Potential of miR-21 to Predict Incomplete Response to Chemoradiotherapy in Rectal Adenocarcinoma

Background: Patients with locally advanced rectal adenocarcinoma (LARC) are treated with neoadjuvant chemoradiotherapy (CRT). However, biomarkers for patient selection are lacking, and the association between miRNA expression and treatment response and oncological outcomes is unclear. Objectives: To investigate miRNAs as predictors of response to neoadjuvant CRT and its association with oncological outcomes. Methods: This retrospective study analyzed miRNA expression (miR-16, miR-21, miR-135b, miR-145, and miR-335) in pre- and post-chemoradiation rectal adenocarcinoma tissue and non-neoplastic mucosa in 91 patients treated with neoadjuvant CRT (50.4 Gy) and proctectomy. Two groups were defined: a pathological complete responders group (tumor regression grade—TRG 0) and a pathological incomplete responders group (TRG 1, 2, and 3). Results: miR-21 and miR-135b were upregulated in tumor tissue of incomplete responders comparing with non-neoplastic tissue (p = 0.008 and p < 0.0001, respectively). Multivariate analysis showed significant association between miR-21 in pre-CRT tumor tissue and response, with a 3.67 odds ratio (OR) of incomplete response in patients with higher miR-21 levels (p = 0.04). Although with no significance, patients treated with 5-fluorouracil (5-FU) presented reduced odds of incomplete response compared with those treated with capecitabine (OR = 0.19; 95% confidence interval (CI) 0.03–1.12, p = 0.05). Moreover, significant differences were seen in overall survival (OS) in relation to clinical TNM stage (p = 0.0004), cT (p = 0.0001), presence of distant disease (p = 0.002), mesorectal tumor deposits (p = 0.003), and tumor regression grade (p = 0.04). Conclusion: miR-21 may predict response to CRT in rectal cancer (RC).info:eu-repo/semantics/publishedVersio

Prevalence of spontaneous, induced labour or planned caesarean section and factors associated with caesarean scetion and factors associated with caesarian section in low-risk women in southern Brazil

Objective This study aimed to examine the prevalence of spontaneous labour, induced labour and planned caesarean section in low-risk women; to identify the contribution of each group to the overall caesarean section rate; and to estimate factors associated with caesarean section in low-risk women according to spontaneous labour, induced labour and planned caesarean section. Design Cross-sectional hospital-based study of postpartum women and newborns, using data from the survey Birth in Brazil, Southern region. In the sample of 2,668 low-risk women, a descriptive analysis was undertaken and a Multinomial Logistic Regression model was applied to verify associations among caesarean section and spontaneous labour, induced labour and planned caesarean section in comparison with vaginal birth. Measurements and Findings The results showed the prevalence of spontaneous labour (48.0%), induced labour (14.0%) and planned caesarean sections (38.0%); these frequencies contributed to an overall caesarean section rate of 50.5%. Obstetric characteristics like previous vaginal birth or previous caesarean section were differentially associated with caesarean section, independently of the labour. Caesarean section without labour was significantly associated with age ≥ 35 years (ORadj 5.45 95%CI 3.16-9.39), economic class A and B (ORadj 3.10 95%CI 1.92-4.99), pregnancy between 37 and 38 weeks (ORadj 1.65 95%CI 1.22-2.24), same obstetrician in prenatal and childbirth (ORadj 13.83 95%CI 8.85-21.61) and private payment source at birth (ORadj 11.50 95%CI 6.64-19.93). Key conclusion For low-risk women in Southern Brazil, the results identify high planned caesarean section rates, not associated with socioeconomic, obstetric, institutional or prenatal factors that justify these rates

Potential of miR-21 to Predict Incomplete Response to Chemoradiotherapy in Rectal Adenocarcinoma

Funding: This work has received funding from European Structural and Investment Funds through the COMPETE Programme Grant LISBOA-01-0145-FEDER-016405, from National Funds through Fundação para a Ciência e Tecnologia Programme grant SAICTPAC/0019/2015 and by a cholar from the Portuguese Society of Coloproctology as Investigation in Coloproctology Research Prize 2016–2018.Background: Patients with locally advanced rectal adenocarcinoma (LARC) are treated with neoadjuvant chemoradiotherapy (CRT). However, biomarkers for patient selection are lacking, and the association between miRNA expression and treatment response and oncological outcomes is unclear. Objectives: To investigate miRNAs as predictors of response to neoadjuvant CRT and its association with oncological outcomes. Methods: This retrospective study analyzed miRNA expression (miR-16, miR-21, miR-135b, miR-145, and miR-335) in pre- and post-chemoradiation rectal adenocarcinoma tissue and non-neoplastic mucosa in 91 patients treated with neoadjuvant CRT (50.4 Gy) and proctectomy. Two groups were defined: a pathological complete responders group (tumor regression grade—TRG 0) and a pathological incomplete responders group (TRG 1, 2, and 3). Results: miR-21 and miR-135b were upregulated in tumor tissue of incomplete responders comparing with non-neoplastic tissue (p = 0.008 and p < 0.0001, respectively). Multivariate analysis showed significant association between miR-21 in pre-CRT tumor tissue and response, with a 3.67 odds ratio (OR) of incomplete response in patients with higher miR-21 levels (p = 0.04). Although with no significance, patients treated with 5-fluorouracil (5-FU) presented reduced odds of incomplete response compared with those treated with capecitabine (OR = 0.19; 95% confidence interval (CI) 0.03–1.12, p = 0.05). Moreover, significant differences were seen in overall survival (OS) in relation to clinical TNM stage (p = 0.0004), cT (p = 0.0001), presence of distant disease (p = 0.002), mesorectal tumor deposits (p = 0.003), and tumor regression grade (p = 0.04). Conclusion: miR-21 may predict response to CRT in rectal cancer (RC).publishersversionpublishe

Good practices for a literature survey are not followed by authors while preparing scientific manuscripts

The number of citations received by authors in scientific journals has become a major parameter to assess individual researchers and the journals themselves through the impact factor. A fair assessment therefore requires that the criteria for selecting references in a given manuscript should be unbiased with respect to the authors or the journals cited. In this paper, we advocate that authors should follow two mandatory principles to select papers (later reflected in the list of references) while studying the literature for a given research: i) consider similarity of content with the topics investigated, lest very related work should be reproduced or ignored; ii) perform a systematic search over the network of citations including seminal or very related papers. We use formalisms of complex networks for two datasets of papers from the arXiv repository to show that neither of these two criteria is fulfilled in practice

Impact of metabolic comorbidity on the association between body mass index and heatlh-related quality of life: a Scotland-wide cross-sectional study of 5,608 participants

&lt;p/&gt;Background: The prevalence of obesity is rising in Scotland and globally. Overall, obesity is associated with increased morbidity, mortality and reduced health-related quality of life. Studies suggest that "healthy obesity" (obesity without metabolic comorbidity) may not be associated with morbidity or mortality. Its impact on health-related quality of life is unknown. &lt;p/&gt;Methods: We extracted data from the Scottish Health Survey on self-reported health-related quality of life, body mass index (BMI), demographic information and comorbidity. SF-12 responses were converted into an overall health utility score. Linear regression analyses were used to explore the association between BMI and health utility, stratified by the presence or absence of metabolic comorbidity (diabetes, hypertension, hypercholesterolemia or cardiovascular disease), and adjusted for potential confounders (age, sex and deprivation quintile). &lt;p/&gt;Results: Of the 5,608 individuals, 3,744 (66.8%) were either overweight or obese and 921 (16.4%) had metabolic comorbidity. There was an inverted U-shaped relationship whereby health utility was highest among overweight individuals and fell with increasing BMI. There was a significant interaction with metabolic comorbidity (p = 0.007). Individuals with metabolic comorbidty had lower utility scores and a steeper decline in utility with increasing BMI (morbidly obese, adjusted coefficient: -0.064, 95% CI -0.115, -0.012, p = 0.015 for metabolic comorbidity versus -0.042, 95% CI -0.067, -0.018, p = 0.001 for no metabolic comorbidity). &lt;p/&gt;Conclusions: The adverse impact of obesity on health-related quality of life is greater among individuals with metabolic comorbidity. However, increased BMI is associated with reduced health-related quality of life even in the absence of metabolic comorbidity, casting doubt on the notion of "healthy obesity"

The Type and the Position of HNF1A Mutation Modulate Age at Diagnosis of Diabetes in Patients with Maturity-Onset Diabetes of the Young (MODY)-3

OBJECTIVE—The clinical expression of maturity-onset diabetes of the young (MODY)-3 is highly variable. This may be due to environmental and/or genetic factors, including molecular characteristics of the hepatocyte nuclear factor 1-α (HNF1A) gene mutation. RESEARCH DESIGN AND METHODS—We analyzed the mutations identified in 356 unrelated MODY3 patients, including 118 novel mutations, and searched for correlations between the genotype and age at diagnosis of diabetes. RESULTS—Missense mutations prevailed in the dimerization and DNA-binding domains (74%), while truncating mutations were predominant in the transactivation domain (62%). The majority (83%) of the mutations were located in exons 1- 6, thus affecting the three HNF1A isoforms. Age at diagnosis of diabetes was lower in patients with truncating mutations than in those with missense mutations (18 vs. 22 years, P = 0.005). Missense mutations affecting the dimerization/DNA-binding domains were associated with a lower age at diagnosis than those affecting the transactivation domain (20 vs. 30 years, P = 10−4). Patients with missense mutations affecting the three isoforms were younger at diagnosis than those with missense mutations involving one or two isoforms (P = 0.03). CONCLUSIONS—These data show that part of the variability of the clinical expression in MODY3 patients may be explained by the type and the location of HNF1A mutations. These findings should be considered in studies for the search of additional modifier genetic factors

Safety and Health at Work: Assessment tool- Bakery/Pastry Products

This manual aims to assist the Work Health and Safety Assessment Tool – Bread/Pastry Products user, in carrying out a simplified and easy-to-use occupational risk assessment with a view to adopting risk control solutions at workplaces. The design of this tool trie to provide an instrument capable of being used without internet access or specific software installation. In addition to its main purpose, this tool can also be used for workers consultation or training actions, provided as a complement of the other instruments developed within the scope of this project. The tool is organized in three distinct parts (see Figure 1): the first, where a checklist is filled out, from which a graphical overview is obtained, which will give the overview of the level of risk control (second part). This synthesis of results allows the user to immediately visualize the level of control of the main risks and in which will have to make major interventions. Finally, the third part appears, where a report is generated with solutions, particularized for each one of the risks in which the adoption of measures proves necessary.info:eu-repo/semantics/publishedVersio