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This study investigated the effects of sumac and molasses on nutrient composition, in vitro degradability and fermentation quality of alfalfa silage. Alfalfa was ensiled in quadruplicate in vacuum jars untreated group (A) or after the following treatments: sumac group at 10% (AS), molasses group at 5% (AM), and sumac (10%) and molasses (5%) group (ASM). Silos (n = 64) were stored for 0, 21, 45 or 60 days. The results showed that dry matter (DM) contents of the AS, AM and ASM groups were statistically higher than the control group (p < 0.001). Only on the 21st day of fermentation the crude ash content of the AS group was found to be significantly higher than the other groups (p < 0.05). In vitro, DM and organic matter degradation values of the AMS group increased significantly (p < 0.001). A significant decrease in alfalfa silage's pH values was determined with sumac and molasses additives (p < 0.001). The ammonia nitrogen (NH3-N) values of the control, AS, AM and ASM groups at Day 60 were determined as 9.08%, 7.22%, 7.00% and 6.81% respectively (p < 0.05). The water-soluble carbohydrate (WSC) values of all groups on the 60th day were significantly decreased compared to the 0th day (p < 0.001). When the groups were evaluated within themselves, there was a statistically significant difference between the 0th and 60th day lactic acid values. The acetic acid content of the A group on the 60th day was found to be significantly higher than the other groups (p < 0.01). There was a significant decrease in propionic acid levels on Days 21, 45 and 60 compared to Day 0 of fermentation (p < 0.001). The highest butyric acid (BA) level was determined in the A group on the 21st, 45th and 60th days of fermentation (p < 0.05). In conclusion, sumac prevents proteolysis depending on its tannin content. It improves silage fermentation positively thanks to its organic acid content, while the molasses additive is effective in silage fermentation, mainly depending on the WSC level. However, it was determined that neither additive could reduce the silage pH to the appropriate value ranges due to the low doses, and they could not mainly prevent the formation of BA.
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Fermentação , Medicago sativa , Melaço , Silagem , Medicago sativa/química , Silagem/análise , Animais , Digestão/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição AnimalRESUMO
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has rarely been used in the field of therapeutic drug monitoring, partly because of the complexity of the ionization processes between the compounds to be quantified and the many MALDI matrices available. The development of a viable MALDI-MS method that meets regulatory guidelines for bioanalytical method validation requires prior knowledge of the suitability of (i) the MALDI matrix with the analyte class and properties for ionization, (ii) the crystallization properties of the MALDI matrix with automation features, and (iii) the MS instrumentation used to achieve sensitive and specific measurements in order to determine low pharmacological drug concentrations in biological matrices. In the present hybrid article/white paper, we review the developments required for the establishment of MALDI-MS assays for the quantification of drugs in tissues and plasma, illustrated with concrete results for the different steps. We summarize the necessary parameters that need to be controlled for the successful development of fully validated MALDI-MS methods according to regulatory authorities, as well as currently unsolved problems and promising ways to address them. Finally, we propose an expert opinion on future perspectives and needs in order to establish MALDI-MS as a universal method for therapeutic drug monitoring.
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Monitoramento de Medicamentos/métodos , Preparações Farmacêuticas , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Cristalização , HumanosRESUMO
In this research, 'Pedro' walnut variety (maternal parent) was open pollinated. Offspring genotypes were compared with their maternal parent in terms of morphological and molecular features. Leafing and leaf fall dates were measured as two phenological traits. Genetic differences were identified by molecular fingerprinting using twelve Inter Simple Repetitive Sequence Polymorphism (ISSR) primers. In some progenies, leafing and leaf fall occurred later than the maternal parent ('Pedro'). Progenies were grouped according to their similarities with the maternal parent regarding leafing date. Specifically, 14.44% of the progenies were 'Very close' to the parent, 16.66% were 'Close', 30.00% 'Far' and 38.89% 'Very far'. Regarding the leaf fall date, 7.78% of the progenies were 'Very close' to the parent, 28.88% were 'Close', 36.66% 'Far' and 26.67% 'Very far'. A total of 43 bands were obtained in molecular analyses. These bands were largely polymorphic (95.34%). The average number of the alleles was 3.90, while the polymorphism information content varied between 0.14 and 0.91 among the genotypes. Genetic distances were tested according to the UPGMA (Unweighted Pair Group Method with Arithmetic Average) and by The Structure Analysis. The UPGMA dendrogram divided the genotypes into two main clusters and the similarity coefficient of the genotypes varied between 0.61 and 0.99. This study revealed that 'Pedro' can be used as an excellent parental variety in hybridization programs which prioritize late-leafing in walnut breeding. Furthermore, ISSR primers can be safely used for fingerprinting walnuts in general.
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Sexual reproduction among the black yeasts is generally limited to environmental saprobic species and is rarely observed among opportunists in humans. To date, a complete sexual cycle has not been observed in Exophiala dermatitidis. In this study, we aimed to gain insight into the reproductive mode of E. dermatitidis by characterizing its mating type (MAT) locus, conducting MAT screening of environmental and clinical isolates, examining the expression of the MAT genes and analyzing the virulence of the isolates of different mating types. Similar to other members of the Pezizomycotina, the E. dermatitidis genome harbors a high mobility group (HMG) domain gene (MAT1-2-1) in the vicinity of the SLA2 and APN2 genes. The MAT loci of 74 E. dermatitidis isolates (11 clinical and 63 environmental) were screened by PCR, and the surrounding region was amplified using long-range PCR. Sequencing of theâ¯â¼â¯12-kb PCR product of a MAT1-1 isolate revealed an α-box gene (MAT1-1-1). The MAT1-1 idiomorph was 3544-bp long and harbored the MAT1-1-1 and MAT1-1-4 genes. The MAT1-2 idiomorph was longer, 3771-bp, and harbored only the MAT1-2-1 gene. This structure suggests a heterothallic reproduction mode. The distribution of MAT among 74 isolates wasâ¯â¼â¯1:1 with a MAT1-1:MAT1-2 ratio of 35:39. RT-PCR analysis indicated that the MAT genes are transcribed. No significant difference was detected in the virulence of isolates representing different mating types using a Galleria mellonella model (Pâ¯>â¯0.05). Collectively, E. dermatitidis is the first opportunistic black yeast in which both MAT idiomorphs have been characterized. The occurrence of isolates bearing both idiomorphs, their approximately equal distribution, and the expression of the MAT genes suggest that E. dermatitidis might reproduce sexually.
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Exophiala/fisiologia , Genes Fúngicos Tipo Acasalamento , Exophiala/genética , Exophiala/patogenicidade , Amplificação de Genes , Humanos , Feoifomicose/microbiologia , Reação em Cadeia da Polimerase , RNA Fúngico , Transcrição Gênica , Virulência/genéticaRESUMO
BACKGROUND: Limited data exist regarding the psychosocial aspects of gastroesophageal reflux disease (GERD). Some GERD subgroups, such as functional heartburn and hypersensitive esophagus, might show different psychiatric comorbidities than others. AIM: We aimed to evaluate the psychiatric comorbidities of GERD subgroups using a cross-sectional design. METHODS: A group of GERD patients at a tertiary outpatient clinic were evaluated via upper GIS (gastrointestinal system) endoscopy, esophageal manometry, and 24-h impedance-pH monitoring. Thirty-nine patients diagnosed with erosive reflux disease, 44 with non-erosive reflux disease, 20 with functional heartburn, 11 with hypersensitive esophagus, and 44 healthy controls participated. Psychiatric diagnoses were made using the Structured Clinical Interview for Diagnostics and Statistical Manual of Mental Disorders IV. Psychometric measurements of the patients were performed using the Somatosensory Amplification Scale, Beck Depression Inventory, State-Trait Anxiety Inventory, and Short-Form 36. Healthy controls were evaluated with the same psychometric scales except for the Short-Form 36. RESULTS: All of the GERD subgroups were significantly more depressed than the control group. Depressive disorders were significantly more prevalent in the functional heartburn group than in the non-erosive reflux disease and erosive reflux disease groups. The trait anxiety level of the functional heartburn group was significantly higher than those of the control and non-erosive reflux disease groups. The quality of life scores of the GERD subgroups were significantly lower than the population standards. CONCLUSIONS: Depressive disorders were frequently comorbid in the GERD subgroups studied (30-65 %). It is essential to consider the high prevalence rates of comorbid depression when managing GERD.
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Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/epidemiologia , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Adulto , Comorbidade , Estudos Transversais , Feminino , Refluxo Gastroesofágico/psicologia , Humanos , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , PrevalênciaRESUMO
Obesity increases the risk of gastroesophageal reflux disease (GERD). The majority of the reflux attacks occur postprandially. The influence of the speed of food intake on gastroesophageal reflux events is unclear in obese patients. To determine the influence of the speed of food intake on intraesophageal reflux events in obese patients with and without GERD. A total of 26 obese female patients were recruited. The patients underwent esophageal manometry to evaluate the upper limit of the lower esophageal sphincter and subsequently placement of a Multichannel intraluminal impedance-pH (MII-pH) catheter. All patients were asked to eat the same standard meal (double cheeseburger, 1 banana, 100 g yogurt and 200 mL water; total energy value, 744 kcal; 37.6% carbohydrates, 21.2% proteins and 41.2% lipids) within 5 or 30 minutes under observation in a random order on two consecutive days. All reflux episodes over a 3-hour postprandial period were manually analyzed and compared. The mean age was 46 ± 12 (18-66) years. The mean body mass index (BMI) was 39.9 ± 8.4 kg/m2. There was no difference between the fast- and slow-eating group in the number of refluxes within the 3-postprandial hours. The patients were divided into 2 groups according to the 24-hour MII-pH monitoring results, that is, 16 subjects with normal MII-pH monitoring and 10 patients with pathologic MII-pH monitoring. There was no effect of the speed of food intake in either the patients with or without GERD. In contrast to the general belief, this study suggested that the speed of food intake does not influence the number of refluxes in obese female patients with or without GERD.
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Comportamento Alimentar , Refluxo Gastroesofágico/epidemiologia , Obesidade/epidemiologia , Adolescente , Adulto , Idoso , Ingestão de Alimentos , Esfíncter Esofágico Inferior/fisiopatologia , Monitoramento do pH Esofágico , Feminino , Refluxo Gastroesofágico/fisiopatologia , Humanos , Manometria , Pessoa de Meia-Idade , Período Pós-Prandial , Adulto JovemRESUMO
Tuberculosis is a very important disease all over the world despite the advanced diagnostic and treatment regimens. Resistant tuberculosis, which has increased in recent years in particular, is a global problem and prevents the fight against tuberculosis. For this reason, it is important to determine the etiologic agent early and its sensitivity against antituberculosis drugs. Resistance profiles of the isolates and the gene mutations causing resistance are determined for epidemiological purposes and mutation regions of the isolates are being investigated on the basis of countries. The aim of our study was to determine the minimal inhibitor concentration (MIC) of isoniazid (INH) and to investigate the relationship between mutations in resistance genes and MIC values. For this purpose, 25 isoniazid (INH) monoresistant and 25 multidrug resistant (MDR), in total 50 clinical isolates were used and gene mutations causing INH resistance and the relationship of these mutations with minimal inhibitor concentrations (MICs) were searched by GenoType MTBDRplus (Hain Lifescience GMBH, Nehren, Germany) and antibiotic gradient test (E-test, AB BIODISK, Solna, Sweden) methods. The concordance of GenoType MTBDRplus and antibiotic gradient test methods for INH sensitivity, was 88% in INH monoresistant isolates, 80% in MDR isolates and 84% in all isolates. The most frequent mutation zone in INH monoresistant isolates was inhA C15T promotor zone (12 isolates, 54.5%) however, MIC of INH was > 256 µg/ml in two isolates and mutation in katG S315T was observed in both of these isolates. The most frequent mutation zone in MDR isolates was katG S315T (14 isolates, 56%) codon. MIC of INH was > 256 µg/ml in 10 isolates and mutation was observed in katG S315T codon in 5 (50%) isolates, in katG S315T codon and inhA C15T promotor zone in 3 (30%) isolates and in inhA promotor zone in 2 (20%) isolates, respectively. When all the isolates were analyzed, the most frequent mutation was found in katG S315T codon (24 isolates, 48%), MIC of INH was > 256 µg/ml among 12 isolates and the most frequent mutation zone in these isolates which have high MIC for INH was katG S315T codon. In conclusion, the results of this study have shown that the value of MICs for INH is high in isolates with katG S315T mutation, nevertheless, further investigations are needed to support this result.
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Antituberculosos/farmacologia , Isoniazida/farmacologia , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Farmacorresistência Bacteriana/genética , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/isolamento & purificação , TurquiaRESUMO
The purpose of this study was to evaluate the air kinetics of well- and poor-speaking patients and their upper (UES) and lower (LES) esophageal sphincter pressures . The esophageal speech capability of 23 total laryngectomy patients was assessed with the Wepman scale. LES and UES points and pressures were measured, and air kinetics were compared. All patients were male, with an average age of 58 years. Both the LES and UES pressures were not statistically different between good-speaking and poor-speaking patients (p > 0.05). The ability to speak was estimated only by looking at tracings. Good speakers are able to retain air successfully and on a long-term basis between the upper and lower esophageal sphincters. During short and/or rapid speech, these patients are able to rapidly suck and then expel the air from their upper esophagus. During long speeches, after sucking the air into their distal esophagus, they used the air in the upper part of the esophagus during the speech, only later seeming to fill the lower esophagus with the air as a possible reserve in the stomach. It has been shown that the basic requirement for speaking is the capacity to suck and store the air within the esophagus. For successful speech, the air should be stored inside the esophagus. MII technology contributes to our understanding of speech kinetics and occupies an important place in patient training as a biofeedback technique.
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Esfíncter Esofágico Superior/fisiopatologia , Laringectomia/reabilitação , Voz Esofágica/métodos , Impedância Elétrica , Humanos , Cinética , Laringectomia/métodos , Masculino , Pessoa de Meia-Idade , Pressão , Prognóstico , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to evaluate the effect of different positions of Mandibular third molar impaction teeth on dental and periodontal lesions of mandibular second molars and correlate the lesion severity with patient age. MATERIALS AND METHODS: This retrospective study assessed 212 CBCT images of patients who visited the department of Oral and Maxillofacial radiology of XX university between 2017 and 2021. Periodontal and dental lesion effects of impacted third molars on mandibular second molars were evaluated. While dental lesions were classified as mild, moderate, and severe, periodontal lesions were classified as mild in cases not exceeding 2/3 of the root, and severe in cases exceeding 2/3 of the root. Pearson's chi-square tests, Mann-Whitney U or Kruskal-Wallis test were used for data analsis. A multivariate logistic regression model was constructed for further analysis. RESULTS: Periodontal lesions were frequently observed in the second molar adjacent to the third molar (157 teeth, 74.1%), dental lesions were observed in 10%. Among the third molar positions, the mesioangular position was associated with a high (88%) prevalence of periodontal lesions (p<0.001), followed by the horizontal position (71%). The periodontal lesion was more severe in cases 30-39 years old and over 40 years old than in cases under 20 years old and 21-24 years old. Distoangular, horizontal and vertical/inverse positions are less likely to increase the severity of the periodontal lesion than the mesioangular position. (OR = 0.02; p <0.001, OR = 0.28; p =0.008, OR = 0.14; p <0.001,respectively). CONCLUSIONS: The third molars are often impacted in the mesioangular position, and this position most increases the risk of periodontal infection in the second molars. Accurate diagnosis and evaluation can minimize complications, and CBCT is a reliable imaging technique in which the position of the third molars and their relationship with the 2nd molars can be evaluated.
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Dente Serotino , Dente Impactado , Humanos , Adulto , Adulto Jovem , Estudos Retrospectivos , Dente Molar/patologia , Dente Impactado/complicações , Dente Impactado/epidemiologia , Tomografia Computadorizada de Feixe CônicoRESUMO
The industrial revolution has dramatically altered the environment and ecosystem. So many scholars have empirically attempted to reveal the most influential anthropogenic factors on environmental degradation. For this purpose, this study examines the leading determinants of CO2 emissions in the context of economic policy uncertainty (EPU) for 14 developed countries within the framework of the extended stochastic impacts by regression on population, affluence and technology (STIRPAT) environmental model from 1997-2018. For empirical modeling, CO2 emission is treated as the dependent variable, which is a strong proxy for environmental degradation. In addition to the GDP per capita, population density, and energy intensity (a proxy for technology), the basic model is extended to include variables such as EPU, renewable energy, trade openness, globalization, and information and communications technology (ICT) index. While the estimation results by the dynamic conditional correlation (DCC) estimator, which are also supported by robustness analysis, suggest that GDP per capita and energy intensity are the main contributors to emission levels, population density has no significant impact on CO2. Furthermore, while renewable energy (in model 2), trade openness (in model 4), and globalization (in model 6) have negative impacts on CO2 emission, technology (in models 5 and 6) and EPU (in model 6) make marginal contributions to CO2.
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Dióxido de Carbono , Desenvolvimento Econômico , Países Desenvolvidos , Dióxido de Carbono/análise , Incerteza , Ecossistema , Poluição Ambiental/análise , Energia RenovávelRESUMO
OBJECTIVE: The aim of the study was to evaluate the effects of vitamin D deficiency on the mandibular bone structure by fractal analysis and panoramic morphometric indices. METHODS: Ninety participants were divided into three groups as 30 individuals with severe vitamin D deficiency, 30 individuals with vitamin D deficiency, and 30 individuals with vitamin D sufficiency. Fractal dimension analysis (FD), panoramic mandibular index (PMI), mandibular cortical index (MCI), and mandibular cortical thickness measurement (CTM) were evaluated on panoramic radiographs. RESULTS: FD values of the patients with vitamin D deficiency were found to be statistically lower than the patients with vitamin D sufficiency (p < 0.05). FD value of supracortical area above the angulus mandible (FD2) in patients with severe vitamin D deficiency was significantly lower than FD values (p = 0.002). There was no statistically significant difference between the groups in the CTM (p > 0.05). PMI was significantly lower in patients with severe vitamin D deficiency (p < 0.001). There was a significant difference in MCI values between the groups (p < 0.05). CONCLUSION: Vitamin D deficiency causes a decrease in bone mineral density in the mandible, and an increase in alveolar porosity. FD analysis and radiomorphometric indices in panoramic radiographs can be used to assess osteoporotic changes in patients with vitamin D deficiency.
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Mandíbula , Deficiência de Vitamina D , Humanos , Estudos Retrospectivos , Mandíbula/diagnóstico por imagem , Densidade Óssea , Vitamina D , Deficiência de Vitamina D/diagnóstico por imagemRESUMO
Objective: The purpose of this in vitro study was to evaluate the effects of four over-the-counter (OTC) whitening products on the microhardness, surface roughness, color, shear bond strength (SBS) and surface charecteristics of human enamel compared with a product used for dentist-supervised home whitening. Materials and methods: Seventy eight enamel specimens allocated into 6 groups (n=13): 1-Opalescence PF 10% (OP) dentist prescribed home whitening product, 2-Opalescence Go prefilled tray (PT), 3-Opalescence Whitening Toothpaste (WT), 4-Listerine Healthy White whitening mouth rinse (WMR), 5-Cavex Bite&White whitening pen (WP) and 6- no treatment (Con). The microhardness (VHN), surface roughness (Ra) and color of the specimens were measured (T0). The specimens were then subjected to whitening protocols for 14 days (T1.) followed by artificial saliva storage for 14 days (T2). The measurements were repeated at T1 and T2. The SBS test was done after the application of 35% phosphoric acid (Scotchbond Universal Etchant), followed by a universal adhesive (G-Premio Bond) and a micro hybrid/universal resin composite (Essentia) into a Teflon tube attached to the enamel surface (p<0.05). Surface morphologies of the enamel surfaces were examined by SEM. p value was set at 0.05. Results: Application of OP, PT and WP decrased the microhardness of enamel specimens (p<0.05) whereas, no significant changes were seen in the microhardness of enamel specimens treated with WT and WMR (p>0.05). Ra values of enamel specimens increased with the application of OP, PT and WT (p<0.05); whereas no changes were observed after the applications of WMR and WP (p>0.05). OP, PT, WMR, and WP changed the color of the enamel(p<0.05). There were not any significant differences among the SBSs groups, apart from OP applied enamel specimens. OP showed the least SBS values (p=0.001). SEM observations revealed smooth enamel surfaces. Conclusions: The whitening products affected the microhardness, surface roughness, color of enamel differently. Only OP decreased the SBS of the enamel.
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OBJECTIVE: The aim of this study was to evaluate the effects of psoriasis vulgaris on mandibular structure by calculating fractal dimension (FD) and radiomorphometric indices. STUDY DESIGN: Panoramic radiographs of 58 patients with psoriasis and 58 healthy participants were assessed. FD was used to analyze trabecular bone architecture in the condyle, angle, and 2 sites in the alveolar bone. Five radiomorphometric indices based on cortical thickness and the mandibular cortical index (MCI) for structure were used to assess cortical bone porosity. Comparisons were made between sites in trabecular and cortical bone. Quantitative and categorical data were statistically analyzed with the significance level at P < .05. RESULTS: FD was significantly lower in the patients with psoriasis than in the controls in the alveolar bone sites (P ≤ .035). Differences between measurement sites were insignificant in psoriasis (P ≥ .617), but the FD values of some measurement sides in the control group differed significantly (P ≤ .004). All quantitative radiomorphometric indices were significantly lower in patients with psoriasis (P ≤ .034) with significant differences between some sites in both groups. No significant difference was found in MCI frequency distribution between the groups (P = .782). CONCLUSIONS: Trabecular architecture and cortical thickness were negatively affected in patients with psoriasis, but no differences in cortical porosity were detected between groups.
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Densidade Óssea , Psoríase , Osso Cortical , Fractais , Humanos , Mandíbula/diagnóstico por imagem , Psoríase/diagnóstico por imagem , Radiografia Panorâmica/métodosRESUMO
Innovation roadmaps are important, because they encourage the actors in an innovation ecosystem to creatively imagine multiple possible science future(s), while anticipating the prospects and challenges on the innovation trajectory. In this overarching context, this expert review highlights the present unmet need for therapeutic innovations for pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas. Although there are many drugs used in practice to treat PitNETs, many of these drugs can have negative side effects and show highly variable outcomes in terms of overall recovery. Building innovation roadmaps for PitNETs' treatments can allow incorporation of systems biology approaches to bring about insights at multiple levels of cell biology, from genes to proteins to metabolites. Using the systems biology techniques, it will then be possible to offer potential therapeutic strategies for the convergence of preventive approaches and patient-centered disease treatment. Here, we first provide a comprehensive overview of the molecular subtypes of PitNETs and therapeutics for these tumors from the past to the present. We then discuss examples of clinical trials and drug repositioning studies and how multi-omics studies can help in discovery and rational development of new therapeutics for PitNETs. Finally, this expert review offers new public health and personalized medicine approaches on cases that are refractory to conventional treatment or recur despite currently used surgical and/or drug therapy.
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Tumores Neuroendócrinos , Neoplasias Hipofisárias , Reposicionamento de Medicamentos , Ecossistema , Humanos , Recidiva Local de Neoplasia , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismoRESUMO
Colorectal cancer (CRC) is the most commonly diagnosed fatal cancer in both women and men worldwide. CRC ranked second in mortality and third in incidence in 2020. It is difficult to diagnose CRC at an early stage as there are no clinical symptoms. Despite advances in molecular biology, only a limited number of biomarkers have been translated into routine clinical practice to predict risk, prognosis and response to treatment. In the last decades, systems biology approaches at the omics level have gained importance. Over the years, several biomarkers for CRC have been discovered in terms of disease diagnosis and prognosis. On the other hand, a few drugs are being developed and used in clinics for the treatment of CRC. However, the development of new drugs is very costly and time-consuming as the research and development takes about 10 years and more than $1 billion. Therefore, drug repositioning (DR) could save time and money by establishing new indications for existing drugs. In this review, we aim to provide an overview of biomarkers for the diagnosis and prognosis of CRC from the systems biology perspective and insights into DR approaches for the prevention or treatment of CRC.
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Pancreatic cancer is one of the most fatal malignancies and the seventh leading cause of cancer-related deaths related to late diagnosis, poor survival rates, and high incidence of metastasis. Unfortunately, pancreatic cancer is predicted to become the third leading cause of cancer deaths in the future. Therefore, diagnosis at the early stages of pancreatic cancer for initial diagnosis or postoperative recurrence is a great challenge, as well as predicting prognosis precisely in the context of biomarker discovery. From the personalized medicine perspective, the lack of molecular biomarkers for patient selection confines tailored therapy options, including selecting drugs and their doses or even diet. Currently, there is no standardized pancreatic cancer screening strategy using molecular biomarkers, but CA19-9 is the most well known marker for the detection of pancreatic cancer. In contrast, recent innovations in high-throughput techniques have enabled the discovery of specific biomarkers of cancers using genomics, transcriptomics, proteomics, metabolomics, glycomics, and metagenomics. Panels combining CA19-9 with other novel biomarkers from different "omics" levels might represent an ideal strategy for the early detection of pancreatic cancer. The systems biology approach may shed a light on biomarker identification of pancreatic cancer by integrating multi-omics approaches. In this review, we provide background information on the current state of pancreatic cancer biomarkers from multi-omics stages. Furthermore, we conclude this review on how multi-omics data may reveal new biomarkers to be used for personalized medicine in the future.
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BACKGROUND: The diagnosis of laryngopharyngeal reflux is currently based on a combination of the patient history of multichannel intraluminal impedance and ambulatory pH (MII-pH); however, none of these findings alone is specific for the diagnosis of laryngopharyngeal reflux. We aimed to compare the baseline characteristics and esophageal baseline impedance values between patients with and without laryngopharyngeal reflux symptoms. METHODS: We retrospectively analyzed data from two groups of patients with laryngopharyngeal reflux according to their reflux finding score (RFS) as scored by ENTs. Control patients were nonerosive reflux disease patients without laryngopharyngeal reflux. All MII-pH parameters and baseline impedance were analyzed from six levels and the proximal and distal baseline impedance and the ratio of the proximal to distal baseline impedance levels was calculated. RESULTS: Altogether 123 patients with laryngopharyngeal reflux and 49 control patients were included. A total of 81 of 123 patients had RFS ≥ 7, and 42 of 123 patients had RFS < 7. Baseline impedance analysis showed that patients with laryngopharyngeal reflux symptoms had significantly lower proximal baseline impedance values (1997 ± 51 vs 2245 ± 109, p < 0.05) than the control group. Additionally, patients with laryngopharyngeal reflux symptoms had a significantly lower proximal-to-distal ratio (1.28 ± 0.05 vs 1.53 ± 0.09, p < 0.05). In the subgroup analysis, patients with RFS < 7 were found to have a significantly lower acid exposure time than either the patients with RFS ≥ 7 (3.85 ± 0.65 vs 8.2 ± 1.52, p < 0.05) or the control group (3.85 ± 0.65 vs 6.1 ± 0.81, p < 0.05). Additionally, patients with RFS ≥ 7 had significantly lower proximal baseline impedance levels than the control group (1970 ± 63 vs 2245 ± 109, p < 0.05). CONCLUSIONS: Patients with pathologic laryngopharyngeal reflux symptom scores had lower proximal baseline impedance levels and lower proximal-to-distal ratios, which may reflect the proximal mucosal noxious effect of the refluxate. These results may indicate that laryngopharyngeal reflux symptoms may be due to chronic acid exposure in the proximal segments of the esophagus, and the proximal-to-distal ratio may be used as a new metric for diagnosis.
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BACKGROUND: The role of sexual activity on gastroesophageal reflux disease (GERD) is an under-recognized concern of patients, and one rarely assessed by physicians. OBJECTIVE: The objective of this article is to determine the influence of sexual activity on the intraesophageal acid exposure and acid reflux events in GERD patients. METHODS: Twenty-one patients with the diagnosis of GERD were prospectively enrolled. Intraesophageal pH monitoring was recorded for 48 hours with a Bravo capsule. All patients were instructed to have sexual intercourse or abstain in a random order two hours after the same refluxogenic dinner within two consecutive nights. Patients were requested to have sex in the standard "missionary position" and women were warned to avoid abdominal compression. The patients completed a diary reporting the time of the sexual intercourse and GERD symptoms. The percentage of reflux time and acid reflux events were compared in two ways: within 30 and 60 minutes prior to and after sexual intercourse on the day of sexual intercourse and in the same time frame of the day without sexual intercourse. RESULTS: Fifteen of 21 GERD patients were analyzed. The percentage of reflux time and number of acid reflux events did not show a significant difference within the 30- and 60-minute periods prior to and after sexual intercourse on the day of sexual intercourse and on the day without sexual intercourse, as well. CONCLUSION: Sexual activity does not predispose to increased intraesophageal acid exposure and acid reflux events. Larger studies are needed to confirm our findings in patients who define reflux symptoms during sexual intercourse.
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BACKGROUND: There is a general belief that gastro-oesophageal reflux increases after meals and especially following a rapid intake. OBJECTIVE: To evaluate the impact of rapid vs. slow food intake on gastro-oesophageal reflux disease (GORD) patients. MATERIALS AND METHODS: Forty-six GORD patients with heartburn and / or acid regurgitation once a week or more often common were included in this study. Participants were asked to eat the same standard meal within either 5 or 30 minutes under observation in a random order on 2 consecutive days. A total of 28 hours of recording were obtained by intraoesophageal impedance pH and number of liquid and mixed reflux episodes within 3 hours of the slow- and fast-eating postprandial periods were calculated. RESULTS: While all patients defined GORD symptoms, 10 (21.7%) had pathological 24-h intraoesophageal impedance measurement, 15 (32.6%) had pathological DeMeester and 21.7% had erosive oesophagitis. No difference has been shown according to the eating speed when all reflux episodes were taken together (754 vs. 733). Speed of food intake also did not have an impact on patients with normal vs. pathological 24-h intraoesophageal impedance or erosive vs. non-erosive. During the first postprandial hour, approximately half of the reflux events were non-acid, compared to 34.2% during the second hour and 26.8% during the third hour (p < 0.001). The number of acid reflux episodes was significantly higher than non-acid reflux especially during the second and third hours and in total for 3 hours. CONCLUSIONS: This first study addressing the effect of eating speed on reflux episodes in GORD patients did not support the general belief that reflux increases following fast eating. Acid and non-acid reflux were similar at the first postprandial hour, then acid reflux episodes were predominantly higher, which implicate the importance of acid pockets.