Integration of transcriptome and metabolome provides unique insights to pathways associated with obese breast cancer patients

Information regarding transcriptome and metabolome has significantly contributed to identifying potential therapeutic targets for the management of a variety of cancers. Obesity has profound effects on both cancer cell transcriptome and metabolome that can affect the outcome of cancer therapy. The information regarding the potential effects of obesity on breast cancer (BC) transcriptome, metabolome, and its integration to identify novel pathways related to disease progression are still elusive. We assessed the whole blood transcriptome and serum metabolome, as circulating metabolites, of obese BC patients compared them with non-obese BC patients. In these patients' samples, 186 significant differentially expressed genes (DEGs) were identified, comprising 156 upregulated and 30 downregulated. The expressions of these gene were confirmed by qRT-PCR. Furthermore, 96 deregulated metabolites were identified as untargeted metabolomics in the same group of patients. These detected DEGs and deregulated metabolites enriched in many cellular pathways. Further investigation, by integration analysis between transcriptomics and metabolomics data at the pathway levels, revealed seven unique enriched pathways in obese BC patients when compared with non-obese BC patients, which may provide resistance for BC cells to dodge the circulating immune cells in the blood. In conclusion, this study provides information on the unique pathways altered at transcriptome and metabolome levels in obese BC patients that could provide an important tool for researchers and contribute further to knowledge on the molecular interaction between obesity and BC. Further studies are needed to confirm this and to elucidate the exact underlying mechanism for the effects of obesity on the BC initiation or/and progression

Differential enzymatic activity of common haplotypic versions of the human acidic Mammalian chitinase protein

FWN – Publicaties zonder aanstelling Universiteit Leide

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

The associations between alcohol intake and cardiometabolic risk in African-origin adults spanning the epidemiologic transition.

Cardiometabolic (CM) risk affects approximately 25% of adults globally, and is diagnosed by meeting 3 out of 5 of the following CM risk factors: elevated blood pressure, high triglycerides, elevated blood sugar, low high-density lipoprotein (HDL) level, and abdominal obesity. Adults with CM risk are approximately 22% more likely to have higher mortality rates, and alcohol consumption may be associated with higher CM risk. While previous studies have investigated this potential connection, the majority of them did not include African-origin adults. Therefore, the study aimed to explore the association between alcohol intake and CM risk in 5 African-origin cohorts, spanning the epidemiologic transition in Ghana, South Africa, Jamaica, Seychelles and the United States of America. Measurements included clinical measures for CM risk and self-reported alcohol consumption. Each participant was categorized into one of three drinking categories: non-drinker, light drinker (1-3 drinks daily for men and 1-2 drinks daily for women) and heavy drinker (4 or more drinks every day for men and 3 or more drinks per day for women). Using non-drinker status as the reference, the association between alcohol consumption status and prevalence of each of the five CM risk factors and overall elevated CM risk (having 3 out of 5 risk factors) was explored, adjusting for site, age and sex. Associations were explored using logistic regression and significance was determined using odds ratios (OR) and 95% confidence intervals. Neither light nor heavy drinking was associated with increased odds for having higher CM risk compared to nondrinkers (OR = 1.05, p = 0.792 and OR = 1.11, p = 0.489, respectively). However, light drinking was associated with lower odds for having low high density lipoproteins (HDL) cholesterol (OR = 0.69, p = 0.002) and increased risk for high triglycerides (OR = 1.48, p = 0.030). Heavy drinking was associated with elevated blood pressure (OR = 1.59, p = 0.002), high triglycerides (OR = 1.73, p = 0.006) and decreased risk of low HDL-cholesterol (OR = 0.621, p < 0.0005). Finally, country-specific analyses indicated that the relationship between heavy drinking and elevated CM risk varied widely across sites. While several CM risk factors were associated with alcohol consumption, the associations were inconsistent and varied widely across five international cohorts of African-origin. Future studies should focus on understanding the individual site-related effects

Influence of Sapindus mukorossi extract in comparison to 17% EDTA as final root canal irrigant on the sealer penetration and microleakage of dentinal tubules

OBJECTIVE: The study evaluated the effect of Sapindus mukorossi (SM) extract as a final root canal irrigant on sealer penetration (SP) in dentinal tubules and microleakage. MATERIALS AND METHODS: Samples were selected based on inclusion and exclusion criteria. An access opening in all samples was performed and the working length was decided using pro taper for canal finishing along with constant irrigation. Specimens were randomly divided into 3 groups. Group 1 was irrigated with 3 ml of 17% EDTA; group 2 was irrigated with SM irrigant and group 3 samples were irrigated with 0.9% saline. After obturation, samples were vertically placed in 1% methylene blue dye cut in half longitudinally, and viewed under a stereomicroscope. Analysis of SP in the dentinal tubule was assessed using scanning electron microscopy (SEM). For microleakage assessment, mean and standard deviation were reported and One-Way ANOVA was applied. SP was compared using Kruskal-Wallis’ test. For inspecting the interaction between SM/EDTA and NaOCl, Fisher’s exact test was applied. No statistically significant difference between microleakage in any of the tested groups was observed. The control group showed minimum leakage as compared to EDTA and SM. RESULTS: The results displayed that there was no significant difference, (p=0.67), between dentinal tubule SP at 2 mm. A significant difference between dentinal tubule SP among groups at 5 mm was observed (p<0.05). CONCLUSIONS: SM ethanolic extract showed comparable outcomes of smear layer removal and sealer penetration to 17% EDTA, as a final irrigant in root canal cleaning. Therefore, SM has the potential to be used as an adjuvant final irrigant in conjunction with NaOCl

Relationship between physician and industry in Aragon (Spain) Relación entre los médicos y la industria en Aragón (España)

Objective: To describe the relationship between industry and physicians and to analyze the physician characteristics associated with the probability of receiving benefits from industry in Aragon (Spain). Methods: We carried out an observational, cross-sectional study in which Aragonese physicians (north-east region in Spain) from public and private settings completed an anonymous questionnaire on a web page between June and November 2008. Visits/month with industry, samples, gifts, reimbursements and payments were used as dependant variables in the regression analyses. Year of medical license, specialty, work setting, time spent on direct care, articles read/month and being a resident's tutor were used as independent variables. Results: A total of 659 questionnaires were considered valid for the analysis. Overall, 87% (n=573) of the respondents reported they had received some benefit in the previous year and 90.1% (n=593) reported having held meetings with industry representatives monthly. Non-clinical specialists received fewer gifts (odds ratio [OR]=0.38; 95% confidence interval [95%CI]: 0.18-0.77), reimbursements (OR=0.14; 95%CI: 0.06-0.35) and payments (OR=0.30; 95%CI: 0.13-0.74) than their clinical colleagues. The probability of receiving reimbursements (OR=0.37; 95%CI: 0.15-0.89) and payments (OR=0.39; 95%CI: 0.20-0.77) was lower in primary care physicians. Conclusions: This study, performed in a sample of physicians from a southern European region, demonstrates differences in the intensity of the physician-industry relationship depending on physician specialty and work setting. These results provide important information for improving transparency and for future research on the appropriateness and efficiency of prescription in Spain and other countries with similar health systems.<br>Objetivo: Describir, en Aragón, la relación entre los médicos y la industria, y analizar las características de los médicos que se asocian con la probabilidad de recibir beneficios. Métodos: Estudio transversal en el cual médicos aragoneses del sector público y privado rellenaron un cuestionario anónimo en una página web, entre junio y noviembre de 2008. El número de visitas/mes con la industria, muestras, regalos, dietas y pagos se incluyeron como variables dependientes en los modelos de regresión. Las variables año de licenciatura, especialidad, lugar de trabajo, tiempo de atención, artículos leídos/mes y ser tutor de residentes se utilizaron como variables independientes. Resultados: Se consideraron válidos 659 cuestionarios completados. En general, el 87% de los que respondieron contestaron que habían recibido algún beneficio en el último año, y un 90,1% (n=593) respondieron que habían tenido alguna entrevista con representantes de la industria mensualmente. Las especialidades no clínicas recibieron menos regalos (odds ratio [OR]=0,38; intervalo de confianza del 95% [IC95%]: 0,18-0,77), dietas (OR=0,14; IC95%: 0,06-0,35) y pagos (OR=0,30; IC95%: 0,13-0,74) que sus colegas clínicos. La probabilidad de recibir dietas (OR=0,37; IC95%: 0,15-0,89) y pagos (OR=0,39; IC95%: 0,20-0,77) fue menos probable para los médicos de atención primaria. Conclusiones: Este estudio muestra diferencias en la intensidad de la relación médico-industria en función de la especialidad y el lugar de trabajo del médico. Esta información se considera importante para mejorar la transparencia y para desarrollar investigaciones futuras sobre la adecuación y la eficiencia de la prescripción en nuestro país y en otros con sistemas sanitarios similares