Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer / A regulação positiva de GINS1 destacou um bom potencial diagnóstico e prognóstico de sobrevivência em três subtipos diferentes de câncer humano

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Evaluation of blood Bisphenol A contents: a case study / Evaluación de las concentraciones de Bisfenol A en la sangre: estudio de caso

OBJECTIVE: It has been recently reported that Bisphenol A (BPA) may leach out into food, beverages and water samples from the plastic ware in which it is stored. Serious health hazards have been reported from BPA. The purpose of this study is to assess the BPA contents in blood and to assess the risk of cancer. METHOD: A total of 100 individuals were selected for study according to the following five age groups: 5-10, 11-20, 21-30, 31-40 and 41-50 years. They were then further divided into normal and diseased. Age, gender, education, source of drinking water, type of food, smoking habit, any exposure to chemicals and history of cancer were elicited during interview. Blood samples were collected and processed for analysis using reversed phase-high performance liquid chromatography (rp-HPLC) in isocratic mode. The mobile phase consisted of acetonitrile and water (1:1) at a flow-rate of 1 ml min-1. RESULTS: Bisphenol A contents found in blood samples of all age groups ranged from 1.53-3.98 (mean = 2.94, SD = 0.9). P-values, for the exposed people and those having a history of cancer, were < 0.05 showing a significant relationship between BPA and cancer. The United States Environmental Protection Agency (US EPA) has established a reference dose of 50 µg/L. Odd ratios and relative risk for smoking habit were < 1 while for all others they were > 1. CONCLUSION: It was concluded from the study that people using bottled water, packaged food, having a history ofcancer and who had been exposed to any type ofchemicals are at higher risk ofdisease.

OBJETIVO: Se ha reportado recientemente que el bisfenol A (BPA) puede filtrarse a alimentos, bebidas y agua, a partir de los recipientes plásticos en que aquellos se almacenan. En tal sentido, se han reportado serios casos de riesgo para la salud a causa del BPA. El propósito de este estudio es evaluar la concentración de BPA en sangre, y el consiguiente riesgo de enfermedades cancerosas. MÉTODO: Un total de 100 individuos fueron seleccionados para el estudio, de acuerdo con los siguientes cinco grupos etarios: 5-10, 11-20, 21-30, 31-40 y 41-50 años. Dichos grupos fueron divididos entonces sobre la base de sujetos normales frente a enfermos. En la entrevista se tomó nota de la edad, el género, la educación, la fuente de agua potable, el tipo de comida, el hábito de fumar, cualquier exposición a productos químicos, así como la historia de cáncer. Las muestras de sangre fueron recogidas y procesadas para realizar análisis, utilizando cromatografía líquida de alta eficacia de fase reversa (rp-HPLC) en modo isocrático. La fase móvil consistió en acetonitrilo y agua (1:1) con una tasa de flujo de 1 ml min-1. RESULTADOS: Las concentraciones de bisfenol-A halladas en las muestras de sangre de todos los grupos etarios, oscilaron de 1.53 - 3.98 (M = 2.94, SD = 0.9). Los valores P para las personas expuestas y con una historia de cáncer, fueron < 0.05, indicando una relación directa entre el BPA y el cáncer. La Agencia de Protección Ambiental de los Estados Unidos (US EPA) ha establecido una dosis de referencia de 50 µg/L. El cociente de probabilidades (odd ratios) y el riesgo relativo con respecto al hábito de fumar fueron < 1 mientras que para todos los otros casos otros fueron >1. CONCLUSIÓN: A partir del estudio se concluye que las personas que usan agua embotellada, alimentos empaquetados, así como las personas que poseen una historia de cáncer, y los individuos que habían estado expuestos a cualquier tipo de productos químicos, presentan un mayor riesgo de enfermedad.

Pharmacokinetic concerns in the management of drug induced vomiting in co-morbid tuberculosis patient: A case report from Malaysia.

A 46 years old patient with history of type II diabetes mellitus (DM) approached chest clinic with complaints of productive cough, low grade fever and night sweating. Positive sputum smear and cavities in upper lobe of left lung confirmed him as a pulmonary tuberculosis patient (PTB). He was prescribed World Health Organization recommended six months therapy for tuberculosis (TB). During treatment, patient suffered from persistent vomiting for which he was prescribed metoclopramide tablet (10mg). Total duration of TB treatment was prolonged up to 10 months which was attributed to frequent vomiting and uncontrolled blood sugar level throughout therapy. Appropriate glycaemic control is cornerstone in management of PTB patients with type II DM. According to United State Pharmacopoeia, dissolution time specification for rifampicin in fixed dose combination (FDC) is 45 minutes. This indicates that anti TB drugs must remain in gastrointestinal tract for at least 45 minutes. Administration of metoclopramide at least one hour before taking anti TB drugs can trim down episodes of vomiting.

Gestion d'une epidemie d' infections associees aux soins

L'objectif de cet article etait de detailler les differentes etapes de l'investigation et de la gestion d'une epidemie d'infections associees aux soins. Une epidemie est la survenue en exces; par rapport a ce qui est observe habituellement; de cas de maladie en un lieu et une periode de temps. Dans le contexte d'infections associees aux soins; l'epidemie peut toucher un service ou plusieurs services d'un meme hopital; et contrairement aux epidemies communautaires; plusieurs micro-organismes peuvent etre a l'origine d'une meme epidemie. L'investigation d'epidemies d'infections associees aux soins comporte plusieurs etapes que sont la confirmation du diagnostic d'infection; la definition de cas; la confirmation du caractere epidemique et la recherche active des cas. Une enquetedescriptive est realisee en premier permettant d'enoncer des hypotheses sur le mode de transmission de l'infection et sur les causes de l'epidemie. Ces hypotheses pourront etre testees dans un deuxieme temps par une enquete epidemiologique analytique; le plussouvent par des enquetes cas-temoins. Parallelement; la mise en place de mesures de controle a pour objectif d'enrayer le phenomene epidemique. Un travail collaboratif entre les differents professionnels de sante est necessaire a la bonne investigation de toute epidemie et conditionne son controle

Effect of near-total thyroidectomy on thyroid orbitopathy due to toxic goiter

The relative merit of operation in the treatment of Graves' ophthalmopathy as well as the extent of surgical resection is still a matter of debate. This work aimed at reporting the assessment of the impact of near-total thyroidectomy on the course of ophthalmopathy including exophthalmos. A total of 20 patients, with thyrotoxic goiters suffering from mild to moderate exophthalmos were enrolled onto this prospective study. Preoperative evaluation of ophthalmopathy was accomplished through the NOSPECS classification, MRI scanning for measuring the extraocular muscle diameters and measurement of the exophthalmos using Hertel's exophthalmometer. Six months postoperatively, ophthalmopathy including exophthalmos was re-evaluated using the same parameters mentioned before. Clinical activity evaluation, exophthalmometry and extraocular muscles measurement by MRI revealed that the majority of the cases experienced improvement of their ophthalmopathy [65%]. This improvement was statistically significant In addition, no major postoperative complications were observed. However, the study, unlike a number of reported retrospective ones, failed to specify any statistically significant prognostic factors affecting the course of ophthalmopathy possibly due to the limited number of cases in general In addition, all of the cases were of relatively young age and thyrotoxic, and the majority were females and non-smoking. Beside the fact that near-total thyroidectomy adds the advantages of total thyroidectomy [no recurrence] to those of subtotal thy-roidectomy [low incidence of temporary and permanent hypoparathyroidism], it has a significant positive impact on thyroid-associated orbitopathy

Morphofunctional characteristics of the interatrial septum in cardiac diseases transesophageal echocardiographic study

Both the morphology and the functions of the interatrial septum in different clinical situations have been addressed only in a few studies, where the attention has been focused particularly on its congenital abnormalities. Our purpose was to study whether the changes of thickness and thinning of the interatrial septum may be related to the age, left atrial dimension and left ventricular functions. So we studied these changes using the transesophageal echocardiography in [60] patients of four groups of cardiovascular discuses. These groups were: Group I: Ischemic heart disease 20 patients. Group II: Dilated cardiomyopathy 20 patients. Group III: Hypertension with stroke 8 patients. Group IV: Corpulmonale 12 patients. All the patients were subjected to thorough clinical examination, 12 leads resting electrocardiography, chest X-ray postero-anterior view and echocardiography in which we made both transthoracic and esophageal approach for each patients. The interatrial septum thinning was calculated as the difference between the thickness of the IAS at atrial systolic phase and the thickness of the IAS at end-ventricular systolic phase. The value was expressed also as percentage of thinning at the end of ventricylar systolic phase. The IAS thickness increases with the age while there is no significant increase in thinning and thinning percentage. The IAS thickness increases in patients of left ventricular dysfunction e.g. [dilated cardiomyopathy, ischemic heart diseases, and hypertensive patients] also it increases in patients of corpulmonale. There is a negative correlation between the IAS thickness and the left atrial dimension, but there is a positive correlation between the IAS thinning and IAS thinning percentage with the left atrial dimension. Patients with prolonged deceleration time of E and isovolumic relaxation time and decreased E/A with or without lower ejection fraction and fractional shortening had less IAS thinning%. On the other hand, patients with shorter deceleration time of E and isovolumic relaxation time and increased E/A with or without lower ejection fraction and fractional shortening had a comparable IAS thinning%.

Cerebral tuberculoma: a role for polymerase chain reaction [PCR] in early diagnosis

Diagnosis of intracranial tuberculomata [ICT] is limited due to the inherent difficulties in isolation of the mycobacterium tuberculosis [MBTb] and the lack of specificity of radiological scans. In this case report, polymerase chain technique [PCR] was used to detect MBTb targeted DNA in the cerebrospinal fluid [CSF] of a patient with intracranial space occupying lesion. The test provided a rapid diagnostic tool confirming MBTb infection and was useful in the management of that patient

Platelet aggregation index and femoropopliteal graft patency

Platelet aggregation index [PAI], based on the aggregation pattern and platelet count, was determined in the 40 patients available for platelet analysis who underwent 53 femoropopliteal bypasses with 6-mm, externally-supported, knitted Dacron grafts from 1982 to1992 mean follow up 50 months]. This index was found to be stable both pre-and postoperatively. The PAI value, the patient's age, history of hypertension atherosclerotic heart disease, diabetes, and/or smoking, the site of the distal anastomosis, previous ipsilateral bypass and state of runoff determined by preoperative angiography were analyzed for predicting closure, using the Cox proportional hazards regression model. Of the studied risk factors, the PAI was the most highly predictive variable for graft closure [P < 0.0001]. An increase of 10 units was associated with an increased relative risk of 2.02. Throughout the follow up period, 15 of l6 grafts remained patent in patients with an PAI < 15, whereas only 2 grafts out of 17 remained patent in patients with a PAI > 30. These data suggest that the PAI is an accurate predictor of the Outcome of femoropopliteal bypass using externally-supported, knitted Dacron grafts