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Background and Purpose: Otological symptoms (OS) are highly prevalent in individuals with temporomandibular disorders (TMD). Individuals with TMD and OS have more neck disability and decreased deep neck muscles endurance when compared to individuals without OS. However, no studies have evaluated whether OS is associated with lower Quality of Life (QoL) and worse levels of physical activity. This study aimed to evaluate the QoL and level of physical activity of individuals with TMD with and without OS., Methods: In this cross-sectional study, 62 individuals with TMD were allocated into 2 groups: TMD with OS (n = 36) or TMD without OS (n = 26). Self-reported complaints of dizziness, vertigo, tinnitus, earache, ear fullness, or hypoacusis were considered as OS. QoL was assessed with the WHOQOL-Bref and physical activity with the IPAQ-SF. Independent t-test and chi-squared test were used for analysis between-groups. Effect sizes were reported using Cohen's d. A Pearson correlation was used to compare the number of OS and QoL scores. A significance level of p < 0.05% and 95% confidence intervals were considered statistically significant., Results: The total generic scores for QoL were not different between-groups (p = 0.076), but individuals with TMD with OS had lower satisfaction (p = 0.015; d: 0.63) and physical domain (p = 0.015; d: 0.64) scores with a moderate effect size. In TMD with OS, 69.4% of individuals were irregularly active and 50% for the TMD without OS, with no statistical significance (p > 0.05). The number of OSs was inversely and weakly associated with the QoL total score., Conclusion: Individuals with TMD and OS are associated with worsened QoL (physical domain and satisfaction) when compared to individuals with TMD without OS. The higher the number of OS, the worse the QoL score. Individuals with TMD with and without OS had similar levels of physical activity, but a high prevalence of irregularly active and sedentary individuals within TMD diagnosed population was found., (© 2024 John Wiley & Sons Ltd.)

Although a growing body of evidence demonstrates that altered mtDNA content (mtDNAc) has clinical implications in several types of solid tumours, its prognostic relevance in acute promyelocytic leukaemia (APL) patients remains largely unknown. Here, we show that patients with higher-than-normal mtDNAc had better outcomes regardless of tumour burden. These results were more evident in patients with low-risk of relapse. The multivariate Cox proportional hazard model demonstrated that high mtDNAc was independently associated with a decreased cumulative incidence of relapse. Altogether, our data highlights the possible role of mitochondrial metabolism in APL patients treated with ATRA., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Heart failure (HF) is the most prevalent disease among chronic diseases and has been associated with a high prevalence of erectile dysfunction (ED)., Objective: this study aims to analyze research that has as its object of study the sexual activity of patients with HF., Methods: A high-sensitivity search was performed in databases (PUBMED via MEDLINE, Cochrane, EMBASE, Web of Science, SCOPUS AND CINAHL) using descriptors linked to sexuality and heart failure., Results: Fifteen studies from 7 countries with a total sample of 6244 participants were included., Conclusion: It was identified that patients with HF have alterations in their sexual activities, which are more common in males. Among men, it was noticed that the most reported sexual disorder was erectile dysfunction., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Stathmin 1 (STMN1) is a microtubule-destabilizing protein highly expressed in hematological malignancies and involved in proliferation and differentiation. Although a previous study found that the PML-RARα fusion protein, which contributes to the pathophysiology of acute promyelocytic leukemia (APL), positively regulates STMN1 at the transcription and protein activity levels, little is known about the role of STMN1 in APL. In this study, we aimed to investigate the STMN1 expression levels and their associations with laboratory, clinical, and genomic data in APL patients. We also assessed the dynamics of STMN1 expression during myeloid cell differentiation and cell cycle progression, and the cellular effects of STMN1 silencing and pharmacological effects of microtubule-stabilizing drugs on APL cells. We found that STMN1 transcripts were significantly increased in samples from APL patients compared with those of healthy donors (all p < 0.05). However, this had no effect on clinical outcomes. STMN1 expression was associated with proliferation- and metabolism-related gene signatures in APL. Our data confirmed that STMN1 was highly expressed in early hematopoietic progenitors and reduced during cell differentiation, including the ATRA-induced granulocytic differentiation model. STMN1 phosphorylation was predominant in a pool of mitosis-enriched APL cells. In NB4 and NB4-R2 cells, STMN1 knockdown decreased autonomous cell growth (all p < 0.05) but did not impact ATRA-induced apoptosis and differentiation. Finally, treatment with paclitaxel (as a single agent or combined with ATRA) induced microtubule stabilization, resulting in mitotic catastrophe with repercussions for cell viability, even in ATRA-resistant APL cells. This study provides new insights into the STMN1 functions and microtubule dynamics in APL., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The aim was to describe the criteria for construction, validation of content, and appearance of a questionnaire for the identification of violence in affective relationships in adolescence. Transverse methodological study, with a quantitative approach, conducted in the period between June and November 2017, with the construction of a questionnaire and validation of the content and appearance, by means of a Delphi survey with 20 experts on the area of violence and adolescence. To evaluate the clarity and pertinence of the items of the questionnaire, a pilot test was conducted with 76 adolescents, and analysis of the validity of content and reliability of the items by means of Content Validity Index (CVI), the Interrater Agreement (IRA), and the Cronbach alpha. The data were analyzed and processed by means of the Excel and Stata , version 14.0, programs. The indexes calculated in the first round of Delphi provided the following results: CVI = 0.93 and IRA = 0.93, showing evidence of the validity and reliability of the construct content, and in the second round, the questionnaire yielded a percentage of 100% agreement among the professionals and researchers. Verification of the internal consistency presented a mean value of 0.803, calculated by means of the Cronbach alpha. The questionnaire has validity of content and appearance in accordance with the proposed objective, bearing in mind that the indexes of faithfulness and agreement and the Cronbach alpha attained values above those of the established pattern of 80%.

Objetive: To evaluate the effects of Chinese scalp acupuncture in patients diagnosed with temporomandibular disorders (TMD) on pain, sleep, and quality of life (QOL), and compare these results with the results from traditional therapies., Methods: Sixty patients diagnosed with TMD using the research diagnostic criteria for temporomandibular disorders (RDC/TMD) were allocated into four treatment groups: counseling (C = 15), occlusal splint (OS = 15), scalp acupuncture (SA = 15), and manual therapy (MT = 15). Participants were re-evaluated within 1 month. Three questionnaires were used to access sleep disorders, QOL, and pain: The Pittsburgh Sleep Quality Index (PSQI), World Health Organization Quality of Life (WHOQOL-bref), and the Visual Analogue Scale (VAS), respectively. The data obtained were analyzed using the Statistical Package for the Social Science program (SPSS 22.0)., Results: The SA group significantly improved pain (P = .015), as well as the OS (P = .01) and MT groups (P = .014). Only the OS (P = .002) and MT (P = .029) groups improved sleep. MT group significantly improved QOL in terms of the physical domain of the WHOQOL-bref (P = .011) and the OS group in the psychological domain (P = .012)., Conclusions: The scalp acupuncture proved to be another alternative for pain relief in patients with TMD, demonstrating positive results in the short term. However, it was not as effective in improving quality of life and sleep., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To analyze the prevalence and factors associated with sexual violence against children and adolescents in the city of Petrolina/Pernambuco., Method: Ecological study carried out with data from children and adolescents who were victims of sexual violence, collected in the Information System for Notifiable Diseases and analyzed according to descriptive and inferential statistics, with multiple logistic regression., Results: A total of 1,232 cases of sexual violence against children and adolescents were registered, with a prevalence of 30.6%. Sexual violence was more likely to occur among female victims (Odds Ratio = 11.39), in their own home (Odds Ratio = 1.96), and the father was the most likely aggressor (Odds Ratio = 8.97). Alcohol use by the aggressor increased the chance for the outcome (Odds Ratio = 2.26)., Conclusion: The prevalence of sexual violence and associated factors point to the need to implement humane practices within a network of health services integrated with other public systems, with the objective of promoting, protecting and defending the rights of children and adolescents.

Introduction: Temporomandibular dysfunction (TMD) is a condition that affects the stomatognathic system., Objective: To determine the effect of treatment with an occlusal splint (OS), manual therapy (MT), counselling (CS) and the combination of an occlusal splint and counselling (OSCS) on pain and anxiety in patients with TMD., Materials and Methods: A randomised clinical trial was conducted with 89 patients diagnosed with TMD through RDC/TMD (Research Diagnostic Criteria for Temporomandibular Disorders) and divided into four groups of treatment: OSCS (n = 25); OS (n = 24); MT (n = 21); and CS (n = 19). Participants were assessed before and after 1 month of therapy for pain, anxiety and TMD diagnosis. Pain was measured by a visual analogue scale. To assess anxiety, Hospital Anxiety and Depression Scale (HADS), Beck Anxiety Inventory (BAI) and the State-Trait Anxiety Inventory (STAI-S and T) were used. The data were analysed using SPSS (Statistical Package for Social Science) 22.0., Results: The four groups obtained a significant reduction (P < 0.001) in the pain after 1 month of treatment. Treatment in all groups promoted a significant reduction in anxiety symptoms 1 month after completion, HADS (P < 0.001), BAI (P < 0.001), STAI-T (P = 0.006). Thus, no group was superior to the other in reducing the studied variables., Conclusion: The therapies used were effective in reducing pain and anxiety in patients diagnosed with TMD. However, no treatment was superior to the other in reducing the studied variables., (© 2020 FDI World Dental Federation.)

Objective: To understand the performance of the protection network for children, adolescents, and their families in situations of intrafamily violence, from the perspective of professionals of the Specialized Reference Center for Social Assistance., Method: A qualitative study conducted with five Specialized Reference Center for Social Assistance professionals in a Pernambucan municipality. Data collection was conducted from October 2017 to January 2018 by means of a semi-structured interview, with data analyzed by the thematic content technique., Results: The professionals know how the protection network works, but they see the deductive logic of the team; the lack of material resources; the difficulty of articulation; and the logistics of care flow as limiting factors for maintaining effective care., Conclusion: The performance of the protection network must be able to ensure the rights of children, adolescents, and their families in situations of violence, through articulated and integrated care, aiming at changing attitudes and breaking the cycle of violence.

Objective: To evaluate the clinical evolution and survival of neurocritical patients in Hospital Units., Method: Cohort with hospitalized patients in follow-up treatment in public and private hospitals between September 2012 and June 2016. Data were initially analyzed from descriptive and inferential statistics. The Kaplan-Meier indicator was applied as a form of survival analysis. The Cox proportional hazards regression model was used to analyze the prognostic factors by calculating the hazard ratio., Results: Participation of 1,289 patients in the study. Patients with a higher score on the Glasgow Coma Scale presented greater survival, and the one-point increase in the scale score corresponded to 42% improvement in their survival. In the analysis of survival, sex and the use of vasoactive drugs showed a significant difference., Conclusion: Female patients with a better score on the Glasgow Coma Scale and using vasoactive drugs had higher survival rates.

Objective: To evaluate the morphology of filler particles, chemical composition, microhardness (MH), water sorption (WSp), and solubility (WSl) of a regular viscosity bulk fill and traditional composite resins., Methods: Eighty samples (Ø:5 mm; height: 4 mm) were prepared according to the factors "composite" (Aura/SDI, FiltekZ250 XT/3M, Aura Bulk Fill/SDI, and Filtek Bulk Fill/3M) and "filling technique" (incremental and bulk) (n = 10). Vickers MH was measured on the top and bottom surfaces of each samples, and then WSp and WSl were obtained by means of mass gain and loss. Morphology of filler particles and chemical characteristics of composites were evaluated by scanning electron microscopy (SEM) and energy dispersity spectroscopy (EDS) in additional samples (n = 1/group). Data were analyzed using two- and three-way ANOVA and Tukey's tests (p < .05)., Results: No significant difference was found for WSp among the groups. Comparing composites in the incremental technique, Aura bulk fill composite showed lower WSI than the other materials and in the bulk fill technique, Filtek Bulk Fill showed the lowest value. Filtek Bulk Fill showed higher MH than the other composites on the bottom surface when samples were produced by bulk filling., Conclusion: The composites presented good physical properties, but the bulk fill ones showed better results for the bottom microhardness and solubility, although chemical elements and morphology were similar in general., (© 2019 Wiley Periodicals, Inc.)

Bacteriological and technical agars are in short supply with potential consequences for research, public health, and clinical labs around the world. To diagnose bottlenecks and sustainability problems that may be putting the industry at risk, we analyzed the available time series for the global landings of Gelidium , the most important raw materials for the industry. Data on the harvest of Gelidium spp. have been reported since1912, when Japan was the only producer. After World War II the diversification of harvested species and producing countries resulted in a strong increase in global landings. Maximum harvest yields of almost 60,000 t year -1 in the 1960s were sustained until the 1980s, after which landings decreased continuously to the present. In the 2010s, a reduction in the global production to about 25,000 t year -1 was observed, which was lower than the yields of the 1950s. Landings by important producers such as Japan, Korea, Spain, and Portugal have collapsed. This is the ultimate cause of the present shortage of bacteriological and technical agars. However, an important factor at play is the concentration of the global landings of Gelidium in Morocco, as its relative contribution increased from 23% in the 1960s to the present 82%. Two specific bottlenecks were identified: restrictive export quotas of unprocessed Gelidium in favor of the national agar industry and resource management regulations that were apparently not enforced resulting in over-harvesting and resource decline. The global industry may well be dependent on resource management basics. Simple harvest statistics must be gathered such as the harvest effort and the variation of harvest yields along the harvest season. We discuss how this information is fundamental to manage the resource. The available harvest statistics are generally poor and limited and vary significantly among different sources of data. Probable confusions between dry and wet weight reporting and poor discrimination of the species harvested need to be resolved.

The aim of this study was to compare the number of CD57+ natural killer (NK) cells and CD8+ T lymphocytes between periapical granulomas (PGs) and radicular cysts (RCs). Twenty-fives cases of PGs and 25 of RCs were submitted to histological analysis and immunohistochemistry using anti-CD57 and anti-CD8 biomarkers. Positive cells were counted in 10 fields (400× magnification) and the median value was calculated for each case. Statistical tests were used to evaluate differences in the number of CD57+ NK cells and CD8+ T lymphocytes according to type of lesion, intensity of the infiltrate and thickness of the lining epithelium. The number of CD57+ NK cells and CD8+ T lymphocytes was higher in PGs than in RCs (p = 0.129 and p = 0.541, respectively). Comparison of the number of CD57+ NK cells in atrophic and hyperplastic epithelium revealed a larger number of cells in the atrophic epithelium (p = 0.042). A larger number of CD57+ NK cells and CD8+ T lymphocytes were observed in grade III infiltrates compared to grade I/II (p = 0.145 and p = 0.725, respectively). CD8+ T lymphocytes were more prevalent than CD57+ NK cells in most cases when PGs and RCs were analyzed separately or in combination (p < 0.0001). CD57+ NK cells and CD8+ T lymphocytes play a key role in antiviral defense and the presence of these cells supports evidence suggesting the participation of these microorganisms in the pathogenesis of PGs and RCs. The response mediated by CD8+ T lymphocytes was more frequent, indicating greater participation of the adaptive immunity in these chronic lesions.

The retinal tissue of warm-blooded vertebrates performs surprisingly complex and accurate transduction of visual information. To achieve precision, a multilayered neuroglia structure is established throughout the embryonic development, and the presence of radial Müller (glial) cells ensure differentiation, growth and survival for the neuronal elements within retinal environment. It is assumed that Müller cells serve as a dynamic reservoir of progenitors, capable of expressing transcription factors, differentiating and proliferating as either neuronal or glial cells depending on extrinsic cues. In the postnatal period, Müller glia may re-enter cell cycle and produce new retinal neurons in response to acute damage. In this context, glutathione (GSH), a virtually ubiquitous tripeptide antioxidant, which is found at milimolar concentrations in central glial cells, plays a vital role as a reducing agent, buffering radical oxygen species (ROS) and preventing cell death in severely injured retinal tissues. Despite its antioxidant role, data also point to GSH as a signaling agent, suggesting that GABA release and P2X 7 R-mediated calcium inwards occur in Müller cells in a GSH-enriched environment. These phenomena indicate a novel mechanistic response to damage in the vertebrate retinal tissue, particularly in neuron-glia networks.

Objective: To evaluate the indications for performing magnetic resonance imaging of the female pelvis at a referral center for cancer., Materials and Methods: This was a retrospective, single-center study, conducted by reviewing medical records and imaging reports. We included 1060 female patients who underwent magnetic resonance imaging of the pelvis at a cancer center between January 2013 and June 2014. The indications for performing the examination were classified according to the American College of Radiology (ACR) criteria., Results: The mean age of the patients was 52.6 ± 14.8 years, and 49.8% were perimenopausal or postmenopausal. The majority (63.9%) had a history of cancer, which was gynecologic in 29.5% and nongynecologic in 34.4%. Of the patients evaluated, 44.0% had clinical complaints, the most common being pelvic pain (in 11.5%) and bleeding (in 9.8%), and 34.7% of patients had previously had abnormal findings on ultrasound. Most (76.7%) of the patients met the criteria for undergoing magnetic resonance imaging, according to the ACR guidelines. The main indications were evaluation of tumor recurrence after surgical resection (in 25.9%); detection and staging of gynecologic neoplasms (in 23.3%); and evaluation of pelvic pain or of a mass (in 17.1%)., Conclusion: In the majority of the cases evaluated, magnetic resonance imaging was clearly indicated according to the ACR criteria. The main indication was local recurrence after surgical treatment of pelvic malignancies, which is consistent with the routine protocols at cancer centers.

Objective: To evaluate factors predictive for relapse in a cohort of adult patients with acute promyelocytic leukemia monitored by molecular methods during consolidation and during at least one month of maintenance therapy., Methods: The charts and laboratory data of 65 adult patients with acute promyelocytic leukemia treated according to the International Consortium on Acute Promyelocytic Leukemia 2006 protocol were reviewed. The identification of the promyelocytic leukemia-retinoic acid receptor-alpha gene rearrangement at diagnosis, post-induction, post-consolidation and during maintenance treatment was performed by qualitative and quantitative reverse transcription polymerase chain reaction., Results: Eighty-nine patients were diagnosed with acute promyelocytic leukemia over a seven-year period and of these 65 were eligible for treatment with the protocol. Among the 45 patients who received consolidation and maintenance treatment, six (13%) relapsed, three of whom presented hematologic and three presented molecular relapse. The first relapses occurred at a median of 39 months. Relapsed patients were from all risk groups (low, intermediate and high) and both morphological types (M3 and M3variant) were found. Three of these patients are alive and in molecular remission after salvage treatment. There were no statistically significant differences regarding gender, age, risk group, morphology, promyelocytic leukemia breakpoint cluster region, use of all-trans retinoic acid, development of differentiation syndrome and number of days to complete remission between the patients who relapsed and those who did not., Conclusion: Our results reinforce the importance of prolonged monitoring of acute promyelocytic leukemia patients using molecular methods to detect relapse early., (Copyright © 2016 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.)

Neuroglia interactions are essential for the nervous system and in the retina Müller cells interact with most of the neurons in a symbiotic manner. Glutathione (GSH) is a low-molecular weight compound that undertakes major antioxidant roles in neurons and glia, however, whether this compound could act as a signaling molecule in neurons and/or glia is currently unknown. Here we used embryonic avian retina to obtain mixed retinal cells or purified Müller glia cells in culture to evaluate calcium shifts induced by GSH. A dose response curve (0.1-10 mM) showed that 5-10 mM GSH, induced calcium shifts exclusively in glial cells (later labeled and identified as 2M6 positive cells), while neurons responded to 50 mM KCl (labeled as βIII tubulin positive cells). BBG 100 nM, a P2X7 blocker, inhibited the effects of GSH on Müller glia. However, addition of DNQX 70 μM and MK-801 20 μM, non-NMDA and NMDA blockers, had no effect on GSH calcium induced shift. Oxidized glutathione (GSSG) at 5 mM failed to induce calcium mobilization in glia cells, indicating that the antioxidant and/or structural features of GSH are essential to promote elevations in cytoplasmic calcium levels. Indeed, a short GSH pulse (60s) protects Müller glia from oxidative damage after 30 min of incubation with 0.1% H2O2. Finally, GSH induced GABA release from chick embryonic retina, mixed neuron-glia or from Müller cell cultures, which were inhibited by BBG or in the absence of sodium. GSH also induced propidium iodide uptake in Müller cells in culture in a P2X7 receptor dependent manner. Our data suggest that GSH, in addition to antioxidant effects, could act signaling calcium shifts at the millimolar range particularly in Müller glia, and could regulate the release of GABA, with additional protective effects on retinal neuron-glial circuit.

Introduction: Obesity is a disease in which inflammation is directly involved and can lead to impaired renal function., Objective: To evaluate the influence of short term exposure to cafeteria diet on kidney tissue inflammation and advanced glycation end products (AGEs) in the rat plasma., Methods: Male Wistar rats (10 weeks of age, weighing 350 g) were assigned to receive commercial chow diet (C; n = 8 animals/group, 5% of energy from fat) or cafeteria diet (CAF-D, n = 8 animals/group: 29% energy fat) and sucrose in drinking water (300 g/L) for 6 weeks., Results: adiposity index at six weeks was higher in CAF-D group compared to C. The same behavior was observed for plasma levels of glucose, triglycerides, leptin, insulin and AGEs. The gene expression of IL-6 and TNF-α in renal tissue was higher in CAF-D group and no significant difference in adipose tissue. There was no increase of these cytokines in plasma and kidney or histologically. There was a significant decrease of adiponectin in the CAF-D group., Conclusion: The short exposure CAF-D reflects changes in metabolism, increased plasma levels of AGEs, which may reflect the increased expression of inflammatory cytokines in the kidney.

Background: Traffic noise is a highly relevant environmental impact in cities. Models to estimate traffic noise, in turn, can be useful tools to guide mitigation measures. In this paper, the applicability of models to estimate noise levels produced by a continuous flow of vehicles on urban roads is investigated. The aim is to identify which models are more appropriate to estimate traffic noise in urban areas since several models available were conceived to estimate noise from highway traffic., Results: First, measurements of traffic noise, vehicle count and speed were carried out in five arterial urban roads of a brazilian city. Together with geometric measurements of width of lanes and distance from noise meter to lanes, these data were input in several models to estimate traffic noise. The predicted noise levels were then compared to the respective measured counterparts for each road investigated. In addition, a chart showing mean differences in noise between estimations and measurements is presented, to evaluate the overall performance of the models. Measured Leq values varied from 69 to 79 dB(A) for traffic flows varying from 1618 to 5220 vehicles/h. Mean noise level differences between estimations and measurements for all urban roads investigated ranged from -3.5 to 5.5 dB(A)., Conclusions: According to the results, deficiencies of some models are discussed while other models are identified as applicable to noise estimations on urban roads in a condition of continuous flow. Key issues to apply such models to urban roads are highlighted.

The TP73 gene transcript is alternatively spliced and translated into the transcriptionally active (TAp73) or inactive (ΔNp73) isoforms, with opposite effects on the expression of p53 target genes and on apoptosis induction. The imbalance between ΔNp73 and TAp73 may contribute to tumorigenesis and resistance to chemotherapy in human cancers, including hematologic malignancies. In acute promyelocytic leukemia (APL), both isoforms are expressed, but their relevance in determining response to therapy and contribution to leukemogenesis remains unknown. Here, we provide the first evidence that a higher ΔNp73/TAp73 RNA expression ratio is associated with lower survival, lower disease-free survival, and higher risk of relapse in patients with APL homogeneously treated with all-trans retinoic acid and anthracycline-based chemotherapy, according to the International Consortium on Acute Promyelocytic Leukemia (IC-APL) study. Cox proportional hazards modeling showed that a high ΔNp73/TAp73 ratio was independently associated with shorter overall survival (hazard ratio, 4.47; 95% confidence interval, 1.64-12.2; P = .0035). Our data support the hypothesis that the ΔNp73/TAp73 ratio is an important determinant of clinical response in APL and may offer a therapeutic target for enhancing chemosensitivity in blast cells., (© 2015 by The American Society of Hematology.)

Front-line treatment of acute promyelocytic leukaemia (APL) consists of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. In this setting, a comparison of idarubicin and daunorubicin has never been carried out. Two similar clinical trials using ATRA and chemotherapy for newly diagnosed APL were compared using matched-pair analysis. One was conducted by the PETHEMA/HOVON group with idarubicin and the other by the International Consortium on APL (IC-APL) using daunorubicin. Three hundred and fifty patients from the PETHEMA/HOVON cohort were matched with 175 patients in the IC-APL cohort, adjusting for the significantly unbalanced presenting features of the two entire cohorts. Complete remission (CR) rate was significantly higher in the PETHEMA/HOVON (94 %) than in the IC-APL cohort (85 %) (P = 0.002). The distribution of causes of induction failure and the time to achieve CR were similar in both cohorts. Patients who achieved CR had comparable cumulative incidence of relapse and disease-free survival rates, but lower overall and event-free survivals were observed in the IC-APL cohort, which was mainly due to a higher death rate during induction therapy. A higher death rate during consolidation therapy was also observed in the IC-APL. These results show that daunorubicin and idarubicin have similar antileukaemic efficacy in terms of primary resistance, molecular persistence, as well as molecular and haematological relapse rates when combined with ATRA in treatment of APL. However, a higher toxic death rate during induction and consolidation therapy was observed in the IC-APL cohort. This trial was registered at www.clinicaltrials.gov as #NCT00408278 [ClinicalTrials.gov].

Aim: The aim was to evaluate the biomechanical behavior of the supporting bony structures of replanted teeth and the periodontal ligament (PDL) of adjacent teeth when orthodontic wires with different mechanical properties are applied, with three-dimensional finite element analysis., Materials and Methods: Based on tomographic and microtomographic data, a three-dimensional model of the anterior maxilla with the corresponding teeth (tooth 13-tooth 23) was generated to simulate avulsion and replantation of the tooth 21. The teeth were splinted with orthodontic wire (Ø 0.8 mm) and composite resin. The elastic modulus of the three orthodontic wires used, that is, steel wire (FA), titanium-molybdenum wire (FTM), and nitinol wire (FN) were 200 GPa, 84 GPa, and 52 GPa, respectively. An oblique load (100 N) was applied at an angle of 45° on the incisal edge of the replanted tooth and was analyzed using Ansys Workbench software. The maximum (σmax) and minimum (σmin) principal stresses generated in the PDL, cortical and alveolar bones, and the modified von Mises (σvM) values for the orthodontic wires were obtained., Results: With regard to the cortical bone and PDL, the highest σmin and σmax values for FTM, FN, and FA were checked. With regard to the alveolar bone, σmax and σmin values were highest for FA, followed by FTM and FN. The σvM values of the orthodontic wires followed the order of rigidity of the alloys, that is, FA > FTM > FN., Conclusion: The biomechanical behavior of the analyzed structures with regard to all the three patterns of flexibility was similar., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objectives: This project is a continuation of a larger project entitled "Treatment with intragastric balloon (IGB) in patients with overweight and obesity in Recife" developed by Professor Dr. Gustavo Lopes de Carvalho. It is a project studying the effectiveness of treatment with IGB evaluating the loss of weight and body mass index and its impact on blood pressure, blood glucose, triglycerides, total cholesterol and fractions. It also assesses the lifestyle of patients studying whether treatment with IGB interferes in smoking, alcohol consumption, eating habits and physical exercises performed by patients. The present study added a larger project, the separate evaluation of the different types of abdominal fat-visceral fat and subcutaneous cell tissue fat - and was conducted to discover which of the 2 types of fat undergoes the greater reduction after IGB treatment. To measure these 2 types of fat, we used the ultrasonography technique, because it has been shown to be accurate and noninvasive., Methods: Twenty-five patients were evaluated before and after 6 months of IGB treatment., Results: The patients' ages ranged from 20 to 61 years, with 60% being 40 years of age or older. The majority (72%) were women. All variables (weight, body mass index [BMI], VF, and SCTF) showed a significant reduction (P < .05) in mean values after treatment. The difference was highest in the SCTF (17.5%) and ranged from an 11.4% to an 11.6% reduction in all other variables. The average loss of SCTF was highest among the patients who had lost up to 10.0% of their initial weight (19.2% for the ≤10.0% group vs 15.9% for the >10.0% group); however, the difference was not significant (P = .66). The average loss of VF was higher in the subgroup of patients who had lost >10.0% of their initial weight (16.2% vs 6.3%; P = .003). The Pearson correlation between the reductions in SCTF vs VF was negative, low, and nonsignificant (-0.17; P = .41)., Conclusions: After 6 months of IGB treatment, there was no significant difference between the reduction in abdominal SCTF and VF, but the results signify a possible correlation between the percentage of body weight loss and the type of abdominal fat reduced, as the impact on the VF was higher when the patients lost >10.0% of their initial weight.

Activating internal tandem duplication (ITD) mutations in the fms-like tyrosine kinase 3 (FLT3) gene (FLT3-ITD) are associated with poor outcome in acute myeloid leukemia, but their prognostic impact in acute promyelocytic leukemia (APL) remains controversial. Here, we screened for FLT3-ITD mutations in 171 APL patients, treated with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. We identified FLT3-ITD mutations in 35 patients (20 %). FLT3-ITD mutations were associated with higher white blood cell counts (P < 0.0001), relapse-risk score (P = 0.0007), higher hemoglobin levels (P = 0.0004), higher frequency of the microgranular morphology (M3v) subtype (P = 0.03), and the short PML/RARA (BCR3) isoform (P < 0.0001). After a median follow-up of 38 months, FLT3-ITD(positive) patients had a lower 3-year overall survival rate (62 %) compared with FLT3-ITD(negative) patients (82 %) (P = 0.006). The prognostic impact of FLT3-ITD on survival was retained in multivariable analysis (hazard ratio: 2.39, 95 % confidence interval [CI] 1.17-4.89; P = 0.017). Nevertheless, complete remission (P = 0.07), disease-free survival (P = 0.24), and the cumulative incidence of relapse (P = 0.94) rates were not significantly different between groups. We can conclude that FLT3-ITD mutations are associated with several hematologic features in APL, in particular with high white blood cell counts. In addition, FLT3-ITD may independently predict a shorter survival in patients with APL treated with ATRA and anthracycline-based chemotherapy.

The ganglioside 9-O-acetyl GD3 is overexpressed in peripheral nerves after lesioning, and its expression is correlated with axonal degeneration and regeneration in adult rodents. However, the biological roles of this ganglioside during the regenerative process are unclear. We used mice lacking GD3 synthase (Siat3a KO), an enzyme that converts GM3 to GD3, which can be further converted to 9-O-acetyl GD3. Morphological analyses of longitudinal and transverse sections of the sciatic nerve revealed significant differences in the transverse area and nerve thickness. The number of axons and the levels of myelin basic protein were significantly reduced in adult KO mice compared to wild-type (WT) mice. The G-ratio was increased in KO mice compared to WT mice based on quantification of thin transverse sections stained with toluidine blue. We found that neurite outgrowth was significantly reduced in the absence of GD3. However, addition of exogenous GD3 led to neurite growth after 3 days, similar to that in WT mice. To evaluate fiber regeneration after nerve lesioning, we compared the regenerated distance from the lesion site and found that this distance was one-fourth the length in KO mice compared to WT mice. KO mice in which GD3 was administered showed markedly improved regeneration compared to the control KO mice. In summary, we suggest that 9-O-acetyl GD3 plays biological roles in neuron-glia interactions, facilitating axonal growth and myelination induced by Schwann cells. Moreover, exogenous GD3 can be converted to 9-O-acetyl GD3 in mice lacking GD3 synthase, improving regeneration.

Objective: This study investigated the occurrence of the p190 and p210 breakpoint cluster region-Abelson (BCR-ABL) rearrangements in adults with acute lymphoblastic leukemia and possible associations with clinical and laboratory characteristics and survival., Methods: Forty-one over 18-year-old patients with acute lymphoblastic leukemia of both genders followed-up between January 2008 and May 2012 were included in this study. Clinical and laboratory data were obtained from the medical charts of the patients. Reverse transcription polymerase chain reaction (RT-PCR) using specific primers was employed to identify molecular rearrangements., Results: At diagnosis, the median age was 33 years, and there was a predominance of males (61%). The most common immunophenotype was B lineage (76%). BCR-ABL rearrangements was detected in 14 (34%) patients with the following distribution: p190 (28%), p210 (50%) and double positive (22%). Overall survival of patients with a mean/median of 331/246 days of follow up was 39%, respectively, negative BCR-ABL (44%) and positive BCR-ABL (28%)., Conclusion: These results confirm the high frequency of BCR-ABL rearrangements and the low survival rate of adult Brazilian patients with acute lymphoblastic leukemia., (Copyright © 2014 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.)

The KMT2E (MLL5) gene encodes a histone methyltransferase implicated in the positive control of genes related to haematopoiesis. Its close relationship with retinoic acid-induced granulopoiesis suggests that the deregulated expression of KMT2E might lead acute promyelocytic leukaemia (APL) blasts to become less susceptible to the conventional treatment protocols. Here, we assessed the impact of KMT2E expression on the prognosis of 121 APL patients treated with ATRA and anthracycline-based chemotherapy. Univariate analysis showed that complete remission (P = 0·006), 2-year overall survival (OS) (P = 0·005) and 2-year disease-free survival (DFS) rates (P = 0·037) were significantly lower in patients with low KMT2E expression; additionally, the 2-year cumulative incidence of relapse was higher in patients with low KMT2E expression (P = 0·04). Multivariate analysis revealed that low KMT2E expression was independently associated with lower remission rate (odds ratio [OR]: 7·18, 95% confidence interval [CI]: 1·71-30·1; P = 0·007) and shorter OS (hazard ratio [HR]: 0·27, 95% CI: 0·08-0·87; P = 0·029). Evaluated as a continuous variable, KMT2E expression retained association with poor remission rate (OR: 10·3, 95% CI: 2·49-43·2; P = 0·001) and shorter survival (HR: 0·17, 95% IC: 0·05-0·53; P = 0·002), while the association with DFS was of marginal significance (HR: 1·01; 95% CI: 0·99-1·02; P = 0·06). In summary, low KMT2E expression may predict poor outcome in APL patients., (© 2014 John Wiley & Sons Ltd.)

It has been well established that estrogen plays an important role in the progression and treatment of breast cancer. However, the role of triiodothyronine (T₃) remains controversial. We have previously shown its capacity to stimulate the development of positive estrogen receptor breast carcinoma, induce the expression of genes (PR, TGF-alpha) normally stimulated by estradiol (E₂), and suppress genes (TGF-beta) normally inhibited by E₂. Since T₃ regulates growth hormones, metabolism, and differentiation, it is important to verify its action on other genes normally induced by E₂. Therefore, we used DNA microarrays to compare gene expression patterns in MCF-7 breast adenocarcinoma cells treated with E₂ and T₃. Several genes were modulated by both E₂ and T₃ in MCF-7 cells (Student's t-test, P < 0.05). Specifically, we found eight genes that were differentially expressed after treatment with both E₂ and T₃, including amphiregulin, fibulin 1, claudin 6, pericentriolar material 1, premature ovarian failure 1B, factor for adipocyte differentiation-104, sterile alpha motif domain containing 9, and likely ortholog of rat vacuole membrane protein 1 (fold change > 2.0, pFDR < 0.05). We confirmed our microarray results by real-time PCR. Our findings reveal that certain genes in MCF-7 cells can be regulated by both E₂ and T₃.

Thanks to modern treatment with all-trans retinoic acid and chemotherapy, acute promyelocytic leukemia (APL) is now the most curable type of leukemia. However, this progress has not yielded equivalent benefit in developing countries. The International Consortium on Acute Promyelocytic Leukemia (IC-APL) was established to create a network of institutions in developing countries that would exchange experience and data and receive support from well-established US and European cooperative groups. The IC-APL formulated expeditious diagnostic, treatment, and supportive guidelines that were adapted to local circumstances. APL was chosen as a model disease because of the potential impact on improved diagnosis and treatment. The project included 4 national coordinators and reference laboratories, common clinical record forms, 5 subcommittees, and laboratory and data management training programs. In addition, participating institutions held regular virtual and face-to-face meetings. Complete hematological remission was achieved in 153/180 (85%) patients and 27 (15%) died during induction. After a median follow-up of 28 months, the 2-year cumulative incidence of relapse, overall survival (OS), and disease-free survival (DFS) were 4.5%, 80%, and 91%, respectively. The establishment of the IC-APL network resulted in a decrease of almost 50% in early mortality and an improvement in OS of almost 30% compared with historical controls, resulting in OS and DFS similar to those reported in developed countries.

This study was designed to determine the genotoxicity of a supraphysiological dose of triiodothyronine (T3) in both obese and calorie-restricted obese animals. Fifty male Wistar rats were randomly assigned to one of the two following groups: control (C; n = 10) and obese (OB; n = 40). The C group received standard food, whereas the OB group was fed a hypercaloric diet for 20 weeks. After this period, half of the OB animals (n = 20) were subjected to a 25%-calorie restriction of standard diet for 8 weeks forming thus a new group (OR), whereas the remaining OB animals were kept on the initial hypercaloric diet. During the following two weeks, 10 OR animals continued on the calorie restriction diet, whereas the remaining 10 rats of this group formed a new group (ORS) given a supraphysiological dose of T3 (25 µg/100 g body weight) along with the calorie restriction diet. Similarly, the remaining OB animals were divided into two groups, one that continued on the hypercaloric diet (OB, n = 10), and one that received the supraphysiological dose of T3 (25 µg/100 g body weight) along with the hypercaloric diet (OS, n = 10) for two weeks. The OB group showed weight gain, increased adiposity, insulin resistance, increased leptin levels and genotoxicity; T3 administration in OS animals led to an increase in genotoxicity and oxidative stress when compared with the OB group. The OR group showed weight loss and normalized levels of adiposity, insulin resistance, serum leptin and genotoxicity, thus having features similar to those of the C group. On the other hand, the ORS group, compared to OR animals, showed higher genotoxicity. Our results indicate that regardless of diet, a supraphysiological dose of T3 causes genotoxicity and potentiates oxidative stress.

Introduction: There is controversy about the effect of dietary patterns during the first year of life and the occurrence of food allergy. The objective of this study was to evaluate the association between family history of allergy, allergic manifestations and dietary patterns during the first year of life in infants with and without food allergy., Population and Methods: We performed a descriptive cross-sectional study in children under 2 years of age (n= 99), sorted in two groups: allergic group (n= 50) and control group (n= 49), matched by socioeconomic status, age and gender. Food allergy was deifned by internationally approved clinical criteria, prick and patch tests, and response to diet. Information on diet, clinical data and history of allergy in the parents were collected. The sample size was estimated for logistic regression (Freeman), and Student X² and Mann-Withney tests were used. The study and consent forms were approved by the Ethics Committee of the Institute of Nutrition and Food Technology (Instituto de Nutrición y Tecnología de los Alimentos, INTA) and the Universidad de Chile., Results: The allergic group showed a significantly higher prevalence (p <0.0001) of family history of allergy (84%) than the control group (16%). Diarrhea was the symptom most frequently reported by the mothers of allergic infants during the first year of life. Bottle feeding was introduced earlier in the allergic group than in the control group (3 versus 6 months [p < 0.03]); no differences regarding the start age for supplementary feeding was found. When performing logistic regression, only the family history of allergy was associated with a higher risk of food allergy (OR: 48.2; CI= 14.2-164; p < 0.001)., Conclusions: The early introduction of milk formula could promote the occurrence of food allergy in infants frequently presenting family history of allergy.

Objectives: Several clinical trials conducted in Europe and US reported favorable outcomes of patients with APL treated with the combination of all trans retinoic acid (ATRA) and anthracyclines. Nevertheless, the results observed in developing countries with the same regimen was poorer, mainly due to high early mortality mainly due bleeding. The International Consortium on Acute Promyelocytic Leukemia (IC-APL) is an initiative of the International Members Committee of the ASH and the project aims to reduce this gap through the establishment of international network, which was launched in Brazil, Mexico and Uruguay., Methods: The IC-APL treatment protocol is similar to the PETHEMA 2005, but changing idarubicin to daunorubicin. All patients with a suspected diagnosis of APL were immediately started on ATRA, while bone marrow samples were shipped to a national central lab where genetic verification of the diagnosis was performed. The immunofluorescence using an anti-PML antibody allowed a rapid confirmation of the diagnosis and, the importance of supportive measures was reinforced., Results: The interim analysis of 97 patients enrolled in the IC-APL protocol showed that complete remission (CR) rate was 83% and the 2-year overall survival and disease-free survival were 80% and 90%, respectively. Of note, the early mortality rate was reduced to 7.5%., Discussion: The results of IC-APL demonstrate the impact of educational programs and networking on the improvement of the leukemia treatment outcome in developing countries.

Several mechanisms underlying ethanol action in GABAergic synapses have been proposed, one of these mechanisms is on GABA release. Here, we report that in ovo exposure to ethanol induces an increase on GABA release in the embryonic chick retina. Eleven-day-old chick embryos (E11) received an injection of either phosphate buffer saline (PBS) or ethanol (10%, v/v, diluted in PBS), and were allowed to develop until E16. A single glutamate stimulus (2 mM) showed approximately a 40% increase on GABA release in E16 retinas when compared to controls. The effect was dependent on NMDA receptors and GAD65 mRNA levels, which were increased following the ethanol treatment. However, the numbers of GABA-, GAD-, and NR1-immunoreactive cells, and the expression levels of these proteins, were not affected. We conclude that ethanol treatment at a time point when synapses are being formed during development selectively increases GABA release in the retina via a NMDA receptor-dependent process., (Copyright 2009 ISDN. Published by Elsevier Ltd. All rights reserved.)

Most cases of a predisposition to venous thrombosis are caused by resistance to activated protein C, associated in 95% of cases with the Factor V Leiden allele (FVL or R506Q). Several recent studies report a further increased risk of thrombosis by an association between the AB alleles of the ABO blood group and Factor V Leiden. The present study investigated this association with deep vein thrombosis (DVT) in individuals treated at the Hemocentro de Pernambuco in northeastern Brazil. A case-control comparison showed a significant risk of thrombosis in the presence of Factor V Leiden (OR = 10.1), which was approximately doubled when the AB alleles of the ABO blood group were present as well (OR = 22.3). These results confirm that the increased risk of deep vein thrombosis in the combined presence of AB alleles and Factor V Leiden is also applicable to the Brazilian population suggesting that ABO blood group typing should be routinely added to FVL in studies involving thrombosis.

Acute promyelocytic leukemia (APL) is characterized by the presence of rearrangements involving the retinoic acid receptor alpha (RARalpha) gene and a variable incidence in different populations. The hybrid gene PML-RARalpha, present in 98% of cases, encodes a fusion protein essential to the pathogenesis of the disease. Depending of the PML's gene breakpoint in chromosome 15, the transcript subtypes bcr1, bcr2 and bcr3 may be formed. The correlation between these transcript subtypes and clinical parameters is still controversial. The objective of this study was to determine the frequencies of the PML-RARalpha transcripts and subtypes in a series of 32 APL patients from Northeast Brazil and to evaluate the association of these subtypes to different parameters. The method used was RT-PCR. The frequency of our APL cases is approximately 28% of the acute leukemias. The results showed the presence of PML-RARalpha isoform in all patients and a higher frequency of the bcr1/2 subtype. No significant statistical association was found between molecular subtypes and age, sex, French-American-British (FAB) classification, leukocyte and platelet count, hemoglobin level or coagulation tests. In conclusion, these data suggest similar molecular and biological features for our APL patients at diagnosis in comparison with those reported in current scientific literature.

Glia represents the most numerous group of nervous system cells and CNS development and function depend on glial cells. We developed a purified Muller glia culture to investigate the expression of several neurotransmitter markers on these cells, such as dopaminergic, cholinergic, GABAergic and peptidergic receptors or enzymes, based on functional assays measuring second messenger levels or Western blot for specific proteins. Purified Muller cell culture was obtained from 8-day-old (E8) embryonic chick. Glial cells cultured for 15 days (E8C15) expressed D1A and D1B receptors mRNAs, but not D1D, as detected by RT-PCR. The binding of [3H]-SCH 23390 revealed an amount of expressed receptors around 40 fmol/mg protein. Dopamine (100 microM), PACAP (50 nM) and forskolin (10 microM) induced a 50-, 30- and 40-fold cAMP accumulation on glial cells, respectively, but not ip3 production. The dopamine-promoted cAMP accumulation was blocked by 2 microM SCH 23390. Carbachol stimulated a 3-fold ip3 accumulation. Western blot analysis also revealed the expression of tyrosine hydroxylase, L-dopa decarboxylase, PAC1 receptor, GAD67 and beta2-nicotinic receptor subunit by these cells. These results indicate that several components of neurotransmitter signaling and metabolism are found in cultured Muller cells.

1. Previous studies have shown that phorbol esters induce protein kinase C (PKC) mediated phosphorylation of the vesicular acetylcholine transporter (VAChT) and change its interaction with vesamicol. However, it is not clear whether physiological activation of receptors coupled to PKC activation can alter VAChT behavior. 2. Here we tested whether activation of kaianate (KA) receptors alters VAChT. Several studies suggest that the cholinergic amacrine cells display KA/AMPA receptors that mediate excitatory input to these neurons. In addition, KA in the chicken retina can generate intracellular messengers with the potential to regulate cellular functions. 3. In cultured chicken retina (E8C11) KA reduced vesamicol binding to VAChT by 53%. This effect was potentiated by okadaic acid, a protein phosphatase inhibitor, and was totally prevented by BIM, a PKC inhibitor. 4. Phorbol myristate acetate (PMA), but not alpha-PMA, reduced in more than 85% the number of L-[3H]-vesamicol-specific binding sites in chicken retina, confirming that activation of PKC can influence vesamicol binding to chicken VAChT. 5. The data show that activation of glutamatergic receptors reduces [3H]-vesamicol binding sites (VAChT) likely by activating PKC and increasing the phosphorylation of the ACh carrier.

The distribution of lymphocyte subsets in blood, thymus, spleen, mesenteric lymph nodes, Peyer's patches and bone marrow was evaluated in an experimental model of secondary hemochromatosis in rats. The values of CD2, CD4, CD8, B and NK cells in these different lymphoid compartments did not differ between the control group and the experimental group. These results suggest that the abnormalities of lymphocyte subsets previously reported in patients with secondary hemochromatosis may be due to factors other than iron overload.

A previously healthy girl, without heart disease, who ingested 2400 mg of verapamil developed hypotension, trifasicular block pattern, mental confusion, mild metabolic acidosis, and hyperglycemia. She recovered with symptomatic and supportive therapy. A discussion is presented about the action mechanism of the drug.