ASSESSMENT OF INTAKE AND NUTRITIONAL STATUS OF VITAMIN B1, B2, AND B6 IN MEN AND WOMEN WITH DIFFERENT PHYSICAL ACTIVITY LEVELS

The purpose of the present study was to examine the nutritional status of vitamin B1, B2, and B6 in respect to dietary intake of these vitamins and activity coefficients of the erythrocyte enzymes transketolase, glutathione reductase, and aspartic aminotransferase in young men and women with different physical activity levels. The participants of this study were 20 women and 20 men with high physical activity (groups HAW and HAM, respectively), and 20 women and 20 men with low physical activity (groups LAW and LAM, respectively). The intake of vitamins B1, B2, B6, proteins, and calorie content of the diet was based on the average of the 4-day dietary recalls. To assess nutritional status of vitamin B1, B2, and B6, the activity coefficients (α) of erythrocyte transketolase (ETK), erythrocyte glutathione reductase (EGR), and erythrocyte aspartic aminotransferase (EAST) were estimated in blood hemolysates. The intake of the studied vitamins in the diet was statistically significantly lower in the female groups compared with the respective male groups. Deficiency of vitamin B6 in the diet was present more often in women than in men (in terms of the recommended dietary allowances [RDA]). Values of the activity coefficient αETK indicated that none of the groups in this study suffered the risk of vitamin B1 deficiency. The value of the activity coefficient αEGR indicated that the groups of women and men with low physical activity were more prone to vitamin B2 deficiency compared with the high physical activity groups. The risk of vitamin B6 deficiency (αEAST) in both male groups was higher than in both female groups. The obtained results do not allow for unequivocal determination of the impact of sex and the level of physical activity on intake and nutritional status of vitamin B1, B2, and B6. Independently of sex and the level of physical activity, the women and men consumed insufficient quantities of vitamins B1 and B6, although this was not always related to increased values of corresponding activity coefficients

A preliminary study on MTDH expression as a potential prognostic cancer marker

Background: Clinical studies have revealed that MTDH is overexpressed in various malignancies andis associated with disease progression and poor clinical outcomes. In order to study MTDH prognosticpotential, we decided to evaluate MTDH expression changes using cancerous and non-cancerous cellslines. Secondly, for the first time, we evaluated MTDH expression in prostate cancer cell lines representingdifferent metastatic potential in vivo. Methods: MTDH and PBGD (control) genes expression were measured by reverse transcription-quantitativepolymerase chain reaction assay using Universal Probe Library in cancerous and non-cancerous cell lines. Results: MTDH gene expression analysis showed a decrease in colorectal cancer cell lines (Caco2, HT29)compared to non-cancerous cells lines (VH10, VH25, Hek293). The mean level of the MTDH mRNA expression,normalized in relation to the reference gene PBGD, increased in the prostate cancer cell linesas follows: PC3 (0.62 ± 0.07), PC3M (1.02 ± 0.17), PC3MPro4 (1.20 ± 0.22), and reached the highestvalue in PC3M4 (1.86 ± 0.48). In VH10, the expression of this gene was at 1.0 ± 0.07. Conclusions: Our MTDH gene expression data are consistent with Mtdh protein expression analyzed inThe Human Protein Atlas (HPA). Increasing MTDH expression is a promising prognostic factor

Zastosowanie wysokowydajnych technologii w diagnostyce molekularnej chorób nowotworowych

The existence of prognostic and predictive point mutations and chromosomal aberrations caused that genetic analysis has become an essential tool in the field of cancer diagnostics. Unfortunately, classical analytical techniques currently used on a large scale have several limitations and imperfections — are relatively time-consuming and inefficient, and at the same time do not provide full information about the disease. The development of technology has contributed to the creation of a number of new, highly advanced solutions, such as techniques based on the use of microarrays, quantitative gene expression analysis using mass spectrometry or modern mechanisms of DNA and RNA sequencing. These solutions allow more accurate and highly efficient analysis of genetic material. Their use allows us not only to reveal the existence of genetic changes which were previouslyimpossible to detect, but also to conduct research in new areas of cancer genetics, such as changes in expression of certain genes or influence of epigenetic factors on the activity of specific regions of genome. In addition, it has became possible to conduct effective association studies, revealing the correlation between the occurrenceof specific mutations or polymorphisms, and the emergence of certain forms of cancer. It is expected that in the near future technological development will lead to the creation of next generation of analytical methods which will be characterized by a higher degree of accuracy and performance, or will allow previously inaccessible aspects of cancer genetics to be widely studied.Istnienie mutacji punktowych i aberracji chromosomowych o znaczeniu prognostycznym i predykcyjnym sprawiło, że analiza genetyczna staje się niezbędnym narzędziem w dziedzinie diagnostyki chorób nowotworowych. Niestety, stosowane obecnie na szeroką skalę klasyczne techniki analityczne wykazują wiele ograniczeń i niedoskonałości — są stosunkowo czasochłonne i mało wydajne, a przy tym nie pozwalają na uzyskanie pełnej informacji o danym przypadku choroby. Postępujący rozwój technologii przyczynił się do opracowania wielu nowych, wysoce zaawansowanych rozwiązań, takich jak techniki oparte na zastosowaniu mikromacierzy, ilościowa analiza ekspresjigenów przy wykorzystaniu spektrometrii mas czy też nowoczesne mechanizmy sekwencjonowania DNA i RNA. Rozwiązania te umożliwiają dokładniejszą i bardziej wydajną analizę materiału genetycznego. Ich zastosowanie pozwala nie tylko na stwierdzenie występowania niemożliwych wcześniej do wykrycia zmian genetycznych, ale również na prowadzenie badań w nowych obszarach onkogenetyki, takich jak wahania ekspresji genów lub oddziaływania czynników epigenetycznych na aktywność poszczególnych regionów genomu. Ponadto możliwestało się prowadzenie wydajnych badań asocjacyjnych, ujawniających korelacje między wystąpieniem konkretnych mutacji lub polimorfizmów a pojawieniem się określonej formy nowotworu. Przewiduje się, że w niedalekiej przyszłości dalszy postęp technologiczny doprowadzi do stworzenia kolejnej generacji metod analitycznych, charakteryzujących się jeszcze wyższym stopniem dokładności i wydajności lub też umożliwiających badanie niedostępnych dotąd aspektów genetyki nowotworów

Impact of specific KRAS Mutation in Exon 2 on clinical outcome of chemotherapy- and radiotherapy-treated colorectal adenocarcinoma patients

BACKGROUND AND OBJECTIVES: Knowledge obtained via high-throughput technologies, used for tumor genome sequencing or identifying gene expression and methylation signatures, is clinically applicable thanks to molecular characterization in the context of tumor development and progression. This study was conducted to assess the impact of specific KRAS mutation in codons 12 and 13 on clinical outcome of chemotherapy and radiotherapy in colorectal cancer patients. METHODS: A total of 239 samples of colorectal adenocarcinoma underwent histological evaluation and DNA isolation. RESULTS AND CONCLUSIONS: Patients with a mutation in KRAS codon 13 experienced worse outcome than those with a mutation in KRAS codon 12. Moreover, the cases of mutations in KRAS codons 12 or 13 were associated with a significantly higher mortality than the cases of wild-type KRAS, and some patients with KRAS mutated in codon 12 had an exceptionally long overall survival. Finally, primary preoperative radiation therapy followed by surgery significantly increased overall survival more efficiently than surgery followed by chemotherapy. This should be investigated in further studies. The fact that all patients treated with radiotherapy + surgery were alive, again focused our attention on the effect of preoperative radiation therapy on the prognosis for colorectal cancer patients. However, the number of patients in this subgroup is too small to allow any specific explanation for this observation. We should, rather, point out a problem for further investigation

Long-term survival in patients with NSCLC treated with single-fraction vs. multi-fraction palliative radiotherapy in the case of lung tumor, brain metastases and bone metastases

Background: Patients with advanced non-small cell lung cancer (NSCLC) are candidates for different types of treatment, including chemotherapy and radiotherapy or supportive care. Despite the fatal prognosis in advanced disease, many experienced radiation oncologists will apply radiation at low doses with the intention of palliative care. Methods: We used an extensive database of medical patients diagnosed with NSCLC, treated with palliative radiotherapy at the Oncology Centre in Bydgoszcz, from June 1998 to December 2013. A group of 3202 patients was divided into subgroups: Group A)1762 patients irradiated on the lung tumor (without distant metastases): Total dose: A1) 6Gy/1 fr.(n=19); A2) 8Gy/1fr.(n=276); A3) 20Gy/5fr.(n=1349); A4) 30Gy/10fr.(n=118). Group B) 548 patients irradiated on the central nervous system (CNS) metastases: B1) 20Gy/5fr.(n=476); B2) 30Gy/10fr.(n=72). Group C) 892 patients irradiated on the bone metastases: C1) 8Gy/1fr.(n=452); C2) 10Gy/1fr.(n=30); C3) 20Gy/5fr.(n=341); C4) 30Gy/10fr.(n=69). Results: Patients with irradiation of a lung tumor: The longest OS was observed in the group of patients irradiated with doses of 20 Gy (76%) and 30 Gy (7%). Patients with irradiation of bone metastases: No significant differences in OS were observed between the employed fractionation regimens. Patients with irradiation of CNS metastases: The choice of a higher dose of radiation therapy did not demonstrate differences in median OS values compared to a lower dose. Conclusions: The patients who were prescribed single fraction palliative radiotherapy did not have poorer prognoses or experience shorter survival than patients who were prescribed multi-fraction pRT in the case of lung tumor, brain metastases and bone metastases

An Alu-derived intronic splicing enhancer facilitates intronic processing and modulates aberrant splicing in ATM

We have previously reported a natural GTAA deletion within an intronic splicing processing element (ISPE) of the ataxia telangiectasia mutated (ATM) gene that disrupts a non-canonical U1 snRNP interaction and activates the excision of the upstream portion of the intron. The resulting pre-mRNA splicing intermediate is then processed to a cryptic exon, whose aberrant inclusion in the final mRNA is responsible for ataxia telangiectasia. We show here that the last 40 bases of a downstream intronic antisense Alu repeat are required for the activation of the cryptic exon by the ISPE deletion. Evaluation of the pre-mRNA splicing intermediate by a hybrid minigene assay indicates that the identified intronic splicing enhancer represents a novel class of enhancers that facilitates processing of splicing intermediates possibly by recruiting U1 snRNP to defective donor sites. In the absence of this element, the splicing intermediate accumulates and is not further processed to generate the cryptic exon. Our results indicate that Alu-derived sequences can provide intronic splicing regulatory elements that facilitate pre-mRNA processing and potentially affect the severity of disease-causing splicing mutations

Zagrożenia zdrowotne wśród dzieci i młodzieży. T. 3

Praca recenzowana / Peer-reviewed pape

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348