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Objectives: Meglumine antimoniate (MA; Glucantime®), the 80-year-old first-line systemic treatment for all forms of American tegumentary leishmaniasis (ATL) caused by Leishmania (Viannia) braziliensis, Leishmania (Viannia) guyanensis and Leishmania (Leishmania) amazonensis, is highly toxic, presents adverse side-effects and may not attain clinical and parasitological cure. This critical review examines the necessity for intramuscular/intravenous administration of MA, the alternatives to this approach, and the possibilities of developing affordable, accessible and non-toxic drugs or new delivery methods., Method: PubMed searches were performed using the terms 'cutaneous leishmaniasis' or 'American tegumentary leishmaniasis' in combination with 'meglumine antimoniate' or 'N-methyl glucamine' or 'drug repositioning' or 'nanotechnology'. Searches covered a period of 20 years of peer reviewed journals and technical bulletins. We explored the mode of action, pharmacokinetics, toxicity and efficacy of MA, evaluated the progress of ATL therapy in Brazil, and examined the potential of drug repositioning and nanotechnology in accelerating the introduction and/or optimisation of an alternative treatment., Results: The evidence suggests that ATL therapy will continue to rely on systemic MA in the foreseeable future even though an intralesional subcutaneous route has evolved over the last 10 years. The chances of developing a novel drug for ATL or a new mode of delivery of MA are low. While MA nanocarriers afford a promising approach, this technology is still in its infancy. A more immediate solution would be the production of a bioequivalent of miltefosine, an efficacious oral agent no longer protected by patent., Conclusion: Development of a contemporary treatment requires governmental commitment in bringing together private and public sectors., (© 2019 John Wiley & Sons Ltd.)

In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection.

Introduction: This study was undertaken to identify which minimally invasive technique medical students prefer for cholecystectomy and what factors determine their decision., Methods: Brazilian medical students watched a video reviewing the advantages and disadvantages of six different surgical approaches to cholecystectomy: open surgery, conventional laparoscopy, mini-laparoscopy (MINI), single-incision laparoscopic surgery, natural-orifice transluminal endoscopic surgery, and robotic surgery. Respondents then answered questions about hypothetical situations in which the participants would be submitted to elective cholecystectomy., Results: One hundred eleven medical students completed the survey, 60 females (54%) and 51 males (46%). Most students were 19-26 years old. When asked whether they would consider an open cholecystectomy if minimally invasive surgery (MIS) techniques were available, only 9% answered yes. Senior medical students were the least willing to consider open surgery ( P = .036). When asked if they would prefer conventional laparoscopy, MINI, or robotic surgery for their cholecystectomy, 85% of the women and 63% of the men chose MINI ( P = .025). When asked if they would consider a single-incision laparoscopic surgery or natural-orifice transluminal endoscopic surgery approach, 94 respondents (84%) answered no. When asked to rank which factors they consider the most important when choosing a surgical technique, they ranked safety of the procedure first (58%) and surgeon experience second (30%)., Conclusion: When Brazilian medical students were asked to select a surgical approach for cholecystectomy, most chose MINI. The preference for MINI was strongest amongst female medical students. Both female and male medical students ranked safety as the most important factor., Competing Interests: Conflicts of Interest: All authors declare no conflict of interest regarding the publication of this article.

The role of the concomitant intake of zinc, potassium, calcium, and magnesium in the glycemic control of individuals with type 2 diabetes mellitus (T2DM) has not been extensively discussed. We evaluated the relationship between the dietary intake of these micronutrients and glycemic markers in 95 individuals with T2DM (mean age 48.6 ± 8.4 years). Hierarchical grouping analysis was used to divide the individuals into two clusters according to their micronutrient intake, and differences between clusters were statistically assessed. Effects of individual and combination intake of micronutrients on glycated hemoglobin percentage (%HbA1c) were assessed using multiple linear regression and binary logistic regression analysis. We observed a high likelihood of inadequate intake of the four micronutrients. The group with lower micronutrient intake (cluster 1) displayed higher %HbA1c ( p = 0.006) and triglyceride ( p = 0.010) levels. High %HbA1c showed an association with cluster 1 (odds ratio (OR) = 3.041, 95% confidence interval (CI) = 1.131; 8.175) and time of T2DM diagnosis (OR = 1.155, 95% CI = 1.043; 1.278). Potassium (β = -0.001, p = 0.017) and magnesium (β = -0.007, p = 0.015) intakes were inversely associated with %HbA1c. Reduced concomitant intake of the four micronutrients studied proved to be associated with risk of increased %HbA1c in individuals with T2DM, which was particularly predicted by magnesium and potassium intakes.

The present study evaluated the cytokine profile in PBMC supernatants and the humoral response in mucosal leishmaniasis (ML) patients and in healthy subjects living in an endemic area. Four proteins, which had previously proven to be antigenic in the human disease, were tested: LiHyM, enolase, eukaryotic initiation factor 5a, and Beta-tubulin. Results showed that all of the proteins stimulated human cells with higher IFN-γ and lower IL-4 and IL-10 levels. The analysis of antibody isotypes correlated with cell response, since the IgG2 production was higher than IgG1 in both groups. By contrast, a Th2 response was found when an antigenic Leishmania extract was used. Serological analyses revealed high sensitivity and specificity values for the serodiagnosis of the disease, when compared to the data obtained using the antigenic preparation. In conclusion, this study presents new candidates to be evaluated as biomarkers in tegumentary leishmaniasis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To describe head computed tomography (CT) findings in neonates with congenital Zika virus infection confirmed in cerebrospinal fluid., Materials and Methods: This was a study of 16 newborn infants who exhibited abnormal head CT findings during an outbreak of Zika virus infection. Those infants had the following features: brain imaging suggestive of congenital infection; brain calcifications and negative results on tests for other main infectious causes of primary microcephaly, namely toxoplasmosis, cytomegalovirus, rubella, and HIV; positivity for Zika virus on IgM antibody capture enzyme-linked immunosorbent assay in cerebrospinal fluid., Results: Decreased brain volume was observed in 13 (81.2%) of the infants. All of the infants showed cortico-subcortical calcifications, mainly located in the frontal lobe. In 15 neonates (93.7%), ventriculomegaly was observed. Colpocephaly was a common finding, being observed in 10 patients (62.5%). A prominent occipital bone was identified in 9 patients (56.2%)., Conclusion: Our study proves that Zika virus infection can cause congenital brain damage, with or without microcephaly. Some predominant head CT findings in neonates with congenital Zika virus infection, although not pathognomonic, are strongly suggestive of a pattern.

Objective: The objective of this study was to assess the clinical value of 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) after the first cycle of induction chemotherapy (IC) in locally advanced squamous cell carcinoma of the head and neck (LASCCHN)., Methods and Findings: A prospective, single-arm, single center study was performed, with patients enrolled between February 2010 and July 2013.Patients (n = 49) with stage III/IVA-B LASCCHN who underwent IC with taxanes, cisplatin, and fluorouracil were recruited. Staging procedures included loco-regional and chest imaging, endoscopic examination, and PET/CT scan. On day 14 of the first cycle, a second PET/CT scan was performed. Patients with no early increase in regional lymph node maximum 18F-FDG standard uptake value (SUV), detected using 18F-FDG PET/CT after first IC had better progression-free survival (hazard ratio (HR) = 0.18, 95%, confidence interval (CI) 0.056-0.585; p = 0.004) and overall survival (HR = 0.14, 95% CI 0.040-0.498; p = 0.002), and were considered responders. In this subgroup, patients who achieved a reduction of ≥ 45% maximum primary tumor SUV experienced improved progression-free (HR = 0.23, 95% CI 0.062-0.854; p = 0.028) and overall (HR = 0.11, 95% CI 0.013-0.96; p = 0.046) survival., Conclusions: These results suggest a potential role for early response evaluation with PET/CT examination in patients with LASCCHN undergoing IC. Increased regional lymph node maximum SUV and insufficient decrease in primary tumor uptake predict poorer outcomes., Competing Interests: The authors have declared that no competing interests exist.

Mesenchymal stem/stromal cells (MSCs) have been investigated for the treatment of diseases that affect the cardiovascular system, including Chagas disease. MSCs are able to promote their beneficial actions through the secretion of proregenerative and immunomodulatory factors, including insulin-like growth factor-1 (IGF-1), which has proregenerative actions in the heart and skeletal muscle. Here, we evaluated the therapeutic potential of IGF-1-overexpressing MSCs (MSC_IGF-1) in a mouse model of chronic Chagas disease. C57BL/6 mice were infected with Colombian strain Trypanosoma cruzi and treated with MSCs, MSC_IGF-1, or vehicle (saline) six months after infection. RT-qPCR analysis confirmed the presence of transplanted cells in both the heart and skeletal muscle tissues. Transplantation of either MSCs or MSC_IGF-1 reduced the number of inflammatory cells in the heart when compared to saline controls. Moreover, treatment with MSCs or MSC_IGF-1 significantly reduced TNF- α , but only MSC treatment reduced IFN- γ production compared to the saline group. Skeletal muscle sections of both MSC- and MSC_IGF-1-treated mice showed a reduction in fibrosis compared to saline controls. Importantly, the myofiber area was reduced in T. cruzi -infected mice, and this was recovered after treatment with MSC_IGF-1. Gene expression analysis in the skeletal muscle showed a higher expression of pro- and anti-inflammatory molecules in MSC_IGF-1-treated mice compared to MSCs alone, which significantly reduced the expression of TNF- α and IL-1 β . In conclusion, our results indicate the therapeutic potential of MSC_IGF-1, with combined immunomodulatory and proregenerative actions to the cardiac and skeletal muscles.

Genetic modification of mesenchymal stem cells (MSCs) is a promising strategy to improve their therapeutic effects. Granulocyte-colony stimulating factor (G-CSF) is a growth factor widely used in the clinical practice with known regenerative and immunomodulatory actions, including the mobilization of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Here we evaluated the therapeutic potential of MSCs overexpressing G-CSF (MSC_G-CSF) in a model of inflammatory cardiomyopathy due to chronic Chagas disease. C57BL/6 mice were treated with wild-type MSCs, MSC_G-CSF, or vehicle (saline) 6 months after infection with Trypanosoma cruzi . Transplantation of MSC_G-CSF caused an increase in the number of circulating leukocytes compared to wild-type MSCs. Moreover, G-CSF overexpression caused an increase in migration capacity of MSCs to the hearts of infected mice. Transplantation of either MSCs or MSC_G-CSF improved exercise capacity, when compared to saline-treated chagasic mice. MSC_G-CSF mice, however, were more potent than MSCs in reducing the number of infiltrating leukocytes and fibrosis in the heart. Similarly, MSC_G-CSF-treated mice presented significantly lower levels of inflammatory mediators, such as IFNγ, TNFα, and Tbet, with increased IL-10 production. A marked increase in the percentage of Tregs and MDSCs in the hearts of infected mice was seen after administration of MSC_G-CSF, but not MSCs. Moreover, Tregs were positive for IL-10 in the hearts of T. cruzi -infected mice. In vitro analysis showed that recombinant hG-CSF and conditioned medium of MSC_G-CSF, but not wild-type MSCs, induce chemoattraction of MDSCs in a transwell assay. Finally, MDSCs purified from hearts of MSC_G-CSF transplanted mice inhibited the proliferation of activated splenocytes in a co-culture assay. Our results demonstrate that G-CSF overexpression by MSCs potentiates their immunomodulatory effects in our model of Chagas disease and suggest that mobilization of suppressor cell populations such as Tregs and MDSCs as a promising strategy for the treatment of chronic Chagas disease. Finally, our results reinforce the therapeutic potential of genetic modification of MSCs, aiming at increasing their paracrine actions.

New candidates for serological markers against leishmaniasis are required to be identified, since the presence of high titers of anti-Leishmania antibodies remain detected in sera of treated and cured patients, when current antigens have being employed. In this study, the diagnostic performance of a conserved Leishmania hypothetical protein was evaluated against a human and canine serological panel. The serological follow-up of the patients was also evaluated, using this recombinant antigen (rLiHyS) in ELISA assays. In the results, high sensitivity and specificity values were found when rLiHyS was used in the serological tests, while when the recombinant A2 (rA2) protein or an antigenic Leishmania preparation were used as controls, low sensitivity and specificity were found. Regarding the serological follow-up of the patients, significant reductions in the anti-rLiHyS antibody levels were found and, one year after the treatments, the anti-protein IgG production was similar to this found in the non-infected groups, reflecting a drop of the anti-rLiHyS antibody production. In conclusion, the present study shows for the first time a new recombinant antigen used to identify tegumentary and visceral leishmaniasis, as well as being able to serologically distinguish treated and cured patients from those developing active disease., (Copyright © 2018 Elsevier B.V. All rights reserved.)

There has been a significant increase in concern towards improving aesthetic and functional outcomes without compromising the oncologic effectiveness in head and neck surgery. The aim of the current study is to assess the feasibility and oncological outcome of the retroauricular approach for endoscopic and robot-assisted selective neck dissection (SND) for oral cancer in comparison with the conventional SND. A retrospective single institute cohort study was designed. Patients undergoing an SND for oral cavity carcinoma were included and allocated into two groups: (1) retroauricular approach group for endoscopic-assisted or robot-assisted SND or (2) transcervical approach group for the conventional SND. Primary endpoint was the perioperative and postoperative treatment outcomes. Secondary endpoint was the early oncologic outcome. Sixty patients were included (17 retroauricular; 43 conventional). For the primary outcome, only a significant longer operative time in the retroauricular group was identified. No unintentional injury or conversion to the conventional surgery was recorded. There was no significant difference identified in the early oncologic outcome, including number of retrieved lymph nodes and disease-free survival. Postoperative aesthetic results were considered superior when subjectively compared to the conventional approaches. Endoscopic and robot-assisted SND via a retroauricular approach is feasible, safe, and oncologically efficient when compared with the conventional surgery in a short follow-up scenario. It can be used for selected cases with a clear cosmetic benefit. However, further research with longer follow-up and patient satisfaction analysis is mandatory.

Background: Obesity is associated with numerous cardiac complications, including arrhythmias, cardiac fibrosis, remodeling and heart failure. Here we evaluated the therapeutic potential of mesenchymal stromal cells (MSCs) and their conditioned medium (CM) to treat cardiac complications in a mouse model of high-fat diet (HFD)-induced obesity., Methods: After obesity induction and HFD withdrawal, obese mice were treated with MSCs, CM or vehicle. Cardiac function was assessed using electrocardiography, echocardiography and treadmill test. Body weight and biochemical parameters were evaluated. Cardiac tissue was used for real time (RT)-polymerase chain reaction (PCR) and histopathologic analysis., Results/discussion: Characterization of CM by protein array showed the presence of different cytokines and growth factors, including chemokines, osteopontin, cystatin C, Serpin E1 and Gas 6. HFD-fed mice presented cardiac arrhythmias, altered cardiac gene expression and fibrosis reflected in physical exercise incapacity associated with obesity and diabetes. Administration of MSCs or CM improved arrhythmias and exercise capacity. This functional improvement correlated with normalization of GATA4 gene expression in the hearts of MSC- or CM-treated mice. The gene expression of connexin 43, troponin I, adiponectin, transforming growth factor (TGF) β, peroxisome proliferator activated receptor gamma (PPARγ), insulin-like growth factor 1 (IGF-1), matrix metalloproteinase-9 (MMP9) and tissue inhibitor of metalloproteinases 1 (TIMP1) were significantly reduced in MSCs, but not in CM-treated mice. Moreover, MSC or CM administration reduced the intensity of cardiac fibrosis., Conclusion: Our results suggest that MSCs and CM have a recovery effect on cardiac disturbances due to obesity and corroborate to the paracrine action of MSCs in heart disease models., (Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Changes in body temperature can profoundly affect survival. The dramatic longevity-enhancing effect of cold has long been known in organisms ranging from invertebrates to mammals, yet the underlying mechanisms have only recently begun to be uncovered. In the nematode Caenorhabditis elegans , this process is regulated by a thermosensitive membrane TRP channel and the DAF-16/FOXO transcription factor, but in more complex organisms the underpinnings of cold-induced longevity remain largely mysterious. We report that, in Drosophila melanogaster , variation in ambient temperature triggers metabolic changes in protein translation, mitochondrial protein synthesis, and posttranslational regulation of the translation repressor, 4E-BP (eukaryotic translation initiation factor 4E-binding protein). We show that 4E-BP determines Drosophila lifespan in the context of temperature changes, revealing a genetic mechanism for cold-induced longevity in this model organism. Our results suggest that the 4E-BP pathway, chiefly thought of as a nutrient sensor, may represent a master metabolic switch responding to diverse environmental factors., Competing Interests: The authors declare no conflict of interest.

Past research has shown the importance of zinc in several metabolic processes, such as the glucidic metabolism. The present systematic review aims to discuss zinc's participation in the glycemic control of type 2 diabetes mellitus (DM2) patients. In order to accomplish that, a systematic search was performed in the Pubmed database using the following indexed and theme-related descriptors: "zinc" AND "type 2 diabetes mellitus", AND MeSH terms related to glycemic control combined with the boolean operator OR. In total, 1078 articles were retrieved from the research, of which 15 articles of original studies conducted with DM2 patients were included, with three being about the effect of mineral supplementation and 12 reporting observational studies. The main findings of these studies consisted of low body contents of zinc and high excretion of zinc in urine. Hyperglycemia was one of the mechanisms that caused these alterations owing to its interference in zinc reabsorption via renal cells. Another evidence was the negative correlation between the glycated hemoglobin percentage (%HbA1c) and the plasma zinc levels. Additionally, it has been observed that zinc supplementation in DM2 patients has improved glycemic control, since the %HbA1c significantly reduced in these individuals. This present review shows the positive effect of adequate zinc levels on glycemic control, whether it is through dietetic ingestion or supplementation, since its role in insulin homeostasis is clear.

Background and Purpose: To assess the role of MR venography (MRV) for detecting transverse sinus stenosis, to determine the importance of this finding in idiopathic intracranial hypertension (IIH), and to propose an index that contributes to this diagnosis., Materials and Methods: We retrospectively assessed consecutive intracranial MRV of patients aged >18 years diagnosed with IIH according to the diagnostic criteria, between January 2010 and July 2012. The assessments were randomly analyzed by three radiologists. Stenoses in the right and left transverse sinuses were independently classified according to the following scale: 0, normal; 1, stenosis <33%; 2, stenosis 33-66%; 3, stenosis >66%; and 4, hypoplasia or agenesis. We established an index based on multiplication of the stenosis scale values for each transverse sinus. A point and range estimate of the sensitivity, specificity, and the area under the receiver operating characteristic curve was performed to obtain cut-off points to differentiate between controls and patients., Results: 63 individuals were included in this study: 32 (50.8%) diagnosed with IIH (31 (96.9%) women and 1 (3.1%) man) and 31 (49.2%) controls. According to all of the examiners, the IIH group showed a higher degree of stenosis than the control group. Index values ≥4 for a diagnosis of IIH had a sensitivity and specificity of 94.7% and 93.5%, respectively., Conclusions: MRV should be used to assess patients with suspected IIH, and bilateral transverse sinus stenosis should be considered for the diagnosis. The stenosis classifying index proposed here is a fast and accessible method for diagnosing IIH., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Therapies based on transplantation of mesenchymal stromal cells (MSC) hold promise for the management of inflammatory disorders. In chronic Chagas disease cardiomyopathy (CCC), caused by chronic infection with Trypanosoma cruzi , the exacerbated immune response plays a critical pathophysiological role and can be modulated by MSC. Here, we investigated the role of galectin-3 (Gal-3), a beta-galactoside-binding lectin with several actions on immune responses and repair process, on the immunomodulatory potential of MSC. Gal-3 knockdown in MSC did not affect the immunophenotype or differentiation potential. However, Gal-3 knockdown MSC showed decreased proliferation, survival, and migration. Additionally, when injected intraperitoneally into mice with CCC, Gal-3 knockdown MSC showed impaired migration in vivo. Transplantation of control MSC into mice with CCC caused a suppression of cardiac inflammation and fibrosis, reducing expression levels of CD45, TNF α , IL-1 β , IL-6, IFN γ , and type I collagen. In contrast, Gal-3 knockdown MSC were unable to suppress the immune response or collagen synthesis in the hearts of mice with CCC. Finally, infection with T. cruzi demonstrated parasite survival in wild-type but not in Gal-3 knockdown MSC. These findings demonstrate that Gal-3 plays a critical role in MSC survival, proliferation, migration, and therapeutic potential in CCC.

Background: Quality assessment is a major tool for evaluation of health care delivery. In head and neck surgery, the University of Texas MD Anderson Cancer Center (MD Anderson) has defined quality standards by publishing benchmarks., Methods: We conducted an analysis of 360 head and neck surgeries performed at the AC Camargo Cancer Center (AC Camargo). The procedures were stratified into low-acuity procedures (LAPs) or high-acuity procedures (HAPs) and outcome indicators where compared to MD Anderson benchmarks., Results: In the 360 cases, there were 332 LAPs (92.2%) and 28 HAPs (7.8%). Patients with any comorbid condition had a higher incidence of negative outcome indicators (p = .005). In the LAPs, we achieved the MD Anderson benchmarks in all outcome indicators. In HAPs, the rate of surgical site infection and length of hospital stay were higher than what is established by the benchmarks., Conclusion: Quality assessment of head and neck surgery is possible and should be disseminated, improving effectiveness in health care delivery. © 2015 Wiley Periodicals, Inc. Head Neck 38: 1002-1007, 2016., (© 2015 Wiley Periodicals, Inc.)

Objective: Evaluate the correlation between spinal cord lesion length and pyramidal function system score in a cohort of patients with NMO., Methodology: Retrospective retrieval of all exams performed in our center from January 2004 to December 2012 for patients with NMO. The exams were evaluated for lesion length, contrast enhancement and T1 hypointensity; these variables were correlated with the functional system score from the EDSS, performed no more than three months from the scan., Results: 41 patients were included. Although patients with lesion extension ≥2 vertebral segments did not present worse pyramidal scores in a direct comparison, the influence of lesion length was not so strong when patients were separated in 3 groups (≥2, ≥3 or ≥4 vertebral segments) and evaluated with a receiving operating characteristics (ROC) curves. Gadolinium enhancement also contributed to more severe pyramidal system scores, but T1 hypointensity did not., Conclusion: Although patients with spinal cord lesion extending ≥3 vertebral segments had more pyramidal disability, its difference was not so strong when compared to patients with ≥2 or ≥4 vertebral segments. This suggests that lesion extension might not be the most important factor in favoring a worse prognosis in spinal cord lesions in NMO., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To validate two scores quantifying the ability of patients to use metered dose inhalers (MDIs) or dry powder inhalers (DPIs); to identify the most common errors made during their use; and to identify the patients in need of an educational program for the use of these devices., Methods: This study was conducted in three phases: validation of the reliability of the inhaler technique scores; validation of the contents of the two scores using a convenience sample; and testing for criterion validation and discriminant validation of these instruments in patients who met the inclusion criteria., Results: The convenience sample comprised 16 patients. Interobserver disagreement was found in 19% and 25% of the DPI and MDI scores, respectively. After expert analysis on the subject, the scores were modified and were applied in 72 patients. The most relevant difficulty encountered during the use of both types of devices was the maintenance of total lung capacity after a deep inhalation. The degree of correlation of the scores by observer was 0.97 (p < 0.0001). There was good interobserver agreement in the classification of patients as able/not able to use a DPI (50%/50% and 52%/58%; p < 0.01) and an MDI (49%/51% and 54%/46%; p < 0.05)., Conclusions: The validated scores allow the identification and correction of inhaler technique errors during consultations and, as a result, improvement in the management of inhalation devices.

Aim: To describe the neuroradiological features and their prevalence in patients with neuromyelitis optica (NMO)., Materials and Methods: Two neuroradiologists independently reviewed 35 spinal cord and 37 brain MRI studies from patients with NMO. The examinations were analysed for the presence of lesion, topography, enhancement, and brain lesions suggestive of multiple sclerosis and/or NMO., Results: Seventy percent of the spinal cord lesions involved over three or more vertebral segments. Seventy-eight percent of brain scans were abnormal, and the most prevalent findings were non-specific foci of T2 hyperintensities in the cerebral white matter (55%) and brainstem lesions (52%). One patient had lesions disseminated in space compatible with multiple sclerosis according to 2010 revised McDonald criteria. Brain lesions suggestive of NMO occurred at least once in 17 (59%) patients., Conclusion: Spinal cord lesions were often longitudinally extensive and brain lesions were common, with the majority of patients having at least one distinctive NMO lesion., (Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Melanocytomas are rare pigmented primary lesions of the central nervous system arising from melanocytes of leptomeninges. They occur most frequently in the posterior fossa, Meckel's cave, or along the cervical and thoracic spinal cord. Orbital melanocytomas have been rarely reported. Nevus of Ota is a melanocytic lesion that can be associated with cutaneous and meningeal melanocytic neoplasms., Methods and Results: We describe a case of an orbital melanocytoma associated with ipsilateral Nevus of Ota. A 28-year-old man presented with proptosis and an ipsilateral congenital facial melanocytic lesion (Nevus of Ota). After imaging evaluation, a retro-orbital mass was discovered. A needle biopsy was performed and the diagnosis of melanocytoma rendered. The patient underwent complete surgical excision of the lesion., Conclusion: In order to make the correct diagnosis and to choose the appropriate therapy, it is important to be aware of this rare presentation and its association with Nevus of Ota., (© 2014 Wiley Periodicals, Inc.)

Objectives: To compare drugs prescribed on hospital admission with the list of drugs taken prior to admission for adult patients admitted to a cardiology unit and to identify the role of a pharmacist in identifying and resolving medication discrepancies., Method: This study was conducted in a 300 bed university hospital in Brazil. Clinical pharmacists taking medication histories and reconciling medications prescribed on admission with a list of drugs used prior to admission. Discrepancies were classified as justified (e.g., based on the pharmacotherapeutic guidelines of the hospital studied) or unintentional. Treatments were reviewed within 48 hours following hospitalization. Unintentional discrepancies were further classified according to the categorization of medication error severity. Pharmacists verbally contacted the prescriber to recommend actions to resolve the discrepancies., Results: A total of 181 discrepancies were found in 50 patients (86%). Of these discrepancies, 149 (82.3%) were justified changes to the patient's home medication regimen; however, 32 (17.7%) discrepancies found in 24 patients were unintentional. Pharmacists made 31 interventions and 23 (74.2%) were accepted. Among unintentional discrepancies, the most common was a different medication dose on admission (42%). Of the unintentional discrepancies 13 (40.6%) were classified as error without harm, 11 (34.4%) were classified as error without harm but which could affect the patient and require monitoring, 3 (9.4%) as errors could have resulted in harm and 5 (15.6%) were classified as circumstances or events that have the capacity to cause harm., Conclusion: The results revealed a high number of unintentional discrepancies and the pharmacist can play an important role by intervening and correcting medication errors at a hospital cardiology unit.

Unlike the nonexcitable cell membranes that are ubiquitous in all domains of life, excitable membranes are found almost exclusively in animal organisms (Protozoa and Metazoa). Their transient permeability to ion flow makes possible the rapid detection of, and response to, external stimuli, and results in the phenomena that most clearly distinguish fauna from flora: perception, cognition, and motor activity. Interestingly, all known forms of membrane excitability are a consequence of one unique mechanism: the influx of positively charged ions into the normally alkaline cytoplasm. Here, we suggest that the sudden reversal of the membrane potential during the sensory potential and the action potential is an electrostatic disturbance of homeostasis that is the necessary first step in the processes of 'sentience' and 'irritability'., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the characteristics of thyroid carcinoma cases treated at a reference hospital for cancer between 2008 and 2010., Methods: we studied 807 cases and analyzed the following clinicopathologic variables: symptoms, risk factors, diagnostic tests, staging, histological type, treatment performed and complications., Results: Females were more affected, with 660 cases (82%). The average age at diagnosis was 44.5 years. Prior exposure to ionizing radiation was reported by 22 (3%) patients, a family history of thyroid cancer by 89 (11%), and 289 (36%) individuals reported other types of cancer in the family. The fine needle aspiration biopsy was the main parameter for surgical indication and was suggestive of carcinoma in 463 patients (57%). Papillary carcinoma was the most common histological type, with 780 cases (96.6%). There were 728 (90%) total thyroidectomies, 43 (5.3%) reoperations or partial thyroidectomies followed by totalization, 23 (2.8%) extended thyroidectomies and only 13 (1.6%) partial thyroidectomies (lobectomy with isthmectomy). Neck dissection associated with thyroidectomy was done in 158 patients (19.5%). We observed a predominance of tumors classified as T1 in 602 (74.6%) patients. Transient hypocalcemia was the most frequent complication., Conclusion: The results show that the worldwide increase in the incidence of thyroid cancer has changed the profile of patients seen at a referral service. In addition, there were changes in the type of surgical treatment used, with increased use of total thyroidectomy in relation to partial and subtotal ones, and decreased use of elective neck dissections.

Food intake is a fundamental parameter in animal studies. Despite the prevalent use of Drosophila in laboratory research, precise measurements of food intake remain challenging in this model organism. Here, we compare several common Drosophila feeding assays: the capillary feeder (CAFE), food labeling with a radioactive tracer or colorimetric dye and observations of proboscis extension (PE). We show that the CAFE and radioisotope labeling provide the most consistent results, have the highest sensitivity and can resolve differences in feeding that dye labeling and PE fail to distinguish. We conclude that performing the radiolabeling and CAFE assays in parallel is currently the best approach for quantifying Drosophila food intake. Understanding the strengths and limitations of methods for measuring food intake will greatly advance Drosophila studies of nutrition, behavior and disease.

Schistosoma mansoni tegument is involved in essential functions for parasite survival and represents a target for screening candidates for vaccine and diagnosis. Our group using reverse vaccinology selected six candidates, previously demonstrated by proteomics studies to be expressed in the parasite tegument, among them was Sm200. In this work we have cloned and expressed a recombinant form of Sm200 C-terminal (1069-1520) region. The efficacy of rSm200 (1069-1520) in the diagnosis of schistosomiasis and in the formulation of a vaccine against S. mansoni was assessed respectively in an ELISA based diagnostic assay and immunization protocols in mice. Significant differences between non-infected and acutely infected or chronically infected animals were observed and no cross-recognition was observed with sera from Ascaris suum or Ancylostoma ceylanicum infected mice. rSm200-ELISA test could also discriminate infected individuals from healthy donors not living in endemic area for schistosomiasis but failed to discriminate between individuals from a low endemic area for schistosomiasis known to have positive or negative stools after examination. Recombinant Sm200 also failed to induce protection against schistosomiasis, demonstrating that the C-terminal part of Sm200 is unable to induce protective immune response in mice. Therefore rSm200 (1069-1520)-ELISA represents an important tool to be used in the diagnosis of schistosomiasis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In this note we describe the standard technical maneuver used in our department to protect the skin during thyroidectomy in order to get the best aesthetic result. We use surgical gloves to protect the skin during these operations to reduce the negative impact of thermal trauma and mechanical retractors and energy delivery devices at the edges of the skin incised. This practice is effective, inexpensive, rapid, reproducible and showed no complication in our experience of over 2,500 thyroidectomies.

Dietary restriction extends lifespan in a variety of organisms, but the key nutritional components driving this process and how they interact remain uncertain. In Drosophila, while a substantial body of research suggests that protein is the major dietary component affecting longevity, recent studies claim that carbohydrates also play a central role. To clarify how nutritional factors influence longevity, nutrient consumption and lifespan were measured on a series of diets with varying yeast and sugar content. We show that optimal lifespan requires both high carbohydrate and low protein consumption, but neither nutrient by itself entirely predicts lifespan. Increased dietary carbohydrate or protein concentration does not always result in reduced feeding-the regulation of food consumption is best described by a constant daily caloric intake target. Moreover, due to differences in food intake, increased concentration of a nutrient within the diet does not necessarily result in increased consumption of that particular nutrient. Our results shed light on the issue of dietary effects on lifespan and highlight the need for accurate measures of nutrient intake in dietary manipulation studies., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Schwannomas are benign, encapsulated, slow-growing and usually solitary tumours originating from Schwann cells of the peripheral nerve sheath. Approximately 25-40% of cases are seen in the head and neck region, of which 1% in the oral cavity. We report a rare case of lingual schwannoma in a young woman who was treated with complete transoral excision, and also review the literature of the past two decades, analyzing epidemiological and clinical data of the 35 cases reported. Lingual schwannomas generally present as a painless lump with an average size of 2 cm in the fourth decade of life and with no gender predilection. Complete transoral excision can be considered standard treatment for these tumours, with no recurrences documented in the literature.

The aim of this study was to evaluate swallowing, speech and quality of life in patients undergoing surgery for malignant tumors involving soft palate. We performed a cross sectional study of 23 patients (aged 32-80 years), submitted to soft palate resection, free of disease for at least 1 year. Primary closure of the surgical defect was performed in 5 patients (21.7 %), adaptation of a palatal obturator prosthesis in 2 (8.7 %), myocutaneous flap in 5 (21.7 %), local flap in 2 (8.7 %) and microsurgical free flap in 9 (39.1 %). All patients were submitted to fibreoptic endoscopic evaluation and completed functional and quality of life questionnaires. Functional evaluation of swallowing showed higher prevalence of pooling of food in the nasopharynx in patients submitted to regional flap reconstruction or primary closure (53.9 %). Swallowing difficulties were predominantly related to solid foods (54.5 %) and were associated with more extensive palatal resections. Most individuals submitted to reconstruction with microsurgical flaps had satisfactory velopharyngeal mobility (87 %). The presence of nasal air escape or velopharyngeal gap was minimal in most of the sample. Hypernasality contributed minimally to imprecisions in speech articulation or intelligibility. Vocal alteration did not impact patients' quality of life. Pharyngeal phase of swallowing was satisfactory in most patients. However, nasal reflux and penetration were present in a few patients. Most patients had minimal phono-articulatory alterations as a global outcome. Scores of swallowing and speech parameters regarding the questionnaires used were high, demonstrating minor impact on quality of life.

Virus dissociation and inactivation by high pressure have been extensively studied in recent decades. Pressure-induced dissociation of viral particles involves a reduction in the Gibbs free energy of dissociation and a negative change in volume. In this work, we investigated the combined effect of high pressure and temperature on the dissociation of tobacco mosaic virus (TMV). We assumed the presence of two states of TMV with different tendencies to dissociate. Thus one form presents a low tendency (L) and the other a high tendency (H) to dissociate. Based on the model described here, the L-H transition was favored by an increase in pressure and a decrease in temperature. The volume change of dissociation was pressure- and temperature-dependent, with a highly negative value of -80 mL/mol being recorded at 0 °C and atmospheric pressure. The entropy and enthalpy of dissociation were very temperature- and pressure-dependent, with values of entropy of 450 to -1300 kJ/mol and values of enthalpy of 5.5 × 10(4) to 2.4 × 10(4) kJ/mol. The dissociation of TMV was enthalpy-driven at all temperatures and pressures investigated. Based on these findings, we conclude that the model presented allows accurate predictions of viral dissociation behavior in different experimental conditions.

The development of a more sensitive diagnostic test for schistosomiasis is needed to overcome the limitations of the use of stool examination in low endemic areas. Using parasite antigens in enzyme linked immunosorbent assay is a promising strategy, however a more rational selection of parasite antigens is necessary. In this study we performed in silico analysis of the Schistosoma mansoni genome, using SchistoDB database and bioinformatic tools for screening immunogenic antigens. Based on evidence of expression in all parasite life stage within the definitive host, extracellular or plasmatic membrane localization, low similarity to human and other helminthic proteins and presence of predicted B cell epitopes, six candidates were selected: a glycosylphosphatidylinositol-anchored 200 kDa protein, two putative cytochrome oxidase subunits, two expressed proteins and one hypothetical protein. The recognition in unidimensional and bidimensional Western blot of protein with similar molecular weight and isoelectric point to the selected antigens by sera from S. mansoni infected mice indicate a good correlation between these two approaches in selecting immunogenic proteins.

Lanthanide orthotantalates RETaO(4) (RE = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) were synthesized by solid-state reaction in optimized conditions of temperature (1300 °C) and time (up to 14 h) to yield crystalline materials. The crystal structures of the obtained compounds were investigated by X-ray diffraction and Raman scattering. All the samples exhibited monoclinic structures, but with different arrangements as a function of the ionic radius of the rare-earth metal occupying the A-site. For compounds with the largest ionic radii (La-Pr), the ceramics crystallized in the monoclinic structure, P2(1)/c (C(2h)(5), #14, Z = 4), while the compounds with intermediate ionic radii (Nd-Tb) exhibited the fergusonite M-type structure, I2/a (C(2h)(6), #15, Z = 4). Samples with the smallest ionic radii (Dy-Lu) presented the fergusonite M'-type structure, P2/a (C(2h)(4), #13, Z = 2). These last two groups of compounds exhibited phase transitions, which can be related to the processing temperature. The compounds belonging to the M-type structure are stable at high temperatures, whilst materials belonging to the M'-type structure are stable at low temperatures. The results from XRD and Raman scattering allows us to understand the differences between these two structures in terms of the vibrational-active modes assigned to each space group. Also, the Raman patterns in addition to group-theory calculations for this complete lanthanide series were reported for the first time. The experimental results are in perfect agreement with theoretical calculations: samples with P2(1)/c (#14) structure showed 36 Raman-active modes, while both I2/a (#15) and P2/a (#13) structures exhibited 18 Raman modes.

Malaria is an acute infectious disease caused by the protozoa of the genus Plasmodium. The antigens of the Duffy Blood Group System, in addition to incompatibilities in transfusions and hemolytic disease of the newborn, are of great interest in medicine due to their association with the invasion of red blood cells by the parasite Plasmodium vivax. For invasions to occur an interaction between the parasites and antigens of the Duffy Blood Group System is necessary. In Caucasians six antigens are produced by the Duffy locus (Fya, Fyb, F3, F4, F5 and F6). It has been observed that Fy(a-b-) individuals are resistant to Plasmodium knowlesi and P. vivax infection, because the invasion requires at least one of these antigens. The P. vivax Duffy Binding Protein (PvDBP) is functionally important in the invasion process of these parasites in Duffy / DARC positive humans. The proteins or fractions may be considered, therefore, an important and potential inoculum to be used in immunization against malaria.

Dietary restriction (DR) is a widely conserved intervention leading to lifespan extension. Despite considerable effort, the mechanisms underlying DR remain poorly understood. In particular, it remains unclear whether DR prolongs life through conserved mechanisms in different species. Here, we show that, in the most common experimental conditions, lifespan extension by DR is abolished by providing Drosophila with ad libitum water, without altering food intake, indicating that DR, as conventionally studied in flies, is fundamentally different from the phenomenon studied in mammals. We characterize an alternative dietary paradigm that elicits robust lifespan extension irrespective of water availability, and thus likely represents a more relevant model for mammalian DR. Our results support the view that protein:carbohydrate ratio is the main dietary determinant of fly lifespan. These findings have broad implications for the study of lifespan and nutrition.

Methuselah (Mth) is a G protein-coupled receptor (GPCR) associated with longevity in Drosophila melanogaster. Previously, Stunted (Sun) was identified as a peptide agonist of Mth. Here, we identify two additional activators of Mth signaling: Drosophila Sex Peptide (SP) and a novel peptide (Serendipitous Peptide Activator of Mth, SPAM). Minimal functional sequences and key residues were identified from Sun and SPAM by studying truncation and alanine-scanning mutations. These peptide agonists share little sequence homology and illustrate the promiscuity of Mth for activation. mth mutants exhibit no defects in behaviors controlled by SP, casting doubt on the biological significance of Mth activation by any of these agonists, and illustrating the difficulty in applying in vitro studies to their relevance in vivo. Future studies of Mth ligands will help further our understanding of the functional interaction of agonists and GPCRs.

Traditionally, the raw materials for beer production are barley, hops, water, and yeast, but most brewers use also different adjuncts. During the alcoholic fermentation, the contribution of aroma compounds from other ingredients to the final beer flavor depends on the wort composition, on the yeast strain, and mainly on the process conditions. In this context, banana can also be a raw material favorable to alcoholic fermentation being rich in carbohydrates and minerals and providing low acidity. In this work, the objective was to evaluate the performance of wort adjusted with banana juice in different concentrations. For this, static fermentations were conducted at 15 degrees C at pilot scale (140 L of medium). The addition of banana that changed the concentration of all-malt wort from 10 degrees P to 12 and 15 degrees P were evaluated ( degrees P is the weight of the extract or the sugar equivalent in 100 g solution, at 20 degrees C). The results showed an increase in ethanol production, with approximately 0.4 g/g ethanol yield and 0.6 g/L h volumetric productivity after 84 h of processing when concentrated wort was used. Thus, it was concluded that banana can be used as an adjunct in brewing methods, helping in the development of new products as well as in obtaining concentrated worts.

Banana, an important component in the diet of the global population, is one of the most consumed fruits in the world. This fruit is also very favorable to industry processes (e.g., fermented beverages) due to its rich content on soluble solids and minerals, with low acidity. The main objective of this work was to evaluate the influence of factors such as banana weight and extraction time during a hot aqueous extraction process on the total soluble solids content of banana. The extract is to be used by the food and beverage industries. The experiments were performed with 105 mL of water, considering the moisture of the ripe banana (65%). Total sugar concentrations were obtained in a beer analyzer and the result expressed in degrees Plato (degrees P, which is the weight of the extract or the sugar equivalent in 100 g solution at 20 degrees C), aiming at facilitating the use of these results by the beverage industries. After previous studies of characterization of the fruit and of ripening performance, a 2(2) full-factorial star design was carried out, and a model was developed to describe the behavior of the dependent variable (total soluble solids) as a function of the factors (banana weight and extraction time), indicating as optimum conditions for extraction 38.5 g of banana at 39.7 min.

In Drosophila, genetic techniques relying on stochastic chromosomal rearrangements involve the generation and screening of a large number of fly stocks to isolate a few lines of interest. Here, we describe a PCR-based method allowing non-lethal molecular characterization of single flies. Using this procedure, individual candidate recombinant animals can be genotyped and selected one generation earlier than with extant methodology and, importantly, before stocks are established. This advance should significantly facilitate several of the most fundamental and routine techniques in Drosophila genetics.

Studies of feeding behavior in genetically tractable invertebrate model systems have been limited by the lack of proper methodology. We introduce the Capillary Feeder (CAFE), a method allowing precise, real-time measurement of ingestion by individual or grouped fruit flies on the scale of minutes to days. Using this technique, we conducted the first quantitative analysis of prandial behavior in Drosophila melanogaster. Our results allow the dissection of feeding into discrete bouts of ingestion, defining two separate parameters, meal volume and frequency, that can be uncoupled and thus are likely to be independently regulated. In addition, our long-term measurements show that flies can ingest as much as 1.7x their body mass over 24 h. Besides the study of appetite, the CAFE can be used to monitor oral drug delivery. As an illustration, we used the CAFE to test the effects of dietary supplementation with two compounds, paraquat and ethanol, on food ingestion and preference. Paraquat, a prooxidant widely used in stress tests, had a strong anorexigenic effect. In contrast, in a feeding preference assay, ethanol-laced food, but not ethanol by itself, acted as an attractant.

Mating elicits a dramatic reprogramming of female behavior in numerous insect species. In Drosophila, this postmating response (PMR) comprises increased egg-laying rate and reduced sexual receptivity and is controlled by the products of the male accessory glands, a family of approximately 80 small peptides transferred in the male seminal fluid . Here, we show that copulation strongly stimulates female food intake. Remarkably, this change is abolished if the males lack a single, small seminal protein, the Sex Peptide (SP). Ectopic expression of SP in virgin females mimics the effect of mating on feeding behavior, demonstrating that SP is the main agent controlling this behavioral paradigm. Our observations identify enhanced feeding behavior as a novel component of the Drosophila PMR and suggest that SP represents a molecular link between energy acquisition and reproductive investment.

Dietary restriction extends the lifespan of numerous, evolutionarily diverse species. In D. melanogaster, a prominent model for research on the interaction between nutrition and longevity, dietary restriction is typically based on medium dilution, with possible compensatory ingestion commonly being neglected. Possible problems with this approach are revealed by using a method for direct monitoring of D. melanogaster feeding behavior. This demonstrates that dietary restriction elicits robust compensatory changes in food consumption. As a result, the effect of medium dilution is overestimated and, in certain cases, even fully compensated for. Our results strongly indicate that feeding behavior and nutritional composition act concertedly to determine fly lifespan. Feeding behavior thus emerges as a central element in D. melanogaster aging.

Objective: To detect the prevalence of systemic hypertension in children and to establish the relation between blood pressure levels and sex, age, ethnicity, weight, and height., Methods: The prevalence of systemic hypertension and its relation to sex, age, ethnicity, weight, and height were studied in 611 students aged 7 to 14 years out of 19.928 students classified according to age, ethnicity, and sex, who underwent anthropometric evaluation and blood pressure measurement. Hypertensive individuals were considered those whose blood pressure level was > the 95th percentile for age and sex, confirmed on 3 examinations., Results: The prevalence of hypertension was 16.6% in the first evaluation, and 4.6% and 2.5% in the subsequent evaluations. The mean blood pressure levels increased with age. Weight was important, not only to determine blood pressure in healthy children, but also to determine systemic hypertension in children, which was not observed with height despite the different studies. The prevalence of systemic hypertension in the different ethnic groups and the mean blood pressure levels according to sex were similar., Conclusion: In addition to routine physical examinations, age, weight, and appropriate cuff size should be considered when assessing blood pressure in children to prevent hypertension, morbidity and mortality, and to avoid placing a financial burden on health care providers.