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Introduction: Chronic childhood encephalopathy (CCE), still called cerebral palsy worldwide, is defined as a set of motor disorders caused by non-progressive disorders of the central nervous system, resulting in changes in muscle tone and posture. These changes are established in the pre, peri or postnatal period and numerous physical therapy modalities have been suggested for the management of these changes. Virtual reality (VR) has been used as an innovative therapeutic tool, with a motor approach that involves the individual and a computerized interaction field, with the simulation of exercises capable of stimulating movements in real time, motivation and sensory feedback. Objective: To evaluate the motor benefits of VR as a therapeutic modality in childrenwith CCE. Materials and methods: A narrative review was carried out, with articles found in the Bireme database (BVS) and in the virtual library Scientific Eletronic Library Online (SciELO). The descriptors used were: physiotherapy, virtual reality, children and CCE. Results: Only five articles were selected. Conclusion: The articles consulted suggest that the use of VR influences the improvement mainly of the child’s balance, helping kinesiotherapeutic treatment. However, with a small number of publications focused on the pediatric physiotherapeutic approach through VR, further studies are needed for better scientific proof of this tool.

Made available in DSpace on 2021-06-25T12:40:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-03-16 KU Leuven UNESP Many of the phenotypic manifestations present in social insects are related to the development of exocrine glands, well represented by the nest-building behaviors. Among bees, four tribes compose the corbiculate bees, including both solitary and eusocial species: Apini, Bombini, Euglossini and Meliponini, which use wax as an endogenous product to construct several structures of their nests. Previous works described the presence of wax glands dorsally in meliponine bees, ventrally in Apis, and dorsally and ventrally in Bombus. In euglossine bees, there is some confusion about the presence and location of wax glands. This work, therefore, aims to investigate the position of the wax glands in the four tribes regarding the literature uncertainty. In addition, gathering more information allows a better interpretation of the evolution of this structure and provides more information on the evolution of corbiculate bees. In this work, we collected females from the four tribes of corbiculate bees in the active building area of the nest. Our data showed the presence of wax glands dorsally in Meliponini, ventrally in Apini, and ventrally and dorsally in Bombini; however, no trace of the wax gland was found in Euglossini. Therefore, the absence of wax products in Euglossini suggests that wax glands are an important component of social life and it should be understood as a unique acquisition of the clade formed by the three eusocial corbiculate bee tribes (Bombini, Meliponini and Apini). Univ Estadual Paulista, Dept Zool & Bot, Cristovao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto FF, Dept Biol, Ave Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP, Brazil Katholieke Univ Leuven, Zool Inst, Naamsestr 59,Box 2466, B-3000 Leuven, Belgium Univ Estadual Paulista, Dept Zool & Bot, Cristovao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil KU Leuven: 3E150873 UNESP: 3E150873

Purpose: To objectively evaluate the visual function in children with congenital Zika syndrome using pattern-reversal visual evoked potential (PR-VEP). Methods: This was a cross-sectional study composed of two patient groups: children aged between 18 and 24 months who were positive for the Zika virus (congenital Zika syndrome group) and age-matched healthy children (control group). All patients underwent a comprehensive ophthalmologic examination and PR-VEP was performed binocularly in a room with constant dim illumination. The P100 peak time in the 60' arc stimuli was used, and the results were correlated with visual acuity, cephalic perimeter at birth, and funduscopic findings. Results: Thirty-seven children were included in the congenital Zika syndrome group and 15 in the control group. The mean age was 18.5 ± 0.9 months (range: 17 to 20 months) in the congenital Zika syndrome group and 24.3 ± 1.6 months (range: 21 to 28 months) in the control group. The P100 response was normal in 7 patients (18.9%) with congenital Zika syndrome, borderline in 2 (5.4%), abnormal with prolonged latency in 18 (48.6%), and abnormal with no response in 10 (27.0%). A significant correlation between the visual acuity and P100 peak time was observed ( P < .001). The P100 values were not correlated significantly with the cephalic perimeter at birth ( P = .412) or the funduscopic findings ( P = .510). PR-VEP in children with congenital Zika syndrome and no funduscopic findings was significantly worse than in the control group ( P = .001). Conclusions: Children with congenital Zika syndrome have characteristically abnormal PR-VEPs regardless of the funduscopic findings and severe microcephaly. The PR-VEP findings supported the diagnosis of cortical visual impairment in these children. [ J Pediatr Ophthalmol Strabismus . 2021;58(2):78–83.]

Calcium-binding proteins are heterogeneous proteins that act binding this ion in specific domains, performing numerous functions.In the present review, we aim to gather principal information about S100B protein in the Central Nervous System (CNS), highlighting its particularities, mapping, functionalities, and consequences on CNS dysfunction.The research was carried out by searching Pubmed, Medline, Science Direct, Lilacs, the Cochrane Library, and Web of Science databases using the following descriptors: S100 protein; Central Nervous System; Nervous Lesions, as well as their corresponding terms in Portuguese and Spanish. The terms were first searched separately, then together.Due to its ability to bind with calcium, S100B is involved in the regulation of several intra- and extracellular physiological processes. As well as being multifunctional, this protein can be considered both a "marker" and "signaling" since it is capable of triggering functions of detection of and protection in situations of injury to the CNS.In-depth studies are necessary to discover the innumerable actions of this protein which are still unknown. It is expected that these can bring varied benefits by elucidating its therapeutic potential in preclinical and clinical situations.

Introduction Despite its importance, there are some barriers to patient compliance in preventive therapy (PT) of tuberculosis (TB). The purpose of this study was to evaluate the compliance to appointments, PT and follow-up in a pediatric population after TB exposure, followed in a single TB outpatient center, and the subsequent identification of compliance determinants. Methods Retrospective analysis of all pediatric patients who underwent PT in Gaia TB outpatient center from January 2015 to June 2016. Patients were divided into two groups: compliant and non-compliant, according to adherence to screening, visits and medication. The data collection was based on review of medical records. Results A total of 72 patients were enrolled, 33 (45.8%) on chemoprophylaxis and 39 (54.2%) on latent tuberculosis infection (LTBI) treatment. The majority of patients were compliant (63.9%, n = 46). Non-compliance was found in 36.1% (n = 26): in 12 patients to contact screening, in 11 patients to PT and 22 patients did not attend medical appointments in the first place. In 10 patients, non-compliance was related to social problems/family dysfunction (low socioeconomic status and parent's unemployment). After putting in place several strategies, such as telephone contact, activating social services and direct observation of therapy, a compliance of 98.6% was achieved. Isoniazid was the main drug used (91.7%), during 9 months for LBTI. Conclusion PT compliance in TB can be challenging, probably related to the lack of risk perception and caregiver's reluctance to undergo a prolonged treatment to an asymptomatic condition. We conclude that implementing interventions can considerably improve treatment compliance and reduce the risk of future tuberculosis development. We emphasize the success in compliance to a 9 month regimen of isoniazid in the vast majority of patients with LTBI.

Although regular combined aerobic-resistance exercises can ameliorate the inflammatory status and redox balance in elderly population, it is unclear whether protein or specific amino acid supplementation could improve such benefits. Therefore, we aimed to evaluate the inflammatory status and redox indexes through of the saliva of 34 elderly subject nonpractitioners (NP group, 73.3±6.6 years) and 49 elderly subject practitioners of a combined-exercise training in moderate intensity (CET group, 71.9±5.8 years) before (pre) and after (post) 30 days of supplementation with L-glutamine (Gln) or placebo (PL). Our results showed that, both in pre- and postsupplementation, the salivary levels of nitric oxide (NO⋅) and TNF-α were lower, whereas the levels of uric acid and IL-10 (as well as IL-10/TNF-α ratio) were higher in the CET groups than in the NP groups. In postsupplementation, both groups supplemented with Gln (NP-Gln and CET-Gln) showed higher salivary uric acid levels compared to baseline. In addition, lower NO⋅ levels were found in the CET-Gln group postsupplementation than presupplementation values. Whereas the CET-Gln group showed lower GSH levels postsupplementation, NP-Gln subjects showed lower GSSG levels at the same time point, both compared to baseline. Interestingly, salivary peroxidase activity was lower only in NP groups (NP-PL and NP-Gln) postsupplementation than baseline values. A positive significant correlation between salivary peroxidase activity and GSH levels, and also between salivary peroxidase activity and uric acid levels were observed in the CET-Gln group both pre- and postsupplementation. No differences were found in albumin, total antioxidant activity (TEAC), and reducing power analysis between groups, pre- or postsupplementation. In conclusion, the elderly subjects from the CET group showed a better inflammatory response and redox balance and, for the first time, it was shown that daily supplementation with Gln for 30 days can improve these benefits with putative association with a healthy aging.

Background The management of laparoscopic sleeve gastrectomy leaks remains a challenge. This can be treated with placement of self-expandable metal stents, which are most effective in the acute and early settings. However, migration is a frequent adverse event (AE). Novel, fully covered stents with a larger proximal flare to limit migration designed specifically to treat postsleeve leaks were recently introduced. Objectives The aim of this study was to evaluate the safety and efficacy of a novel stent specifically designed for postsleeve leaks treatment. Setting Multicenter retrospective study. Methods This is a multicenter study, including patients with acute and early post laparoscopic sleeve gastrectomy leaks, treated with a large bariatric stent. The outcomes include technical success, clinical success, and safety profile. A multivariable regression was performed to assess predictors of success. Results Thirty-seven patients were included (10 acute and 27 early leaks), with 30 stents in the postpyloric (POST) and 7 in the prepyloric position. Technical success was 100%. Mean stent dwell time was 29.08 days. Clinical success was achieved in 78.37%. Leak duration, leak size, and stent dwell time did not correlate with clinical success. During follow-up, 8 patients had stent migration (21.62%) and all were in a POST position. AE poststent removal were also evaluated (prepyloric: 57.14% vs POST: 33.3%, P = .45). There was no difference between prepyloric and POST position in the severe AE analysis. Conclusions This novel, large-caliber, fully covered stent specifically designed for sleeve leaks appears to be effective at treating acute and early leaks. However, the large flanges and long stent length do not appear to reduce migration rate and may be associated with higher overall severe AE rates. Avoiding placement in the POST position may help mitigate migration risk; however, owing to the risk profile this stent should be used with caution.

Background: In Brazil, secondary data for epidemiology are largely available. However, they are insufficiently prepared for use in research, even when it comes to structured data since they were often designed for other purposes. To date, few publications focus on the process of preparing secondary data. The present findings can help in orienting future research projects that are based on secondary data.Objective: Describe the steps in the process of ensuring the adequacy of a secondary data set for a specific use and to identify the challenges of this process.Methods: The present study is qualitative and reports methodological issues about secondary data use. The study material was comprised of 6,059,454 live births and 73,735 infant death records from 2004 to 2013 of children whose mothers resided in the State of São Paulo - Brazil. The challenges and description of the procedures to ensure data adequacy were undertaken in 6 steps: (1) problem understanding, (2) resource planning, (3) data understanding, (4) data preparation, (5) data validation and (6) data distribution. For each step, procedures, and challenges encountered, and the actions to cope with them and partial results were described. To identify the most labor-intensive tasks in this process, the steps were assessed by adding the number of procedures, challenges, and coping actions. The highest values were assumed to indicate the most critical steps.Results: In total, 22 procedures and 23 actions were needed to deal with the 27 challenges encountered along the process of ensuring the adequacy of the study material for the intended use. The final product was an organized database for a historical cohort study suitable for the intended use. Data understanding and data preparation were identified as the most critical steps, accounting for about 70% of the challenges observed for data using.Conclusion: Significant challenges were encountered in the process of ensuring the adequacy of secondary health data for research use, mainly in the data understanding and data preparation steps. The use of the described steps to approach structured secondary data and the knowledge of the potential challenges along the process may contribute to planning health research.

Introduction and importance Inflammatory fibroid polyps (IFPs) are rare, benign tumors that can arise throughout the gastrointestinal tract, they are usually asymptomatic, and clinical presentation depends on the site of involvement. Gastric and colon IFPs are traditionally identified incidentally, whereas small intestinal lesions are often encountered in the setting of intussusception or during imaging studies. Complete resection via endoscopy or surgery is recommended. Case presentation Patient is a 52-year-old male without past medical history; he had a five-month history of mild colicky abdominal pain. A mass was detected in the small bowel, and surgery was decided. Since the mass was small a cooperative approach with an intraoperative enteroscopy was needed to locate the mass and achieve complete resection. Discussion IFPs of the small bowel require complete resection. Surgery should be performed as early as possible to prevent complications like intussusceptions, ischemia, and necrosis. Conclusions In these rare tumors, the collaboration between surgeons and endoscopists is indispensable to improve the patient's prognosis., Highlights • Inflammatory fibroid polyp is a rare benign tumor. • Availability of multiple surgical techniques and support from the medical staff can improve the patient's prognosis. • Collaboration between surgeons and endoscopists is vital to improve patients outcome.

Background Population-based studies analyzing neonatal deaths in middle-income countries may contribute to design interventions to achieve the Sustainable Development Goals, established by United Nations. This study goal is to analyze the annual trend of neonatal mortality in São Paulo State, Brazil, over a 10-year period and its underlying causes and to identify maternal and neonatal characteristics at birth associated with neonatal mortality. Method A population-based study of births and deaths from 0 to 27 days between 2004 and 2013 in São Paulo State, Brazil, was performed. The annual trend of neonatal mortality rate according to gestational age was analyzed by Poisson or by Negative Binomial Regression models. Basic causes of neonatal death were classified according to ICD-10. Association of maternal demographic variables (block 1), prenatal and delivery care variables (block 2), and neonatal characteristics at birth (block 3) with neonatal mortality was evaluated by Poisson regression analysis adjusted by year of birth. Results Among 6,056,883 live births in São Paulo State during the study period, 48,309 died from 0 to 27 days (neonatal mortality rate: 8.0/1,000 live births). For the whole group and for infants with gestational age 22–27, 28–31, 32–36, 37–41 and ≥ 42 weeks, reduction of neonatal mortality rate was, respectively, 18 %, 15 %, 38 %, 53 %, 31 %, and 58 %. Median time until 50 % of deaths occurred was 3 days. Main basic causes of death were respiratory disorders (25 %), malformations (20 %), infections (17 %), and perinatal asphyxia (7 %). Variables independently associated with neonatal deaths were maternal schooling, prenatal care, parity, newborn sex, 1st minute Apgar, and malformations. Cesarean delivery, compared to vaginal, was protective against neonatal mortality for infants at 22–31 weeks, but it was a risk factor for those with 32–41 weeks. Conclusions Despite the significant decrease in neonatal mortality rate over the 10-year period in São Paulo State, improved access to qualified health care is needed in order to avoid preventable neonatal deaths and increase survival of infants that need more complex levels of assistance.

Background: Since aging affects the immune responses against vaccination, the present study evaluated the effects of L-glutamine (Gln) supplementation in the humoral and cellular immune responses in elderly subjects, practitioners or not, of physical exercise training. Methods: Eighty-four elderly people (aged 72.6 &plusmn, 6.1), non-practitioners (NP, n = 31), and practitioners of combined-exercise training (CET, n = 53) were submitted to Influenza virus vaccination and supplemented with Gln (0.3 g/kg of weight + 10 g of maltodextrin, groups: NP-Gln (n = 14), and CET-Gln (n = 26)), or placebo (10 g of maltodextrin, groups: NP-PL (n = 17), and CET-PL (n = 27)). Blood samples were collected pre (baseline) and 30 days post-vaccination and supplementation. Results: Comparing with the baseline values, whereas the NP-Gln and CET-PL groups showed higher specific-IgM levels, the CET-Gln group showed higher specific-IgM and IgA levels post-vaccination. The titer rate of hemagglutination inhibition was higher in the CET-Gln, NP-PL, and NP-Gln groups post-vaccination than baseline values. The absolute number of naive and effector CD4+ T cells was higher especially in the NP-Gln and CET-Gln groups, whilst activated CD4+ T cells were higher in CET subgroups post-vaccination. Conclusion: Our results showed that both l-glutamine supplementation and combined-exercise training can improve the immune responses to the Influenza virus vaccine in elderly subjects.

L-glutamine (LG) supplementation boost the immune system and benefit elderly, who present immunosenescence. However, no study has evaluated its effects on the humoral immune response of upper airways of elderly. Thus, this study evaluated the effects of LG in elderly sedentary (Sed) and physically active (CET=combined-exercise training: aerobic+resistance exercise), supplemented or not with LG, on pulmonary function and the levels of IL-6, IL-10 and IL-6/IL-10 ratio in the nasal lavage fluid (NLF) and in the saliva, as biomarkers of humoral immune response of upper airways. Four experimental groups were tested: Sed+Pl (n=15), Sed+LG (n=19), CET+Pl (n=26) and CET+LG (n=23), after 30 days of supplementation with L-glutamine (LG=0.3g/kg/day + 10g/day maltodextrin) or placebo (Pl=10g/day maltodextrin). No differences in forced vital capacity and in forced expiratory volume in the first second was observed among all groups. The levels of salivary IL-6 of Sed+Pl before supplementation and Sed-PI and Sed-LG after supplementation were lower, as well as the IL-10 levels of Sed groups (Sed and Sed+LG) before and after supplementation compared to CET groups. In a different way, it was observed higher levels of IL-6 in the NLF of Sed-Pl before supplementation and Sed-Pl and Sed-LG after supplementation compared to CET groups. The differences in the NLF IL-10 levels were like observed in saliva. On the other hand, the IL-6/IL-10 ratio were lower in the CET-Pl before and after supplementation and in the CET-LG after supplementation. In conclusion, LG supplementation improves the humoral immune response of upper airways of sedentary and physically active elderly.

Induced pluripotent stem cells (iPSC) have been the focus of several studies due to their wide range of application, including in cellular therapy. The use of iPSC in regenerative medicine is limited by their tumorigenic potential. Extracellular vesicles (EV) derived from stem cells have been shown to support renal recovery after injury. However, no investigation has explored the potential of iPSC-EV in the treatment of kidney diseases. To evaluate this potential, we submitted renal tubule cells to hypoxia-reoxygenation injury, and we analyzed cell death rate and changes in functional mitochondria mass. An in vivo model of ischemia-reperfusion injury was used to evaluate morphological and functional alterations. Gene array profile was applied to investigate the mechanism involved in iPSC-EV effects. In addition, EV derived from adipose mesenchymal cells (ASC-EV) were also used to compare the potential of iPSC-EV in support of tissue recovery. The results showed that iPSC-EV were capable of reducing cell death and inflammatory response with similar efficacy than ASC-EV. Moreover, iPSC-EV protected functional mitochondria and regulated several genes associated with oxidative stress. Taken together, these results show that iPSC can be an alternative source of EV in the treatment of different aspects of kidney disease.

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.

This paper presents a study on the incubation effect during fs-laser micromachining of gallium nitride films with three different wavelengths (1030, 515 and 343 nm) by varying the number of laser pulses applied per sample surface area and measuring the damage threshold fluence using the zero damage method. As we implemented the exponential defect accumulation model to the experimental incubation data, we determined the value of the incubation parameter of (0.02 ± 0.01) for 1030 nm, (0.07 ± 0.01) for 515 nm and (0.4 ± 0.1) for 343 nm. This shows that for excitation in the green and infrared spectral region, GaN requires approximately 100 overlapping pulses in order for the incubation to take place while, for ultraviolet excitation, the incubation was achieved faster, with the overlap of about 10 pulses. Furthermore, we compared our data for the single pulse damage threshold with a theoretical model that takes into account multiphoton and avalanche ionization. Our results indicate that at 343 nm and 515 nm, micromachining is dominated by multiphoton ionization, while at 1030 nm other effects, such as tunneling ionization, must also be contributing. Finally, we believe this paper brings relevant information on the fs-laser micromachining of GaN.

This is invasive rhino-orbito-cerebral mucormycosis on the face of a woman in her 50s (fig 1). Fig 1 She presented to her doctor with a history of nasal obstruction and right facial tenderness, with a background of uncontrolled diabetes, and …

Although essential for inflammatory responses, leukocyte recruitment to blood vessel walls in response to inflammatory stimuli, such as TNF-α, can contribute to vascular occlusion in inflammatory diseases, including atherosclerosis. We aimed to further characterize the mechanisms by which TNF stimulates adhesive and morphologic alterations in neutrophils. Microfluidic and intravital assays confirmed the potent effect that TNF has on human and murine neutrophil adhesion and recruitment in vitro and in vivo, respectively. Inhibition of actin polymerization by cytochalasin D significantly diminished TNF-induced human neutrophil adhesion in vitro and abolished TNF-induced membrane alterations and cell spreading. In contrast, TNF-induced increases in β2-integrin (Mac-1 and LFA-1) expression was not significantly altered by actin polymerization inhibition. Consistent with a role for cytoskeletal rearrangements in TNF-induced adhesion, TNF augmented the activity of the Rho GTPase, RhoA, in human neutrophils. However, inhibition of the major RhoA effector protein, Rho kinase (ROCK), by Y-27632 failed to inhibit TNF-induced neutrophil adhesion. In contrast, the formin FH2 domain inhibitor, SMIFH2, abolished TNF-induced human neutrophil adhesion and diminished leukocyte recruitment in vivo. SMIFH2 also inhibited TNF-induced cytoskeletal reorganization in human neutrophils and abolished the alterations in β2-integrin expression elicited by TNF stimulation. As such, Rho GTPase/mDia formin-mediated cytoskeletal reorganization appears to participate in the orchestration of TNF-induced neutrophil-adhesive interactions, possibly mediated by formin-mediated actin nucleation and subsequent modulation of β2-integrin activity on the neutrophil surface. This pathway may represent a pharmacologic target for reducing leukocyte recruitment in inflammatory diseases.

Universidade de Bras?lia. Faculdade de Medicina. Laborat?rio Multidisciplinar de Pesquisa em Doen?a de Chagas. Bras?lia, DF, Brasil. Universidade de Bras?lia. Faculdade de Medicina. Laborat?rio Multidisciplinar de Pesquisa em Doen?a de Chagas. Bras?lia, DF, Brasil. Universidade de Bras?lia. Faculdade de Medicina. Laborat?rio Multidisciplinar de Pesquisa em Doen?a de Chagas. Bras?lia, DF, Brasil. Universidade de Bras?lia. Faculdade de Medicina. Laborat?rio Multidisciplinar de Pesquisa em Doen?a de Chagas. Bras?lia, DF, Brasil. Universidade de Bras?lia. Faculdade de Medicina. Laborat?rio Multidisciplinar de Pesquisa em Doen?a de Chagas. Bras?lia, DF, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade de Bras?lia. Faculdade de Medicina. Laborat?rio Multidisciplinar de Pesquisa em Doen?a de Chagas. Bras?lia, DF, Brasil. Universidade de Bras?lia. Faculdade de Medicina. Laborat?rio Multidisciplinar de Pesquisa em Doen?a de Chagas. Bras?lia, DF, Brasil. Universidade de Bras?lia. Faculdade de Medicina. Laborat?rio Multidisciplinar de Pesquisa em Doen?a de Chagas. Bras?lia, DF, Brasil. Universidade de Bras?lia. Faculdade de Medicina. Laborat?rio Multidisciplinar de Pesquisa em Doen?a de Chagas. Bras?lia, DF, Brasil. Universidade de Bras?lia. Faculdade de Medicina. Laborat?rio Multidisciplinar de Pesquisa em Doen?a de Chagas. Bras?lia, DF, Brasil. BACKGROUND: The Trypanosoma cruzi infection endemic in Latin America has now spread to several countries across four continents; this endemic involves triatomine vector-free protists. We hypothesised that the sexual transmission of T. cruzi contributes to the ongoing spread of Chagas disease. OBJECTIVES: A short-term longitudinal study was conducted to evaluate this hypothesis. METHODS: The study population comprised 109 subjects from four families, among whom 21 had been diagnosed with acute Chagas disease by direct parasitological analysis. Blood mononuclear cells and serum samples were obtained from each study subject once per year for three consecutive years. Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence serological examinations were used to detect specific T. cruzi antibodies. Polymerase chain reaction of T. cruzi DNA revealed 188-nucleotide bands, which hybridised to a specific radiolabelled probe and were confirmed by cloning and sequencing. RESULTS: Three independent assessments at different time points revealed T. cruzi nuclear DNA footprints in 76% (83/109) of the study population with active infection. In contrast, the ELISA and indirect immunofluorescence assays detected the T. cruzi antibody in 28.4% (31/109) of the study samples. Moreover, the semen from 82.6% (19/23) of subjects people revealed harboured the 188- bp base pair T. cruzi footprint. Interestingly, the ejaculates of nuclear DNA-positive Chagas patient transmitted the T. cruzi upon peritoneal injection or infusion in the vagina of mice, and amastigotes were detected in the skeletal muscle, myocardium, vas deferens, and uterine tube. MAIN CONCLUSIONS: T. cruzi infections can be transmitted from females or males to na?ve mates through intercourse, and progeny showed discrepancies between the ratios of nuclear DNA footprints and specific antibody that can be explained by the tolerance attained during early embryo growth. Additional studies are needed to develop drugs to eradicate the infections. Additionally, the importance of a vigorous education, information, and communication program to prevent sexually transmitted Chagas disease in humans cannot be underemphasised.

INTRODUCTION Primary central nervous system (CNS) germ cell tumors (GCT) account for 2–3% brain tumors children/adolescents in Western hemisphere. The report aim is to present the results of a Brazilian CNSGCT consortium protocol. METHODS Since 2013, 45 patients with histologic and/or tumor marker (TM) diagnosis of germinoma with/without HCGβ levels≤200mIU/ml (n=33), four between 100-200mIU/ml and NGGCT (n=12), received carboplatin/etoposide/cyclophosphamide (4–6 cycles), followed by 18Gy ventricular field irradiation and primary site(s) boost. Autologous bone marrow transplant (ABMT) was conducted for NGGCT low responders. RESULTS Mean age 12.9 years (4.7-20y), 34 males. Diagnosis was made by TM (n=9), surgery (n=19), both (n=15). Two bifocal cases, (-)TM were treated as germinoma. Primary tumor location was pineal (n=20), suprasellar (n=13), bifocal (n=11) and basal ganglia/thalamus (n=1). Fourteen had ventricular/spinal spread. Second-look surgery occurred in 5 patients. For the germinoma group, 26 achieved complete response (CR) after chemotherapy, seven showed residual teratoma/scar. For the NGGCT after 2/4 cycles, four patients showed CR, 2 failure/progression and 6 partial response (4 (-)TM). Two were submitted to ABMT. Radiotherapy was performed as described, except in three. One recurrence to date. Two patients died (endocrinologic complications/progression). Toxicity was mostly grade ¾ neutropenia/thrombocytopenia during chemotherapy. At a median follow-up of 38 months, OS was 100% for Germinoma and 85% NGGCT. CONCLUSION The treatment is tolerable and VFI dose reduction to 18Gy seems to preserve efficacy. Further follow-up is warranted to assess the NG group and the slow-responder patients.

The complex pathophysiology of sickle cell anemia (SCA) involves intravascular hemolytic processes and recurrent vaso-occlusion, driven by chronic vascular inflammation, which result in the disease's severe clinical complications, including recurrent painful vaso-occlusive episodes. Hydroxyurea, the only drug frequently used for SCA therapy, is a cytostatic agent, although it appears to exert nitric oxide/soluble guanylyl cyclase (sGC) modulating activity. As new drugs that can complement or replace the use of hydroxyurea are sought to further reduce vaso-occlusive episode frequency in SCA, we investigated the effects of the sGC agonists BAY 60-2770 (sGC activator) and BAY 41-2272 (sGC stimulator) in the presence or absence of hydroxyurea on SCA vaso-occlusive mechanisms and cell recruitment both ex vivo and in vivo. These agents significantly reduced stimulated human SCA neutrophil adhesive properties ex vivo in association with the inhibition of surface β2-integrin activation. A single administration of BAY 60-2770 or BAY 41-2272 decreased tumor necrosis factor cytokine-induced leukocyte recruitment in a mouse model of SCA vaso-occlusion. Importantly, the in vivo actions of both agonists were significantly potentiated by the coadministration of hydroxyurea. Erythroid cell fetal hemoglobin (HbF) elevation is also a major goal for SCA therapy. BAY 41-2272 but not BAY 60-2770 at the concentrations employed significantly induced γ-globin gene transcription in association with HbF production in cultured erythroleukemic cells. In conclusion, sGC agonist drugs could represent a promising approach as therapy for SCA, for use either as stand-alone treatments or in combination with hydroxyurea. SIGNIFICANCE STATEMENT: This preclinical study demonstrates that stimulators and activators of sGC are potent inhibitors of the adhesion and recruitment of leukocytes from humans and in mice with sickle cell anemia (SCA) and may represent a promising approach for diminishing vaso-occlusive episode frequency in SCA. Hydroxyurea, a drug already frequently used for treating SCA, was found to potentiate the beneficial effects of sGC agonists in in vivo studies, implying that these classes of compounds could be used alone or in combination therapy.

Background. Although Lactobacillus casei Shirota (LcS) can benefit the immune status, the effects of LcS in the immune/inflammatory responses of marathon runners has never been evaluated. Therefore, here we evaluated the effect of daily ingestion of fermented milk containing or not LcS in the systemic and upper airway immune/inflammatory responses before and after a marathon. Methods. Forty-two male marathon runners ingested a fermented milk containing 40 billion of LcS/day (LcS group, n = 20) or placebo (unfermented milk, n = 22) during 30 days pre-marathon. Immune/inflammatory parameters in nasal mucosa and serum, as well as concentrations of secretory IgA (SIgA) and antimicrobial peptides in saliva, were evaluated before and after fermented milk ingestion, immediately, 72 h, and 14 d post-marathon. Results. Higher proinflammatory cytokine levels in serum and nasal mucosa, and also lower salivary levels of SIgA and antimicrobial peptides, were found immediately post-marathon in the placebo group compared to other time points and to LcS group. In opposite, higher anti-inflammatory levels and reduced neutrophil infiltration on nasal mucosa were found in the LcS group compared to other time points and to the placebo group. Conclusion. For the first time, it is shown that LcS is able to modulate the systemic and airways immune responses post-marathon.

Introduction The current approach in living-donor kidney transplant is to preserve the best kidney for the donor and harvest the contralateral one. Due to a shorter renal vein and a greater incidence of venous thrombosis, left kidneys are more frequently elected. Notwithstanding, arterial anatomy may be complex and thus render the transplantation procedure more difficult and prone to complications. Objectives To analyze the outcomes after multiple-artery left kidney nephrectomy (MALKN) and right kidney nephrectomy (RKN). Results Seventy-three cases were performed from 1999 to 2017 in our institution: 34 MALKN and 39 RKN. The mean operative time was significantly longer in MALKN. Warm ischemia time, donor and receptor hospital stay, and postoperative complications did not differ between groups. There was a positive correlation between renal arteries' ostia distance in MALKN and the duration of warm ischemia period. There was no significant difference in the incidence of acute tubular necrosis, first-year variations in serum creatinine, and glomerular filtration rate between groups. Long-term graft survival did not significantly differ between groups. Three cases of vein thrombosis after RKN were reported with graft loss. Conclusion The safety and efficacy of MALKN does not differ from RKN, although there appears to be a higher incidence of vein thrombosis after right kidney transplantation. Despite being technically more demanding, particularly in cases with distant artery ostia, MALKN could be a better option than RKN for living donation, expanding the available donor pool, although more studies are needed to affirm this conclusion.

The main sources of food for stingless bees are the nectar and pollen harvested from flowers, whereas one important kind of nesting material (i.e. wax) is produced by their own abdominal glands. Stingless bees can, nonetheless, obtain alternative resources of food and wax from exudates released by sap-sucking insects as honeydew and waxy cover, respectively. To date, there are no comprehensive studies investigating how diversified and structured the network interactions between stingless bees and sap-sucking insects are. Here, we conducted a survey of the data on relationship between stingless bees and sap-sucking insects to evaluate: (1) which resources are collected by which stingless bee species; (2) how diverse the interaction network is, using species degree and specialisation index as a proxy; and if (3) there would be any phylogenetic signal in the species degree and specialisation indices. Our findings demonstrate that approximately 21 stingless bee species like Trigona spp. and Oxytrigona spp. have been observed interacting with 11 sap-sucking species, among which Aethalion reticulatum is the main partner. From ca. 50 records, Brazil is the country with most observations (n = 38) of this type of ecological interaction. We found also that stingless bees harvest fivefold more honeydew than waxy covers on sap-sucking insects. However, we did not find any phylogenetic signal for the occurrence of this interaction, considering species degree and specialisation indices, suggesting that both traits apparently evolved independently among stingless bee species. We suggest that specific ecological demands may drive this opportunistic behaviour exhibited by stingless bees, because major sources of food are obtained from flowers and these bees produce their own wax.

Foundation for the Advancement of Science (FAPDF) ; National Research Council, Ministry of Science and Technology (CNPq/MCT) ; Agency for Training Human Resources, Ministry of Education (CAPES/ME), Brazil . Universidade de Brasilia. Faculdade de Medicina. Multidisciplinar de Pesquisa em Doen?as de Chagas. Brasilia, DF, Brazil. Universidade de Brasilia. Faculdade de Medicina. Multidisciplinar de Pesquisa em Doen?as de Chagas. Brasilia, DF, Brazil. Universidade de Brasilia. Faculdade de Medicina. Multidisciplinar de Pesquisa em Doen?as de Chagas. Brasilia, DF, Brazil. Universidade de Brasilia. Faculdade de Medicina. Multidisciplinar de Pesquisa em Doen?as de Chagas. Brasilia, DF, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade de Brasilia. Faculdade de Medicina. Multidisciplinar de Pesquisa em Doen?as de Chagas. Brasilia, DF, Brazil. American trypanosomiasis is transmitted to humans by triatomine bugs through the ingestion of contaminated food, by blood transfusions or accidently in hospitals and research laboratories. In addition, the Trypanosoma cruzi infection is transmitted congenitally from a chagasic mother to her offspring, but the male partner's contribution to in utero contamination is unknown. The findings of nests and clumps of amastigotes and of trypomastigotes in the theca cells of the ovary, in the goniablasts and in the lumen of seminiferous tubules suggest that T. cruzi infections are sexually transmitted. The research protocol herein presents the results of a family study population showing parasite nuclear DNA in the diploid blood mononuclear cells and in the haploid gametes of human subjects. Thus, three independent biological samples collected one year apart confirmed that T. cruzi infections were sexually transmitted to progeny. Interestingly, the specific T. cruzi antibody was absent in the majority of family progeny that bore immune tolerance to the parasite antigen. Immune tolerance was demonstrated in chicken refractory to T. cruzi after the first week of embryonic growth, and chicks hatched from the flagellate-inoculated eggs were unable to produce the specific antibody. Moreover, the instillation of the human semen ejaculates intraperitoneally or into the vagina of naive mice yielded T. cruzi amastigotes in the epididymis, seminiferous tubule, vas deferens and uterine tube with an absence of inflammatory reactions in the immune privileged organs of reproduction. The breeding of T. cruzi-infected male and female mice with naive mates resulted in acquisition of the infections, which were later transmitted to the progeny. Therefore, a robust education, information and communication program that involves the population and social organizations is deemed necessary to prevent Chagas disease.

Background: Although glutamine is able to improve the immune response, its action in the upper airway immunity against the influenza virus vaccine remains unclear. Therefore, we aimed to evaluate the L-glutamine supplementation effect on the mucosal immune/inflammatory response of elderly subjects vaccinated against the influenza virus. Methods: Saliva sampling from 83 physically active elderly volunteers were collected pre- and 30 days after influenza virus vaccination and supplementation with L-glutamine (Gln, n = 42) or placebo (PL, n = 41). Results: Gln group showed higher salivary levels of interleukin (IL)-17, total secretory immunoglobulin A (SIgA), and specific-SIgA post-vaccination than values found pre-vaccination and in the PL group post-vaccination. Whereas higher salivary levels of IL-6 and IL-10 were observed post-vaccination in the Gln group, IL-37 levels were lower post-vaccination in both groups than the values pre-vaccination. Tumor necrosis factor (TNF)-α levels were unchanged. Positive correlations between IL-6 and IL-10 were found in all volunteer groups pre- and post-vaccination and also between IL-17 and IL-6 or IL-10 in the Gln group post-vaccination. A negative correlation between IL-37 and IL-10 was found pre- and post-vaccination in the PL group. Conclusion: Gln supplementation was able to modulate salivary cytokine profile and increase SIgA levels, both total and specific to the influenza virus vaccine, in physically active elderly subjects.

BACKGROUND Pineal is the melatonin-producing gland, with this hormone importantly acting as a central and peripheral chronobiotic, antioxidant and in energy metabolism. The urinary dosage of 6-sulfatoxymelatonin (aMT6s), a melatonin metabolite, is an indirect marker to estimate the total melatonin nocturnal production, ranging in clinically normal individuals from 10–50 micrograms(ug). The purpose of this study was to evaluate aMT6s in patients with diagnosis of intracranial germ cell tumors (iGCT) treated at IOP/GRAACC/UNIFESP. METHODS After an interview to collect data about therapies employed and medications, night urine samples (from 8:00pm to first void in the morning) were collected and analyzed by ELISA. RESULTS Twenty patients between 5–42 years old (mean 20.9 years), all male, were analyzed. Thirteen patients had diagnosis of Germinoma, 1 with Imature Teratoma, 5 NGGCT and 2 Mature Teratoma. The first site was pineal (N=15) and bifocal (N=5). The treatment was surgery/biopsy/2º look surgery in 17 patients associated with chemotherapy/ radiotherapy, except in 2 (pure teratoma-surgery only) and 1 (chemo only). Three patients had diagnosis by tumor markers treated with chemo only (N=1) and chemotherapy/radiotherapy (N=2). The levels of aMT6s were between 0.2–3.2ug in all participants, except in one (14.8ug-biopsy, chemo and RT). CONCLUSION aMT6s levels found in most patients are below the expected for the general population suggesting that this is an appropriate marker for pineal tumors with melatonin deficiency. It may contribute to support future studies in this area and adoption of follow-up protocols, with eventual hormone supplementation and consequently improved quality of life.

INTRODUCTION Choroid plexus tumors (CPT) are rare intraventricular neoplasms of epithelial origin. They usually occur in the 2nd year of life, corresponding to 0.4–0.6% of intracranial tumors in this age group. They are sub classified, according to WHO 2016, in choroid plexus carcinoma (CPC), atypical choroid plexus papilloma (ACPP) and choroid plexus papilloma (CPP). Li-Fraumeni syndrome (LFS) is present in 50% of patients with CPC. In Brazil, the TP53 p.R337H mutation affects 0.3% of the population in the South/Southeast. OBJECTIVE Evaluate the incidence of genetic mutations in patients with choroid plexus tumors and therefore the importance of genetic evaluation. PATIENTS AND METHODS Between 1992–2019, 38 patients were diagnosed with CPT in our institution, 23 with CPC. From 2012, 21 patients were referred for genetic evaluation, 16 of which had CPC (2 had previously CPP). Positive family history for neoplasms was present in 87.5%; 37.5% compatible with LFS, 50% of them with mutations. All the patients with positive, but unspecific, family history of neoplasms, had pathogenic mutation. The molecular investigation of the TP53 gene in patients with CPC was performed and positive in 56.2%: R337H (5 patients), R110C, R158H, H179R, R196* (1 patient each). Of those with R337H, p53 protein immunohistochemistry resulted in 90–100% positivity. One of the patients with CPP that evolved to CCP had the H179R mutation. Clinical course was similar among them, and with those without mutations. CONCLUSION These results confirm the need for genetic evaluation in patients with choroid plexus tumors for adequate therapeutic management and long-term follow-up.

BACKGROUND The management of progressive unresectable low-grade glioma (PULGG) remains controversial. Some series suggests that chemotherapy may delay or even avoid radiotherapy and/or surgery in a group of patients. Within this context, we performed at IOP/GRAACC/UNIFESP an institutional protocol with IV vinorelbine, a semi-synthetic vinca alkaloid that showed activity against PULGG. The objective of this study was to evaluate the response as long as the tolerability of oral vinorelbine in PULGG. PATIENTS AND METHODS From April 2013 to Aug 2017, 17 patients with recurrent (n=5) and newly-diagnosed (n=12) optic-pathway glioma (OPG) were treated with oral vinorelbine in a dose of 90 mg/m² days 0, 8 and 22 for 18 cycles. Response criteria used a combination of magnetic resonance imaging, physical and visual evaluation. RESULTS Mean age 8.6 years (4.8–17.9y). Three children with neurofibromatosis type 1. Eleven patients had neurosurgical intervention revealing grade I (n=8) and grade II astrocytoma (n=3). Twelve patients were assessable after 8 cycles of vinorelbine with 2 objective response (OR), 8 stable disease (SD) and 2 progressive disease (PD), one died after surgery and 1 alive in different protocol. After 18 cycles, eight patients were assessable to date for response with 1 OR, 7 SD. The most important toxicity was gastrointestinal observed in 12 patients- six of them switched to IV vinorelbine (3OR, 3SD). None of the patients showed neurotoxicity. CONCLUSION These results suggest that oral vinorelbine, as the IV formulation, may show some activity in OPG. However, gastrointestinal toxicity should be considered.

Defocusing microscopy (DM) is a bright-field optical microscopy technique often used to obtain structural parameters of objects with low difference in refractive index in relation to the surrounding medium (phase objects). We show a use of this technique to measure the refractive index (n) profile of waveguides produced by femtosecond laser micromachining inside the bulk of a sodalime glass. The results are used to analyze the influence of production parameters on n. The methodology requires only a bright-field optical microscope and has proved to be easily applied. Results provide important insights on the waveguide microfabrication process, since translation speed, rather than intensity, has shown to be more important for achieving greater variations in refractive indices. Index of refraction differences between the waveguide and the substrate of the order of 10-4 were measured for a series of straight waveguides fabricated with different parameters. Low sample scan speeds and pulse energies near 1.20 μJ used for fabrication showed the highest values of refractive index change for waveguides in sodalime glasses.

Background Neck circumference (NC) is associated with traditional cardiovascular risk factors (CVRF), but its usefulness to identify earlier atherogenic risk has been scarcely examined. Associations of NC with non-traditional CVRF were investigated in participants at low-to-moderate risk from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods 807 individuals (35–54 years) without obesity, diabetes or cardiovascular disease was stratified into quartiles of NC (cut-off for men: 36.5; 37.9 and 39.5 cm; women: 31.4; 32.5 and 34 cm) and traditional and non-traditional risk factors (lipoprotein subfractions by Vertical Auto Profile, adiponectin, leptin, E-selectin) were compared across groups. In linear regression models, associations of NC with non-traditional risk factors were tested for the entire sample and for low-risk group (≤ 2 CVRF). Results In both sexes, BMI, waist circumference, systolic and diastolic blood pressure, fasting and 2-h plasma glucose, HOMA-IR, triglycerides, leptin, E-selectin, small dense LDL-cholesterol, IDL-cholesterol, VLDL3-cholesterol and TG/HDL ratio increased significantly, while HDL2-cholesterol and HDL3-cholesterol decreased across NC quartiles. In linear regression models, a direct association [β(95% CI)] of NC with leptin [(0.155 (0.068–0.242); 0.147 (0.075–0.220)], E-selectin [(0.105 (0.032–0.177); 0.073 (0.006 to 0.140)] and small-dense LDL [(1.866 (0.641–3.091); 2.372 (1.391–3.353)] and an inverse association with HDL2-cholesterol [(− 0.519 (− 0.773 to − 0.266); − 0.815 (− 1.115 to 0.515)] adjusted for age were detected for men and women, respectively. Conclusion Our findings indicate that measurement of NC may be useful for an earlier identification of unfavorable atherogenic metabolic profile in middle-aged individuals at lower cardiovascular risk level.

Objective: To contribute to the discussion on the research findings indicating the sexual transmission of American trypanosomiasis and Chagas disease in humans. Methods: A review of the literature was performed to investigate the routes of transmission of Trypanosoma cruzi parasites and to evaluate the distribution of Chagas disease, which is now found across five continents. Results: The epidemiological profile of American trypanosomiasis, which is still considered a neglected disease of the poor people of Latin America, has changed over time. A family-based study demonstrated that the blood protozoan T. cruzi can be transmitted sexually from infected males and females to naïve mates. Conclusions: Evidence that Chagas disease can be transmitted sexually, coupled with the migration of individuals with Chagas disease to previously non-endemic countries and increased travel to endemic countries, has implications for public health. Improved screening of blood supplies and prenatal care are required to prevent congenital spread. Keywords: Trypanosoma cruzi, Chagas disease, Sexual transmission, Humans, Mouse model system, Vertical transmission, Diagnosis, Prevention

Traditional sugarcane cultivars (Saccharum officinarum) proved highly susceptible to diseases, and this led breeders to progress to interspecific crosses resulting in disease resistance. A backcrossing program to S. officinarum was then required to boost sucrose content. Clonal selection across generations and incorporation of other germplasm into cultivated backgrounds established the (narrow) genetic base of modern cultivars (Saccharum spp.), which have a man-made genome. The genome complexity has inspired several molecular studies that have elucidated aspects of sugarcane genome constitution, architecture, and cytogenetics. However, there is a critical shortage of information on chromosome behaviour throughout meiosis in modern cultivars. In this study, we examined the microsporogenesis of a contemporary variety, providing a detailed analysis of the meiotic process and chromosome association at diakinesis, using FISH with centromeric probes. Chromosomal abnormalities were documented by examining high quality preparations of pollen mother cells (700 in total). Approximately 70% of the cells showed abnormalities, such as metaphase chromosomes not lined up at the plate, lagging chromosomes and chromosomal bridges, and tetrad cells with micronuclei. Some dyads with asynchronous behavior were also observed. Due to the hybrid composition of the sugarcane genome, we suggest that bivalent incomplete pairing may occur in the first prophase leading to univalency. The presence of rod bivalents showing the lagging tendency is consistent with a reduction in chiasma frequency. Finally, the presence of chromatin bridges indicates the indirect occurrence of chromosomal inversions, although chromosome fragments were not clearly recognized. Possible reasons for such meiotic abnormalities and the large prevalence of bivalent formation are discussed.

As hypoxia-induced inflammatory angiogenesis may contribute to the manifestations of sickle cell disease, we compared the angiogenic molecular profiles of plasma from sickle cell disease individuals and correlated these with in vitro endothelial cell-mediated angiogenesis-stimulating activity and in vivo neovascularization. Bioplex demonstrated that plasma from patients with steady-state sickle cell anemia contained elevated concentrations of pro-angiogenic factors (angiopoietin-1, basic fibroblast growth factor, vascular endothelial growth factor, vascular endothelial growth factor-D and placental growth factor) and displayed potent pro-angiogenic activity, significantly increasing endothelial cell proliferation, migration and capillary-like structure formation. In vivo neovascularization of Matrigel plugs was significantly greater in sickle cell disease mice than in non-sickle cell disease mice, consistent with an up-regulation of angiogenesis in the disease. In plasma from patients with hemoglobin SC disease without proliferative retinopathy, anti-angiogenic endostatin and thrombospondin-2 were significantly elevated. In contrast, plasma from hemoglobin SC individuals with proliferative retinopathy had a pro-angiogenic profile and more significant effects on endothelial cell proliferation and capillary formation than plasma from patients without retinopathy. Hydroxyurea therapy was associated with significant reductions in plasma angiogenic factors and inhibition of endothelial cell-mediated angiogenic mechanisms and neovascularization. Thus, individuals with sickle cell anemia or hemoglobin SC disease with retinopathy present a highly angiogenic circulating milieu, capable of stimulating key endothelial cell-mediated angiogenic mechanisms. Combination anti-angiogenic therapy to prevent the progression of unregulated neovascularization and associated manifestations in sickle cell disease, such as pulmonary hypertension, may be indicated; furthermore, the benefits and drawbacks of the potent anti-angiogenic effects of hydroxyurea should be clarified.

Introduction: Quality control programs are required to ensure the effectiveness of Pap smear, which still remain a key strategy for control of cervical cancer worldwide. Objective: This study was based on the retrospective and quantitative analysis of the post-analytical phase indicators from the internal quality monitoring (IQM) program for cytopathology laboratories, such as: positivity rate, atypical squamous cell (ASC)/satisfactory exams ratio, ASC/abnormal test results ratio, ASC/squamous intraepithelial lesions (SIL) ratio, percentage of tests compatible with high-grade squamous intraepithelial lesion (HSIL), and total of false negative. Materials and methods: The information was extracted from the computerized system of the Section for Integrated Technology in Cytopathology (Seção Integrada de Tecnologia em Citopatologia [SITEC]), a reference institution for cancer cytopathology, from July 2013 to June 2014. From a total of 156,888 Pap smears, 157,454 were considered satisfactory for indicator analysis and 566 were excluded because they were considered unsatisfactory and/or rejected for analysis. The data was organized in tables using Microsoft Excel 2010 software, and categorized as indicators. Results: The averages for the indicators were: 7.2% for positivity rate, 56.9 for ASC/abnormal test ratio, 4.1 for ASC/satisfactory tests ratio, 1.4 for ASC/SIL ratio, 0.6% percentage for tests compatible with HSIL, and 2.1% for false-negative rate. Conclusion: The results show that an Internal Quality Monitoring Program is essencial to ensure quality for cytopathology laboratories, and a randomized review of at least 10% of the negative exams, as recommended by the Brazilian Ministry of Health/Instituto Nacional de Câncer (INCA), since is an effective method, especially for large laboratories.

Intravascular hemolysis can occur in a number of diseases,including sepsis, malaria and the hemolytic anemias [sicklecell disease (SCD), paroxysmal nocturnal hemoglobinuria,etc.], as well as following certain events such as mismatchedtransfusions. The pathophysiological significance of intravas-cular hemolysis had been largely ignored in diseases suchas SCD save for its effect on red cell numbers, however, rel-atively recent studies have shed light on the major effectsthat hemolyticprocesseshaveonvascularbiology,particularlyon the endothelium, inflammatory processes and oxidativestress.Under normal circumstances, hemoglobin (Hb) is con-tained in the red blood cells (RBCs), and employed primarilyfor oxygen transport. However, the destruction of RBC (i.e.hemolysis) results in the release of Hb into the circulation.If this hemoglobin is not neutralized immediately into lesstoxic metabolites by specialized scavenger proteins, such ashaptoglobin and hemopexin, as can occur when extensivehemolysis overwhelms innate protective mechanisms, thiscell-free Hb causes chaos.

Lymph node (LN) is a secondary lymphoid organ with highly organized and compartmentalized structure. Lymph nodes harbor B, T, and other cells among which fibroblastic reticular cells (FRCs). FRCs are characterized by both podoplanin (PDPN/gp38) expression and by the lack of CD31 expression. FRCs are involved in several immune response processes but mechanisms underlying their function are still under investigation. Double negative cells (DNCs), another cell population within LNs, are even less understood. They do not express PDPN or CD31, their localization within the LN is unknown and their phenotype and function remain to be elucidated. This study evaluates the gene expression and cytokines and chemokines profile of human LN-derived FRCs and DNCs during homeostasis and following inflammatory stimuli. Cytokines and chemokines secreted by human FRCs and DNCs partially diverged from those identified in murine models that used similar stimulation. Cytokine and chemokine secretion and their receptors expression levels differed between stimulated DNCs and FRCs, with FRCs expressing a broader range of chemokines. Additionally, dendritic cells demonstrated increased migration towards FRCs, possibly due to chemokine-induced chemotaxis since migration was significantly decreased upon neutralization of secreted CCL2 and CCL20. Our study contributes to the understanding of the biology and functions of FRCs and DNCs and, accordingly, of the mechanisms involving them in immune cells activation and migration.

This study evaluated the use of three solid brewery wastes: brewer's spent grain, hot trub and residual brewer's yeast, as alternative media for the cultivation of lactic acid bacteria to evaluate their potential for proteolytic enzyme production. Initially, a mixture experimental design was used to evaluate the effect of each residue, as well as different mixtures (with the protein content set at 4%) in the enzyme production. At predetermined intervals, the solid and liquid fractions were separated and the extracellular proteolytic activity was determined. After selecting the best experimental conditions, a second experiment, factorial experimental design, was developed in order to evaluate the protein content in the media (1 to 7%) and the addition of fermentable sugar (glucose, 1 to 7%). Among the wastes, residual yeast showed the highest potential for the production of extracellular enzymes, generating a proteolytic extract with 2.6 U/mL in 3 h. However, due to the low content of the fermentable sugars in the medium, the addition of glucose also had a positive effect, increasing the proteolytic activity to 4.9 U/mL. The best experimental conditions of each experimental design were reproduced for comparison, and the enzyme content was separated by ethanol precipitation. The best medium produced a precipitated protein with proteolytic activity of 145.5 U/g.

Descreve-se o primeiro caso de granuloma leproide canino na região amazônica, Brasil, em um canino da raça Boxer, procedente do município de Castanhal, Pará, que apresentava lesões nodulares, alopécicas, firmes, ulceradas e não pruriginosas nas duas pinas. Os nódulos foram retirados cirurgicamente e enviados para análise histopatológica. O exame microscópico revelou marcada infiltração inflamatória constituída por macrófagos, plasmócitos, neutrófilos, linfócitos e células gigantes. A técnica de Ziehl-Neelsen evidenciou grande quantidade de bacilos álcool-ácido resistentes no interior de macrófagos e de células gigantes. Houve forte reatividade ao exame imuno-histoquímico para Mycobacterium spp. This study describes the first case of canine leproid granuloma in the Amazon region, Brazil. A Boxer dog from the city of Castanhal, Pará presented nodular, alopecic, firm, ulcerated, non-pruritic lesions on both pinnae. The nodules were removed surgically and submitted to histopathological analysis. The microscopic exam revealed marked inflammatory infiltrate composed of macrophages, plasma cells, neutrophils, lymphocytes and giant cells. The Ziehl-Neelsen staining technique showed a large amount of alcohol-acid resistant bacilli inside macrophages and giant cells. The samples exhibited a strong immunohistochemical reaction to Mycobacterium spp.

O objetivo deste trabalho foi avaliar as principais doenças de pele não neoplásicas em cães atendidos no Hospital Veterinário da Universidade Federal de Mato Grosso no ano de 2011. Nesse período, 112 casos dermatológicos foram atendidos, dos quais sistematicamente realizou-se biópsia de pele. Em 93,7% foi possível estabelecer o diagnóstico definitivo por meio de análise histopatológica junto a métodos diagnósticos complementares. As doenças cutâneas de maior prevalência eram de origem parasitária, imunológica, bacteriana e fúngica. Nesses grupos, as afecções cutâneas que mais ocorreram foram a demodicidose (20,9%), a leishmaniose visceral (12,4%), a atopia (10,5%), a dermatofitose (10,5%) e a piodermite superficial disseminada (8,6%). Essas cinco condições perfizeram juntas, pouco mais da metade de todas as doenças de pele de cães diagnosticadas neste estudo. The aim of this study was to evaluate the main non-neoplastic skin diseases in dogs examined at the Veterinary Hospital of the Federal University of Mato Grosso in 2011. During that period, 112 dermatological cases were treated followed by systematical skin biopsy. In 93.7% of the cases it was possible to establish a definite diagnosis through histopathology along with supplementary diagnostic methods. The most prevalent skin diseases were of parasitic, immunological, bacterial and fungal origins. In these groups, the skin disorders that occurred more often were demodicosis (20.9%), visceral leishmaniasis (12.4%), atopy (10.5%), dermatophytosis (10.5%), and disseminated superficial pyoderma (8.6%). These five conditions together made up just over half of all skin diseases of dogs diagnosed in this study.

Inhibition of leukocyte adhesion to the vascular endothelium represents a novel and important approach for decreasing sickle cell disease (SCD) vaso-occlusion. Using a humanized SCD–mouse-model of tumor necrosis factor-α–induced acute vaso-occlusion, we herein present data demonstrating that short-term administration of either hydroxyurea or the phosphodiesterase 9 (PDE9) inhibitor, BAY73-6691, significantly altered leukocyte recruitment to the microvasculature. Notably, the administration of both agents led to marked improvements in leukocyte rolling and adhesion and decreased heterotypic red blood cell-leukocyte interactions, coupled with prolonged animal survival. Mechanistically, these rheologic benefits were associated with decreased endothelial adhesion molecule expression, as well as diminished leukocyte Mac-1-integrin activation and cyclic guanosine monophosphate (cGMP)–signaling, leading to reduced leukocyte recruitment. Our findings indicate that hydroxyurea has immediate beneficial effects on the microvasculature in acute sickle-cell crises that are independent of the drug's fetal hemoglobin-elevating properties and probably involve the formation of intravascular nitric oxide. In addition, inhibition of PDE9, an enzyme highly expressed in hematopoietic cells, amplified the cGMP-elevating effects of hydroxyurea and may represent a promising and more tissue-specific adjuvant therapy for this disease.

The increasing interest of consumers in health and alcohol abuse issues motivates breweries to expand the assortment of products with low alcohol content. The goal of producing beers with low alcohol content can be achieved by two main strategies; namely by gentle removal of alcohol from regular beer and by limited ethanol formation during the beer fermentation. Within these two basic strategies, there are a number of techniques that vary in performance, efficiency and usability. This paper presents an overview and comparison of these techniques and provides an evaluation of sensorial properties of low-alcohol and an alcohol-free beer produced as well as suggests possibilities for their additional improvement.