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BACKGROUND: Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS: This randomized phase III trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1 : 1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n = 103 without upfront PTR, n = 101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (interquartile range 59-71 years). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% confidence interval 16.0-22.2 months) compared with 20.1 months (95% confidence interval 17.0-25.1 months) in the upfront PTR arm (P = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (P = 0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSIONS: Addition of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.
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This research investigates the potential use of Jurinea mesopotamica Hand.-Mazz. (Asteraceae) in cancer treatment. In this study, a plant extract was prepared using all parts of J. mesopotamica, and its effect on the proliferation of cancer and normal cells was tested using the MTT method. It was found to have a selective cytotoxic effect on prostate cancer cells, with the lowest IC50 (half-maximal inhibitory concentration) of 10µg/mL found in the butanol extract (JMBE). The extract suppressed the proliferation of prostate cancer cells (67 %), disrupted organelle integrity (49 %), increased reactive oxidative stress (66 %), and triggered cell death (51 %). In addition, apoptotic gene expressions and protein levels increased, and the profile of amino acids related to energy metabolism was elevated. Based on LC-MS/MS results, the plant contained higher levels of flavonoids, including isoquercitrin, cosmosiin, astragalin, nicotiflorin, luteolin, and apigenin. These results suggest that J. mesopotamica has a selective effect on prostate cancer due to its high flavonoid content and might be a promising natural alternative for cancer treatment.
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Asteraceae , Neoplasias de la Próstata , Masculino , Humanos , Cromatografía Liquida , Apoptosis , Espectrometría de Masas en Tándem , Neoplasias de la Próstata/tratamiento farmacológico , Flavonoides/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Línea Celular TumoralRESUMEN
OBJECTIVE: The aim of this study is to investigate the frequency of fragmented QRS and its associations with clinical findings and prognosis in children diagnosed with dilated cardiomyopathy with or without left ventricular non-compaction. METHODS: This retrospective study was conducted between 2010 and 2020. Patients with dilated cardiomyopathy were classified into two groups according to the presence of left ventricular non-compaction: Dilated cardiomyopathy with left ventricular non-compaction and dilated cardiomyopathy without left ventricular non-compaction. Patients were also divided into two groups according to the presence of fragmented QRS (fragmented QRS group and non-fragmented QRS group). RESULTS: Twenty-three of 44 patients (52.3%) were male. Among left ventricular non-compaction patients, the fragmented QRS group had more complex ventricular arrhythmias (p = 0.003). Patients with fragmented QRS had a significantly higher rate of major adverse cardiac events and/or cardiac death in both cardiomyopathy groups (p = 0.003 and p = 0.005). However, the rate of major adverse cardiac events and/or cardiac death was similar between dilated cardiomyopathy patients with and without left ventricular non-compaction. Multivariate logistic regression analysis showed that the presence of fragmented QRS strongly predicts major adverse cardiac events and/or cardiac death (odds ratio, 31.186; 95% confidence interval, 2.347-414.307). Although the survival rates between cardiomyopathy groups were similar, patients with fragmented QRS had a markedly lower survival rate during the follow-up period, as mean of 15 months (p = 0.001). CONCLUSION: Our study showed that the presence of fragmented QRS may be an important ECG sign predicting an major adverse cardiac event and/or cardiac death in patients with dilated cardiomyopathy. We believe that recognising fragmented QRS could be valuable in forecasting patient prognosis and identifying high-risk patients who require additional support.
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Cardiomiopatía Dilatada , Niño , Humanos , Masculino , Femenino , Cardiomiopatía Dilatada/complicaciones , Cardiomiopatía Dilatada/diagnóstico , Estudios Retrospectivos , Electrocardiografía , Arritmias Cardíacas/etiología , Arritmias Cardíacas/complicaciones , Pronóstico , MuerteRESUMEN
OBJECTIVE: This study aimed to determine the serum level of Ubiquitin C-terminal hydrolase 1 enzyme during a migraine attack and after its treatment. METHODS: Blood samples of 43 patients and 30 healthy controls who presented to the emergency department with migraine attacks were analysed. Study sample was classified into three groups: Group 1 (patients presenting with migraine attack), Group 2 (4thhour after dexketoprofen treatment) and Group 3 (healthy control). Demographic data of patients, visual analogue scale and Ubiquitin C-terminal hydrolase 1 levels were analysed. RESULTS: Median (IQR) Ubiquitin C-terminal hydrolase 1 levels were 13.70 (10.75-18.92) in Group 1, 9.45 (6.95-11.56) in Group 2 and 6.04 (3.88-8.72) ng/mL in Group 3; the Kruskal-Wallis test result showed a significant difference between the groups (P<0.001). Following the Kruskal-Wallis test, the post-hoc Dunn test was performed for binary comparison between the groups, which revealed significant differences between all groups (Group 1-Group 2, Group 1-Group 3 and Group 2-Group 3 with P=0.001, P<0.001 and P=0.008, respectively). Moreover, a significant positive correlation was found between VAS score and UCHL1 levels before treatment (r=0.884, P<0.001). CONCLUSION: UCHL1 levels of patients with migraine increase during acute attack and they can be used to assess the severity of attack and response to treatment.
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Trastornos Migrañosos , Ubiquitina Tiolesterasa , Humanos , Servicio de Urgencia en Hospital , Dimensión del DolorRESUMEN
Intercellular Adhesion Molecule-1 (ICAM-1) is considered to be a cancer biomarker in the assessment of metastatic potential in patients and an early indicator of atherosclerosis. A labelless biosensor based on the surface plasmon resonance (SPR) signal from the specific affinity interaction of an aptamer and a soluble ICAM-1 protein was developed for blood samples. The developed aptasensor provided real-time information on the concentration of the ICAM-1 protein in blood when integrated to a purification step based on a magnetic pull-down separation. The SPR aptasensor was highly specific with a limit of detection of 1.4/0.2 ng ml-1, which was achieved through aptamer-functionalized silica-coated magnetic nanoparticles.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Oro , Humanos , Molécula 1 de Adhesión Intercelular , Límite de Detección , Resonancia por Plasmón de SuperficieRESUMEN
Heavy metal contamination in the coastal and marine ecosystems is becoming a serious risk to aquatic organisms and humans. This study reports the effects, including genetic damage, of accumulations of trace metals on Liza aurata, which is used as a bio-indicator species, in the Payas coast of Iskenderun Bay, north-eastern Mediterranean by COMET Assay. L. aurata were seasonally collected from a sampling site and a reference site for one year. Physicochemical parameters in water and trace metals in the tissues of fish collected from these sites were determined by electrochemical techniques. High DNA damage frequency in L. aurata was observed along the Payas coast of Iskenderun Bay compared to the reference site because of pollutants. The detected high levels of Cd, Pb, Fe and Cu accumulation in L. aurata exceed the maximum levels allowed by the national and international limit values. Significant positive correlations between Cd, Pb, Hg, Cr, Fe, Zn, and Cu accumulations and DNA damage parameters were observed in the present study. Additionally, we first reported the successful use of the electrochemical technique in the determination of trace metal concentrations in mullet. Moreover, L. aurata constitutes a key tool as a sentinel organism for biomonitoring of coastal ecosystems.
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Metales Pesados , Perciformes , Smegmamorpha , Oligoelementos , Contaminantes Químicos del Agua , Animales , Humanos , Monitoreo del Ambiente/métodos , Bioacumulación , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Ecosistema , Cadmio , Plomo , Metales Pesados/toxicidad , Daño del ADNRESUMEN
1. This study evaluated the effect of a higher incubation temperature on body weight, plasma profile, histology and expression of myogenin (MYOG), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor A (VEGFA) genes in breast muscle of embryos and broilers from two commercial strains.2. A total of 784 eggs from Ross 308 and Cobb 500 broiler breeder flocks were used. Half of the eggs per strain were incubated at control temperature (37.8°C), whereas the other half were exposed to heat treatment (HT) of 38.8°C between embryonic day (ED) 10 and 14, for 6 h/day. Embryos and chicks were sampled on ED 19 and at hatch. A total of 480, one-day-old chicks per strain and incubation temperature were reared up to 42 d post-hatch.3. The HT increased hatch weight of Ross chicks and 42-d body weight of broilers from both strains. Lower plasma triacylglycerol levels were measured for HT embryos and broilers on ED 19 and 42 d post-hatch, respectively. HT reduced plasma T3 levels in Ross embryos and broilers for the same periods. Hepatic TBARS concentrations were elevated by HT compared to the control incubation.4. The HT reduced breast muscle VEGFA gene expression of Cobb embryos on ED 19, whereas expression was stimulated in day-old chicks. At 42 d post-hatch, fibre area was increased by HT regardless of strain. Compared to the control incubation, HT increased the breast yield of Ross broilers and leg yield of Cobb. Ross-HT broilers had a higher pH at 24 h after slaughter and better water holding capacity than Cobb-HT broilers.5. These results suggested that HT increased body weight, fibre area, IGF-I gene expression and lowered plasma triacylglycerol levels of broiler chickens from both strains at 42 d. However, HT influenced the expression of VEGF-A and MYOG genes and meat quality differently between the broiler strains.
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Pollos , Factor A de Crecimiento Endotelial Vascular , Animales , Peso Corporal , Pollos/genética , Óvulo , Músculos Pectorales , Temperatura , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
People's day-to-day routines have changed drastically since the outbreak of the COVID-19 pandemic. One of the changes to take place has been the transition to online learning due to the changing conditions in learning environments. One of the factors that guide students through learning environments is their emotions. The few existing scales that measure the emotions of adolescents in learning environments have been developed with consideration of face-to-face learning environments and their items do not adequately express the state of online environments. For this reason, this study aimed to develop a scale which reveals the emotions of adolescents that may affect their academic success with regard to this transition of learning environments as they attend online lessons. A total of 3,655 middle and high school students living in Istanbul, Turkey, participated in the study. The scoring system was designed with regard to the frequency with which each student reading an item experiences the relevant emotion for the item in the online learning environment. Exploratory and confirmatory factor analyses conducted show the scale to possess a four-dimensional structure. These dimensions are enjoyment-pride, boredom-hopelessness, loneliness and anxiety. For all dimensions of the scale, Cronbach alpha values range between .93 and .83. 'Positive and Negative Affects Schedule-Children' was used to confirm the scale's criterion-related validity, and correlations between dimensions were examined. After validity and reliability studies, the Adolescent Emotion Scale for Online Lessons was found to be sufficient. The scale can be used by experts and teachers who wish to determine adolescents' emotions during a period of online learning.
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INTRODUCTION: This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. METHODS: Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. RESULTS: In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval [CI] 2.8-87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%-15%) and 8% (95% CI 2%-15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI -1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum ß-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%-28%). CONCLUSIONS: After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.
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Meropenem , Combinación Piperacilina y Tazobactam , beta-Lactamasas , Antibacterianos/efectos adversos , Antibacterianos/farmacología , Humanos , Meropenem/efectos adversos , Meropenem/farmacología , Pruebas de Sensibilidad Microbiana , Mortalidad , Combinación Piperacilina y Tazobactam/efectos adversos , Combinación Piperacilina y Tazobactam/farmacología , Reproducibilidad de los Resultados , beta-Lactamasas/genéticaRESUMEN
CD55 and CD59 are complement regulatory proteins suggested to be related with progression of diabetes and its complications. The stromal cell-derived factor 1 (SDF-1) and C-X-C chemokine receptor type 4 (CXCR-4) are chemokine proteins. We aimed to investigate the relation of CD55 and CD59 expression levels and polymorphisms of SDF-1 and CXCR-4 with type 2 diabetes mellitus (T2DM) and its complications. Seventy-five T2DM patients and 73 controls were enrolled. Expression levels of CD55 and CD59 were measured by FACS Calibur; qRT-PCR was used to determine SDF-1 and CXCR-4 gene polymorphisms. CD55 and CD59 expressions in patients with nephropathy, retinopathy and cardiovascular disease were significantly lower than controls. Frequency of CXCR-4 T allele carrying was high in patients and created 1.6 fold risk for the disease (p = .07). CXCR-4 a allele carriers had decreased nephropathy; although there was no statistical significance in carrying CXCR-4 T allele, presence of nephropathy was approximately 2 times higher (p = .254). The nephropathy risk increased 10-fold in CXCR-4 TT genotype carriers (p = .02). All SDF-1 CC genotype carriers had retinopathy, so, it was considered that the CC genotype was effective in retinopathy development (p = .031). For the presence of cardiovascular disease, significant difference was observed for SDF-1 genotypes. Increased cardiovascular risk of 5- and 1.9-fold in SDF-1 T (p = .007) and CXCR-4 T (p = .216) allele carriers, respectively, was observed. We suggest that CD55 and CD59 protein levels and SDF-1 and CXCR-4 have predictive importance in process, complications and tendency of T2DM.
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Antígenos CD55/metabolismo , Antígenos CD59/metabolismo , Enfermedades Cardiovasculares/genética , Quimiocina CXCL12/genética , Diabetes Mellitus Tipo 2/inmunología , Genotipo , Receptores CXCR4/genética , Anciano , Antígenos CD55/genética , Antígenos CD59/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo GenéticoRESUMEN
OBJECTIVE: To investigate the changes in semen quality and bioavailable testosterone concentrations in acromegalic male patients according to their disease activity and compare them with patients with non-functional pituitary adenoma (NFA) and healthy controls (HC). METHODS: Twenty-four acromegalic patients with active disease, 22 acromegalic patients in remission, 10 HCs, and 10 patients with NFA were included. RESULTS: Total and calculated bioavailable testosterone concentrations were lower in patients with pituitary disease. Patients with acromegaly had more severely impaired total testosterone levels and semen parameters in comparison to HCs and patients with NFA. The degree of impairment was more prominent in acromegalic patients with active disease than acromegalic patients in remission. Acromegalic patients in remission had residual impairments in both semen quality and testosterone concentrations. Patients with NFA had the lowest concentrations of calculated bioavailable testosterone, followed by acromegalic patients with active disease and acromegalic patients in remission. Increasing growth hormone (GH) levels were found to be associated with both more severely impaired semen quality and androgen concentrations. CONCLUSION: Growth hormone hypersecretion can disturb reproductive biology and thereof semen quality. The reduction in semen quality and androgen levels may not fully recover upon disease control. Clinicians should be aware of the increased risk of impaired semen parameters and reduced total/bioavailable levels in acromegalic patients, especially in the setting of active disease.
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Acromegalia , Hormona del Crecimiento , Neoplasias Hipofisarias , Análisis de Semen/métodos , Testosterona , Acromegalia/diagnóstico , Acromegalia/epidemiología , Acromegalia/metabolismo , Acromegalia/fisiopatología , Aptitud Genética/fisiología , Hormona del Crecimiento/análisis , Hormona del Crecimiento/biosíntesis , Hormona del Crecimiento/sangre , Humanos , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Enfermedades de la Hipófisis/diagnóstico , Enfermedades de la Hipófisis/etiología , Enfermedades de la Hipófisis/metabolismo , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/metabolismo , Inducción de Remisión , Testosterona/análisis , Testosterona/sangre , Turquía/epidemiologíaRESUMEN
In this study, the use of the three-dimensional modeling method was tested in taking some body measurements in camels with a practical method and was compared with other measurement methods. As the animal material of the study, 12 single-humped dromedary female camels and 14 double-humped Camelus dromedarius × Camelus bactrianus: F1 male camels, a total of 26 camels, were used in three camel farms in Incirliova district of Aydin province. The body measurements are taken from each animal by using different three methods, namely by the manual method (MM), by the photography method (PM), and by the three-dimensional modeling method (3D) were the withers height (WH), the back height (BH), the rump height (RH), the body length (BL), the brisket height (BRH), the abdominal height (AH), the shoulder width (SW), and the rump width (RW), and these values were compared with each other. As a result of this study, the mean values of MM and 3D measurement values were very close to each other and the difference between them was found to be statistically insignificant (P < 0.05). The difference between the means of PM and MM/3D measurement values was found to be significant (P < 0.05). In the measurements taken by MM, 3D, and PM methods in male camels, the values obtained by MM and 3D methods for WH, BH, RH, BRH, AH, BL, and SW were very close to each other and the differences between them were found insignificant statistically (p < 0.05). On the determined regression graph, a linear was found between MM and 3D measurement values. As a result of this study, it has been determined that the 3D modeling method can be used as a remote and more practical method in determining the morphological features of large-scale animals such as camels more reliably, more easily, and more practically.
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Camelus , Animales , Femenino , MasculinoRESUMEN
OBJECTIVES: Although the data in the literature regarding the etiopathogenesis of adrenal adenomas are scarce, the neutrophil/lymphocyte ratio (NLR) is an easy-to-calculate parameter that has gained popularity in recent years as an indicator of subinflammation. In this study, we aimed to show the changes in NLR in patients with adrenal incidentaloma. METHODS: The anamnesis, laboratory and radiology records of the patients with adrenal incidentaloma in the last 1 year were examined. Functional adrenal incidentalomas were excluded. RESULTS: The records of clinical, laboratory and radiological findings of 60 patients were examined. The mean neutrophil/lymphocyte ratio was found to be 2.49±1.29 (0.89-6.84). There was no relationship between NLR, biochemical parameters and hormone levels. A weakly positive correlation was found between NLR and mass size (p=0.04; r=0.26). CONCLUSION: Adrenal incidentaloma has become one of the clinical problems frequently encountered by endocrinologists in recent years. Even when they are nonfunctional, they are thought to be associated with various metabolic disorders and inflammation. With this study, we have captured a clue to inflammation, and we are sharing the findings described herein (Tab. 1, Ref. 28) Keywords: adrenal, neutrophil, lymphocyte.
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Neoplasias de las Glándulas Suprarrenales , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Humanos , Hallazgos Incidentales , Linfocitos , NeutrófilosRESUMEN
BACKGROUND: Patients with brain metastases (BM) from human epidermal growth factor receptor 2 (HER2)-positive breast cancer represent a difficult-to-treat population. Trastuzumab emtansine (T-DM1) has shown potential activity in this subset of patients in small clinical series. PATIENTS AND METHODS: KAMILLA is an ongoing, phase IIIb study of T-DM1 in patients with HER2-positive locally advanced/metastatic breast cancer with prior HER2-targeted therapy and chemotherapy. Patients received T-DM1 3.6 mg/kg every 3 weeks (intravenously) until unacceptable toxicity, withdrawal of consent, or disease progression. Tumor response and clinical outcomes in patients with baseline BM were evaluated in this post hoc, exploratory analysis. The main outcome measures were best overall response rate (complete response + partial response) and clinical benefit rate (complete response + partial response + stable disease lasting ≥6 months) by RECIST v1.1 criteria, progression-free survival, overall survival, and safety. RESULTS: Of 2002 treated patients, 398 had baseline BM. In 126 patients with measurable BM, the best overall response rate and clinical benefit rate were 21.4% [95% confidence interval (CI) 14.6-29.6] and 42.9% (95% CI 34.1-52.0), respectively. A reduction in the sum of the major diameters of BM ≥30% occurred in 42.9% (95% CI 34.1-52.0), including 49.3% (95% CI 36.9-61.8) of 67 patients without prior radiotherapy to BM. In the 398 patients with baseline BM, median progression-free survival and overall survival were 5.5 (95% CI 5.3-5.6) months and 18.9 (95% CI 17.1-21.3) months, respectively. The adverse event profile was broadly similar in patients with and without baseline BM, although nervous system adverse events were more common in patients with [208 (52.3%)] versus without [701 (43.7%)] baseline BM. CONCLUSION: This exploratory analysis of patients with HER2-positive metastatic breast cancer and BM enrolled in a prospective clinical trial shows that T-DM1 is active and well-tolerated in this population. T-DM1 should be explored further in this setting. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01702571.
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Neoplasias Encefálicas , Neoplasias de la Mama , Maitansina , Ado-Trastuzumab Emtansina , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias de la Mama/tratamiento farmacológico , Humanos , Maitansina/efectos adversos , Estudios Prospectivos , Receptor ErbB-2/genética , Trastuzumab/efectos adversosRESUMEN
Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation-contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term.
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Cardiotónicos/uso terapéutico , Acoplamiento Excitación-Contracción/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Choque Cardiogénico/tratamiento farmacológico , Enfermedad Aguda , Animales , Antioxidantes/efectos adversos , Antioxidantes/uso terapéutico , Calcio/metabolismo , Cardiotónicos/efectos adversos , Estudios de Casos y Controles , Catecolaminas/efectos adversos , Catecolaminas/uso terapéutico , Ensayos Clínicos como Asunto , Diástole/efectos de los fármacos , Dobutamina/efectos adversos , Dobutamina/uso terapéutico , Perros , Metabolismo Energético/efectos de los fármacos , Insuficiencia Cardíaca/mortalidad , Humanos , Mitocondrias/metabolismo , Modelos Animales , Contracción Miocárdica/efectos de los fármacos , Óxidos de Nitrógeno/efectos adversos , Óxidos de Nitrógeno/uso terapéutico , Oxidación-Reducción/efectos de los fármacos , Inhibidores de Fosfodiesterasa/efectos adversos , Inhibidores de Fosfodiesterasa/uso terapéutico , Placebos/administración & dosificación , Receptores Adrenérgicos/efectos de los fármacos , Sarcómeros/efectos de los fármacos , Sarcómeros/metabolismo , Choque Cardiogénico/mortalidad , Simendán/efectos adversos , Simendán/uso terapéutico , Porcinos , Sístole/efectos de los fármacos , Urea/efectos adversos , Urea/análogos & derivados , Urea/uso terapéuticoRESUMEN
BACKGROUND: X-linked agammaglobulinemia (XLA) is characterized by absent or severely reduced B cells, low or undetectable immunoglobulin levels, and clinically by extracellular bacterial infections which mainly compromise the respiratory tract. We aimed to analyze the clinical, immunological and genetic characteristics of 22 male children with XLA. METHODS: Twenty-two children with XLA from 12 unrelated families were enrolled in this study. Clinical and demographic features of patients, serum immunoglobulin levels, percentage of B cells and BTK gene mutations were reviewed retrospectively. RESULTS: We identified 12 different mutations in 22 patients from 12 unrelated families. The most frequent type of mutation was premature stop codon (33.3%). Ten mutations had been reported previously including three missense mutations (c.1774T>C, c.1684C>T, c.83G>T), three premature stop codons (c.1558C>T, c.1573C>T, c.753G>A), two splice-site (c.683-1G>A, c.1567-12_1567-9delTTTG) and two small nucleotide deletions (c.902-904_delAAG, c.179_181delAGA). Two novel mutations of the BTK gene were also presented and included one splice-site mutation (c.391+1G>C) and one premature stop codon mutation (c.1243_1243delG). Six out of 12 mutations of the BTK gene were located in the SH1 domain, two in the PH domain, two in the SH3 domain and two in the SH2 domain. Three patients had a history of severe infection before diagnosis. We did not identify any correlation between severity of clinical symptoms and the genotype. CONCLUSIONS: Our results show that mutations in southeast Turkey could be different from those in the rest of the world and molecular genetic tests are an important tool for early confirmed diagnosis of XLA.
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Agammaglobulinemia Tirosina Quinasa/genética , Agammaglobulinemia/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Genotipo , Mutación/genética , Adolescente , Agammaglobulinemia/fisiopatología , Niño , Preescolar , Progresión de la Enfermedad , Estudios de Asociación Genética , Enfermedades Genéticas Ligadas al Cromosoma X/fisiopatología , Predisposición Genética a la Enfermedad , Perfil Genético , Humanos , Lactante , Masculino , Linaje , Polimorfismo Genético , Turquía , Adulto JovenAsunto(s)
Demencia , Gabapentina , Pregabalina , Agitación Psicomotora , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Conducta Motora Aberrante en la Demencia/tratamiento farmacológico , Aminas/uso terapéutico , Demencia/tratamiento farmacológico , Demencia/complicaciones , Gabapentina/uso terapéutico , Ácido gamma-Aminobutírico/uso terapéutico , Pregabalina/uso terapéutico , Agitación Psicomotora/tratamiento farmacológico , Agitación Psicomotora/etiologíaRESUMEN
INTRODUCTION: In this research, it is planned to investigate the differences in neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, reticulocyte distribution width, and platelet distribution width values of groups of benign laryngeal lesion, precancerous laryngeal lesion, and laryngeal squamous cell carcinoma and among patients with different stages of tumors in laryngeal carcinoma and precancerous laryngeal lesion groups, and whether these values carry a prognostic features. MATERIALS AND METHODS: The investigated parameters determined from preoperative blood samples of patients have been compared among the groups and in the subgroups according to severity of illness in laryngeal carcinoma and precancerous laryngeal lesion groups. Also, the laryngeal carcinoma and precancerous laryngeal lesion groups were divided into two subgroups as good and poor prognosis and were compared with patients having good prognosis requiring no additional treatment during the follow-up, and the statistical significance of the differences was examined. RESULTS: On comparison, statistically significant differences were only observed between the gross larynx carcinoma group and other lesions. Apart from that, when the values were evaluated in terms of prognosis, no significant statistical results were found in any of the values. CONCLUSION: Despite the significant statistical results seen in the gross tumors, it is known that there are more objective methods for identifying those lesions in clinical use. We conclude that caution should be exercised when using these new hematological parameters, which can be affected by many factors.
Asunto(s)
Neoplasias Laríngeas/sangre , Lesiones Precancerosas/sangre , Carcinoma de Células Escamosas de Cabeza y Cuello/sangre , Adulto , Anciano , Índices de Eritrocitos , Femenino , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Monocitos , Neutrófilos , Recuento de Plaquetas , Lesiones Precancerosas/patología , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
A novel ratiometric colorimetric and fluorescent dual probe based on Eriochrome Black T (EBT)-Eu3+ complex was designed to detect dipicolinic acid (DPA), a major constituent of bacterial spores, with high sensitivity and selectivity. UV-vis titration experiments demonstrated that EBT and Eu3+ ions formed a 1:1 coordination pair in water. In the presence of Eu3+ ions, the blue solution of EBT changed to magenta, however, upon the addition of DPA, the magenta color changed to blue immediately and characteristic fluorescence emission from DPA-Eu3+ complex was observed. In addition, the sensitivity of the system was further evaluated on Geobacillus stearothermophilus spores and as low as 2.5 × 105 spores were detected.
Asunto(s)
Compuestos Azo/química , Europio/química , Colorantes Fluorescentes/química , Geobacillus stearothermophilus/química , Ácidos Picolínicos/análisis , Esporas Bacterianas/química , Técnicas Biosensibles/métodos , Colorimetría/métodos , Complejos de Coordinación/química , Geobacillus stearothermophilus/aislamiento & purificación , Espectrometría de Fluorescencia/métodos , Esporas Bacterianas/aislamiento & purificaciónRESUMEN
AIM: Several trials have shown that preoperative (chemo)radiotherapy (CRT) reduces local recurrence rates (LRRs) in rectal cancer (RC). The use of CRT varies greatly between countries. It is unknown whether the restrictive use of CRT in Denmark results in a higher LRR relative to other countries. The aim was to evaluate the LRR in a national Danish consecutive cohort of patients with RC. METHODS: All data from patients with RC in Denmark in 2009-2010 who were operated on with curative intent were retrieved from the Danish Colorectal Cancer Group database. Patients with metastases at the time of diagnosis, patients with synchronous colon cancer, and patients, in whom only local surgical procedures were performed, were excluded. In total, 1633 patients met the inclusion criteria. Clinical follow-up was at least five years with a cut-off date of 31 December 2015. RESULTS: Clinical follow-up was 5.4 years (median) with an interquartile range of 4.5-6.1 years. Of all included patients, 479 (29%) were treated with preoperative long-course CRT. Local recurrence was found in 68 patients, resulting in an LRR of 4.2%, and 182 (11%) patients developed distant metastases. Five-year overall survival was 74% (95% CI: 71.64-75.91). CONCLUSIONS: Five-year follow-up of curatively treated patients with RC in Denmark revealed a low LRR. This figure is identical to those reported in other Nordic countries, despite Denmark's considerably stricter guidelines for CRT. The obtained results justify the currently adopted restrictive use of preoperative CRT in Denmark.