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Recent studies have shown that cows with subclinical hypocalcemia (SCH) at 4 d in milk (DIM), regardless of their blood Ca concentration before that time point, suffer from an increased early-lactation disease risk and reduced milk yield, whereas cows experiencing a transient reduction in blood Ca that regain normocalcemia by 4 DIM are at a reduced risk of disease and have greater milk yields. With a goal of improving outcomes for dyscalcemic cows with SCH at 4 DIM, our primary objective was to assess the effect of a herd-level oral Ca bolus strategy that delayed supplementation to 24 and 48 h postpartum on productive performance of multiparous Holstein cows. Our secondary objectives were to assess the effects of delayed Ca bolus supplementation on blood Ca concentration, disease incidence within 30 DIM, and pregnancy risk to first service. At calving, multiparous cows on a single commercial dairy farm in Iran were randomly assigned to 1 of 3 treatment groups: (1) control, no Ca bolus administration (CON; n = 95); (2) traditional bolus, one Ca bolus administered immediately following calving and a second Ca bolus administered 24 h after calving (TRD, n = 102); or (3) experimental bolus, one Ca bolus administered 24 h after calving with a second Ca bolus administered 48 h after calving (EXP, n = 99). Blood samples were collected at 0, 24, 48, 72, and 96 h, and 7 d after parturition, with sampling occurring before bolus administration for the TRD (0 and 24 h) and EXP (24 and 48 h) groups. A general linear mixed model was created to analyze the change milk yield over the first 4 monthly tests and serum Ca concentrations over 7 DIM. Given the lack of disease events diagnosed within 30 DIM, no statistical analysis was conducted for this outcome. The effect of treatment group on risk of pregnancy to first service was assessed using Poisson regression. The incidence of dyscalcemia within CON cows was 72%. We found no difference in mean monthly milk yield among treatment groups across the first 4 tests, with an average monthly production of 51.8 ± 8.8 kg/d for CON cows, 52.5 ± 8.7 kg/d for TRD cows, and 51.8 ± 8.7 kg/d for EXP cows. Mean blood Ca concentration also did not differ across 7 DIM among treatment groups and was 2.04 mmol/L [95% confidence interval (CI) = 2.00 to 2.07 mmol/L] for CON cows, 2.06 mmol/L (95% CI = 2.03 to 2.09 mmol/L) for TRD cows, and 2.09 mmol/L (95% CI = 2.05 to 2.12 mmol/L) for EXP cows. The risk of pregnancy to first service was numerically greater for CON than TRD and EXP cows but not statistically different; however, our study was underpowered for this outcome. Under the conditions of our study, our findings suggest that delaying oral Ca bolus supplementation to 24 and 48 h postpartum has no effect on milk production across the first 4 monthly tests.
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Doenças dos Bovinos , Hipocalcemia , Gravidez , Feminino , Bovinos , Animais , Cálcio , Leite , Doenças dos Bovinos/epidemiologia , Período Pós-Parto , Lactação , Cálcio da Dieta , Hipocalcemia/veterinária , ParidadeRESUMO
The general-purpose particle transport code, FLUKA, was used to model the GE Advance Positron Emission Tomography (PET) scanner (GEMS). The required spatial and energy data were extracted using the FLUKA phase-space card, USERDUMP, with its user-routine, mgdraw, consisting of full-events information. Several point and volumetric sources were modeled and the corresponding locations of the sources were identified using three different proposed algorithms which eliminate the use of conventional image-reconstruction packages. Also, having extracted the time information, the time-of-flight approach in PET (TOF-PET) was used to reconstruct the images of several volumetric positron-emitting sources, representing the best results according to the chi-square analysis data. The post-processing calculations, both on CPU and GPU, were undertaken either with MATLAB or Fortran programming.
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Processamento de Imagem Assistida por Computador , Tomografia por Emissão de Pósitrons , Algoritmos , Simulação por Computador , Método de Monte Carlo , Imagens de Fantasmas , Tomografia por Emissão de Pósitrons/métodosRESUMO
INTRODUCTION: Although most asthma is mild to moderate, severe asthma accounts for disproportionate personal and societal costs. Poor co-ordination of care between primary care and specialist settings is recognised as a barrier to achieving optimal outcomes. The Primary Care Severe Asthma Registry and Education (PCSAR-EDU) project aims to address these gaps through the interdisciplinary development and evaluation of both a 'real-world' severe asthma registry and an educational programme for primary care providers. This manuscript describes phase 1 of PCSAR-EDU which involves establishing interdisciplinary consensus on criteria for the: (1) definition of severe asthma; (2) generation of a severe asthma registry and (3) definition of an electronic-medical record data-based Clinician Behaviour Index (CBI). METHODS AND ANALYSIS: In phase 1, a modified e-Delphi activity will be conducted. Delphi panellists (n≥13) will be invited to complete a 30 min online survey on three separate occasions (i.e., three separate e-Delphi 'rounds') over a 3-month period. Expert opinion will be collected via an open-ended survey ('Open' round 1) and 5-point Likert scale and ranking surveys ('Closed' round 2 and 3). A fourth and final Delphi round will occur via synchronous meeting, whereby panellists approve a finalised ideal 'core criteria list', CBI and corresponding item weighting. ETHICS AND DISSEMINATION: Ethical approval has been obtained for the activities involved in phase 1 from the University of Toronto's Human Research Ethics Programme (approval number 39695). Future ethics approvals will depend on information gathered in the proceeding phase; thus, ethical approval for phase 2 and 3 of this study will be sought sequentially. Findings will be disseminated through conference presentations, peer-reviewed publications and knowledge translation tools.
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Asma , Asma/terapia , Consenso , Técnica Delphi , Humanos , Atenção Primária à Saúde , Sistema de RegistrosRESUMO
OBJECTIVE: To facilitate distinction between asthma and chronic obstructive pulmonary disease (COPD) in day-to-day primary care practice, and provide practical treatment strategies using spirometric cases to outline how to recognize the clinical and spirometric overlap between asthma and COPD. SOURCES OF INFORMATION: The approaches described here were developed using evidence-based guidelines and the expertise of the authors, including research findings by the authors in the areas of asthma, COPD management, and spirometric testing in primary care. MAIN MESSAGE: There are patients with clinical or spirometric features of both asthma and COPD. Both asthma and COPD are associated with some degree of inflammation of the respiratory tract, mediated by the increased expression of inflammatory proteins. However, there are clear differences between asthma and COPD in the pattern of inflammation that occurs in the lungs. Diagnostic confusion between COPD and asthma is most likely to arise in older patients with respiratory complaints, particularly against a background that includes cigarette smoke or workplace exposure. Both asthma and COPD are clinical diagnoses based on patient history, symptoms, physical examination findings, and objective measures of lung function. Postbronchodilator spirometry is always needed to confirm a new diagnosis of COPD and should also be performed prebronchodilator for the diagnosis of asthma. However, in many cases, the interpretation of spirometry results is not straightforward. CONCLUSION: Understanding the nature and extent of the spirometric overlap between asthma and COPD is critical for tailoring a therapeutic strategy that is based on factors that include medical and family history, signs and symptoms, and a clear interpretation of spirometry data. This information will be leveraged differently for individual patients to arrive at the correct clinical diagnosis and to select the most appropriate therapy.
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Asma , Doença Pulmonar Obstrutiva Crônica , Idoso , Asma/diagnóstico , Humanos , Pulmão , Atenção Primária à Saúde , Doença Pulmonar Obstrutiva Crônica/diagnóstico , EspirometriaRESUMO
OBJECTIF: Faciliter la distinction entre l'asthme et la maladie pulmonaire obstructive chronique (MPOC) en pratique de première ligne de tous les jours, et fournir des stratégies thérapeutiques pratiques à l'aide de cas de spirométrie pour illustrer comment reconnaître le chevauchement clinique et spirométrique entre l'asthme et la MPOC. SOURCES D'INFORMATION: Les approches décrites ici s'appuient sur les lignes directrices factuelles et sur l'expertise des auteurs, y compris des observations de recherches menées par les auteurs dans les domaines de l'asthme, de la prise en charge de la MPOC et des examens de spirométrie en première ligne. MESSAGE PRINCIPAL: Certains patients présentent des caractéristiques cliniques communes à l'asthme et à la MPOC. Ces deux maladies sont associées à un certain degré d'inflammation des voies respiratoires, médiée par l'expression accrue de protéines inflammatoires. Il existe toutefois des différences évidentes entre l'asthme et la MPOC pour ce qui est de l'inflammation présente dans les poumons. La confusion diagnostique entre la MPOC et l'asthme survient le plus souvent chez les patients âgés qui se plaignent de symptômes respiratoires, surtout en contexte de tabagisme ou d'exposition professionnelle. Les diagnostics cliniques d'asthme et de MPOC sont fondés sur les antécédents du patient, les symptômes, l'examen physique et les mesures objectives de la fonction respiratoire. La spirométrie après bronchodilatation est toujours nécessaire pour confirmer un nouveau diagnostic de MPOC et elle doit également être réalisée avant la bronchodilatation pour poser un diagnostic d'asthme. Dans de nombreux cas, toutefois, il n'est pas évident d'interpréter les résultats de la spirométrie. CONCLUSION: Il est essentiel de bien comprendre la nature et la portée du chevauchement spirométrique entre l'asthme et la MPOC afin de concevoir une stratégie thérapeutique qui s'appuie sur des facteurs qui incluent les antécédents médicaux et familiaux, les signes et les symptômes, et l'interprétation claire des données de spirométrie. Cette information sera utilisée différemment auprès de chaque patient pour arriver au bon diagnostic clinique et sélectionner le traitement le plus approprié.
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Acetoacetate (AA) is a ketone body, which generates reactive oxygen species (ROS). ROS production is impacted by the formation of covalent bonds between amino groups of biomacromolecules and reducing sugars (glycation). Glycation can damage DNA by causing strand breaks, mutations, and changes in gene expression. DNA damage could contribute to the pathogenesis of various diseases, including neurological disorders, complications of diabetes, and aging. Here we studied the enhancement of glucose-mediated DNA glycation by AA for the first time. The effect of AA on the structural changes, Amadori and advanced glycation end products (AGEs) formation of DNA incubated with glucose for 4 weeks were investigated using various techniques. These included UV-Vis, circular dichroism (CD) and fluorescence spectroscopy, and agarose gel electrophoresis. The results of UV-Vis and fluorescence spectroscopy confirmed that AA increased the DNA-AGE formation. The NBT test showed that AA also increased Amadori product formation of glycated DNA. Based on the CD and agarose gel electrophoresis results, the structural changes of glycated DNA was increased in the presence of AA. The chemiluminescence results indicated that AA increased ROS formation. Thus AA has an activator role in DNA glycation, which could enhance the adverse effects of glycation under high glucose conditions.
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Our initial hypothesis was that the exogenous supply of nucleotides to neonatal calves would improve the development and functionality of gastrointestinal tissue, thereby enhancing their capacity to efficiently digest and utilize the nutrients in high-solids milk. Twenty 3-d-old male Holstein calves (37.9 ± 2.24 kg of body weight) were distributed randomly to 1 of 2 treatments (1 calf per pen; 10 pens per treatment) without or with added nucleotides to their daily milk. Dry milk powder was added to pasteurized milk and offered as 4 L/d from d 3 to 15, 6 L/d from d 16 to 49 (at 0900 and 1600 h), and 2 L/d in morning feeding from d 50 to 55. High-solids milk (fat = 4.47%, protein = 4.64%, lactose = 8.13%, and total solids = 17.7%) was made through the addition of milk powder into whole milk and supplemented without or with 2 g/d of a commercially available nucleotide product, and then fed until weaning. Nucleotide supplementation had no effect on preweaning growth rate, but tended to increase postweaning daily weight gain (d 56-75). Unexpectedly, nucleotide supplementation tended to increase fecal score within the 10 d of calf life; thereafter (until weaning), no difference was detected in fecal consistency. Nucleotide supplementation tended to increase and increased pre- and postweaning dry matter intake, respectively. Efficiency of feed utilization (kilogram of weight gain per kilogram of dry matter intake) was not influenced with treatment. The net gain (d 1-70) of withers height and hip height tended to be greater in nucleotide-fed calves. Overall, addition of nucleotides to the high-solids milk had marginal effects on preweaning performance and tended to increase fecal scores (looser feces) in the initial phase of life; however, it increased starter feed intake and growth rate after weaning. A longer-feeding experiment is recommended to elucidate the potential effects of nucleotide supplementation in high-solids milk on calf performance.
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Suplementos Nutricionais , Leite , Nucleotídeos/farmacologia , Ração Animal/análise , Animais , Peso Corporal , Bovinos , Dieta/veterinária , Fezes , Masculino , Nutrientes/metabolismo , Desmame , Aumento de PesoRESUMO
The current study evaluated the effects of step-down weaning implementation time on starter feed intake, growth performance, blood metabolites, and ruminal pH in dairy calves. A total of 48 Holstein dairy calves (24 male and 24 female; 3 ± 1 d old; 41.2 ± 1.8 kg of body weight) were assigned (n = 12 per treatment; 6 male and 6 female) to 4 experimental treatments in a completely randomized block design. All calves were fed 6 L/d of milk from d 3 to 10 of age, and the treatments consisted of the following: calves were offered 8 L/d of milk from d 11 to 28 of age and then 4 L/d from d 29 to 63 (Step-28; total milk offered = 326 L); calves were offered 8 L/d of milk from d 11 to 42 of age and then 4 L/d from d 43 to 63 (Step-42; total milk offered = 382 L); calves were offered 8 L/d of milk from d 11 to 56 of age and 4 L/d from d 57 to 63 (Step-56; total milk intake = 438 L); and calves were fed 8 L/d of milk from d 11 to 63 of age and abruptly weaned (control; total milk offered = 466 L). All calves were housed individually in pens and had ad libitum access to water and solid feed throughout the experiment. All calves were completely milk weaned on d 64, and their performance was measured until d 80 of age. During the experiment, the starter intake (kg/d and % of body weight) was greater in calves in the Step-28 group compared with those in the other groups. However, the total metabolizable energy intake was greater in the Step-56 calves compared with the other calves. Overall, the average daily gain (ADG), feed efficiency (ADG/dry matter intake), and ADG/total metabolizable energy intake were similar across the treatments. Circulating glucose, ß-hydroxybutyrate, blood urea nitrogen, albumin, total protein, alanine aminotransferase, and aspartate aminotransferase, as well as ruminal pH, were not affected by the treatments. The implementation of step-down weaning in early life (4-6 wk of age) could stimulate solid feed intake compared with weaning at a later age with no negative effect on performance.
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Ração Animal/análise , Bovinos/crescimento & desenvolvimento , Ingestão de Alimentos , Ingestão de Energia , Leite/metabolismo , Fatores Etários , Animais , Animais Recém-Nascidos , Peso Corporal , Bovinos/sangue , Bovinos/fisiologia , Dieta/veterinária , Feminino , Fermentação , Masculino , Rúmen/metabolismo , DesmameRESUMO
BACKGROUND CONTEXT: Chronic Suppurative Otitis Media (CSOM) is a common cause of hearing impairment and disability. CSOM caused by Pseudomonas aeruginosa is usually treated with topical ciprofloxacin and resistance to ciprofloxacin in CSOM isolates has rarely been reported. CASE PRESENTATION: A 24-year-old male patient with CSOM due to p. aeruginosa was reported. CSOM was prolonged for ten years and physician prescribed topical ciprofloxacin drops, pus suctioning and ear pH alteration. The treatment wasn't effective and the patient came back to the clinic with relapse of suppurative otitis media. P. aeruginosa was isolated as the cause of CSOM and the isolate was resistant to ciprofloxacin, aztreonam, imipenem, gentamicin, doripenem, cefepime, levofloxacin, amikacin and susceptible to colistin and ceftazidime. There were two mutations in gyrA and eight mutations were observed in nfxB genes. Finally, tympanomastoidectomy was done. CONCLUSION: Usually topical antibiotics, especially ciprofloxacin, is effective against ear infections but our case was different and the P. aeruginosa isolated from CSOM was resistant to most of the antibiotics. One reason for CSOM recurrence might be surgery failure. The routine and primary treatment for CSOM did not seem sufficient and tympanomastoidectomy is suggested to be the best treatment approach for these patients.
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Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Otite Média Supurativa/diagnóstico , Infecções por Pseudomonas/diagnóstico , Adulto , Doença Crônica , Ciprofloxacina/farmacologia , Genes MDR , Humanos , Masculino , Mastoidectomia , Testes de Sensibilidade Microbiana , Mutação , Otite Média Supurativa/tratamento farmacológico , Otite Média Supurativa/cirurgia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/cirurgia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Recidiva , Adulto JovemRESUMO
Introduction The Crisis at Christmas Dental Service (CCDS) provides dental treatment for homeless and vulnerably housed people each year during the Christmas period. In 2017, Den-Tech piloted a same-day field-laboratory denture service alongside CCDS to provide new dentures, additions and repairs for people experiencing social exclusion who have limited access to dental care.Objectives To evaluate the service in terms of: (i) treatment need for denture service; (ii) patient-reported feedback; (iii) clinician-reported feedback; and (iv) learning outcomes from the pilot denture service.Methods Clinicians recorded their dental activity on a standard pro forma and records of the dentures were maintained by the Den-Tech volunteer laboratory technicians. Patient feedback was collected on standardised feedback forms at the dental reception and volunteer feedback was collected via an online survey. The team undertook a quality improvement evaluation using the Plan-Do-Study-Act methodology.Results During the seven-day treatment period in 2017, 24 dentures were produced by the Den-Tech technicians, and in 2018, 31 dentures were created for people experiencing homelessness. In 2017, feedback was collected from 353 patients who attended the service: 99.4% were satisfied with their treatment and 98.3% would have recommended the service to others. Similarly, high levels of positive feedback were received in 2018. Of the dental volunteers who responded, 97.8% of volunteers felt that the denture service benefitted the patients.Conclusions The Den-Tech denture service was well-received by patients and volunteers alike. For the first time at Crisis at Christmas, patients were able to have dental extractions and immediate replacement of these teeth without compromising their dignity and overall appearance.Learning outcomes A quality improvement project utilising real-time volunteer and patient feedback can be a useful tool in reflecting upon the challenges and successes of a service as well as supporting its continual development.
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Instituições de Caridade , Pessoas Mal Alojadas , Assistência Odontológica , Prótese Total , Dentaduras , Humanos , VoluntáriosRESUMO
Environmental contamination with heavy metals is of concern as plants have the ability to absorb chemical toxicants facilitating the entry of toxic metals into the food chain. Lettuce (Lactuca sativa Linn.) was cultured in four nutrient solutions containing different concentrations of cadmium (0, 3, 6, and 9â¯mmol). The impact of heavy metal on the morphological features, antioxidant properties and antioxidant enzymes activity were investigated with primary focus on superoxide dismutase, ascorbate peroxidase, peroxidase and catalase enzymes. In silico methods were utilized in the study of the genes of these enzymes. Significant changes were observed in the morphological features of the plant with plants appearing stunted, more spherical and yellow in colour. A decrease in the dry mass of the plant was also detected. The Translocation factor (TF) for cadmium was significantly high in lettuce. Enhanced antioxidant enzymatic activity suggests that these enzymes are integrally involved in the defense mechanism of the plant to heavy metal stress. Also observed was an increase in total soluble protein, and total phenolic content. Total flavonoid content was not significantly affected. Fourteen genes encoding for ascorbate peroxidase and nineteen genes for superoxide dismutase were identified in lettuce. These enzymes varied from each other with regards to the number of exons and amino acids present, as well as their location within the cell. Plants exhibit various response mechanisms to combat heavy metal contamination.
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Estresse Oxidativo , Antioxidantes , Ascorbato Peroxidases , Cádmio , Catalase , Lactuca , Superóxido DismutaseRESUMO
Crops can become contaminated when grown in soils containing heavy metals. Cadmium is a heavy metal that poses a significant health risk to humans. The purpose of this study was to evaluate the effect of cadmium on lettuce (Lactuca sativa Linn) and the contamination risk of lettuce grown in cadmium environments. The results showed that photosynthesis and growth parameters were significantly affected by cadmium. Lettuce has the ability to absorb large amounts of cadmium from the contaminated environment and so is a cadmium hyperaccumulator plant. The study showed that approximately 35% of the total absorbed cadmium is transmitted to aerial and edible parts of lettuce. This study was undertaken as lettuce has the ability to absorb and accumulate high levels of cadmium. There are however are no reports on the PCS gene and the potential for high cadmium accumulation in lettuce. The bioinformatics study revealed that lettuce has two phytochelatin synthase genes that produce 6 PCSs through splicing leading to the ability of lettuce to store high levels of cadmium. These six sequences although different in length have high similarity. Sequence structure, cellular location, three-dimensional structure, phylogeny and a comparison of their catalytic power were evaluated. The high accumulation of cadmium in lettuce and the presence of several PCSs contribute to the accumulation of cadmium in aerial tissues. The cultivation of lettuce in contaminated environments led us to evaluate suspected farms for the presence of cadmium in produce. Lettuce grown in industrial environments contaminated with cadmium can pose a serious threat to human health.
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Aminoaciltransferases/genética , Cádmio/toxicidade , Lactuca/efeitos dos fármacos , Poluentes do Solo/toxicidade , Solo/química , Cádmio/análise , Cádmio/metabolismo , Produtos Agrícolas/efeitos dos fármacos , Produtos Agrícolas/enzimologia , Lactuca/enzimologia , Fotossíntese/efeitos dos fármacos , Poluentes do Solo/análise , Poluentes do Solo/metabolismo , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: During the clinical development of a fixed-dose combination of drugs, it is best practice to conduct dose-finding studies to determine the optimal dose of each component. The aims of this phase II dose-finding study were to confirm the lung function benefit of adding olodaterol to tiotropium, describe the dose-response relationship of olodaterol in combination with tiotropium 5 µg, and compare it with the dose response of olodaterol monotherapy. METHODS: In this double-blind, parallel-group trial, patients were randomized to receive either tiotropium 5 µg or a fixed-dose combination of tiotropium 5 µg with olodaterol 2 µg, 5 µg, or 10 µg, delivered once daily via the Respimat® for 4 weeks (NCT00696020). Patients had a diagnosis of chronic obstructive pulmonary disease and post-bronchodilator forced expiratory volume in 1 s (FEV1) ≥ 30 and < 80% of predicted normal. The primary endpoint was trough FEV1 response (change from baseline) after 4 weeks. Secondary endpoints included FEV1 and forced vital capacity (FVC) over 6 h after dosing. RESULTS: Compared with tiotropium 5 µg, mean (standard error) trough FEV1 increased with the addition of olodaterol 2 µg by 0.024 L (0.027), olodaterol 5 µg by 0.033 L (0.027), and olodaterol 10 µg by 0.057 L (0.027). Statistically significant improvements in FEV1 versus tiotropium were seen across all timepoints up to 6 h with all doses of tiotropium/olodaterol. Similar results were observed for FVC. CONCLUSION: There was a benefit of tiotropium/olodaterol compared with tiotropium monotherapy in FEV1 and FVC. There was a dose-response relationship for olodaterol on top of tiotropium for FEV1 and FVC similar to the dose response previously seen for olodaterol monotherapy. These results, together with the results of a study investigating the dose response of tiotropium on top of olodaterol, helped to inform the dose selection for the phase III studies. FUNDING: Boehringer Ingelheim International GmbH.
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Benzoxazinas , Relação Dose-Resposta a Droga , Doença Pulmonar Obstrutiva Crônica , Brometo de Tiotrópio , Idoso , Benzoxazinas/administração & dosagem , Benzoxazinas/efeitos adversos , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Monitoramento de Medicamentos , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Testes de Função Respiratória/métodos , Brometo de Tiotrópio/administração & dosagem , Brometo de Tiotrópio/efeitos adversos , Resultado do TratamentoRESUMO
Inhaled fixed-dose combinations (FDCs) of a long-acting ß-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) have become the cornerstone for the maintenance treatment of symptomatic COPD patients. In this regard, global COPD treatment guidelines have recognized the importance of inhaler devices as integral contributors to the effectiveness of LABA/LAMA FDCs and recommend regular assessment of inhaler device use by the patients in order to improve long-term clinical outcomes. Optimal disease control is also highly dependent upon patient preferences and adherence to inhaler devices. This review objectively examines and compares the major inhaler devices used to deliver different LABA/LAMA FDCs, discusses the inhaler device characteristics that determine drug deposition in the airways, real-life preference for inhaler devices, and handling of inhaler devices that impact the results of the long-term management of COPD. The introduction of new LABA/LAMA FDCs, new inhaler devices, and more clinical studies have created confusion among physicians in choosing the optimal inhaled therapy for COPD patients; in this context, this review attempts to provide an evidence-based framework for informed decision-making with a particular focus on the inhaler devices.Funding. The preparation of this manuscript was funded by Novartis Pharma AG.
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COPD causes considerable health and economic burden worldwide, with incidence of the disease expected to continue to rise. Inhaled bronchodilators, such as long-acting muscarinic antagonists (LAMAs) and long-acting ß2-agonists (LABAs), are central to the maintenance treatment of patients with COPD. Clinical studies have demonstrated that combined LAMA + LABA therapies improve efficacy while retaining a safety profile similar to LAMA or LABA alone. This has led to the development of several LAMA/LABA fixed-dose combination (FDC) therapies, which provide patients with the convenience of two active compounds in a single inhaler. GFF MDI (Bevespi Aerosphere®) is an FDC of glycopyrrolate/formoterol fumarate 18/9.6 µg formulated using innovative co-suspension delivery technology for administration via metered dose inhaler (MDI). GFF MDI was developed to make a treatment option available for patients who have a requirement or preference to use an MDI, rather than a dry powder or soft mist inhaler. Now that several LAMA/LABA FDCs have been approved for use in COPD, we review the impact of dual-bronchodilator treatment on COPD therapy and discuss recent clinical studies that are helping to develop a more comprehensive understanding of how LAMA/LABA FDCs can improve patient outcomes.
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Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Broncodilatadores/uso terapêutico , Fumarato de Formoterol/uso terapêutico , Glicopirrolato/uso terapêutico , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/química , Broncodilatadores/química , Combinação de Medicamentos , Composição de Medicamentos/métodos , Fumarato de Formoterol/química , Glicopirrolato/química , Humanos , Antagonistas Muscarínicos/química , Resultado do TratamentoRESUMO
Surface coated magnetite nanoparticles (Fe3O4 NPs) with 3-mercaptopropionic acid were immobilized on amidoximated polyacrilonitrile (APAN) nanofibers using electrospinning followed by crosslinking. The prepared composite nanofibers were characterized with Scanning Electron Microscopy (SEM), and Fourier Transform Infrared analysis (FTIR). The composite nanofiber was evaluated for the removal of indigo carmine dye from aqueous solutions. The effects of contact time, initial dye concentration, solution pH and adsorption equilibrium isotherms were studied. The adsorption of indigo carmine was found to be greatly affected by solution pH. The maximum loading capacity was determined to be 154.5 mg g-1 at pH = 5. The experimental kinetic data were fitted well using a pseudo-first order model. The adsorption isotherm studies showed that the adsorption of indigo carmine fits well with the Langmuir model. The reuse of the composite nanofiber was also investigated in which more than 90% of indigo carmine was recovered in 5 min. The results of stability studies showed that the adsorption efficiency can remain almost constant (90%) after five consecutive adsorption/desorption cycles.
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Glioblastoma multiforme (GBM) is a high grade glial tumor, primarily located in cerebral hemispheres. The most common clinical presentations are slowly progressive neurological deficit such as motor weakness, seizure, and headaches that last less than three months. Calvarium and extra-axial invasion are very rare and generally occur after a brain biopsy or surgery, or secondary to radiotherapy of primary intra-axial glial tumors. We report a case of GBM with calvarium involvement in a 60-year-old man who presented with a frontal bump and left-sided clumsiness. Imaging studies revealed a tumoral lesion that destroyed the frontal bone with white matter involvement of the frontal lobe and extension into the corpus callosum. Histopathological examination of intra-axial and extra-axial lesions revealed pleomorphic high-grade tumor with large areas of necrosis and hemorrhage. Immunohistochemical (IHC) studies confirmed GBM that spread directly into the dura, galea, and calvarium (positive reaction for GFAP, S-100, CD68, OLIG2, and p53). The patient was treated with radiotherapy (60Gy/30 fractions) and concomitant temozolomide. Unfortunately, the patient died seven months after the initial diagnosis.
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Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Neoplasias Cranianas/terapia , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/cirurgia , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Crânio/diagnóstico por imagem , Crânio/cirurgia , Neoplasias Cranianas/diagnóstico por imagem , Neoplasias Cranianas/secundário , TemozolomidaRESUMO
This analysis provides a comprehensive clinical assessment of the long-term safety of the licensed dose of olodaterol (5 µg once daily [QD] via Respimat® inhaler) in patients with chronic obstructive pulmonary disease by exploring the occurrence of acknowledged side effects of long-acting ß2-agonists as well as those included in the olodaterol and formoterol labels. We analysed pooled data from two replicate, double-blind studies of olodaterol (5 µg QD via Respimat®) compared to formoterol (12 µg twice daily [BID]) or placebo over 48 weeks (1222.13, NCT00793624; 1222.14, NCT00796653). Patients could continue their background treatment. The analysis considered adverse events (AEs) typically associated with ß2-agonists, including cardiovascular events, as well as administration-related events. Descriptive statistics were provided for the incidence of AEs and aggregated AEs. The analysis included 1379 patients: 460 placebo, 459 olodaterol and 460 formoterol; AEs were reported by 70.9, 71.7 and 69.1% of patients, respectively. Exposure-adjusted incidence rates of cardiac AEs (arrhythmia and myocardial ischaemia) and cough were numerically lower in the olodaterol group than the formoterol group, while nasopharyngitis, throat irritation, metabolism and psychiatric disorders were numerically higher in the olodaterol group. The most frequent event in the olodaterol group was nasopharyngitis (placebo 8.0%; olodaterol 12.9%; formoterol 10.0%). Except for cough (incidence rate ratio of 0.46 [95% confidence interval 0.24, 0.89] in favour of olodaterol), there were no significant differences between active groups. In conclusion, olodaterol 5 µg QD was well tolerated over 48 weeks with a typical ß2-agonist safety profile comparable to formoterol 12 µg BID.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Benzoxazinas/uso terapêutico , Broncodilatadores/uso terapêutico , Fumarato de Formoterol/uso terapêutico , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Benzoxazinas/administração & dosagem , Benzoxazinas/efeitos adversos , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Preparações de Ação Retardada , Método Duplo-Cego , Feminino , Fumarato de Formoterol/administração & dosagem , Fumarato de Formoterol/efeitos adversos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disease in reproductive age women. The present study aimed to determine the effects of Dietary Approaches to Stop Hypertension (DASH) diet on reproductive hormones, plasma total antioxidant status and anthropometric indices in overweight and obese PCOS women. METHODS: In this randomised controlled clinical trial, 60 women with PCOS were randomly assigned to one of two diets with energy restriction: the DASH diet and a control diet. The DASH and control diets consisted of 50-55% carbohydrate, 15-20% protein and 25-30% total fat. The DASH diet was designed to be rich in vegetables, fruits, whole grains and low-fat dairy products, as well as low in saturated fats, cholesterol, refined grains and sweets. In the present study, the anthropometric indices, body composition, total testosterone, androstenedione, sex hormone binding globulin (SHBG), free androgen index and 2,2'-diphenyl-1-picryylhydrazyl (DPPH) scavenging activity were measured before and after 3 months. RESULTS: The consumption of DASH diet compared to the control diet was associated with a significant reduction in weight [-5.78 (1.91) kg versus -4.34 (2.87) kg, P = 0.032], body mass index (BMI) [-2.29 (0.15) kg m-2 versus -1.69 (0.20) kg m-2 , P = 0.02], fat mass [-3.23(1.66) kg versus -2.13 (1.26) kg, P = 0.008] and serum androstenedione [-1.75 (1.39) ng mL-1 versus -1.02 (0.72) ng mL-1 , P-value = 0.019]. Increased concentrations of SHBG [28.80 (21.71) versus 11.66(18.82) nmol L-1 , P = 0.003) and DPPH scavenging activity [30.23% (19.09) versus 12.97% (25.12) were also found in the DASH group. CONCLUSIONS: The DASH diet could improve weight loss, BMI and fat mass. Furthermore, it could result in a significant reduction in serum androstenedione and a significant increase in antioxidant status and SHBG.
Assuntos
Androgênios/sangue , Composição Corporal , Abordagens Dietéticas para Conter a Hipertensão , Obesidade/sangue , Sobrepeso/sangue , Síndrome do Ovário Policístico/sangue , Adulto , Androstenodiona/sangue , Antioxidantes/metabolismo , Biomarcadores/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Obesidade/complicações , Sobrepeso/complicações , Síndrome do Ovário Policístico/complicações , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/sangue , Redução de Peso , Adulto JovemRESUMO
INTRODUCTION: Many items are needed for dressing including sterile dressing set, antiseptic and washing solutions, leucoplast tape, waste bin for infectious garbage, waste bin for noninfectious garbage, safe disposal trash for sharp cutting instruments, bedpan and sometimes drugs. All the items are laid out on a simple wheeled trolley. The multiplicity of items together with problems in placing tools on trolley, forgetting some items, disturbing sterile condition, falling and damaging equipment and the need for at least two people for each procedure, all are the reasons to design and develop Automatic Trolley for Washing and Dressing the Wounds. MATERIAL AND METHOD: To develop a mobile unit which meets our needs for dressing, the trolley patents registered in America and different companies were evaluated as well as the materials and methods used while dressing were considered. RESULTS: Automatic Trolley for Washing and Dressing the Wounds was designed and developed. It comprises the followings: drawer, waste bin for infectious garbage, waste bin for noninfectious garbage, shelves for serum and betadine solution, serum stand, peristaltic pump, flexible tube for connecting serum, a place for bedpan, foot pedal for serum flow, two eye-sensor chambers for solution betadine and scrub, an auxiliary work surface. CONCLUSION: Due to the usual requirements for dressing, we have designed an equipped mobile unit which covers all the objectives of dressing and increases the speed of procedure. Moreover, due to the contrived equipment on the trolley, procedures are done quickly and second person is not required to assist. Automatic Trolley for Washing and Dressing the Wounds is made up of stainless steel which could be mass housing and commercializing which would play a deserving role in improving the fundamentals of health care and wound treatment.