’s exact), and the intensity of BS (Mann–Whitney). In all statistical tests, the significance level was 5%. Significant bleaching was observed after the end of bleaching in both groups, with higher bleaching effectiveness for BSB when compared to LSB (p

Background Diagnosing neuritis in leprosy patients with neuropathic pain or chronic neuropathy remains challenging since no specific laboratory or neurophysiological marker is available. Methods In a cross-sectional study developed at a leprosy outpatient clinic in Rio de Janeiro, RJ, Brazil, 54 individuals complaining of neural pain (single or multiple sites) were classified into two groups (“neuropathic pain” or “neuritis”) by a neurological specialist in leprosy based on anamnesis together with clinical and electrophysiological examinations. A neurologist, blind to the pain diagnoses, interviewed and examined the participants using a standardized form that included clinical predictors, pain features, and neurological symptoms. The association between the clinical predictors and pain classifications was evaluated via the Pearson Chi-Square or Fisher’s exact test (p Results Six clinical algorithms were generated to evaluate sensitivity and specificity, with 95% confidence intervals, for clinical predictors statistically associated with neuritis. The most conclusive clinical algorithm was: pain onset at any time during the previous 90 days, or in association with the initiation of neurological symptoms during the prior 30-day period, necessarily associated with the worsening of pain upon movement and nerve palpation, with 94% of specificity and 35% of sensitivity. Conclusion This algorithm could help physicians confirm neuritis in leprosy patients with neural pain, particularly in primary health care units with no access to neurologists or electrophysiological tests.

Stable and efficient walking strategies for humanoid robots usually relies on assumptions regarding terrain characteristics. If the robot is able to classify the ground type at the footstep moment, it is possible to take preventive actions to avoid falls and to reduce energy consumption. In this article, a new terrain identification method that makes use of a convolutional neural network to classify the terrain type is proposed. The input of this network is a bidimensional matrix—a signature image of the impact—composed of raw data from inertial and torque sensors, sampled after the impact between the foot and ground. Six different terrains types were selected for testing the proposed approach: these terrains were tested both in simulation using the Gazebo 9.0 environment and with one real robot, designed to satisfy the requirements for the RoboCup Humanoid Competition. In both robots the ROS framework was used, and the LIPM was the selected approach for the biped walking pattern generation. Results showed that the proposed method was able to classify the terrain type with an accuracy greater than 98% for both real and virtual situations, surpassing current state-of-the-art terrain classification methods for legged robots.

The present study sought to highlight the importance of protection against electric discharges to a school in the public school of the city of Manaus-AM, based on the basic recommendations and guidelines for making decisions presented in the elaboration of a ADPS proposal. The methodology of the work was based on the collection of information on the subject from the theoretical-bibliographic research, as well as the accomplishment of the field research in the school through the technical visits for data collection. The results of the research were presented in the technical verification report of the ADPS need at school, so the study carried out a detailed study on the protection risk management, the analysis of the risk components to the atmospheric discharges, general risk assessment, evaluation the design of the protection system. Based on the report, the research presented the appropriate recommendations to assist school management in decision making, considering the importance of protecting the public heritage from the damages caused by the atmospheric discharges.

Introduction: Leprosy patients may develop immune-mediated inflammatory reactions, which are the main cause of nerve function impairment and disability. Among them, Erythema Nodosum Leprosum (ENL) is a potentially life-threatening systemic condition. There are few data on ENL-associated morbidity and mortality, and the need of hospitalisation due to its complications. Material and methods: We conducted a retrospective cohort study including patients diagnosed at the Souza Araújo Outpatient Clinic, Rio de Janeiro. All patients had a first ENL episode at the clinic or were admitted to the Evandro Chagas Hospital, between 2005–2010. In 2014, we obtained the required data from the patients’ files to describe ENL morbidity and mortality, including treatment-related adverse events. Results: A total of 112 patients (72% male, median age at diagnosis 35 years, 83% had lepromatous leprosy) developed ENL, among the 676 patients diagnosed with leprosy during the study period. Most of the episodes were chronic and severe. Patients were treated with thalidomide and corticosteroids. Half of the patients receiving corticosteroids had adverse events. 14 patients were hospitalised, ten due to ENL complications. Six patients died, four during the ENL episode. None of these deaths could be considered directly caused by ENL or its treatment.Conclusion: In the group of patients studied, although a high morbidity due to the reaction itself and to the adverse effects of its prolonged treatment was observed, mortality due to ENL was not registered. Prospective studies are required in order to recognise leprosy complications, such as ENL, as consequential causes of death.

Background Sarcopenia is characterized by a progressive reduction in muscle mass, strength and function that comes with aging. There is still broad disagreement regarding for understanding and establishment of universal criteria for the screening of sarcopenia. The objective of present study is to assess differences in the diagnosis and classification of sarcopenia by applying six different criteria to the same sample. Methods Study using the criteria proposed by five groups of authors. Body composition was measured by dual-energy X-ray absorption (DXA) using a Lunar DPX densitometer. Results Participated 156 older women. The frequency of sarcopenia varied depending on the criteria used. The above frequencies exhibited statistically significant differences (p = 0.009). Conclusion Diagnosis of sarcopenia in older women varies according to the proposed criteria.

The World Health Organization has raised concerns about the increasing number of Hansen disease (HD) relapses worldwide, especially in Brazil, India, and Indonesia that report the highest number of recurrent cases. Relapses are an indicator of MDT effectiveness and can reflect Mycobacterium leprae persistence or re-infection. Relapse is also a potential marker for the development or progression of disability. In this research, we studied a large cohort of persons affected by HD treated with full fixed-dose multibacillary (MB) multidrug therapy (MDT) followed for up to 20 years and observed that relapses are a rare event. We estimated the incidence density of relapse in a cohort of patients classified to receive MB regime (bacillary index (BI) > 0), diagnosed between September 1997 and June 2017, and treated with twelve-dose MB-MDT at a HD reference center in Rio de Janeiro, Brazil. We obtained the data from the data management system of the clinic routine service. We linked the selected cases to the dataset of relapses of the national HD data to confirm possible relapse cases diagnosed elsewhere. We diagnosed ten cases of relapse in a cohort of 713 patients followed-up for a mean of 12.1 years. This resulted in an incidence rate of 1.16 relapse cases per 1000 person-year (95% CI = 0.5915–2.076). The accumulated risk was 0.025 in 20 years. The very low risk observed in this cohort of twelve-dose-treated MB patients reinforces the success of the current MDT scheme., Author summary People affected by Hansen disease that have many skin patches or lumps receive twelve-dose multibacillary multidrug therapy. After the fixed-dose regime, they are released from treatment and are considered cured. However, some of these people may have a recurrence of skin lesions or peripheral nerve problems after several years. Clinicians, scientists, and the World Health Organization are concerned about this problem, known as relapse, which seems to be increasing in countries where Hansen disease is common, especially in Brazil, India, and Indonesia. It is important to demonstrate regular proof that the therapy remains effective to treat people affected by Hansen disease. In this study, we showed that the recurrence of signs and symptoms of Hansen disease after the twelve-dose multibacillary treatment is rare. These findings are good evidence of the success of the current multibacillary scheme.

Background Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy. Methodology/Principal findings 87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark’s microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase. Conclusions/Significance We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease., Author summary Leprosy, which has been reported throughout human history since Biblical times, still presents unclear aspects in regards to its pathogeny, and represents a public health concern, particularly in developing countries, where poor sanitary conditions of socially disfavored groups is a relevant contributing factor in maintaining disease dissemination. Although its signs and symptoms are primarily found in young adults, the increasing number of elderly individuals with leprosy is a recent phenomenon that requires clarification. Considering the specific biochemical profile of the elderly, as well as the influence thereof on their immune response to infection, this work demonstrates that elderly leprosy patients present increased levels of oxidative damage in blood and skin lesions when compared to younger patients. Such findings appear to be correlated with low gene expression of antioxidant enzymes, particularly among multibacillary patients. This work intends to contribute to a better understanding on the progress of leprosy in elderly groups.

Leprosy is an infectious disease that remains endemic in approximately 100 developing countries, where about 200,000 new cases are diagnosed each year. Moreover, multibacillary leprosy, the most contagious form of the disease, has been detected at continuously higher rates among Brazilian elderly people. Due to the so-called immunosenescence, characterized by several alterations in the quality of the immune response during aging, this group is more susceptible to infectious diseases. In view of such data, the purpose of our work was to investigate if age-related alterations in the immune response could influence the pathogenesis of leprosy. As such, we studied 87 individuals, 62 newly diagnosed and untreated leprosy patients distributed according to the age range and to the clinical forms of the disease and 25 healthy volunteers, who were studied as controls. The frequency of senescent and memory CD8+ leukocytes was assessed by immunofluorescence of biopsies from cutaneous lesions, while the serum levels of IgG anti-CMV antibodies were analyzed by chemiluminescence and the gene expression of T cell receptors' inhibitors by RT-qPCR. We noted an accumulation of memory CD8+ T lymphocytes, as well as reduced CD8+CD28+ cell expression in skin lesions from elderly patients, when compared to younger people. Alterations in LAG3 and PDCD1 gene expression in cutaneous lesions of young MB patients were also observed, when compared to elderly patients. Such data suggest that the age-related alterations of T lymphocyte subsets can facilitate the onset of leprosy in elderly patients, not to mention other chronic inflammatory diseases.

In recent years, destination management organisations have invested heavily in digital marketing, with online advertising accounting for over half of the total budget. This chapter aims to understand how tourism marketing has been adopted by Portugal's national tourism administration and the role of digital marketing in the country's tourism strategy. The country has been awarded as the best destination in the world (2017 to 2019) and Europe's leading destination (2017 to 2020) and has registered a significant evolution of the tourism sector. Turismo de Portugal is responsible for the country's tourism strategy and the international promotion of the destination, having been awarded as the best official tourism body in the world (2017 to 2019). This chapter combines secondary data (statistics and policy documents) and data from an interview with the Director of the Sales Support Direction of Turismo de Portugal. The results show a change in its communication strategy, being currently performed exclusively online, accompanying the consumer during all stages of the travel cycle.

Tourism is one of the economic sectors where information has an essential function and where the impact of social media had more relevance. Today’s digital world has transformed corporate communication as well as its strategies. Digital technologies are increasingly present in our life (social, professional, and personal) and have radically changed the way people think, make decisions, and interact. Consumers are more demanding and informed, supporting their buying decisions in the online world, becoming more flexible (more spontaneous, hybrids, technology fans), more experienced (informed, active), more independent (more adventurous and involved), with new values ​​(seeking unique, more real and authentic experiences), new lifestyles (more free time, travel more, preference for short breaks) and have undergone demographic changes (more singles, smaller families). These changes also have implications in the tourism sector and in the marketing strategies of tourist destinations. Given this new paradigm, the local accommodation units, as the most recent type of accommodation in Portugal, have registered a remarkable growth in the last years and due to the characteristics of the activity itself (more adaptable and personalized) should adapt to these new realities. The main objective of this research is to analyze, from a business perspective, the importance of digital media in local accommodation establishments’ communication strategies with central focus in the city of Aveiro. To achieve this goal, an online survey was carried out to all entrepreneurs of the local accommodation establishments, obtaining a 46% response rate. One of the main conclusions shows that these local accommodation entrepreneurs use the digital world to advertise their services, boost reservations and sales, increase customers and communicate with them. However, few companies are using the digital world to analyze demand, to create a closer relationship with the customer, and to increase brand confidence/awareness.

This study examines whether Portuguese hotel sector firms engage in earnings management (EM) practices to provide specific accounting results and test the main determinants in explaining EM. We use the SABI database to collect panel data regarding 1615 Portuguese SME hotels from 2006–2013. In order to obtain results, a graphical representation of the distribution of the net income and the estimation of the discretionary accruals were used, from which two estimation models were formulated. The results obtained provide empirical evidence that firms in the Portuguese hotel sector seem to engage in earnings management practices and that the main determinants behind them appear to be debt level, return on assets, and firm size. The adoption of earnings management practices by firms is a widespread phenomenon across various sectors and nations. Yet, despite the general awareness regarding the importance of the tourism sector for communities at a financial, social, and cultural level, the lack of empirical studies with application to the accommodation sector makes it pertinent to investigate this phenomenon.

In HIV-infected individuals, a paradoxical clinical deterioration may occur in preexisting leprosy when highly active antiretroviral therapy (HAART)-associated reversal reaction (RR) develops. Leprosy–HIV co-infected patients during HAART may present a more severe form of the disease (RR/HIV), but the immune mechanisms related to the pathogenesis of leprosy–HIV co-infection remain unknown. Although the adaptive immune responses have been extensively studied in leprosy–HIV co-infected individuals, recent studies have described that innate immune cells may drive the overall immune responses to mycobacterial antigens. Monocytes are critical to the innate immune system and play an important role in several inflammatory conditions associated with chronic infections. In leprosy, different tissue macrophage phenotypes have been associated with the different clinical forms of the disease, but it is not clear how HIV infection modulates the phenotype of innate immune cells (monocytes or macrophages) during leprosy. In the present study, we investigated the phenotype of monocytes and macrophages in leprosy–HIV co-infected individuals, with or without RR. We did not observe differences between the monocyte profiles in the studied groups; however, analysis of gene expression within the skin lesion cells revealed that the RR/HIV group presents a higher expression of macrophage scavenger receptor 1 (MRS1), CD209 molecule (CD209), vascular endothelial growth factor (VEGF), arginase 2 (ARG2), and peroxisome proliferator-activated receptor gamma (PPARG) when compared with the RR group. Our data suggest that different phenotypes of tissue macrophages found in the skin from RR and RR/HIV patients could differentially contribute to the progression of leprosy.

Despite the drastic reduction in the number of leprosy cases since the implementation of multidrug therapy (MDT), in 1980, by the WHO, the disease still appears as a relevant public health concern in endemic countries, including Brazil, which reported more than 10% of new cases detected in 2016 around the world.1 The skin and peripheral nerve lesions, traditionally found in leprosy, are associated with the tropism of Mycobacterium leprae both to macrophages and to Schwann cells, which, in turn, are major reservoirs of both the pathogen and of the immune response from hosts. If untreated, the injuries provoked by such a response usually lead to atrophies, paresis, face disfigurement, and even blindness.2 Given the influence of genetic factors on the disease process and on the clinical course of leprosy, the genes that influence the pattern and intensity of immunological response are natural candidates to determine both the occurrence of the disease and the clinical outcome thereof.3 Leprosy presents several clinical manifestations ranging within a spectrum, and the most acceptable classification in scientific studies was provided by Ridley and Jopling,4 in 1966, with the division of the disease into five forms, two of them being polar and the other three borderline forms. On one side, the tuberculoid pole (TT) is characterized by Th1-mediated immune response and a low number of skin lesions, with the appearance of granulomas, lymphocitic infiltrates, and, in unusual cases, bacilli. At the opposite end of the spectrum, the lepromatous pole (LL) is characterized by absent Th1 cellular immunity and high titers of antibodies against M. leprae, which are not effective in controlling the high load of bacilli. The nodular skin lesions disseminated throughout the body of LL patients present a high number of foamy macrophages and histiocytes containing high numbers of acid-fast bacilli with very few lymphocytes in a completely disorganized manner.5,6 The dynamic nature of the immune response to M. leprae leads to spontaneous fluctuations in the clinical state, which are known as leprosy reactions. As disclosed by a prior study performed by our group, more than half of the multibacillary patients are affected by acute inflammation episodes, known as leprosy reactions, either before, during, or after MDT, and even after healing.7 The type 1 reaction (T1R), also referred to as reversal reactions, mostly affects borderline patients, as a cause of the increased frequency of antigen-specific CD8+/CD45RA+ T cells expressing the cutaneous leukocyte-associated antigen molecule, both in the blood and inside the lesions.8 On the other hand, the type 2 reaction (T2R), also known as erythema nodosum leprosum (ENL), is characterized by a sudden exacerbation of the chronic conditions, with the appearance of additional skin lesions, reactivation of former ones, formation of painful nodules, general malaise, and aggravation of neurological damage. An early diagnosis of T2R, together with a suitable therapeutic management, may contribute to reduce the incapacities resulting from these episodes that are often severe.9,10 Several decades ago, it was thought that the participation of immune complexes and the activation of complement components were associated with the genesis of T2R.11 In addition, one study noted a modification in the proportion of CD4 and CD8+ T cells in the skin lesions and blood from LL patients, either with or without reaction.12 More recently, both pro- and anti-inflammatory mediators were shown to be increased in the plasma of T2R patients.13 Nevertheless, one should still clarify the role of different T lymphocyte subsets in the secretion of these cytokines, as well as the way these antagonistic cytokines act in synergy to characterize the reactional episode and the severity thereof. T lymphocyte subsets perform very heterogeneous functional activities and contribute in distinct forms to the dynamics of infectious diseases. Such subsets present differentiations according to their surface molecules. The identification of CCR7 and CD45RA is crucial for the characterization of T lymphocyte subsets.14 The aforesaid two molecules are commonly used to classify the following T lymphocyte subsets: naive (CCR7+/CD45RA+), central memory (CCR7+/CD45RA−), effector memory (CCR7−/CD45RA−), and effector cells (CCR7−/CD45RA+).15 Therefore, this work intends to identify the cytokine (IFN-γ, TNF and IL-10)-producing T cell subsets, the expression of the transcription factors thereof, as well as to compare the relevant results with the clinical manifestations found in the genesis of T2R patients.

O objetivo dessa revisão de literatura é discutir os trabalhos pré-clínicos que avaliaram o efeito dos bisfosfonatos sobre a movimentação dentária induzida por tratamento ortodôntico. Foi executada uma busca de artigos no Pubmed e no Scopus de artigos pré-clínicos entre os anos de Janeiro de 1990 até Dezembro de 2016. Foram utilizados as seguintes combinações de palavras chaves para busca dos artigos: “alendronate” and “orthodontic moviment”; “bisphosphonates” and “orthodontic moviment”; “bisphosphonates” and “orthodontic treatment” e “alendronate” and “orthodontic moviment” sendo que foram detectados 57 artigos. Após a leitura dos abstracts e dos títulos, 16 artigos foram selecionados para leitura integral dos textos. Os resultados desta revisão foram heterogênicos, pois houve diferença entre tipo de medicamento utilizado, intensidade da força, sentido de movimentação dentária, diferentes dosagens dos medicamentos, aplicação antes e depois do início da movimentação ortodôntica, houve diferença entre as análises para medição da movimentação dentária, sendo assim, todas as variáveis supracitadas impediram a execução de uma metanálise. Pode-se concluir que em modelo animal o uso de bisfosfonatos reduz a movimentação ortodôntica, o que pode significar um aumento no tempo de tratamento.

Background The annual new-case detection rate for leprosy, while generally stable over the last decade, shows that transmission rates have remained stagnant despite the successful worldwide administration of multidrug therapy since the 1980s. As such, novel control strategies are urgently needed. Focusing on managing leprosy patient contacts, the most susceptible to contracting the disease, has been seen as a potential strategy in limiting the spread of leprosy as shown by a number of recent epidemiological studies. Immunoprophylaxis with Bacillus Calmette-Guérin (BCG) has been seen as an effective preventive measure due to its ability to stimulate the development of cellular immunity which is essential in controlling the disease, especially in its multibacillary (MB) forms. The association of immunoprophylaxis with chemoprophylaxis in a single dose of rifampicin has been shown to be a promising preventive strategy, although a variety of studies have found instances of early case detection just a few months after BCG vaccination. Methods/design The present study is a phase IV chemoprophylactic clinical trial consisting of administration of a single dose of rifampicin in MB leprosy patient contacts under care at the Souza Araújo Outpatient Clinic/FIOCRUZ as part of a randomized (2:1), double-blind, placebo-controlled study. It is comprised of two groups: 1) rifampicin + BCG; and 2) placebo + BCG. Discussion The aim is to evaluate whether the use of chemoprophylaxis with a single dose of rifampicin in MB leprosy patient contacts prior to the BCG vaccine would be able to prevent the onset of leprosy in those cases that may occur just a few months after vaccination. Contact subclinical infections (polymerase chain reaction) and the immunological parameters (anti-PGL-1, anti-LID-1, and IFN-γ) will be evaluated and the results will be compared after 12 months of follow-up. Trial registration The Brazilian Registry of Clinical Trials (ReBEC), RBR-69QK5P. Retrospectively registered on 1 June 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-2623-6) contains supplementary material, which is available to authorized users.

Background Leprosy, the leading infectious cause of disability worldwide, remains a major public health challenge in the most severely affected countries despite the sharp decline in new cases in recent years. The search for biomarkers is essential to achieve a better understanding of the molecular and cellular mechanisms underlying the disease. Methods Pentraxin-3 (PTX3) analyses of sera from 87 leprosy patients with or without reactions were conducted via enzyme-linked immunosorbent assay. In situ identification of PTX3 in skin lesion was confirmed by quantitative reverse-transcription polymerase chain reaction, immunohistochemistry, and immunofluorescence assays. Results We found that PTX3 serum levels were higher in multibacillary patients when evaluated before the onset of acute erythema nodosum leprosum (ENL) and persistently elevated during reaction. Thalidomide treatment reduced PTX3 in the serum 7 days after starting treatment. In situ analyses have also demonstrated enhancement of PTX3 in ENL lesions and showed that treatment with thalidomide reduced its expression and the prominent neutrophilic infiltrate, a hallmark of the disease. Conclusions In summary, our study provides in vivo evidence that PTX3 is enhanced during ENL but not in reversal reaction and provides a new molecular target in ENL pathogenesis.

Household contacts (HHC) of leprosy patients exhibit high-risk of developing leprosy and contact tracing is helpful for early diagnosis. From 2011 to 2018,2,437 HHC were examined in a clinic in Rio de Janeiro, Brazil and 16S qPCR was used for diagnosis and monitoring of contacts. Fifty-four HHCs were clinically diagnosed with leprosy at intake. Another 25 exhibited leprosy-like skin lesions at intake, 8 of which were confirmed as having leprosy (50% of which were qPCR positive) and 17 of which were diagnosed with other skin diseases (6% qPCR positive). In skin biopsies, qPCR presented a sensitivity of 0.50 and specificity of 0.94. Furthermore, 955 healthy HHCs were followed-up for at least 3 years and skin scrapings were collected from earlobes for qPCR detection. Positive qPCR indicated a non-significant relative risk of 2.52 of developing the disease. During follow-up, those who progressed towards leprosy exhibited 20% qPCR positivity, compared to 9% of those who remained healthy. Disease-free survival rates indicated that age had a significant impact on disease progression, where patients over 60 had a greater chance of developing leprosy [HR = 32.4 (3.6–290.3)]. Contact tracing combined with qPCR may assist in early diagnosis and age is a risk factor for leprosy progression.

Erythema nodosum leprosum (ENL) is an inflammatory complication in leprosy. Yet, the involvement of ENL neutrophils in the inflammatory response against Mycobacterium leprae remains poorly explored. Our primary aim was to investigate the utility of the surface expression of neutrophil IL-10R1 as an ENL biomarker and, secondarily, to evaluate whether leprosy or healthy M. leprae–stimulated neutrophils produce cytokines and are able to respond to IL-10. We, in this study, describe a subpopulation of circulating neutrophils of ENL patients that exclusively expressed IL-10R1, providing evidence that IL-10R1+ neutrophils are present in ENL lesions. It was also found that ENL neutrophils, but not those of nonreactional leprosy controls, were able to secret detectable levels of TNF ex vivo and the addition of IL-10 blocked TNF release. It was likewise observed that M. leprae–stimulated, healthy neutrophils expressed IL-10R1 in vitro, and ENL-linked cytokines were released by M. leprae–cultured neutrophils in vitro. Moreover, consistent with the presence of a fully functional IL-10R, the addition of IL-10 prevented the release of M. leprae–induced cytokines. Most importantly, dead M. leprae revealed its superior capacity to induce CCL4 and IL-8 in primary neutrophils over live Mycobacterium, suggesting that M. leprae may hamper the inflammatory machinery as an immune escape mechanism.

Up to 50% of patients with the multibacillary form of leprosy are expected to develop acute systemic inflammatory episodes known as type 2 reactions (T2R), thus aggravating their clinical status. Thalidomide rapidly improves T2R symptoms. But, due to its restricted use worldwide, novel alternative therapies are urgently needed. The T2R triggering mechanisms and immune-inflammatory pathways involved in its pathology remain ill defined. In a recent report, we defined the recognition of nucleic acids by TLR9 as a major innate immunity pathway that is activated during T2R. DNA recognition has been described as a major inflammatory pathway in several autoimmune diseases, and neutrophil DNA extracellular traps (NETs) have been shown to be a prime source of endogenous DNA. Considering that neutrophil abundance is a marked characteristic of T2R lesions, the objective of this study was to investigate NETs production in T2R patients based on the hypothesis that the excessive NETs formation would play a major role in T2R pathogenesis. Abundant NETs were found in T2R skin lesions, and increased spontaneous NETs formation was observed in T2R peripheral neutrophils. Both the M. leprae whole-cell sonicate and the CpG-Hlp complex, mimicking a mycobacterial TLR9 ligand, were able to induce NETs production in vitro. Moreover, TLR9 expression was shown to be higher in T2R neutrophils, suggesting that DNA recognition via TLR9 may be one of the pathways triggering this process during T2R. Finally, treatment of T2R patients with thalidomide for 7 consecutive days resulted in a decrease in all of the evaluated in vivo and ex vivo NETosis parameters. Altogether, our findings shed light on the pathogenesis of T2R, which, it is hoped, will contribute to the emergence of novel alternative therapies and the identification of prognostic reactional markers in the near future., Author summary Leprosy is caused by a mycobacterium that has a predilection for skin and nerve cells. The chronic course of the disease may be interrupted by acute inflammatory episodes known as reactions, despite effective bacterial killing with antibiotics. Reactions aggravate the patient’s clinical status and may become a medical emergency. Type 2 reactions (T2R) only occur in patients with high bacterial burden and are treated with thalidomide and/or corticosteroids. We are interested in understanding how inflammation is triggered and amplified during T2R. In this study we investigated the potential role of extracellular DNA released by neutrophils (known as NETs) in T2R, since they have been shown to cause inflammation. Abundant NETs were found in T2R skin lesions, and increased spontaneous NETs formation was observed in neutrophils present in the blood of T2R patients. Moreover, bacterial constituents were able to induce NETs production. Finally, treatment of T2R patients with thalidomide resulted in decreased NET formation. Altogether, our findings shed light on the pathogenesis of T2R, which, it is hoped, will contribute to the identification of biomarkers for early diagnosis and emergence of novel alternative therapies in the near future.

A 47-year-old male patient came to the Souza Araujo outpatient clinic of the Oswaldo Cruz Foundation, a reference center for treating leprosy, to confirm mycobacteriosis after living in close contact with a leprosy patient. The patient was emaciated, having lost 12 kg in 2 months, febrile and presented nystagmus. The patient had multiple erythematous-livedoid, hypoesthetic, ulcerated, and purulent wounds in light-exposed areas, which had appeared suddenly 2 months before admission and did not regress after amoxicillin therapy. The patient reported loss of sensitivity, paresthesia, and asthenia in the lower limbs. Adenomegaly and visceromegaly were not observed. The patient had an approximately 25-year history of alcoholism and smoking. The patient also reported having intermittent diarrhea. The patient was instructed to take 300 mg of niacinamide per day, ingest other B-complex vitamins, use amoxicillin-clavulanic acid to treat impetigo, reduce alcohol intake and improve nutrition. On the return visit one month later, the lesions and peripheral neuropathy had regressed significantly, although the patient had used B-complex formulations containing only 50 mg of niacinamide for financial reasons. Pellagra was described in eighteenth-century Europe by Gaspar Casal, related to poverty and low ingestion of animal products. It was a public health problem in the United States at the beginning of the last century, but pellagra is rare today and diagnosed particularly among individuals with alcohol abuse, taking some medications, with desorption syndromes and HIV. The classic triad of symptoms includes dermatitis, diarrhea and dementia. Scaly dermatitis is more common in areas exposed to sunlight.

Up to 50% of patients with the multibacillary form of leprosy is expected to develop acute systemic inflammatory episodes known as type 2 reactions (T2R), thus aggravating their clinical status. Thalidomide rapidly improves T2R symptoms. But, due to its restricted use worldwide, novel alternative therapies are urgently needed. A hallmark of T2R lesions is the presence of a neutrophil-rich inflammatory infiltrate. In this study, the potential involvement of neutrophil extracellular traps (NETs) production in T2R pathogenesis was investigated. Abundant NETs were found in T2R skin lesions, and increased spontaneous NETs formation was observed in T2R peripheral neutrophils. Both the M. leprae whole-cell sonicate and the CpG-Hlp complex, mimicking a mycobacterial TLR9 ligand, were able to induce NETs production in vitro. Moreover, TLR9 expression was shown to be higher in T2R neutrophils, suggesting that DNA recognition via TLR9 may be one of the pathways triggering this process during T2R. Finally, treatment of T2R patients with thalidomide for 7 consecutive days resulted in decreasing all of the evaluated in vivo and ex vivo NETosis parameters. Altogether, our findings shed light on the pathogenesis of T2R, which, it is hoped, will contribute to the emergence of novel alternative therapies in the near future.Author summaryLeprosy is caused by a mycobacterium that has a predilection for skin and nerve cells. The chronic course of the disease may be interrupted by acute inflammatory episodes known as reactions, despite effective bacterial killing with antibiotics. Reactions aggravate patient’s clinical status and may become a medical emergency. Type 2 reactions (T2R) only occur in patients with high bacterial burden and is treated with thalidomide and/or corticosteroids. We are interested in understanding how inflammation is triggered and amplified during T2R. In this study we investigated the potential role of extracellular DNA released by neutrophils (known as NETs) in T2R, since they have been shown to cause inflammation. Abundant NETs were found in T2R skin lesions, and increased spontaneous NETs formation was observed in neutrophils present in the blood of T2R patients. Moreover, bacterial constituents were able to induce NETs production. Finally, treatment of T2R patients with thalidomide resulted in decreased NET formation. Altogether, our findings shed light on the pathogenesis of T2R, which, it is hoped, will contribute to the identification of biomarkers for early diagnosis and emergence of novel alternative therapies in the near future.

Objective The diagnosis of paucibacillary (PB) leprosy cases remains a challenge because of the absence of a confirmatory laboratory method. While quantitative polymerase chain reaction (qPCR) has been shown to provide reliable sensitivity and specificity in PB diagnoses, a thorough investigation of its efficacy in clinical practice has not yet been published. The present study evaluated patients with suspected leprosy skin lesions by using qPCR to identify PB individuals in the Leprosy Outpatient clinic at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Methods One hundred seventy-two suspected PB cases were included in the study. The patients were evaluated by a dermatologist at three different times. The clinical dermato-neurological examination and collected samples were performed on the first visit. On the second visit, the results of the histopathological analysis and PCR assay (DNA-based Mycobacterium leprae qPCR-targeting 16S gene) results were analyzed, and a decision regarding multi-drug therapy was made. A year later, the patients were re-examined, and the consensus diagnosis was established. Results In 58% (100/172) of cases, a conclusive diagnosis via histopathological analysis was not possible; however, 30% (30/100) of these cases had a positive PCR. One hundred ten patients (110/172) attended the third visit. The analysis showed that while the sensitivity of the histopathological test was very low (35%), a qPCR alone was more effective for identifying leprosy, with 57% sensitivity. Conclusion The use of qPCR in suspected PB cases with an inconclusive histology improved the sensitivity of leprosy diagnoses., Author summary Leprosy is a major public health problem in several low- to middle-developed countries where a consistent number of new cases are diagnosed every year. Irrespective of the use of efficient treatment, diagnosis is late because of the absence of a gold standard method. Thus, the multi-drug therapy (MDT) is unable to control of disease transmission even though early diagnosis, adequate MDT treatment of new cases, and contact surveillance have been considered the pillars of leprosy endemic control. Quantitative polymerase chain reaction (qPCR)-based Mycobacterium leprae DNA direct detection in clinical samples has been developed to support diagnosis. This study used qPCR to differentially diagnose suspected cases of paucibacillary leprosy and to follow them after treatment to confirm the consensus diagnosis and therapeutic approaches. It was concluded that qPCR and histopathological analysis increase clinical diagnosis accuracy, and qPCR has higher sensitivity. The routine use of qPCR laboratory tests could therefore improve the precision of early diagnosis for the achievement of leprosy control.

A hanseníase históide representa uma forma atípica de apresentação da hanseníase virchowiana, descrita por Wade em 1963, com características clínicas e anatomopatológicas próprias, que no passado era considerada um marcador de resistência medicamentosa e recidiva. Clinicamente caracteriza-se por placas ou nodulos de aspecto queloidiforme. À microscopia óptica nota-se infiltrado predominantemente constituído por células fusiformes que por vezes simula neoplasia fibrohistiocítica, associada a poucos macrófagos espumosos e numerosos bacilos álcool-ácido-resistentes. Relata-se um caso de hanseníase virchowiana com lesões clinicamente compatíveis com a forma históide, a fim de demonstrar e reforçar o seu grande polimorfismo clínico e a importância do seu conhecimento para diagnóstico e tratamento precoce, para interromper a cadeia de transmissão e diminuir a ocorrência de incapacidades irreversíveis causadas pela doença.

The increasing cost of energy and finite oil and gas reserves have created a need to develop alternative fuels from renewable sources. Due to its abiotic stress tolerance and annual cultivation, high-biomass sorghum (Sorghum bicolor L. Moench) shows potential as a bioenergy crop. Genomic selection is a useful tool for accelerating genetic gains and could restructure plant breeding programs by enabling early selection and reducing breeding cycle duration. This work aimed at predicting breeding values via genomic selection models for 200 sorghum genotypes comprising landrace accessions and breeding lines from biomass and saccharine groups. These genotypes were divided into two sub-panels, according to breeding purpose. We evaluated the following phenotypic biomass traits: days to flowering, plant height, fresh and dry matter yield, and fiber, cellulose, hemicellulose, and lignin proportions. Genotyping by sequencing yielded more than 258,000 single-nucleotide polymorphism markers, which revealed population structure between subpanels. We then fitted and compared genomic selection models BayesA, BayesB, BayesC?, BayesLasso, Bayes Ridge Regression and random regression best linear unbiased predictor. The resulting predictive abilities varied little between the different models, but substantially between traits. Different scenarios of prediction showed the potential of using genomic selection results between sub-panels and years, although the genotype by environment interaction negatively affected accuracies. Functional enrichment analyses performed with the marker-predicted effects suggested several interesting associations, with potential for revealing biological processes relevant to the studied quantitative traits. This work shows that genomic selection can be successfully applied in biomass sorghum breeding programs. Made available in DSpace on 2018-09-25T00:42:59Z (GMT). No. of bitstreams: 1 Genomicprediction.pdf: 1227569 bytes, checksum: 4d1c64b7f50c1e67001257591223fc3b (MD5) Previous issue date: 2018-09-24

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which affects peripheral nerves, skin and mucous membranes. The impairment of neural function as well as sensory or sensory-motor disabilities in leprosy continue to be a problem that requires careful attention in the management of patients with the aim to avoid or minimize their progression to prevent sequelae. One of the most common characteristics of these ulcers is the tendency to chronicity, with variable therapeutic response. In this article, we shall discuss the therapeutic management of thirteen trophic leprosy ulcers in eight patients using polyhexanide 0.2% products.

One of the biggest challenges in treating leprosy is the control of reaction events. Patients with lepromatous leprosy may present reaction type II, or erythema nodosum leprosum, during treatment, and this reaction can remain in a recurrent form after being released from the hospital, requiring the use of thalidomide and/or prednisone for long periods of time, in turn increasing the risk of side effects. Two reports of the use of antiTNF to treat erythema nodosum leprosum were found in the literature. A good response was found after an assay with infliximab and etanercept. This study reports on a patient with lepromatous leprosy and recurrent reaction, controlled by using etanercept and a 10-month follow-up, with the interruption of thalidomide and the maintenance of prednisone at 10 mg/day.

IntroductionErythema nodosum leprosum (ENL) is an immunological complication of leprosy. ENL results in morbidity and disability and if it is not treated can lead to death. The current treatment consists of thalidomide or high doses of oral corticosteroids for prolonged periods. Thalidomide is not available in many leprosy endemic countries. The use of corticosteroids is associated with morbidity and mortality. Identifying treatment regimens that reduce the use of corticosteroids in ENL is essential. Methotrexate (MTX) is used to treat many inflammatory diseases and has been used successfully to treat patients with ENL not controlled by other drugs, including prednisolone and thalidomide. We present the protocol of the ‘MTX and prednisolone study in ENL’ (MaPs in ENL) a randomised controlled trial (RCT) designed to test the efficacy of MTX in the management of ENL.Methods and analysisMaPs in ENL is an international multicentre RCT, which will be conducted in leprosy referral centres in Bangladesh, Brazil, Ethiopia, India, Indonesia and Nepal. Patients diagnosed with ENL who consent to participate will be randomly allocated to receive 48 weeks of weekly oral MTX plus 20 weeks of prednisolone or 48 weeks of placebo plus 20 weeks of prednisolone. Participants will be stratified by type of ENL into those with acute ENL and those with chronic and recurrent ENL. The primary objective is to determine whether MTX reduces the requirement for additional prednisolone. Patients’ reported outcome measures will be used to assess the efficacy of MTX. Participants will be closely monitored for adverse events.Ethics and disseminationResults will be submitted for publication in peer-reviewed journals. Ethical approval was obtained from the Observational/Interventions Research Ethics Committee of the London School of Hygiene & Tropical Medicine (15762); The Leprosy Mission International Bangladesh Institutional Research Board (in process); AHRI-ALERT Ethical Review Committee, Ethiopia; Ethics Committee of the Managing Committee of the Bombay Leprosy Project; and The Leprosy Mission Trust India Ethics Committee; the Nepal Health and Research Council and Health Research Ethics Committee Dr. Soetomo, Indonesia. This study is registered at www.clinicaltrials.gov. This is the first RCT of MTX for ENL and will contribute to the evidence for the management of ENL.Trial registration numberNCT 03775460.

Background Fibrosis in the peripheral nerve is the end stage of leprous neuropathy and the cause of the resulting permanent neural function impairments. Preventive measures to avoid this irreversible pathological state are a relief strategy for leprosy sufferers. Objectives The present study describes the frequency of fibrosis along with its characterisation and pathogenic development. Methods Six-hundred-and-thirteen nerve samples were sorted from 278 neural leprosy (NL) and 335 non-leprosy neuropathy patients (ON). The total number of samples was histologically examined by routine staining methods (haematoxylin-eosin, Wade staining and Gomori's trichrome) and fibrosis was evaluated via semi-quantitative estimation. Findings Fibrosis was most frequent in the NL group (33% against 0.4% in ON) while fibrosis in association with endoneurial microfasciculation was found in 38 (41.3%) of the NL samples in the examination of semithin sections. Pericytic activation in the perivascular environment was confirmed to be the source of the fibroblasts and perineurial cells delimiting microfascicles. End-stage fibrosis in leprosy displays an arrangement of microfascicles devoid of neural components (i.e., Schwann cells and axons) lined by an intermediate phenotype of fibroblastic-perineurial cells filled with bundles of collagen fibres. Main conclusions The present study underscores that fibrosis is frequently the severe end stage of neural leprosy NL pathogeny after analysing the notably distinct development of fibrosis within the neural environment.

Background Mycobacterium leprae and HIV cause infectious diseases of great concern for the public health care sector worldwide. Both are especially worrisome diseases when patients become co-infected and exhibit the expected clinical exuberance. The objective of this study was to evaluate episodes of reversal reaction (RR) and the effect of the use of corticosteroids on the treatment of borderline tuberculoid leprosy patients co-infected with the human immunodeficiency virus (HIV). Methods This is a retrospective cohort study in which the clinical manifestations of the patients and their responses to corticosteroid therapy were observed. Variables were analysed during and after multidrug therapy between the first and last days of prednisone, which occurred up to a maximum of 6 months after initiating corticosteroid therapy. Results A total of 22 HIV-positive and 28 HIV-negative cases were included. Loss of sensitivity and neural thickening were statistically significant while clinically ulcerated lesions were only observed in the co-infected group. Most patients were diagnosed with leprosy in the presence of RR and six patients manifested RR as an immune reconstitution inflammatory syndrome. On average, both groups received similar doses of corticosteroids (difference of 0·1 mg/kg/day).

Improving sorghum cultivation in South America Rafael Augusto da Costa Parrella, Robert Eugene Schaffert, Cicero Bezerra de Menezes, Jose Avelino Santos Rodrigues, Jurandir Vieira Magalhaes, Cynthia Maria Borges Damasceno, Dagma Dionisia da Silva and Simone Martins Mendes, Embrapa Milho e Sorgo, Brazil1 Introduction2 History of sorghum in Brazil3 Improvement of grain and forage sorghum4 Improvement of sorghum for bioenergy5 Sorghum tolerance for aluminium and low levels of phosphorus6 Genetic and molecular approaches to studying biomass production and sorghum quality7 Improving disease resistance8 Sorghum pests9 Conclusion10 Where to look for further information11 ReferencesAgribusiness is a strategic sector for the Brazilian economy, representing 23% of the GDP (CEPEA 2015). Beef cattle, poultry and swine production are predominant Brazilian agribusiness activities on the world stage. Brazil has the second largest cattle herd in the world with about 211 million head. In addition, since 2004, Brazil has taken the lead in meat exports, supplying 20% of internationally traded meat, and sales in over 180 countries. The Brazilian poultry industry has become the world’s third largest producer and leading exporter. The swine industry in Brazil is ranked fourth in world production and exportation of pork (MAPA 2015).

Introduction: The Hazard and Operability Study is considered a feasible tool to assess risks, where complex technologies, require new strategies to guarantee efficiency, safety, and quality of products. Objective: To perform a Hazop publications review, to establish the state of the art, current procedures and perspectives in the pharmaceutical industry. Method: Hazop methodology and improvements to satisfy actual needs were structured. Subsequently, its application and integration with other risk tools, and experts systems, were analyzed to define the current approach and future perspectives. Results: The review allowed the understanding where models, simulations and specialized software offered adequate support to assess risk in current complex processes. In addition, an efficient definition of causes and consequences depends of expert systems, where simulations acquire experience through the creation of databases, reducing the need of specific process knowledge, which is a typical limitation of the conventional Hazop methodology. Conclusions: A review of the Hazop stateof- the-art highlighted the importance to assess risks within the process industry. However, the use of new technologies designed to meet regulatory affairs to guarantee safety and quality principles would require the ongoing improvement of the Hazop methodology, restricting the dependence of specialists, and increasing the use of expert systems. Introducción: El Estudio de Riesgos y Operabilidad se considera una herramienta factible para evaluar los riesgos, cuando las tecnologías complejas requieren nuevas estrategias para garantizar la eficiencia, la seguridad y la calidad de los productos. Objetivo: realizar una revisión de las publicaciones de Hazop, para establecer el estado del arte, los procedimientos actuales y las perspectivas en la industria farmacéutica. Método: fue estructurada la metodología Hazop y las mejoras para satisfacer las necesidades reales. Posteriormente, se analizó su aplicación e integración con otras herramientas de riesgo y sistemas de expertos para definir el enfoque actual y las perspectivas futuras. Resultados: la revisión permitió comprender dónde los modelos, las simulaciones y el software especializado ofrecían el soporte adecuado para evaluar el riesgo en los procesos complejos actuales. Además, una definición eficiente de causas y consecuencias depende de los sistemas expertos, donde las simulaciones adquieren experiencia a través de la creación de bases de datos, lo que reduce la necesidad de un conocimiento específico del proceso, que es una limitación típica de la metodología convencional Hazop. Conclusiones: una revisión del estado del arte de Hazop resaltó la importancia de evaluar los riesgos dentro de la industria de procesos. Sin embargo, el uso de nuevas tecnologías diseñadas para cumplir con los asuntos regulatorios para garantizar los principios de seguridad y calidad requeriría la mejora continua de la metodología Hazop, restringiendo la dependencia de especialistas y aumentando el uso de sistemas expertos. Título PT: Análise de Risco: estado da arte da metodologia Hazop generalizada, aplicações e perspectivas na indústria de processos Introdução: O Estudo de Perigos e Operabilidade (Hazop) é considerado uma ferramenta para avaliação de riscos, na qual tecnologias complexas exigem novas estratégias para garantir a eficiência, a segurança e a qualidade dos produtos. Objetivo: Realizar uma revisão de publicações do Hazop, para estabelecer o estado da arte, os procedimentos e as suas perspectivas na indústria farmacêutica. Método: O procedimento Hazop e suas adequações para satisfazer as necessidades atuais foram estruturados. Posteriormente, aplicações e integração com outras ferramentas de risco e sistemas expertos foram analisadas para definir a abordagem atual e perspectivas futuras. Resultados: A revisão permitiu a compreensão de que modelos, simulações e software especializado oferecem suporte para avaliar riscos em processos complexos. Adicionalmente, a correta definição de causas e consequências depende do uso de sistemas expertos, cujas simulações adquirem experiência através da criação de bancos de dados, reduzindo a necessidade de conhecimento específico do processo, que é uma limitação da metodologia Hazop convencional. Conclusões: A revisão do estado da arte do Hazop destacou a importância de avaliar riscos dentro da indústria de processos. No entanto, novas tecnologias utilizadas para atender quesitos regulatórios de segurança e qualidade precisam da melhoria contínua da metodologia Hazop, reduzindo a dependência de especialista por meio do uso de sistemas especializados.

Neural pain is a frequent symptom in leprosy disease. There is a paucity of data regarding neural pain diagnostics resulting in common prescriptive errors when neuritis is confused with neuropathic or mixed nociceptive-neuropathic pain. The present study identified important demographic, clinical, and neurophysiological features of 42 leprosy neuropathy patients presenting neuropathic pain (NP). During routine evaluations, patients were selected asking if they had ever experienced neural pain. Data analyses of their pain characteristics, clinical examination results, and both the Douleur Neuropathique 4 Questionnaire and Hamilton Depression Scale scores were used to classify these patients. The most common word they used to describe the sensation of pain for 25 (60%) of these patients was "burning." In the early stages of the disease and before leprosy diagnosis, 19 (45%) had already complained about NP and leprosy treatment was unable to prevent its occurrence in 15 (36%). Leprosy reactions, considered NP risk factors, occurred in 32 (76%) cases. Knowledge of typical NP characteristics could be used to develop more effective therapeutic approaches for a notoriously difficult-to-treat pain condition.

Background Leprosy is a chronic dermato-neurological disease caused by Mycobacterium leprae infection. In 2016, more than 200,000 new cases of leprosy were detected around the world, representing the most frequent cause of infectious irreversible deformities and disabilities. Principal findings In the present work, we demonstrate a consistent procoagulant profile on 40 reactional and non-reactional multibacillary leprosy patients. A retrospective analysis in search of signs of coagulation abnormalities among 638 leprosy patients identified 35 leprosy patients (5.48%) which displayed a characteristic lipid-like clot formed between blood clot and serum during serum harvesting, herein named ‘leprosum clot’. Most of these patients (n = 16, 45.7%) belonged to the lepromatous leprosy pole of the disease. In addition, formation of the leprosum clot was directly correlated with increased plasma levels of soluble tissue factor and von Willebrand factor. High performance thin layer chromatography demonstrated a high content of neutral lipids in the leprosum clot, and proteomic analysis demonstrated that the leprosum clot presented in these patients is highly enriched in fibrin. Remarkably, differential 2D-proteomics analysis between leprosum clots and control clots identified two proteins present only in leprosy patients clots: complement component 3 and 4 and inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP). In agreement with those observations we demonstrated that M. leprae induces hepatocytes release of IHRP in vitro. Conclusions We demonstrated that leprosy MB patients develop a procoagulant status due to high levels of plasmatic fibrinogen, anti-cardiolipin antibodies, von Willebrand factor and soluble tissue factor. We propose that some of these components, fibrinogen for example, presents potential as predictive biomarkers of leprosy reactions, generating tools for earlier diagnosis and treatment of these events., Author summary Hemostatic illnesses are frequently associated with acute and chronic infections. In the present work we demonstrated that leprosy patients developed hemostatic abnormalities, like the formation of an atypical lipid clot mass during sera harvesting, a phenomenon previously observed and never unraveled. We characterize the nature of the “leprosum clot”, formed during a protrombotic state developed by some patients. During the proteomic analysis of the leprosum clot we discovered a set of potential serum biomarkers to leprosy reactional episodes diagnosis, which at this moment is based only in clinical features. Taking together, our data suggest that leprosy patients are suffering from a procoagulant status, being beneficiated by the introduction of routine coagulation tests during their treatment, which will aloud physicians to prevent some of the acute clinical symptoms related with superficial vein thrombosis such as cyanosis and tissue necrosis observed during severe cases of leprosy reactional episodes.

Dapsone hypersensitivity syndrome (DHS) can be classified as a 'drug reaction with eosinophilia and systemic symptoms' (DRESS). It has a variable course, it is not dose dependent and may present with different clinical and laboratory abnormalities. In some cases it may be fatal. We describe a 31 year old man with lepromatous leprosy in whom DHS developed 4 weeks after initiation of World Health Organization multibacillary multidrug therapy (dapsone, clofazimine and rifampin). He had fever, dehydration, diffuse rash, pain on abdominal palpation and inguinal painless lymph nodes. Severe anaemia, abnormal liver function and hyperbilirubinaemia were also found. The patient was treated with prednisone 50 mg daily. There was gradual improvement in the clinical and laboratory signs. We encourage health professionals to be aware of the risk of DHS and to have in mind the development of investigative studies related to HLA and MHC in these patients.

Type 1 reaction (T1R) or reversal reaction is the leading cause of physical disabilities and deformities in leprosy. Leprosy patients, even after being considered cured and released from treatment, may suffer from reactional episodes for long periods of time. Early diagnosis is a great challenge for effectively treating and managing T1R. There is an urgent need to identify the most significant biomarkers to prevent recurrent T1R and to differentiate late T1R from relapse. T1R continues to be treated with corticosteroids and complications due to iatrogenic treatment remain frequent. This review aims to provide a framework from which to approach the great challenges that still persist in T1R management and debate key issues in order to reduce the distance between basic research and the clinic.

Leprosy reactions are responsible for incapacities in leprosy and represent the major cause of permanent neuropathy. The identification of biomarkers able to identify patients more prone to develop reaction could contribute to adequate clinical management and the prevention of disability. Reversal reaction may occur in unstable borderline patients and also in lepromatous patients. To identify biomarker signature profiles related with the reversal reaction onset, multibacillary patients were recruited and classified accordingly the occurrence or not of reversal reaction during or after multidrugtherapy. Analysis of skin lesion cells at diagnosis of multibacillary leprosy demonstrated that in the group that developed reaction (T1R) in the future there was a downregulation of autophagy associated with the overexpression of TLR2 and MLST8. The autophagy impairment in T1R group was associated with increased expression of NLRP3, caspase-1 (p10) and IL-1β production. In addition, analysis of IL-1β production in serum from multibacillary patients demonstrated that patients who developed reversal reaction have significantly increased concentrations of IL-1β at diagnosis, suggesting that the pattern of innate immune responses could predict the reactional episode outcome. In vitro analysis demonstrated that the blockade of autophagy with 3-methyladenine (3-MA) in Mycobacterium leprae-stimulated human primary monocytes increased the assembly of NLRP3 specks assembly, and it was associated with an increase of IL-1β and IL-6 production. Together, our data suggest an important role for autophagy in multibacillary leprosy patients to avoid exacerbated inflammasome activation and the onset of reversal reaction.

Acroangiodermatitis is an angioproliferative disease usually related to chronic venous insufficiency, and it is considered a clinical and histological simulator of Kaposi's sarcoma (KS). Immunohistochemistry is the suitable method to differentiate between these two entities. It reveals the following immunostaining profile: immunopositivity with anti-CD34 antibody is restricted to the vascular endothelium in acroangiodermatitis, and diffuse in the KS (endothelial cells and perivascular spindle cells); immunopositivity with anti-HHV-8 only in KS cases. We report the case of an HIV seropositive patient without apparent vascular disease, who presented violaceous and brownish erythematous lesions on the feet, and whose histopathology and immunohistochemistry indicated the diagnosis of acroangiodermatitis.

Relatamos o caso de um paciente masculino de 62 anos, com diagnóstico recente de tuberculose pulmonar que apresentou uma erupção polimórfica devido a uma hiperinfestação por Sarcoptes scabiei. Os autores demonstram achados dermatoscópicos da escabiose humana e enfatizam a importância da utilização da dermatoscopia como ferramenta auxiliar no diagnóstico de doenças infecciosas de apresentação não usuais.

Over the last few centuries, the expansion of urbanization brought bats closer to urbanized areas, increasing the risk of accidents by bat bites. The morphology of bat bites can be varied, usually having an elliptical shape, about 0.5 cm along its greatest length, and the characteristic corkscrew bite pattern. The authors present the case of a patient who was repeatedly bitten by vampire bats for two months. A polymerase chain reaction was performed in the cutaneous nerves at the base of the hair follicles which showed negativity towards the rabies virus. The authors highlight the public health importance of this case, and discuss the morphological characteristics of these hematophagous bat bites.

The diagnosis of single-lesion paucibacillary leprosy remains a challenge. Reviews by expert dermatopathologists and quantitative polymerase chain reaction (qPCR) results obtained from 66 single-plaque biopsy samples were compared. Histological findings were graded as high (HP), medium (MP) or low (LP) probability of leprosy or other dermatopathy (OD). Mycobacterium leprae-specific genes were detected using qPCR. The biopsies of 47 out of 57 clinically diagnosed patients who received multidrug therapy were classified as HP/MP, eight of which were qPCR negative. In the LP/OD (n = 19), two out of eight untreated patients showed positive qPCR results. In the absence of typical histopathological features, qPCR may be utilised to aid in final patient diagnosis, thus reducing overtreatment and delay in diagnosis.

Sebaceous carcinoma is a rare and aggressive skin tumor. It can be located in any area of the body, the most commonly involved area being the periorbital region. It does not entail a typical clinical presentation, which explains the often late diagnosis. The aim of this report is to outline the rarity of the disease and its atypical clinical description, since to this day, inguinal ulcers with clinical manifestation have not been reported. We present and discuss a case of sebaceous carcinoma with an unusual clinical presentation, in an elderly male patient. The precise approach to genital ulcers, as shown in this case, is a diagnostic challenge that requires a great deal of effort on the part of the clinician.

A type 1 reaction or reversal reaction is expressed clinically by inflammatory exacerbation of the skin lesions and nerve trunks, consequently leading to sensory and motor alterations. It occurs in non-polar forms of leprosy, although it can occur in a small percentage of sub-polar LL treated patients. Disabilities, deformities and morbidity, still present in leprosy, are mainly caused by these acute episodes. The recognition of reactional states is imperative for an early approach and efficient management, to avoid the emergence of disabilities that stigmatize the disease. This review aims to describe the clinical aspects, immunopathogenesis, epidemiology, histopathological features and therapeutics of type 1 reactions. A reação do tipo 1 ou reação reversa expressa-se clinicamente por uma exacerbação inflamatória das lesões de pele e de troncos nervosos, levando a alterações sensitivas e motoras. Ocorre nas formas não-polares da hanseníase, embora possa ocorrer numa pequena percentagem de pacientes LL tratados. As incapacidades físicas, deformidades e morbidade, ainda presentes na hanseníase, são causadas principalmente por esses episódios agudos. O reconhecimento dos estados reacionais é imperativo para uma abordagem precoce e manejo adequado, evitando a instalação de incapacidades que tanto estigmatizam a doença. Esta revisão tem como objetivo descrever aspectos clínicos, imunopatogênese, epidemiologia, características histopatológicas e terapêutica do estado reacional do tipo 1.