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BACKGROUND: Blood donation is a safe process though reactions may still occur. We describe a rare vascular complication in a frequent donor, with improvements in the collection process aimed at avoiding future events. METHODS: A 63-year-old woman presented with local pain and an apparent collection in the left arm 8 days after donation. Duplex ultrasound identified a superficial liquid collection and signs of arteriovenous fistula (AVF) between the cubital vein and an arterial branch. A computed tomography (CT)-angio performed 1 day after ultrasound did not identify signs of AVF, followed by a new duplex which confirmed CT-angio findings. It was assumed that a traumatic AVF evolved with spontaneous thrombosis. In the early follow-up (18 days), a progressive regression of hematoma was observed without any sequelae. RESULTS: Investigation showed a faster whole blood bag collection time (3 min; normal: 5-9 min), and the processed packed red blood cell had a brighter red color than usual. The donor reported local bleeding after needle withdrawal, not observed in previous donations and a bruise forming on the same day. No arterial puncture (AP) was noticed by the collection staff during the procedure. The staff was retrained and actions were taken focusing on more active surveillance of late reactions, highlighting the importance of post-donation information by the donors, regardless of any adverse reaction observed, to detect late complications. CONCLUSION: We described an uncommon AP in a donor that was not identified, leading to an AVF that spontaneously thrombosed.

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Diabetes mellitus (DM) and hypothyroidism (HT) are prevalent diseases associated with dry eye (DE). Their impact on the lacrimal functional unit (LFU) is poorly known. This work evaluates the changes in the LFU in DM and HT. Adult male Wistar rats had the disease induced as follows: (a) DM: streptozotocin and (b) HT: methimazole. The tear film (TF) and blood osmolarity were measured. Cytokine mRNA was compared in the lacrimal gland (LG), trigeminal ganglion (TG), and cornea (CO). Oxidative enzymes were evaluated in the LG. The DM group showed lower tear secretion (p = 0.02) and higher blood osmolarity (p < 0.001). The DM group presented lower mRNA expression of TRPV1 in the cornea (p = 0.03), higher Il1b mRNA expression (p = 0.03), and higher catalase activity in the LG (p < 0.001). The DM group presented higher Il6 mRNA expression in the TG (p = 0.02). The HT group showed higher TF osmolarity (p < 0.001), lower expression of Mmp9 mRNA in the CO (p < 0.001), higher catalase activity in the LG (p = 0.002), and higher expression of Il1b mRNA in the TG (p = 0.004). The findings revealed that DM and HT induce distinct compromises to the LG and the entire LFU.

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OBJECTIVE: To analyze the karyotype test and myeloid panel with next-generation sequencing findings in patients with myelofibrosis, and to compare transplant characteristics in patients referred for bone marrow transplantation. METHODS: Retrospective, single-center study with patients diagnosed with myelofibrosis treated at Hospital Israelita Albert Einstein between 2010 and 2020. RESULTS: A total of 104 patients with myelofibrosis were examined. Patients who had not been submitted to tests in our service were excluded. The final sample comprised 69 patients. Of these 69, 56 were submitted to karyotyping and 22 to myeloid panel with next-generation sequencing. Karyotype was normal in 60% of the patients and altered in 40%. The prevalence of high-risk molecular mutations was higher in patients referred for bone marrow transplantation (100% versus 50%). The median follow-up of transplant patients was 2.4 years and the overall survival at 2 years was 80% (95%CI: 62-100%). CONCLUSION: The molecular analysis enables estimating the patient's risk and thus instituting more aggressive treatment such as bone marrow transplant for patients at higher risk, being a relevant tool to guide therapy. Given the significance of molecular analysis for therapeutic decision-making in myelofibrosis, collection and disclosure of data on the prevalence of cytogenetic changes and findings of next-generation sequencing in affected patients is important.

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Abstract Objective: To determine the incidence of MIS-C in Brazil, describe the clinical and sociodemographic characteristics of the pediatric population affected by MIS-C and compare mortality and lethality outcomes with isolated Covid-19 and MIS-C cases. Methods: Observational and retrospective cohort study of cases of MIS-C associated with Covid-19 in the Brazilian population between 04/01/2020 and 04/17/2021. Data from the Ministry of Health's epidemiological bulletin up to the 15th epidemiological week of 2021, were used. The analyzes were descriptive through absolute and relative frequencies. The significance level is 5% in Stata 16.0 package. Results: Between 04/01/2020 and 04/07/2021, 903 cases of MIS-C associated with Covid-19 were notified in Brazil, of which, the largest part (55.26%) were male, between 0 and 4 years old (45.29%), from the Southeast region (38.76%). The deaths (61; 6.7%) were higher in the female gender, between 0 and 4 years old (47.54%) and in the Southeast region (34.43%). It was identified that the risk of death by MIS-C related to Covid-19 is 5.29 (CI = 2.83; 9.87 and P-value = <0.001) times higher in adolescents from 15-19 years old than in other age groups when compared to 0-4 years old children. Also, the residency in North region was as risk factor to death (RR = 3.72, IC = 1.29; 10.74 e P-value = 0.008). Conclusion: In this study, despite the numbers showing more deaths from zero to 4 years old, the risk for teenagers is notably higher. In addition, Brazil's Northern region is a risk factor that reaffirms social inequality and poor access to health.

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OBJECTIVE: To determine the incidence of MIS-C in Brazil, describe the clinical and sociodemographic characteristics of the pediatric population affected by MIS-C and compare mortality and lethality outcomes with isolated Covid-19 and MIS-C cases. METHODS: Observational and retrospective cohort study of cases of MIS-C associated with Covid-19 in the Brazilian population between 04/01/2020 and 04/17/2021. Data from the Ministry of Health's epidemiological bulletin up to the 15th epidemiological week of 2021, were used. The analyzes were descriptive through absolute and relative frequencies. The significance level is 5% in Stata 16.0 package. RESULTS: Between 04/01/2020 and 04/07/2021, 903 cases of MIS-C associated with Covid-19 were notified in Brazil, of which, the largest part (55.26%) were male, between 0 and 4 years old (45.29%), from the Southeast region (38.76%). The deaths (61; 6.7%) were higher in the female gender, between 0 and 4 years old (47.54%) and in the Southeast region (34.43%). It was identified that the risk of death by MIS-C related to Covid-19 is 5.29 (CI = 2.83; 9.87 and P-value = <0.001) times higher in adolescents from 15-19 years old than in other age groups when compared to 0-4 years old children. Also, the residency in North region was as risk factor to death (RR = 3.72, IC = 1.29; 10.74 e P-value = 0.008). CONCLUSION: In this study, despite the numbers showing more deaths from zero to 4 years old, the risk for teenagers is notably higher. In addition, Brazil's Northern region is a risk factor that reaffirms social inequality and poor access to health.

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ABSTRACT Objective To analyze the karyotype test and myeloid panel with next-generation sequencing findings in patients with myelofibrosis, and to compare transplant characteristics in patients referred for bone marrow transplantation. Methods Retrospective, single-center study with patients diagnosed with myelofibrosis treated at Hospital Israelita Albert Einstein between 2010 and 2020. Results A total of 104 patients with myelofibrosis were examined. Patients who had not been submitted to tests in our service were excluded. The final sample comprised 69 patients. Of these 69, 56 were submitted to karyotyping and 22 to myeloid panel with next-generation sequencing. Karyotype was normal in 60% of the patients and altered in 40%. The prevalence of high-risk molecular mutations was higher in patients referred for bone marrow transplantation (100% versus 50%). The median follow-up of transplant patients was 2.4 years and the overall survival at 2 years was 80% (95%CI: 62-100%). Conclusion The molecular analysis enables estimating the patient's risk and thus instituting more aggressive treatment such as bone marrow transplant for patients at higher risk, being a relevant tool to guide therapy. Given the significance of molecular analysis for therapeutic decision-making in myelofibrosis, collection and disclosure of data on the prevalence of cytogenetic changes and findings of next-generation sequencing in affected patients is important.

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ABSTRACT Purpose: This study aimed to compare the changes in the lacrimal functional unit in the following two models of neurogenic dry eye syndrome: sensory denervation of the cornea versus autonomic denervation of the lacrimal gland. Methods: The neural network supports the lacrimal functional unit. It can be divided into afferent (sensory) and efferent (autonomic) pathways and is affected by severe diseases that compromise the lacrimal functional unit. Male Wistar, 8-week-old rats were divided into the following three groups: 1) control naïve (n=16 animals); 2) autonomic denervation: where rats were subjected to right lacrimal gland nerve ablation and evaluated after 1 and 2 months (1M and 2M) after the procedure (n=7 animals per subgroup, autonomic denervation 1M and autonomic denervation 2M, respectively); 3) sensory denervation induced by 0.2% benzalkonium chloride eye drops, twice a day for 7 days in the right eye (n=10 animals). The corneal sensitivity was measured using the eye wipe test with capsaicin (10 µM). The quantitative real-time PCR was performed to compare the mRNA expressions of proinflammatory cytokines, such as Il-1β, Il-6, Tnf, Mmp9, in the cornea, trigeminal ganglion, and lacrimal gland. In addition, the mRNA of the promitotic factors in the lacrimal gland, such as Bmp7, Runx1, Runx3, Fgf10, and Smad1, was compared. Results: Sensory denervation induced corneal hyperalgesia (p=0.001). Sensory denervation and autonomic denervation increased the mRNA of proinflammatory cytokines in the cornea and lacrimal gland (p<0.05), but only sensory denervation increased the mRNA levels of Il-1β and Tnf in the trigeminal ganglion (p<0.05) compared with the control naïve. Conclusions: Autonomic denervation and sensory denervation models can have common features, such as inflammation of different parts of the lacrimal functional unit. However, hyperesthesia and inflammatory markers in the trigeminal ganglion because of sensory denervation and the expression of regenerative mediators in the lacrimal gland owing to autonomic denervation are the distinguishing features of these diseases that can be explored in future studies assessing dry eye syndrome secondary to neural damage of the lacrimal functional unit.

RESUMO Objetivo: O nosso objetivo neste estudo foi comparar as alterações na unidade funcional lacrimal em dois modelos de síndrome do olho seco neurogênica: desnervação sensorial da córnea versus desnervação autonômica da glândula lacrimal. Métodos: A rede neural é um importante suporte para a unidade funcional lacrimal. Pode ser dividido em vias aferentes (sensoriais) e eferentes (autonômicas), sujeitas a doenças graves que comprometem a unidade funcional lacrimal. Ratos Wistar machos, com 8 semanas de idade, foram divididos em três grupos: 1) Controle naïve (n=16 animais); 2) Desnervação autonômica: onde os ratos foram submetidos à ablação do nervo da glândula lacrimal direita e avaliados após um e dois meses (1 M a 2 M) do procedimento (n=7 animais por subgrupo, desnervação autonômica 1M e desnervação autonômica 2M, respectivamente); 3) Desnervação sensorial induzida por colírio a 0,2% de cloreto de benzalcônio, duas vezes ao dia por 7 dias no olho direito (n=10 animais). A sensibilidade da córnea foi medida pelo teste de movimento pata-olho com capsaicina (10 µM). A PCR quantitativa em tempo real foi aplicada para comparar a expressão relativa de mRNA de citocinas pró-inflamatórias: Il1b, Il6, Tnf, Mmp9, na córnea, gânglio trigêmio e glândula lacrimal. O mRNA dos agentes pró-mitóticos Bmp7, Runx1, Runx3, Fgf10 e Smad1 foram comparados na glândula lacrimal. Resultados: A desnervação sensorial induziu hiperalgesia da córnea (p=0,001). Desnervação sensorial e desnervação autonômica aumentaram o mRNA de citocinas pró-inflamatórias no córnea e glândula lacrimal (p<0,05), mas apenas desnervação sensorial aumentou o mRNA de Il1b e Tnf no gânglio trigêmio (p<0,05) quando comparado ao controle naïve. Conclusões: Os modelos de desnervação autonômica e desnervação sensorial podem ter características comuns, como inflamação de diferentes partes da unidade funcional lacrimal. No entanto, a hiperestesia e os marcadores inflamatórios no gânglio trigêmio de desnervação sensorial e a expressão de mediadores regenerativos na glândula lacrimal na desnervação autonômica são características que distinguem essas doenças, podendo ser investigadas em estudos futuros que abordam o olho seco secundário ao dano neural da unidade funcional lacrimal.

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PURPOSE: This study aimed to compare the changes in the lacrimal functional unit in the following two models of neurogenic dry eye syndrome: sensory denervation of the cornea versus autonomic denervation of the lacrimal gland. METHODS: The neural network supports the lacrimal functional unit. It can be divided into afferent (sensory) and efferent (autonomic) pathways and is affected by severe diseases that compromise the lacrimal functional unit. Male Wistar, 8-week-old rats were divided into the following three groups: 1) control naïve (n=16 animals); 2) autonomic denervation: where rats were subjected to right lacrimal gland nerve ablation and evaluated after 1 and 2 months (1M and 2M) after the procedure (n=7 animals per subgroup, autonomic denervation 1M and autonomic denervation 2M, respectively); 3) sensory denervation induced by 0.2% benzalkonium chloride eye drops, twice a day for 7 days in the right eye (n=10 animals). The corneal sensitivity was measured using the eye wipe test with capsaicin (10 µM). The quantitative real-time PCR was performed to compare the mRNA expressions of proinflammatory cytokines, such as Il-1ß, Il-6, Tnf, Mmp9, in the cornea, trigeminal ganglion, and lacrimal gland. In addition, the mRNA of the promitotic factors in the lacrimal gland, such as Bmp7, Runx1, Runx3, Fgf10, and Smad1, was compared. RESULTS: Sensory denervation induced corneal hyperalgesia (p=0.001). Sensory denervation and autonomic denervation increased the mRNA of proinflammatory cytokines in the cornea and lacrimal gland (p<0.05), but only sensory denervation increased the mRNA levels of Il-1ß and Tnf in the trigeminal ganglion (p<0.05) compared with the control naïve. CONCLUSIONS: Autonomic denervation and sensory denervation models can have common features, such as inflammation of different parts of the lacrimal functional unit. However, hyperesthesia and inflammatory markers in the trigeminal ganglion because of sensory denervation and the expression of regenerative mediators in the lacrimal gland owing to autonomic denervation are the distinguishing features of these diseases that can be explored in future studies assessing dry eye syndrome secondary to neural damage of the lacrimal functional unit.

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INTRODUCTION: Capecitabine is an oral anticancer drug which can cause some adverse reactions and the great challenge for its use is to ensure the medication adherence. The aim of this study was to analyze adverse reactions and adherence to capecitabine in patients with gastrointestinal cancer. METHODS: A prospective study was performed in a tertiary teaching hospital in Brazil. Outpatients undergoing capecitabine treatment for colorectal or gastric cancer were followed for three cycles of treatment. Patient demographic and clinical characteristics data were collected. Adverse reactions were analyzed using Common Terminology Criteria for Adverse Events (CTCAE) v.4. Adherence to capecitabine were evaluated using Morisky-Green and MedTake tests. Statistical analysis was conducted using Chi-square, Fisher's exact and McNemer tests. RESULTS: One hundred and four patients were enrolled in this study, with a mean age was 58.5 ± 10.9 years; 51.0% were men and 51.0% Caucasian. Nausea and diarrhea were the most frequently reported adverse reactions (82.7% and 62.5%, respectively), followed by vomiting (54.8%), fatigue (54.8%), and hand-foot syndrome (53.9%). Nausea and diarrhea were also the most severe adverse reactions. Most patients were adherent to capecitabine in all cycles of treatment using the Morisky-Green test. Adherence increased significantly between cycle 1 and cycle 2 by MedTake test (p < 0.001). Some demographic and clinical characteristics were associated with adverse reactions (e.g., age and nausea, gender and nausea and vomiting) and capecitabine adherence (e.g., marital status and educational level) as well as some adverse reactions were associated with capecitabine adherence (hand-foot syndrome and nausea). CONCLUSIONS: Clinical oncology pharmacists must provide patient information on the correct use of capecitabine, manage adverse reactions, and monitor adherence to treatment. Strategies to prevent non-adherence to capecitabine must be adopted to ensure the success of pharmacotherapy.

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ABSTRACT This review is intended to describe the therapeutic approaches for corneal blindness, detailing the steps and elements involved in corneal wound healing. It also presents the limitations of the actual surgical and pharmacological strategies used to restore and maintain corneal transparency in terms of long-term survival and geographic coverage. In addition, we critically review the perspectives of anabolic agents, including vitamin A, hormones, growth factors, and novel promitotic and anti-inflammatory modulators, to assist corneal wound healing. We discuss the studies involving nanotechnology, gene therapy, and tissue reengineering as potential future strategies to work solely or in combination with corneal surgery to prevent or revert corneal blindness.(AU)

RESUMO O presente trabalho traz uma revisão das abordagens terapêuticas para a cegueira da córnea. O estudo detalha as etapas e os elementos envolvidos na cicatrização da córnea. Ele mostra as limitações das estratégias cirúrgicas e farmacológicas usadas para restaurar e manter a transparência da córnea em termos de sobrevida a longo prazo e alcance geográfico. As perspectivas dos agentes anabólicos, incluindo vitamina A, hormônios, fatores de crescimento e novos moduladores pró-mitóticos e anti-inflamatórios para auxiliar a cicatrização da ferida na córnea, são revisadas criticamente. Aqui, apresentamos estudos envolvendo nanotecnologia, terapia gênica e reengenharia de tecidos como possíveis estratégias futuras para atuar de maneira isolada ou combinada com a cirurgia da córnea para prevenir ou reverter a cegueira corneana.(AU)

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Purpose: The aims of this work were a) to describe the histology of the lacrimal gland (LG) and cornea induced by an adenovirus (Ad) vector encoding the human erythropoietin (Epo) gene delivered to the LG and b) to evaluate the therapeutic potential of this strategy to prevent benzalkonium chloride (BAK) corneal toxicity.Methods: Structure and function of male Wistar rats LG were compared in the groups: 1) naïve control and 2) Ad-hEpo in the right LG (RLG). The protective response against BAK eye drops was compared among the groups 1) naïve control, 2) BAK in the right eye, 3) Ad-hEpo RLG + BAK and 4) Ad-hEpo in the right salivary gland (RSG)+BAK. Ad-hEpo groups received an injection of AdLTR2EF1a-hEPO (25 ul, 1010 particles/ml) in the right LG or SG (positive control). The BAK groups received 0.2% BAK in the right cornea twice a day. The tests applied after 7 days, included tear secretion, hEPO mRNA detection by qRT-PCR, LG and cornea histology, LG ELISA for cytokines and hematocrit.Results: hEPO mRNA was present in the Ad-hEpo RLG and RSG, but not kidney or liver samples (negative controls). TNF-α and IL-1ß increased in the LG exposed to Ad-hEpo compared to naïve control (p = .0115 and p = .0397, respectively). BAK reduced tear secretion, but this reduction was prevented by Ad-hEpo RLG+BAK and Ad-hEpo RSG+BAK (p = .017). The corneal epithelia were thinner in the BAK-treated groups independent of Ad-hEpo (p = .0009). Hematocrit increased only in the Ad-hEpo RSG group (p = .01).Conclusions: Ad-hEpo infection of rat LG and SG induces local, but only the SG infection induced systemic changes in rats. Importantly, Ad-hEpo attenuated the BAK-mediated toxic reduction in tear flow. Future studies must consider viral vector tissue tropism, biodistribution and effective therapeutic gene products for ocular surface diseases.

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This review is intended to describe the therapeutic approaches for corneal blindness, detailing the steps and elements involved in corneal wound healing. It also presents the limitations of the actual surgical and pharmacological strategies used to restore and maintain corneal transparency in terms of long-term survival and geographic coverage. In addition, we critically review the perspectives of anabolic agents, including vitamin A, hormones, growth factors, and novel promitotic and anti-inflammatory modulators, to assist corneal wound healing. We discuss the studies involving nanotechnology, gene therapy, and tissue reengineering as potential future strategies to work solely or in combination with corneal surgery to prevent or revert corneal blindness.

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The burden of corneal blindness and visual deficiency can be felt worldwide. Its association with several endemic diseases such as childhood blindness, trauma, infectious keratitis (including variants caused by herpes, hanseniasis, and fungi), vitamin A deficiency, diabetes mellitus, and other dry eye syndromes reflects its poorly understood underlying mechanisms and suggests that the actual frequency of the disease is underestimated. The low effectiveness of preventive and therapeutic strategies against corneal scarring or deformity predicts a high frequency of patients with corneal blindness in the future. Corneal blindness is associated with environmental factors and socioeconomic limitations that restrain health assistance and maintain a modest efficiency of the current therapeutic strategies for resolving corneal diseases in large-scale programs. We present here a critical review of the concepts associated with corneal blindness that need to be considered when planning strategies to prevent and treat corneal blindness worldwide (to be able to leave Plato's cave, where corneal blindness is encaged.

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Rationale: Frailty in chronic obstructive pulmonary disease (COPD) patients has been associated with a higher rate of incidents, longer duration of hospitalization, poorer quality of life, and higher mortality. Objective: To measure the prevalence of frailty among COPD patients and to evaluate associated variables. Methods: A cross-sectional study. Subjects who visited a State Center for High-Cost Medicines to obtain free monthly COPD medicines were considered eligible. Individuals ≥40 years old who had a FEV1/FVC ratio of <0.7 post-bronchodilation were enrolled. The Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight (FRAIL) scale, Medical Research Council dyspnea scale (MRC), COPD Assessment Test (CAT), a combination of CAT/MRC [(CAT/8)+MRC], and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity scale were used to evaluate the enrolled subjects. Variables associated with frailty were analyzed using an ordered logistic regression and a multivariate logistic regression. Results: The prevalence of frailty and pre-frailty among the 153 COPD subjects enrolled was 50.3% (77/153) and 35.3% (54/153), respectively. Frailty scores were correlated with CAT (correlation coefficient [cc]: 0.52, p <0.001) and MRC (cc: 0.48, p <0.001). Ordinal regression models showed that MRC and CAT were associated with fragility (p <0.0001 for both models). Higher odds of frailty were observed in GOLD groups B (p = 0.04) and D (p = 0.02). Multiple logistic regression revealed that the combination CAT/MRC≥5.5 was associated with frailty (OR 6.73; p <0.0001) and had a specificity of 80.3%, sensitivity of 62.3%, and positive and negative predictive values of 76.2% and67.8%, respectively. Conclusion: Frailty prevalence was high and was correlated with higher MRC and CAT scores. The CAT/MRC combination [(CAT/8)+MRC] ≥5.5 was highly associated with frailty, suggesting that an additional specific evaluation for the presence of frailty is indicated.

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Management and prevention of problems related to oncology drugs are particularly important due to the excessive cost, high toxicity, and narrow therapeutic index of the antineoplastic drugs, in addition to the patients' state of health. Therefore, the presence of the pharmacist as a member of the multidisciplinary team is essential to contribute to patient safety. In this work, the interventions performed were identified, quantified, and classified to characterize the work of the clinical oncology pharmacist. This is a prospective and quantitative study, conducted over a period of six months in the outpatient oncology and chemotherapy clinic of the University Hospital of the University of Campinas, Brazil. A total of 3526 medical prescriptions were evaluated for the 780 patients seen and, among these prescriptions, 220 (6.24%) contained errors, representing 6.24% of the total number. The most common error was dose-related with 79 (22.83%) cases of overdosing. Wrong-patient medication error was the least reported (0.29%). Thirty drugs were involved in the pharmaceutical interventions, Carboplatin and Ondansetron being the most frequent. Thirteen types of potential errors were evaluated according to the method proposed by Cardinal and Fernandes. Two (15.38%) included interventions of indication, contraindication, and therapeutic efficacy of a drug. Five of them (38.46%) are related to the treatment regimen, and two (15.38%) were related to prevention of potential adverse events. Four interventions (30.77%) concerned technical interventions in injectable drugs such as dilution, compatibility, and administration time. Of the 346 interventions performed, 1 (0.29%) was classified as potentially lethal, 114 as serious (32.95%), 140 as significant (40.46%), and 91 as minor (26.30%).

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Purpose: The aims of this study were (1) to determine the efficacy of adenovirus vector serotype 5 (Ad) encoding human soluble VEGF receptor 1 (s-VEGFR1) gene transfer to the lacrimal gland (LG); (2) to investigate whether expression of s-VEGFR1 prevents corneal neovascularization (CNV) induced by alkali burns; and (3) to evaluate the safety of the procedure. Methods: AdVEGFR1 vectors (25 µL, 1 × 1010 pfu/mL) were injected in the right LGs of rats and were compared with AdNull vector (25 µL, 1 × 1010 pfu/mL) or 25 µL of saline (Control) before cornea alkali burns with 1 M NaOH. After 7 days, CNV was documented at the slit lamp. Tear secretion was measured with phenol red threads. The animals were tested for s-VEGFR1 mRNA and protein in the LG by quantitative (q)PCR and immunohistochemistry staining, respectively. qPCR was used to compare the mRNA levels of IL-1ß, IL-6, and TNF-α in the LG and ipsilateral trigeminal ganglion (TG). Results: Ad-VEGFR1 transfected 83% (10/12) of the rats. VEGFR1 was present in LG acinar cells. CNV was prevented in 9 of 12 animals in the Ad-VEGFR1 group, compared with the Ad-Null (3:10) and Control groups (1:10) (P = 0.0317). The tear secretion and cytokine mRNA levels in the LG and TG were similar in all three groups (P > 0.05). Conclusions: Adenoviral vector gene transfer was safe for LG structure and function. The LG as the target tissue showed local expression of human s-VEGFR1, and CNV was prevented in most of the eyes exposed to alkali burns.

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INTRODUÇÃO: A tosse, voluntária ou reflexa, é um dos principais mecanismos de depuração para proteção das vias aéreas. O pico de fluxo de tosse (PFT) é um método de avaliação específica, mas que vem demonstrando utilidade para avaliar riscos de complicação pulmonares bem como sua gravidade. Variável muito semelhante ao pico de fluxo expiratório cuja principal diferença consiste no fechamento da glote durante a manobra de tosse. Então avaliar a tosse é importante para identificar pacientes com alterações no pico de fluxo de tosse, e consequente risco de complicações pulmonares. OBJETIVO: Analisar o PFT voluntário e parâmetros clínicos e epidemiológicos em uma população internada nas enfermarias de um hospital de urgências. MÉTODOS: Estudo transversal com pacientes internados nas enfermarias de um Hospital Público de Goiânia. Foram coletados dados epidemiológicos e clínicos. O PFT foi mensurado pelo peak flow meter e a avaliação de dor através da Escala de Dor Visual Numérica associada à Escala de Dor de Faces. RESULTADOS: A amostra foi composta em sua maioria por homens 288 (81,36). A média de idade da população estudada foi de 45,91 anos (±20,14). Sessenta e um por cento dos pacientes (219) apresentaram tosse eficaz, e 43 (12,15%) tosse ineficaz, revelou associação com idade, sexo e diagnóstico. CONCLUSÃO: Os pacientes que mais apresentaram alterações na força de tosse foram os idosos, sexo feminino e vítimas acometidas por desordens neurológicas e toracoabdominais. [AU]

INTRODUCTION. Cough, whether voluntary or reflex, is one of the major clearance mechanisms for airway protection. Peak cough flow is a recent and specific evaluation method, but it has been useful for evaluating pulmonary complications as well as their severity. Variable very similar to the peak of expiratory flow whose main difference consists in the closure of the glottis during the maneuver of cough. Therefore, assessing cough is important to identify patients with changes in peak cough flow, and the consequent risk of pulmonary complications. OBJECTIVE: To analyze the peak flow of voluntary cough and its association with clinical and epidemiological parameters in a population hospitalized in the wards of an emergency hospital. METHODS: A cross-sectional study with 354 patients admitted to the wards of a Public Hospital of Goiânia. Epidemiological and clinical data were collected. Optic cough flow was measured by the peak flow meter and the pain assessment using the Numerical Visual Pain Scale associated with the Face Pain Scale. RESULTS: The sample consisted mostly of 288 (81,36) men. The mean age of the study population was 45,91 years (± 20,14). 61, 86% (219) of the patients had effective cough, and 43 (12,15%) had an ineffective cough. CONCLUSION: Patients who presented the greatest changes in coughing strength were the elderly, females and victims of neurological and thoracoabdominal disorders. [AU]

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This study describes the effects of a promising therapeutic alternative for non-muscle invasive bladder cancer (NMIBC) based on Bacillus Calmette-Guerin (BCG) intravesical immunotherapy combined with Platelet-rich plasma (PRP) in an animal model. Furthermore, this study describes the possible mechanisms of this therapeutic combination involving Toll-like Receptors (TLRs) 2 and 4 signaling pathways. NMIBC was induced by treating female Fischer 344 rats with N-methyl-N-nitrosourea (MNU). After treatment with MNU, the animals were distributed into four experimental groups: Control (without MNU) group, MNU (cancer) group, MNU + PRP group, MNU + BCG group and MNU + PRP + BCG group. Our results demonstrated that PRP treatment alone or associated with BCG triggered significant cytotoxicity in bladder carcinoma cells (HTB-9). Animals treated with PRP associated to BCG clearly showed better histopathological recovery from the cancer state and decrease of urothelial neoplastic lesions progression in 70% of animals when compared to groups that received the same therapies administered singly. In addition, this therapeutic association led to distinct activation of immune system TLRs 2 and 4-mediated, resulting in increased MyD88, TRIF, IRF3, IFN-γ immunoreactivities. Taken together, the data obtained suggest that interferon signaling pathway activation by PRP treatment in combination with BCG immunotherapy may provide novel therapeutic approaches for non-muscle invasive bladder cancer.

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Since the first description of microRNAs (miRNAs) in the 1990s, more than 60 papers have described the role of miRNAs on the ocular surface and lacrimal gland (LG). MicroRNAs (miRNAs) have a role in several physiological events and in mediation of disease. They inhibit gene expression by blocking messenger RNA. Diseases such as Sjögren syndrome (SS), ocular surface neoplasias, and infections are known to increase or reduce the expression of specific miRNAs. These miRNAs play key roles in modulating inflammation, delaying or enhancing wound healing, cell differentiation metabolism, and survival. This review describes the current understanding of miRNAs as biomarkers, mediators of diseases, and potential therapeutic targets in ocular surface diseases.

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RESUMO

PURPOSE: In the lacrimal gland (LG) acinar cells, signaling regulates the release of secretory vesicles through specific Rab and SNARE exocytotic proteins. In diabetes mellitus (DM), the LGs are dysfunctional. The aim of this work was to determine if secretory apparatus changes were associated with any effects on the secretory vesicles (SV) in diabetic rats as well as the expression levels of constituent Rab and members of the SNARE family, and if insulin supplementation reversed those changes. METHODS: DM was induced in male Wistar rats with an intravenous dose of streptozotocin (60 mg/kg). One of the two diabetic groups was then treated every other day with insulin (1 IU). A third control group was injected with vehicle. After 10 weeks, Western blotting and RT-PCR were used to compared the Rab and SNARE secretory factor levels in the LGs. Transmission electron microscopy evaluated acinar cell SV density and integrity. RESULTS: In the diabetes mellitus group, there were fewer and enlarged SV. The Rab 27b, Rab 3d, and syntaxin-1 protein expression declined in the rats with diabetes mellitus. Insulin treatment restored the SV density and the Rab 27b and syntaxin expression to their control protein levels, whereas the Vamp 2 mRNA expression increased above the control levels. CONCLUSIONS: Diabetes mellitus LG changes were associated with the declines in protein expression levels that were involved in supporting exocytosis and vesicular formation. They were partially reversed by insulin replacement therapy. These findings may help to improve therapeutic management of dry eye in diabetes mellitus.

Assuntos