Comparative analysis of Ig and TCR gene rearrangements at diagnosis and at elapse of childhood precursor-B–ALL provides improved strategies for selection of stable PCR targets for monitoring of minimal residual disease

Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements are excellent patient-specific polymerase chain reaction (PCR) targets for detection of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL), but they might be unstable during the disease course. Therefore, we performed detailed molecula

Fusion of the homeobox gene HLXB9 and the ETV6 gene in infant acute myeloid leukemias with the t(7;12)(q36;p13)

Recently, we and others reported a recurrent t(7;12)(q36;p13) found in myeloid malignancies in children < or =18 months of age and associated with a poor prognosis. Fluorescence in situ hybridization studies mapped the 12p13 breakpoint to the first intron of ETV6 and narrowed down the region of 7q36 involved. By using the sequences made public recently by the Human Genome Project, two candidate genes in 7q36 were identified: the homeobox gene HLXB9 and c7orf3, a gene with unknown function. Reverse transcription-PCR of two cases with t(7;12), using primers for c7orf3 and ETV6, was negative. However, reverse transcription-PCR for HLXB9-ETV6 demonstrated alternative splicing; the two major bands corresponded to fusion of exon 1 of HLXB9 to exons 2 and 3, respectively, of ETV6. The reciprocal ETV6-HLXB9 transcript was not detected. It remains to be elucidated if the leukemic phenotype is attributable to the formation of the HLXB9-ETV6 fusion protein, which includes the helix-loop-helix and E26 transformation-specific DNA binding domains of ETV6 or to the disruption of the normal ETV6 protein

Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia

Resistance to L-asparaginase in leukemic cells may be caused by an elevated cellular expression of asparagine synthetase (AS). Previously, we reported that high AS expression did not correlate to L-asparaginase resistance in TEL-AML1-positive B-lineage acute lymphoblastic leukemia (ALL). In the present study we confirmed this finding in TEL-AML1-positive patients (n = 28) using microarrays. In contrast, 35 L-asparaginase-resistant TEL-AML1-negative B-lineage ALL patients had a significant 3.5-fold higher AS expression than 43 sensitive patients (P < .001). Using real-time quantitative polymerase chain reaction (RTQ-PCR), this finding was confirmed in an independent group of 39 TEL-AML1-negative B-lineage ALL patients (P = .03). High expression of AS was associated with poor prognosis (4-year probability of disease-free survival [pDFS] 58% +/- 11%) compared with low expression (4-year pDFS 83% +/- 7%; P = .009). We conclude that resistance to l-asparaginase and relapse risk are associated with high expression of AS in TEL-AML1-negative but not TEL-AML1-positive B-lineage ALL

Regenerating normal B-cell precursors during and after treatment of acute lymphoblastic leukaemia: Implications for monitoring of minimal residual disease

We studied 57 childhood acute lymphoblastic leukaemia (ALL) patients who remained in continuous complete remission after treatment according to the Dutch Childhood Leukaemia Study Group ALL-8 protocols. The patients were monitored at 18 time points during and after treatment [640 bone marrow (BM) and 600 blood samples] by use of cytomorphology and immunophenotyping for the expression of TdT, CD34, CD10 and CD19. Additionally, 60 BM follow-up samples from six patients were subjected to clonality assessment via heteroduplex polymerase chain reaction (PCR) analysis of immunoglobulin VH-JH gene rearrangements. We observed substantial expansions of normal precursor B cells in regenerating BM not only after maintenance therapy but also during treatment. At the end of the 2-week intervals after consolidation and reinduction treatment, B-cell-lineage regeneration was observed in BM with a large fraction of immature CD34+/TdT+ B cells. In contrast, in regenerating BM after cessation of maintenance treatment, the more mature CD19+/CD10+ B cells were significantly increased, but the fraction of immature CD34+/TdT+ B cells

CHANGES IN STUDENTS’ LEARNING BEHAVIOR IN THE COVID-19 PANDEMIC ERA SMA KRISTEN KAPAN

This qualitative research aims to determine changes in students’ learning behaviour during the COVID-19 pandemic, and the impact of changes on students’ learning behaviour at SMA Kristen Kapan. The research subjects were students, teachers, and the headmaster. The data were collected through observation, interviews, and documentation. The data were analysed through data reduction, data display, and drawing conclusions. The study shows that there are changes in students' learning behaviour, namely: the students were less active to ask questions, the students were less enthusiastic about learning, and the students were not active (silent) in joining the learning process. Besides, the impact is that the students begin to forget the school culture, students were more interested in playing online games and social media, lack discipline in learning, the students feel bored, and lack motivation

Gut-directed hypnotherapy in children with irritable bowel syndrome or functional abdominal pain (syndrome): A randomized controlled trial on self exercises at home using CD versus individual therapy by qualified therapists

Background: Irritable bowel syndrome (IBS) and functional abdominal pain (syndrome) (FAP(S)) are common pediatric disorders, characterized by chronic or recurrent abdominal pain. Treatment is challenging, especially in children with persisting symptoms. Gut-directed hypnotherapy (HT) performed by a therapist has been shown to be effective in these children, but is still unavailable to many children due to costs, a lack of qualified child-hypnotherapists and because it requires a significant investment of time by child and parent(s). Home-based hypnotherapy by means of exercises on CD has been shown effective as well, and has potential benefits, such as lower costs and less time investment. The aim of this randomized controlled trial (RCT) is to compare cost-effectiveness of individual HT performed by a qualified therapist with HT by means of CD recorded self-exercises at home in children with IBS or FAP(S).Methods/Design: 260 children, aged 8-18 years with IBS or FAP(S) according to Rome III criteria are included in this currently conducted RCT with a follow-up period of one year. Children are randomized to either 6 sessions of individual HT given by a qualified therapist over a 3-month period or HT through self-exercises at home with CD for 3 months.The primary outcome is the proportion of patients in which treatment is successful at the end of treatment and after one year follow-up. Treatment success is defined as at least 50% reduction in both abdominal pain frequency and intensity scores. Secondary outcomes include adequate relief, cost-effectiveness an

The Pharmacy Game-GIMMICS® a Simulation Game for Competency-Based Education

The profile of the profession of pharmacists has profoundly changed over the last decades. Pharmacy education has moved towards competency-based education. The pharmacy game, called GIMMICS®, developed at the University of Groningen, is unique in combining simulation with serious gaming to teach a wide range of competencies. In this article, we describe the learning goals, the assessment methods, the teaching tools, and the students’ view of the pharmacy game. The learning goals are to train the competencies of collaboration, leadership, communication, and pharmaceutical expertise. The core of the game is the simulation of community pharmacy practice activities, such as patient counseling, processing of prescriptions, and collaboration with other health professionals. Students are assessed individually and as a pharmacy team. The pharmacy team, with the largest number of patients wins the game. Student evaluations show that they value the course. Currently, seven universities from around the globe have adopted the pharmacy game in their curriculum, adjusting the course to their country’s pharmacy practice and educational system

Complex interactions among tissue restricted transcription factors and cofactors are critical for intestine specific gene expression

As might be concluded from the general introduction about gene regulation, our understanding of how transcription factors regulate transcription ofLPH and SI is extensive. Both LPH and SI are enterocyte specific membrane anchored enzymes that are necessary for the digestion of nutrients present in the specific diets of mammals according to their age before and after weaning. Previous work by Grand et. al. has demonstrated that LPH and SI are expressed in complex patterns along the vertical, horizontal, and developmental gradient of the small intestine. LPH and SI expression patterns coincide with important transitions during small intestine development. Furthermore, Krasinski et. al. demonstrated that specific regions in the LPH promoter contain the information necessary for the specific patterns of expression. Krasinski et. al also demonstrated that the vertical, horizontal, and developmental LPH and SI expression patterns are regulated at the level of transcription. Therefore, LPH and SI genes are perfect markers for cell differentiation of small intestine. Seqeunce analysis of the 5 '-flanking regions ofLPH and SI genes revealed consensus binding sites for Cdx-2, HNF-1, and GATA transcription factors. The families of these transcription factors have all been indicated to play a role in cell differentiation and morphogenesis. These transcription factors are turned on in early stages of intestinal development, are only expressed together in the small intestine, and their binding sites are in close proximity to each other and the TAT A-box regions suggesting that they play an important role in cell differentiation and intestine specific gene regulation. The close proximity of these binding sites to each other and the fact that these transcription factors have been shown individually to cooperate with comparable proteins for the regulation of gene expression, it is hypothesized that these factors act in concert to regulate LPH and SI transcriptio

Best packing of rods into boxes

AbstractWe determine the maximum number of 1 × 1 x … × 1 × n rods which will fit inside an arbitrary d-dimensional rectangular box, on condition that they be packed parallel to the edges of the box