Prospective study of patients with persistent symptoms of dengue in Brazil

Dengue is an arboviral infection clinically recognized as an acute and self-limited disease. Persistence of dengue symptoms is known, but it has been little studied. The aim of this study was to characterize persistent symptoms in 113 patients with dengue followed up clinically and by laboratory testing at a tertiary hospital. Symptoms that persisted for more than 14 days were observed in 61 (54.0%) patients, and six (6.2%) of them had symptoms for 6 months or more. The persistent symptoms identified were myalgia, weakness, hair loss, memory loss, reduced resistance to physical effort, headache, reasoning problems, arthralgia, sleepiness- and emotional lability. The progression to persistent symptoms was significantly associated with hospitalization, older age, more severe disease, the presence of bleeding and comorbidities upon univariate analysis. Upon multivariate analysis, the presence of persistent symptoms continued to be significantly associated only with increased age and dengue with warning signs. The platelet count during the acute phase of the disease was significantly lower in the group with persistent symptoms. In conclusion, the frequency of progression to persistent symptoms in dengue is relevant in patients seen at a tertiary hospital and the persistence of symptoms is more common in patients with dengue with warning signs

BFD-22 a new potential inhibitor of BRAF inhibits the metastasis of B16F10 melanoma cells and simultaneously increased the tumor immunogenicity

Benzofuroxan is an interesting ring system, which has shown a wide spectrum of biological responses against tumor cell lines. We investigated, herein, the antitumor effects of benzofuroxan derivatives (BFDs) in vitro and in a melanoma mouse model. Cytotoxic effects of twenty-two BFDs were determined by MTT assay. Effects of BFD-22 in apoptosis and cell proliferation were evaluated using Annexin V-FITC/PI and CFSE staining. In addition, the effects in the cell cycle were assessed. Flow cytometry, western blot, and fluorescence microscopy analysis were employed to investigate the apoptosis-related proteins and the BRAF signaling. Cell motility was also exploited through cell invasion and migration assays. Molecular docking approach was performed in order to verify the BFD-22 binding mode into the ATP catalytic site of BRAF kinase. Moreover, the BFD-22 antitumor effects were evaluated in a melanoma murine model using B16F10. BFD-22 was identified as a potential hit against melanoma cells. BFD-22 induced apoptosis and inhibited cell proliferation of B16F10 cells. BFD-22 has suppressed, indeed, the migratory and invasive behavior of B16F10 cells. Cyclin D1 and CDK4 expression were reduced leading to cell cycle arrest at G0/G1 phase. Of note, phosphorylation of BRAF at Ser338 was strongly down-regulated by BFD-22 in B16F10 cells. The accommodation/orientation into the binding site of BRAF was similar of BAY43-9006 (co-crystallized inhibitor of BRAF, sorafenib). Importantly, BFD-22 presented in vivo antimetastatic effects and showed better therapeutic efficacy than sorafenib and taxol. BFD-22 can be considered as a new lead compound and, then, can be helpful for the designing of novel drug candidates to treat melanoma

A qualitative study of culturally embedded factors in complementary and alternative medicine use

Abstract Background Within the intercultural milieu of medical pluralism, a nexus of worldviews espousing distinct explanatory models of illness, our research aims at exploring factors leading to complementary and alternative medicine (CAM) use with special attention to their cultural context. Methods The results are based on medical anthropological fieldwork (participant observation and in-depth interviews) spanning a period from January 2015 to May 2017 at four clinics of Traditional Chinese Medicine in Budapest, Hungary. Participant observation involved 105 patients (males N = 42); in-depth interviews were conducted with patients (N = 9) and practitioners (N = 9). The interviews were coded with Interpretative Phenomenological Analysis; all information was aggregated employing Atlas.ti software. Results In order to avoid the dichotomization of “push and pull factors,” results obtained from the fieldwork and interviews were structured along milestones of the patient journey. These points of reference include orientation among sources of information, biomedical diagnosis, patient expectations and the physician-patient relationship, the biomedical treatment trajectory and reasons for non-adherence, philosophical congruence, and alternate routes of entry into the world of CAM. All discussed points which are a departure from the strictly western therapy, entail an underlying socio-cultural disposition and must be scrutinized in this context. Conclusions The influence of one’s culturally determined explanatory model is ubiquitous from the onset of the patient journey and exhibits a reciprocal relationship with subjective experience. Firsthand experience (or that of the Other) signifies the most reliable source of information in matters of illness and choice of therapy. Furthermore, the theme of (building and losing) trust is present throughout the patient journey, a determining factor in patient decision-making and dispositions toward both CAM and biomedicine

Complementary and alternative medicine: attitudes, knowledge and use among surgeons and anaesthesiologists in Hungary

BACKGROUND: Despite their worldwide popularity the question of using non-conventional treatments is a source of controversy among medical professionals. Although these methods may have potential benefits it presents a problem when patients use non-conventional treatments in the perioperative period without informing their attending physician about it and this may cause adverse events and complications. To prevent this, physicians need to have a profound knowledge about non-conventional treatments. METHODS: An anonymous questionnaire was distributed among surgeons and anaesthesiologists working in Hungarian university clinics and in selected city or county hospitals. Questionnaires were distributed by post, online or in person. Altogether 258 questionnaires were received from 22 clinical and hospital departments. RESULTS: Anaesthesiologists and surgeons use reflexology, Traditional Chinese Medicine, herbal medicine and manual therapy most frequently in their clinical practice. Traditional Chinese Medicine was considered to be the most scientifically sound method, while homeopathy was perceived as the least well-grounded method. Neural therapy was the least well-known method among our subjects. Among the subjects of our survey only 3.1 % of perioperative care physicians had some qualifications in non-conventional medicine, 12.4 % considered themselves to be well-informed in this topic and 48.4 % would like to study some complementary method. Women were significantly more interested in alternative treatments than men, p = 0.001427; OR: 2.2765. Anaesthesiologists would be significantly more willing to learn non-conventional methods than surgeons. 86.4 % of the participants thought that non-conventional treatments should be evaluated from the point of view of evidence. Both surgeons and anaesthesiologists accept the application of integrative medicine and they also approve of the idea of teaching these methods at universities. CONCLUSIONS: According to perioperative care physicians, non-conventional methods should be evaluated based on evidence. They also expressed a willingness to learn about those treatments that meet the criteria of evidence and apply these in their clinical practice

Novel immunomodulators from hard ticks selectively reprogramme human dendritic cell responses

Hard ticks subvert the immune responses of their vertebrate hosts in order to feed for much longer periods than other blood-feeding ectoparasites; this may be one reason why they transmit perhaps the greatest diversity of pathogens of any arthropod vector. Tick-induced immunomodulation is mediated by salivary components, some of which neutralise elements of innate immunity or inhibit the development of adaptive immunity. As dendritic cells (DC) trigger and help to regulate adaptive immunity, they are an ideal target for immunomodulation. However, previously described immunoactive components of tick saliva are either highly promiscuous in their cellular and molecular targets or have limited effects on DC. Here we address the question of whether the largest and globally most important group of ticks (the ixodid metastriates) produce salivary molecules that specifically modulate DC activity. We used chromatography to isolate a salivary gland protein (Japanin) from Rhipicephalus appendiculatus ticks. Japanin was cloned, and recombinant protein was produced in a baculoviral expression system. We found that Japanin specifically reprogrammes DC responses to a wide variety of stimuli in vitro, radically altering their expression of co-stimulatory and co-inhibitory transmembrane molecules (measured by flow cytometry) and their secretion of pro-inflammatory, anti-inflammatory and T cell polarising cytokines (assessed by Luminex multiplex assays); it also inhibits the differentiation of DC from monocytes. Sequence alignments and enzymatic deglycosylation revealed Japanin to be a 17.7 kDa, N-glycosylated lipocalin. Using molecular cloning and database searches, we have identified a group of homologous proteins in R. appendiculatus and related species, three of which we have expressed and shown to possess DC-modulatory activity. All data were obtained using DC generated from at least four human blood donors, with rigorous statistical analysis. Our results suggest a previously unknown mechanism for parasite-induced subversion of adaptive immunity, one which may also facilitate pathogen transmission

Spatial Evaluation and Modeling of Dengue Seroprevalence and Vector Density in Rio de Janeiro, Brazil

Dengue is a major public health problem in many tropical regions of the world, including Brazil, where Aedes aegypti is the main vector. We present a household study that combines data on dengue fever seroprevalence, recent dengue infection, and vector density, in three neighborhoods of Rio de Janeiro, Brazil, during its most devastating dengue epidemic to date. This integrated entomological–serological survey showed evidence of silent transmission even during a severe epidemic. Also, past exposure to dengue virus was highly associated with age and living in areas of high movement of individuals and social/commercial activity. No association was observed between household infestation index and risk of dengue infection in these areas. Our findings are discussed in the light of current theories regarding transmission thresholds and relative role of mosquitoes and humans as vectors of dengue viruses