The prognostic value of extramural venous invasion in preoperative MRI of rectal cancer patients

Aim This study aimed to examine the prognostic value of extramural venous invasion observed in preoperative MRI on survival and recurrences. Method In total, 778 rectal cancer patients were evaluated in multidisciplinary meetings in Helsinki University Hospital during the years 2016-2018. 635 patients met the inclusion criteria of stage I-III disease and were intended for curative treatment at the time of diagnosis. 128 had extramural venous invasion in preoperative MRI. Results The median follow-up time was 2.5 years. In a univariate analysis extramural venous invasion was associated with poorer disease-specific survival (hazard ratio [HR] 2.174, 95% CI 1.118-4.224, P = 0.022), whereas circumferential margin = T3c or nodal positivity were not. Disease recurrence occurred in 17.3% of the patients: 13.4% had metastatic recurrence only, 1.7% mere local recurrence and 2.2% both metastatic and local recurrence. In multivariate analysis, extramural venous invasion (HR 1.734, 95% CI 1.127-2.667, P = 0.012) and nodal positivity (HR 1.627, 95% CI 1.071-2.472, P = 0.023) were risk factors for poorer disease-free survival (DFS). Circumferential marginPeer reviewe

Molecular cloning and characterization of glucose transporter 1 (glut1) and citrate synthase cDNA in buffalo (Bubalus bubalis)

Glucose transporter type-1 (glut1) and citrate synthase plays crucial role in glucose transport and regulation of tricarboxylic acid cycle (TCA) cycle in mammalian energy metabolism. The present study was aimed to clone and characterize glut1 and citrate synthase cDNA in water buffalo (Bubalus bubalis). Total of 90 cumulus oocyte complexes (COCs) were used for mRNA isolation and reverse transcribed to cDNA, which was further used in polymerase chain reaction (PCR) amplification of glut1 and citrate synthase. PCR products of glut1 and citrate synthase were cloned by T/A cloning using pGEM-T easy vector and further  sequenced. Gene sequence analysis of glut1 and citrate synthase revealed that they have open reading frame of 1479 (encoding 492 aa) and 1401 bp (encoding 466 aa), respectively. Further phylogenic analysis of gene and deduced amino acid sequences suggests that bubaline glut1 shares ∼ 89 to 98% and ∼ 97 to 99% similarity at nucleotide and amino acid level respectively  whereas citrate synthase shared ∼ 89 to 99% at nucleotide and ∼ 96 to 99% at amino acid level respectively with other domestic species and human. Predicted protein structures of buffalo glut1 protein accentuate the presence of crucial amino acids involved in glucose transport moreover the essential catalytic residues are highly conserved in buffalo citrate synthase.Keywords: Buffalo, cloning, characterization, Glut1, citrate synthase

Oxysterol-binding protein related-proteins (ORPs) 5 and 8 regulate calcium signaling at specific cell compartments

Oxysterol-binding protein related-protein 5 and 8 (ORP5/8) localize to the membrane contact sites (MCS) of the endoplasmic reticulum (ER) and the mitochondria, as well as to the ER-plasma membrane (PM) MCS. The MCS are emerging as important regulators of cell signaling events, including calcium (Ca2+) signaling. ORP5/8 have been shown to interact with phosphatidylinositol-4,5-bisphosphate (PIP2) in the PM, and to modulate mitochondrial respiration and morphology. PIP2 is the direct precursor of inositol trisphosphate (IP3), a key second messenger responsible for Ca2+-release from the intracellular Ca2+ stores. Further, mitochondrial respiration is linked to Ca2+ transfer from the ER to the mitochondria. Hence, we asked whether ORP5/8 would affect Ca2+ signaling in these cell compartments, and employed genetically engineered aequorin Ca2+ probes to investigate the effect of ORP5/8 in the regulation of mitochondrial and caveolar Ca2+. Our results show that ORP5/8 overexpression leads to increased mitochondrial matrix Ca2+ as well as to increased Ca2+ concentration at the caveolar subdomains of the PM during histamine stimulation, while having no effect on the cytoplasmic Ca2+. Also, we found that ORP5/8 overexpression increases cell proliferation. Our results show that ORP5/8 regulate Ca2+ signaling at specific MCS foci. These local ORP5/8-mediated Ca2+ signaling events are likely to play roles in processes such as mitochondrial respiration and cell proliferation.Peer reviewe

Aspiration, Achievement and Abandonment in ‘The World’s Best Country’: Merit and Equity or Smoke and Mirrors?

Finland is internationally valorised for its education system, quality of life and high-tech, innovative, competitiveness. However, a critical focus on institutional dynamics and trajectories of higher education careers illuminates questions about the reproduction of global inequities, rather than the societal transformation Finland’s education system was once noted for. The purpose of this self-ethnography of career trajectories within Finnish higher education is designed to call attention to institutional social dynamics that have escaped the attention of scholarly literature and contemporary debates about academic work and practice within highly situated research groups, departments and institutes. Our analysis illuminates emergent stratification, in a country and institution previously characterized by the absence of stratification and the ways in which this reinforces - and is reinforced by – the tension between transnational academic capitalism, methodological nationalism and the resulting global division of academic labour that now cuts across societies, manifesting within the one institution Finland’s general population trusts to explain, engage and ameliorate stratification: Higher Education

Randomized Controlled Trial of the Effectiveness of Genetic Counseling and a Distance, Computer-Based, Lifestyle Intervention Program for Adult Offspring of Patients with Type 2 Diabetes: Background, Study Protocol, and Baseline Patient Characteristics

Relatives of type 2 diabetic patients are at a high risk of developing type 2 diabetes and should be regarded as target of intervention for diabetes prevention. However, it is usually hard to motivate them to implement preventive lifestyle changes, because of lack of opportunity to take advises from medical professionals, inadequate risk perception, and low priority for preventive behavior. Prevention strategy for them therefore should be highly acceptable and suited for them. The parallel, three-group trial is now being conducted to investigate the effects of genetic counseling and/or a computerized behavioral program on the prevention of type 2 diabetes in that population. The preventive strategies used in this study could provide a novel solution to the numbers of genetically high-risk individuals, if found to be effective. The objective of this paper is to describe the background, protocol, and baseline patient characteristics of the trial

Intelligent wearable allows out-of-the-lab tracking of developing motor abilities in infants

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Feasibility of a Responsibility-Based Leadership Training Program for Novice Physical Activity Instructors

Most coaches and instructors would like to teach more than just sport skills to their athletes and children. However, to promote athletes' or children's holistic development and teach them to take responsibility and lead, requires the coaches and instructors to first master the skills themselves. Therefore, feasible, high quality leadership training programs where coaches and physical activity instructors are taught to teach and share leadership are needed. The aim of the current study was to evaluate the feasibility of a leadership training program to optimize it and to determine whether to proceed with its evaluation. In the leadership training program, eight Finnish novice physical activity instructors, aged 18 to 22, were taught to promote positive youth development, personal and social responsibility, and shared leadership in a physical activity context. The participants had minimal to no leadership training or experience. The training program consisted of seven meetings totaling 20 h. Helllison's teaching personal and social responsibility (TPSR) model was the theoretical and practical framework of the training program. Feasibility of the leadership training program was evaluated across four domains of an evidence-based framework: demand, practicality, acceptability, and implementation fidelity. Data of the current complex intervention were collected with application videos, questionnaires, researcher's log, lesson plans, video recordings, and a semi-structured focus group interview. The quantitative data were analyzed using descriptive statistics and the qualitative data using deductive and inductive content analysis. There was a demand for the leadership training program. The training program was perceived as practical and highly acceptable by the novice instructors and the trainers, and implemented with fidelity, indicating high overall feasibility. No implementation issues were found. Consequently, the current leadership training program has a high probability of efficacy and can be accepted for further evaluation.Peer reviewe

Prevalence of high-risk human papillomavirus infection and cancer gene mutations in nonmalignant tonsils

Objectives: To analyze the prevalence of high-risk HPV (human papillomavirus) and genetic alterations in nonmalignant tonsils. Methods: We collected benign fresh tonsillar tissue specimens from 477 patients undergoing tonsillectomy because of chronic tonsillitis or tonsillar hypertrophy in 2012 (Group A, n = 237) and in 2015 (Group B, n = 240). Luminex xMAP technique served to detect E6/E7 DNA from 16 different high-risk HPV types. Tonsillar DNA and peripheral blood leukocyte DNA from the infected individuals were analyzed using Nimblegen SeqCap EZ Comprehensive Cancer Design panel. The panel targets 578 different genes that are relevant in carcinogenesis. HPV negative tonsillar specimens from age-and gender matched individuals were used as controls. All specimens harboring high-risk HPV were analyzed using fluorescence in situ hybridization (FISH). Results: Five of 477 (1.0%) patients tested positive for the following HPV types: HPV16 (two cases), HPV52 (one case), HPV66 (one case), HPV52 and HPV68 (coinfection, one case). FISH analyses showed that the appearance of HPV in specimens infected with HPV 16 was episomal. Benign tonsils infected with high-risk HPV harbored mutations in EP300, NF1, PIK3CA, and RB1 which are considered relevant in the development of HPV-associated head and neck squamous cell carcinoma (SCC). Conclusions: The prevalence of high-risk HPV in nonmalignant tonsils is low. High-risk HPV positive tonsils harbored mutations in genes that are commonly altered in HPV-associated head and neck SCC. The role of these mutations in tonsillar carcinogenesis is an interesting target for future research.Peer reviewe