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Summary: Background. Food allergy can range from mild to severe, life-threatening reactions with various symptoms and organ involvement. The impact of asthma on severe food-induced allergic reactions is not completely understood. In the hypothesis that asthma increases the risk of severe food-induced allergic reactions, the aim of this study is to compare the incidence of severe food-induced allergic reactions in patients with history of asthma compared with patients without history of asthma. Methods. We performed a systematic research on electronic databases, including PubMed, Scopus, and Web of Science. Observational studies, studies reporting medical characteristics of patients diagnosed with food allergy, and studies reporting medical history of patients with allergic reactions were included. The primary outcome was the incidence of severe food-induced allergic reactions in patients with history of asthma compared with patients without history of asthma. The protocol of this review was registered in PROSPERO (CRD42023448293). Results. Eight studies with a total of 90,367 patients met the inclusion criteria and were included, with a total population of 28,166 of patients with food allergy. The incidence of severe food-induced allergic reactions in patients with history of asthma compared with patients without history of asthma was increased (OR = 1.28; 95% CI 1.03-1.59; p = 0.03; I2 = 59%). Conclusions. Individuals with both food allergy and asthma are at high risk of severe, potentially fatal allergic reactions. Healthcare professionals should prioritize prevention and management strategies for these subjects.
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Abstract Life cycle assessment was carried out for a conventional wooden furniture set produced in Mardan division of the Khyber Pakhtunkhwa province of Pakistan during 2018-19. Primary data regarding inputs and outputs were collected through questionnaire surveys from 100 conventional wooden furniture set manufacturers, 50 in district Mardan and 50 in district Swabi. In the present study, cradle-to-gate life cycle assessment approach was applied for a functional unit of one conventional wooden furniture set. Production weighted average data were modelled in the environmental impacts modelling software i.e., SimaPro v.8.5. The results showed that textile used in sofa set, wood preservative for polishing and preventing insects attack and petrol used in generator had the highest contribution to all the environmental impact categories evaluated. Total cumulative energy demand for wooden furniture set manufactured was 30,005 MJ with most of the energy acquired from non-renewable fossil fuel resources.
Resumo A abordagem de avaliação do ciclo de vida foi realizada para um conjunto de móveis de madeira convencional produzido na divisão Mardan da província de Khyber Pakhtunkhwa do Paquistão durante 2018-19. Os dados primários sobre entradas e saídas foram coletados por meio de pesquisas por questionário de 100 fabricantes de conjuntos de móveis de madeira convencionais, 50 no distrito de Mardan e 50 no distrito de Swabi. No presente estudo, a abordagem de avaliação do ciclo de vida do berço ao portão foi aplicada para uma unidade funcional de um conjunto de móveis de madeira convencional. Os dados da média ponderada da produção foram modelados no software de modelagem de impactos ambientais, isto é, SimaPro v.8.5. Os resultados mostraram que os têxteis usados no conjunto de sofás, o preservativo de madeira para polir e prevenir o ataque de insetos e a gasolina usada no gerador tiveram a maior contribuição em todas as categorias de impacto ambiental avaliadas. A demanda total acumulada de energia para o conjunto de móveis de madeira fabricado foi de 30.005 MJ, com a maior parte da energia adquirida de recursos de combustíveis fósseis não renováveis.
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Meio Ambiente , Decoração de Interiores e Mobiliário , PaquistãoRESUMO
Abstract This study aimed to develop and evaluate data driven models for prediction of forest yield under different climate change scenarios in the Gallies forest division of district Abbottabad, Pakistan. The Random Forest (RF) and Kernel Ridge Regression (KRR) models were developed and evaluated using yield data of two species (Blue pine and Silver fir) as an objective variable and climate data (temperature, humidity, rainfall and wind speed) as predictive variables. Prediction accuracy of both the models were assessed by means of root mean squared error (RMSE), mean absolute error (MAE), correlation coefficient (r), relative root mean squared error (RRMSE), Legates-McCabe's (LM), Willmott's index (WI) and Nash-Sutcliffe (NSE) metrics. Overall, the RF model outperformed the KRR model due to its higher accuracy in forecasting of forest yield. The study strongly recommends that RF model should be applied in other regions of the country for prediction of forest growth and yield, which may help in the management and future planning of forest productivity in Pakistan.
Resumo Este estudo teve como objetivo desenvolver e avaliar modelos baseados em dados para previsão da produção florestal em diferentes cenários de mudanças climáticas na divisão florestal Gallies do distrito de Abbottabad, Paquistão. Os modelos Random Forest (RF) e Kernel Ridge Regression (KRR) foram desenvolvidos e avaliados usando dados de produção de duas espécies (pinheiro-azul e abeto-prateado) como uma variável objetiva e dados climáticos (temperatura, umidade, precipitação e velocidade do vento) como preditivos variáveis. A precisão da previsão de ambos os modelos foi avaliada por meio de erro quadrático médio (RMSE), erro absoluto médio (MAE), coeficiente de correlação (r), erro quadrático médio relativo (RRMSE), Legates-McCabe's (LM), índice de Willmott (WI) e métricas Nash-Sutcliffe (NSE). No geral, o modelo RF superou o modelo KRR devido à sua maior precisão na previsão do rendimento florestal. O estudo recomenda fortemente que o modelo RF seja aplicado em outras regiões do país para previsão do crescimento e produtividade florestal, o que pode ajudar no manejo e planejamento futuro da produtividade florestal no Paquistão.
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Mudança Climática , PaquistãoRESUMO
Abstract This study aimed to develop and evaluate data driven models for prediction of forest yield under different climate change scenarios in the Gallies forest division of district Abbottabad, Pakistan. The Random Forest (RF) and Kernel Ridge Regression (KRR) models were developed and evaluated using yield data of two species (Blue pine and Silver fir) as an objective variable and climate data (temperature, humidity, rainfall and wind speed) as predictive variables. Prediction accuracy of both the models were assessed by means of root mean squared error (RMSE), mean absolute error (MAE), correlation coefficient (r), relative root mean squared error (RRMSE), Legates-McCabes (LM), Willmotts index (WI) and Nash-Sutcliffe (NSE) metrics. Overall, the RF model outperformed the KRR model due to its higher accuracy in forecasting of forest yield. The study strongly recommends that RF model should be applied in other regions of the country for prediction of forest growth and yield, which may help in the management and future planning of forest productivity in Pakistan.
Resumo Este estudo teve como objetivo desenvolver e avaliar modelos baseados em dados para previsão da produção florestal em diferentes cenários de mudanças climáticas na divisão florestal Gallies do distrito de Abbottabad, Paquistão. Os modelos Random Forest (RF) e Kernel Ridge Regression (KRR) foram desenvolvidos e avaliados usando dados de produção de duas espécies (pinheiro-azul e abeto-prateado) como uma variável objetiva e dados climáticos (temperatura, umidade, precipitação e velocidade do vento) como preditivos variáveis. A precisão da previsão de ambos os modelos foi avaliada por meio de erro quadrático médio (RMSE), erro absoluto médio (MAE), coeficiente de correlação (r), erro quadrático médio relativo (RRMSE), Legates-McCabes (LM), índice de Willmott (WI) e métricas Nash-Sutcliffe (NSE). No geral, o modelo RF superou o modelo KRR devido à sua maior precisão na previsão do rendimento florestal. O estudo recomenda fortemente que o modelo RF seja aplicado em outras regiões do país para previsão do crescimento e produtividade florestal, o que pode ajudar no manejo e planejamento futuro da produtividade florestal no Paquistão.
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Abstract Life cycle assessment was carried out for a conventional wooden furniture set produced in Mardan division of the Khyber Pakhtunkhwa province of Pakistan during 2018-19. Primary data regarding inputs and outputs were collected through questionnaire surveys from 100 conventional wooden furniture set manufacturers, 50 in district Mardan and 50 in district Swabi. In the present study, cradle-to-gate life cycle assessment approach was applied for a functional unit of one conventional wooden furniture set. Production weighted average data were modelled in the environmental impacts modelling software i.e., SimaPro v.8.5. The results showed that textile used in sofa set, wood preservative for polishing and preventing insects attack and petrol used in generator had the highest contribution to all the environmental impact categories evaluated. Total cumulative energy demand for wooden furniture set manufactured was 30,005 MJ with most of the energy acquired from non-renewable fossil fuel resources.
Resumo A abordagem de avaliação do ciclo de vida foi realizada para um conjunto de móveis de madeira convencional produzido na divisão Mardan da província de Khyber Pakhtunkhwa do Paquistão durante 2018-19. Os dados primários sobre entradas e saídas foram coletados por meio de pesquisas por questionário de 100 fabricantes de conjuntos de móveis de madeira convencionais, 50 no distrito de Mardan e 50 no distrito de Swabi. No presente estudo, a abordagem de avaliação do ciclo de vida do berço ao portão foi aplicada para uma unidade funcional de um conjunto de móveis de madeira convencional. Os dados da média ponderada da produção foram modelados no software de modelagem de impactos ambientais, isto é, SimaPro v.8.5. Os resultados mostraram que os têxteis usados no conjunto de sofás, o preservativo de madeira para polir e prevenir o ataque de insetos e a gasolina usada no gerador tiveram a maior contribuição em todas as categorias de impacto ambiental avaliadas. A demanda total acumulada de energia para o conjunto de móveis de madeira fabricado foi de 30.005 MJ, com a maior parte da energia adquirida de recursos de combustíveis fósseis não renováveis.
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Fischer-Tropsch synthesis (FTS), a significant reaction for effective H2 utilization, is a promising approach for direct production of light olefins from syngas (H2 + CO). For the FT-Olefin process, an efficient catalyst restricting the product distribution of FTS to light olefins is required. Aligned with this goal, we synthesized 24 catalysts comprising Fe and Cu in combination with rare earth metals (La, Ce, Nd, Ho, Er) and zeolite supports (ultrastable Y and mordenite). FT-Olefin performances of these catalysts were screened using a high-throughput test system at atmospheric pressure, and then promising catalysts were tested under high pressure in a conventional test system. Results show that Nd increases selectivity to light olefins and Ho suppresses C5+ and coke formation. It is also demonstrated that zeolite-metal interaction, leading to a mixture of both acidic and basic sites, is significant in increasing light olefin production. The mordenite-supported 20 wt % Fe, 0.5 wt % Cu, and 0.5 wt % Ho catalyst provides the highest light olefin yield with the lowest coke and heavier hydrocarbon selectivity.
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Aims Accurate identification of the successful reduction of a dislocated shoulder could avoid additional episodes of procedural sedation and repeated performance of X-rays. The objective of this study was to assess the diagnostic accuracy of point-of-care-ultrasound (POCUS) in the confirmation of a successful joint reduction in patients with shoulder dislocation. Methods This was a single-centre, prospective observational study set in an urban academic ED in Ireland, with a convenience sample of adult patients with shoulder dislocation on X-ray. Ultrasound was performed on participants before and after joint reduction using a posterior approach technique. The operator's confidence levels were recorded after image acquisition. Results Thirty-three subjects were recruited. All dislocations were correctly identified on pre-reduction US, indicating a sensitivity of 100% (CI 89.42 - 100). Post-reduction US confirmed successful reduction in 30 subjects that were subsequently reported as such on X-Ray, giving it a specificity of 100% (CI 88.43 - 100). Failure to achieve reduction was correctly identified on US in three cases, resulting in post-reduction US Sensitivity of 100% (CI 29.24 - 100) and 100% accuracy (CI 89.42 - 100). Conclusion This study has shown that POCUS, with a posterior approach technique, has 100% sensitivity and specificity in confirming successful shoulder reduction in the ED.
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Sistemas Automatizados de Assistência Junto ao Leito , Luxação do Ombro , Adulto , Serviço Hospitalar de Emergência , Humanos , Ombro , Luxação do Ombro/diagnóstico por imagem , UltrassonografiaRESUMO
Life cycle assessment was carried out for a conventional wooden furniture set produced in Mardan division of the Khyber Pakhtunkhwa province of Pakistan during 2018-19. Primary data regarding inputs and outputs were collected through questionnaire surveys from 100 conventional wooden furniture set manufacturers, 50 in district Mardan and 50 in district Swabi. In the present study, cradle-to-gate life cycle assessment approach was applied for a functional unit of one conventional wooden furniture set. Production weighted average data were modelled in the environmental impacts modelling software i.e., SimaPro v.8.5. The results showed that textile used in sofa set, wood preservative for polishing and preventing insects attack and petrol used in generator had the highest contribution to all the environmental impact categories evaluated. Total cumulative energy demand for wooden furniture set manufactured was 30,005 MJ with most of the energy acquired from non-renewable fossil fuel resources.
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Meio Ambiente , Decoração de Interiores e Mobiliário , PaquistãoRESUMO
Malignancy and treatment effects in head and neck oncology can be devastating to functional aspects of patient life such as swallowing, blinking, speech, salivation, and facial expression. Historically, the subjective nature of patient experience has resulted in difficulty with quantification and measurement of functional outcomes. Patient-Reported Outcomes (PROs) are questionnaires developed with patient input, forming the new gold standard for clinician assessment of subjective functional outcomes. The current review aims to identify and characterize the validation of PROs pertaining to four critical functional outcomes in head and neck oncology: swallowing, speech, dry mouth, and chewing. A literature search was conducted using MEDLINE, EMBASE, and the Cochrane databases for published, English language, peer-reviewed abstracts involving patients ≥ 18 years of age. Of 708 results, 705 were excluded at abstract or full text screening for not meeting inclusion criteria, exclusion of head and neck SCC patients in development, or absence of a functional domain measurement. The three reviewed studies-Xerostomia Questionnaire, Swallowing Outcomes After Laryngectomy, and Edmonton 33-exhibited strong reliability and construct and content validity, though two applied only to individual functional outcomes within specific patient populations receiving radiation or laryngectomy. While many PROs have been developed in head and neck oncology, very few properly employed extensive patient input in the development process. Further work must be committed to increasing head and neck cancer patient input in PRO development, particularly in the functional domains of speech and chewing.
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Neoplasias de Cabeça e Pescoço , Xerostomia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
A meta-analysis was performed to evaluate the effects of supplementary n-3 polyunsaturated fatty acids (PUFA) sources in the diet on the formation of some important n-3 PUFA contents in eggs and to assess factors contributing to the conversion efficiency of omega-3 in laying hens. A dataset was constructed from 34 studies examining the impact of dietary inclusion with ingredients rich in n-3 PUFA on fatty acids profile and production performance of laying hens. The eligibility criteria were developed to obtain studies reporting required information with sufficient quality. The mixed model methodology was employed where the "study" was set as random effects and fatty acid (FA) supplements as fixed effects. Several factors were included in the models as covariates. Discrete analysis for sources of FA was also performed to compare their effects on FA formation in eggs. Significant linear positive associations were observed between the concentration of α-linolenic acid (ALA), total n-3 PUFA, and the ratio of linoleic acid (LA) to ALA (LA/ALA) in diets with the formation of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), total n-3 PUFA, and n6/n3 ratio in egg (P < 0.05) with different magnitudes. ALA and total n-3 PUFAs concentration had no relationship with cholesterol concentration, feed intake, and egg weight. Prediction models for DHA formation was higher for ALA as predictor variables (slope = 0.482; R2 = 0.684) than n-3 PUFAs (slopes = 0.998, R2 = 0.628). Significant interactions were found on the level of ALA × FA sources and n-3 PUFA × FA sources. Fish oil (P = 0.0148, R2 = 0.732) improved the prediction equation to estimate DHA formation. To conclude, levels of ALA, n-3 PUFA, and the ratio of LA/ALA can be used as predictor variables to estimate the formation of n-3 fatty acids in eggs. It was confirmed that although all n-3 FA sources had a positive correlation on DHA and n-3 PUFA deposition, however, fish oil showed the highest prediction model for DHA formation across all FA sources included in the dataset.
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Ácidos Graxos Ômega-3 , Ácidos Graxos , Animais , Galinhas , FemininoRESUMO
This study aimed to develop and evaluate data driven models for prediction of forest yield under different climate change scenarios in the Gallies forest division of district Abbottabad, Pakistan. The Random Forest (RF) and Kernel Ridge Regression (KRR) models were developed and evaluated using yield data of two species (Blue pine and Silver fir) as an objective variable and climate data (temperature, humidity, rainfall and wind speed) as predictive variables. Prediction accuracy of both the models were assessed by means of root mean squared error (RMSE), mean absolute error (MAE), correlation coefficient (r), relative root mean squared error (RRMSE), Legates-McCabe's (LM), Willmott's index (WI) and Nash-Sutcliffe (NSE) metrics. Overall, the RF model outperformed the KRR model due to its higher accuracy in forecasting of forest yield. The study strongly recommends that RF model should be applied in other regions of the country for prediction of forest growth and yield, which may help in the management and future planning of forest productivity in Pakistan.
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Mudança Climática , PaquistãoRESUMO
Cardiovascular disease continues to be the leading cause of morbidity and mortality in the United States and thousands of manuscripts each year are aimed at elucidating mechanisms underlying cardiac disease. The methods for quantifying cardiac performance are quite varied, with each technique assessing unique features of cardiac muscle mechanical properties. Accordingly, in this review, we discuss current ex vivo methods for quantifying cardiac muscle performance, highlighting what can be learned from each method, and how each technique can be used in conjunction to complement others for a more comprehensive understanding of cardiac function. Importantly, cardiac function can be assessed at several different levels, from the whole organ down to individual protein-protein interactions. Here, we take a reductionist view of methods that are commonly used to measure the distinct aspects of cardiac mechanical function, beginning with whole heart preparations and finishing with the in vitro motility assay. While each of the techniques are individually well-documented in the literature, there is a significant need for a comparison of the techniques, delineating the mechanical parameters that can are best measured with each technique, as well as the strengths and weaknesses inherent to each method. Additionally, we will consider complementary techniques and how these methods can be used in combination to improve our understanding of cardiac mechanical function. By presenting each of these methods, with their strengths and limitations, in a single manuscript, this review will assist cardiovascular biologists in understanding the existing literature on cardiac mechanical function, as well as designing future experiments.
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Succinylation is a post-translational modification of protein lysine residues with succinyl groups derived from succinyl CoA. Succinylation is considered a significant post-translational modification with the potential to impact protein function which is highly conserved across numerous species. The role of succinylation in the heart, especially in heart failure and myofibril mechanics, remains largely unexplored. Mechanical parameters were measured in myofibrils isolated from failing hearts of ischemic cardiomyopathy patients and non-failing donor controls. We employed mass spectrometry to quantify differential protein expression in myofibrils from failing ischemic cardiomyopathy hearts compared to non-failing hearts. In addition, we combined peptide enrichment by immunoprecipitation with liquid chromatography tandem mass spectrometry to quantitatively analyze succinylated lysine residues in these myofibrils. Several key parameters of sarcomeric mechanical interactions were altered in myofibrils isolated from failing ischemic cardiomyopathy hearts, including lower resting tension and a faster rate of activation. Of the 100 differentially expressed proteins, 46 showed increased expression in ischemic heart failure, while 54 demonstrated decreased expression in ischemic heart failure. Our quantitative succinylome analysis identified a total of 572 unique succinylated lysine sites located on 181 proteins, with 307 significantly changed succinylation events. We found that 297 succinyl-Lys demonstrated decreased succinylation on 104 proteins, while 10 residues demonstrated increased succinylation on 4 proteins. Investigating succinyl CoA generation, enzyme activity assays demonstrated that α-ketoglutarate dehydrogenase and succinate dehydrogenase activities were significantly decreased in ischemic heart failure. An activity assay for succinyl CoA synthetase demonstrated a significant increase in ischemic heart failure. Taken together, our findings support the hypothesis that succinyl CoA production is decreased and succinyl CoA turnover is increased in ischemic heart failure, potentially resulting in an overall decrease in the mitochondrial succinyl CoA pool, which may contribute to decreased myofibril protein succinylation in heart failure.
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Cardiomiopatias/metabolismo , Insuficiência Cardíaca/metabolismo , Proteínas Mitocondriais/metabolismo , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Miofibrilas/metabolismo , Ácido Succínico/metabolismo , Acilação , Cardiomiopatias/complicações , Humanos , Lisina/metabolismo , Metilação , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Proteômica , Reprodutibilidade dos Testes , Doadores de TecidosRESUMO
BACKGROUND: Chronic alcohol consumption is a significant cause of liver disease worldwide. Several biochemical mechanisms have been linked to the initiation and progression of alcoholic liver disease (ALD) such as oxidative stress, inflammation, and metabolic dysregulation, including the disruption of NAD+/NADH. Indeed, an ethanol-mediated reduction in hepatic NAD+ levels is thought to be one factor underlying ethanol-induced steatosis, oxidative stress, steatohepatitis, insulin resistance, and inhibition of gluconeogenesis. Therefore, we applied a NAD+ boosting supplement to investigate alterations in the pathogenesis of early-stage ALD. METHODS: To examine the impact of NAD+ therapy on the early stages of ALD, we utilized nicotinamide mononucleotide (NMN) at 500 mg/kg intraperitoneal injection every other day, for the duration of a Lieber-DeCarli 6-week chronic ethanol model in mice. Numerous strategies were employed to characterize the effect of NMN therapy, including the integration of RNA-seq, immunoblotting, and metabolomics analysis. RESULTS: Our findings reveal that NMN therapy increased hepatic NAD+ levels, prevented an ethanol-induced increase in plasma ALT and AST, and changed the expression of 25% of the genes that were modulated by ethanol metabolism. These genes were associated with a number of pathways including the MAPK pathway. Interestingly, our analysis revealed that NMN treatment normalized Erk1/2 signaling and prevented an induction of Atf3 overexpression. CONCLUSIONS: These findings reveal previously unreported mechanisms by which NMN supplementation alters hepatic gene expression and protein pathways to impact ethanol hepatotoxicity in an early-stage murine model of ALD. Overall, our data suggest further research is needed to fully characterize treatment paradigms and biochemical implications of NAD+-based interventions.
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Perfilação da Expressão Gênica , Hepatopatias Alcoólicas/tratamento farmacológico , Mononucleotídeo de Nicotinamida/uso terapêutico , RNA/genética , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Doença Crônica , Modelos Animais de Doenças , Etanol , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatopatias Alcoólicas/sangue , Hepatopatias Alcoólicas/genética , Metaboloma , Metabolômica , Camundongos Endogâmicos C57BL , Mononucleotídeo de Nicotinamida/farmacologia , Substâncias Protetoras/metabolismo , RNA/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Mitochondrial dysfunction is one of many key factors in the etiology of alcoholic liver disease (ALD). Lysine acetylation is known to regulate numerous mitochondrial metabolic pathways, and recent reports demonstrate that alcohol-induced protein acylation negatively impacts these processes. To identify regulatory mechanisms attributed to alcohol-induced protein post-translational modifications, we employed a model of alcohol consumption within the context of wild type (WT), sirtuin 3 knockout (SIRT3 KO), and sirtuin 5 knockout (SIRT5 KO) mice to manipulate hepatic mitochondrial protein acylation. Mitochondrial fractions were examined by label-free quantitative HPLC-MS/MS to reveal competition between lysine acetylation and succinylation. A class of proteins defined as "differential acyl switching proteins" demonstrate select sensitivity to alcohol-induced protein acylation. A number of these proteins reveal saturated lysine-site occupancy, suggesting a significant level of differential stoichiometry in the setting of ethanol consumption. We hypothesize that ethanol downregulates numerous mitochondrial metabolic pathways through differential acyl switching proteins. Data are available via ProteomeXchange with identifier PXD012089.
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Acilação/efeitos dos fármacos , Etanol/farmacologia , Mitocôndrias , Proteoma , Animais , Hepatopatias Alcoólicas/metabolismo , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Camundongos , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteoma/química , Proteoma/efeitos dos fármacos , Proteoma/metabolismo , Sirtuína 3/genética , Sirtuína 3/metabolismo , Sirtuínas/genética , Sirtuínas/metabolismoRESUMO
BACKGROUND: Gallbladder cancer (GBC) is the most common malignancy of the biliary tract in India. Despite the recent advancement in the understanding of the cancer biology, the disease still remains a therapeutic challenge with poor prognosis and low survival. Surgery is the primary modality of treatment and rest of the modalities are basically adjuvant in nature. This study was performed to evaluate the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 HER-2/neu) expression in GBC. METHODS: The present study was prospective and done in tertiary super-specialty institute of northern India. This was a pilot study, and at the time of completion, 29 samples were found suitable which were later submitted for EGFR and HER-2/neu evaluation. The sample includes both cases of GBC (n=18) and cholecystitis (n=11) as control. (Table 1) After performing necessary processing, slides were incubated with primary antibody (EGFR) ready to use (RTU) BioGenex, India and HER-2/neu dilution 1:600, Dakopatts (Denmark). Then slides were incubated with secondary antibody (Real Envision Detection Kit, Dakopatts, Denmark). Finally in mounted slides, cell membrane staining was used to assess positivity for EGFR and HER-2/neu. RESULTS: EGFR was positive in 21/29 (72.41%) overall, out of which 14/18 (77.78%) positive in cases and 7/11 (63.64%) positive in control. (Table 1, 3)(Figure 2). For HER-2/neu, it was positive in 21/29 (72.41%) overall, just like in EGFR mentioned above, but positive 12/18 (66.67%) in cases and 9/11 (81.82%) in control respectively. CONCLUSION: Despite the efforts by many investigators, GBC continues to represent a major challenge in oncology. Surgical resection remains the only curative treatment for this disease. The roles of radiation, chemoradiation, and chemotherapy in neoadjuvant and adjuvant settings remained to be defined in prospective studies. With further studies based on molecular understanding and developing new targeted therapies, we will be in better position to manage GBC and increase the survival rate.
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Receptores ErbB/metabolismo , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/terapia , Humanos , Índia , Projetos Piloto , Prognóstico , Estudos ProspectivosRESUMO
Organ donation after brain death (BD) is a major source for obtaining transplantable organs for patients with end-stage organ disease (ESOD). This retrospective, descriptive study was carried out on all potential BD patients admitted in different intensive care units (ICUs) of the Hamad medical Corporation (HMC), Doha, Qatar during a period from January 2011 to April 2012. Our aim was to evaluate various demographic criteria and challenges of organ donation among potential BD organ donors and plan a strategy to improve the rate of organ donation in Qatar. Various aspects of BD patients in the ICUs and their possible effects on organ donation were studied. The time intervals analyzed to determine the possible causes of delay of organ retrieval were: time of diagnosing fixed dilated pupils in the ICU, to performing the first BD test, then to the second BD test, to family approach, to organ retrieval and/or circulatory death (CD) without organ retrieval. There were a total of 116 potential BD organ donors of whom 96 (82.75%) were males and 20 (17.25%) were females. Brain hemorrhage and head injury contributed to 37 (31.9%) and 32 (27.6%) BD cases, respectively. Time interval between diagnosing fixed dilated pupil and performing the first test of BD was delayed >24 h in 79% of the cases and between the first and second BD tests was >6 h in 70.8% of the cases. This delay is not compatible with the Hamad Medical Corporation (HMC) policy for BD diagnosis and resulted in a low number of organs retrieved. BD organ donation, a potential source for organs to save patients with ESOD has several pitfalls and every effort should be made to increase the awareness of the public as well as medical personnel to optimize donation efficacy.
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Morte Encefálica/diagnóstico , Transplante de Órgãos , Doadores de Tecidos/provisão & distribuição , Coleta de Tecidos e Órgãos , Obtenção de Tecidos e Órgãos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/métodos , Catar , Estudos Retrospectivos , Fatores de Tempo , Coleta de Tecidos e Órgãos/métodos , Obtenção de Tecidos e Órgãos/métodos , Obtenção de Tecidos e Órgãos/organização & administração , Adulto JovemRESUMO
Small molecules that increase the presynaptic function of aminergic cells may provide neuroprotection in Parkinson's disease (PD) as well as treatments for attention deficit hyperactivity disorder (ADHD) and depression. Model genetic organisms such as Drosophila melanogaster may enhance the detection of new drugs via modifier or 'enhancer/suppressor' screens, but this technique has not been applied to processes relevant to psychiatry. To identify new aminergic drugs in vivo, we used a mutation in the Drosophila vesicular monoamine transporter (dVMAT) as a sensitized genetic background and performed a suppressor screen. We fed dVMAT mutant larvae â¼ 1000 known drugs and quantitated rescue (suppression) of an amine-dependent locomotor deficit in the larva. To determine which drugs might specifically potentiate neurotransmitter release, we performed an additional secondary screen for drugs that require presynaptic amine storage to rescue larval locomotion. Using additional larval locomotion and adult fertility assays, we validated that at least one compound previously used clinically as an antineoplastic agent potentiates the presynaptic function of aminergic circuits. We suggest that structurally similar agents might be used to development treatments for PD, depression and ADHD, and that modifier screens in Drosophila provide a new strategy to screen for neuropsychiatric drugs. More generally, our findings demonstrate the power of physiologically based screens for identifying bioactive agents for select neurotransmitter systems.
Assuntos
Antiparkinsonianos/farmacologia , Drosophila melanogaster , Avaliação Pré-Clínica de Medicamentos/métodos , Proteínas Vesiculares de Transporte de Monoamina/metabolismo , Animais , Animais Geneticamente Modificados , Dacarbazina/farmacologia , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Feminino , Fertilidade/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/fisiologia , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Mutação , Doença de Parkinson/tratamento farmacológico , Pergolida/farmacologia , Sinapses/efeitos dos fármacos , Proteínas Vesiculares de Transporte de Monoamina/genéticaRESUMO
OBJECTIVES/HYPOTHESIS: Sore throat is a common, benign emergency department (ED) presentation; however, peritonsillar abscess (PTA) is a complication that requires aggressive management. Use of systemic corticosteroids (SCSs) in PTA is occurring without clear evidence of benefit. This study examined the efficacy and safety of SCS treatment for patients with PTA. STUDY DESIGN: Randomized, double-blind, placebo-controlled trial. METHODS: A controlled trial with concealed allocation and double-blinding was conducted at two Canadian EDs. Following written informed consent, eligible patients received 48 hours of intravenous clindamycin and a single dose of the study drug (dexamethasone [DEX] or placebo [PLAC], intravenously [IV]). Follow-up occurred at 24 hours, 48 hours, and 7 days. The primary outcome was pain; other outcomes were side effects and return to normal activities/diet. RESULTS: A total of 182 patients were screened for eligibility; 41 patients were enrolled (21 DEX; 20 PLAC). At 24 hours, those receiving DEX reported lower pain scores (1.4 vs. 5.1; P = .009); however, these differences disappeared by 48 hours (P = .22) and 7 days (P = .4). At 24 hours, more patients receiving DEX returned to normal activities (33% vs. 11%) and dietary intake (38% vs 25%); however, these differences were not significant and disappeared by 48 hours and 7 days. Side effects were rare and did not differ between groups (P > .05). CONCLUSIONS: Combined with PTA drainage and IV antibiotics, 10 mg IV DEX resulted in less pain at 24 hours when compared to PLAC, without any serious side effects. This effect is short-lived, and further research is required on factors associated with PTA treatment success.
Assuntos
Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Abscesso Peritonsilar/tratamento farmacológico , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Carcinoma of stomach is the leading cause of cancer related death in the last century worldwide. However in many parts of the world, the incidence has gradually decreased due to changes in food habit and the environment. The proximal gastric and gastro-esophageal junction (GE junction) cancer has markedly increased in the last three decades. The only proven curative treatment is surgery, but due to high recurrence rate, efforts are still going on regarding better systemic and regional adjuvant therapies. The present study is a retrospective analysis of all the post-operative (post-op) cases of carcinoma stomach and the GE junction being registered and treated in our department from June 1995 to February 2008. The total number (no.) of patients (pts) were 69 (54 stomach, 15 GE junction), males 49, females 20, KPS 50-90 (median 80), length of the lesion was <5cm in 28 pts, transmural infiltration along with serosa involvement was found in 40 pts. Histologically, adenocarcinoma was detected in 61 pts and metastatic spread in 50 pts. Thirty-six pts had surgery in another center prior to registration. Forty-nine pts had subtotal gastrectomy, while lymph nodes dissection was done in 64 pts. Chemo-radiotherapy (CRT) was given in 49 pts, and 54 pts received >30 Gy dose of radiation. Macdonald's regimen was used in 49 pts. Treatment compliance was found in 53 pts, but only 05 pts were hospitalized for supportive management. Pts were followed up from 01-69 months (median 12 months) and the recurrence was found in 13 pts (median 14 months). The multimodality intervention is better treatment option in the management of carcinoma of stomach.