A novel protein isoform of the RON tyrosine kinase receptor transforms human pancreatic duct epithelial cells.

The MST1R gene is overexpressed in pancreatic cancer producing elevated levels of the RON tyrosine kinase receptor protein. While mutations in MST1R are rare, alternative splice variants have been previously reported in epithelial cancers. We report the discovery of a novel RON isoform discovered in human pancreatic cancer. Partial splicing of exons 5 and 6 (P5P6) produces a RON isoform that lacks the first extracellular immunoglobulin-plexin-transcription domain. The splice variant is detected in 73% of xenografts derived from pancreatic adenocarcinoma patients and 71% of pancreatic cancer cell lines. Peptides specific to RON P5P6 detected in human pancreatic cancer specimens by mass spectrometry confirm translation of the protein isoform. The P5P6 isoform is found to be constitutively phosphorylated, present in the cytoplasm, and it traffics to the plasma membrane. Expression of P5P6 in immortalized human pancreatic duct epithelial (HPDE) cells activates downstream AKT, and in human pancreatic epithelial nestin-expressing cells, activates both the AKT and MAPK pathways. Inhibiting RON P5P6 in HPDE cells using a small molecule inhibitor BMS-777607 blocked constitutive activation and decreased AKT signaling. P5P6 transforms NIH3T3 cells and induces tumorigenicity in HPDE cells. Resultant HPDE-P5P6 tumors develop a dense stromal compartment similar to that seen in pancreatic cancer. In summary, we have identified a novel and constitutively active isoform of the RON tyrosine kinase receptor that has transforming activity and is expressed in human pancreatic cancer. These findings provide additional insight into the biology of the RON receptor in pancreatic cancer and are clinically relevant to the study of RON as a potential therapeutic target

Application of Markov Chain Model in Studying progression Of Secondary School Students by Sex During The Free Secondary Education: A Case Study of Kisii Central District

Enrollment forecasting is an essential element in budgeting, resource allocation, and the overall planning for the growth of education sector. This paper demonstrates the use of Markov chain techniques in studying progression of secondary school students from the time of entry/enrollment in form one to graduation after the expected four years in Kenya’s secondary school level of education. The target population included all the secondary school students in Kisii Central District. The model was used to determine the district’s secondary school completion/dropout rate, retention rate and the expected duration of schooling by sex. It was established that completion rates for male students was higher than that of female students and dropout rates for female students was higher than that of male students. In the long run, it was established that the completion and dropout rates were the absorbing rates. Female students had lower expectation of schooling compared to male students in Kisii Central District. The model is only appropriate in making short period projections. Keywords: Absorbing States, Absorbing Markov Chain, Transition Rates, Dropout Rates, Completion Rates, Fundamental Matri

Participation in environmental health research by placenta donation – a perception study

<p>Abstract</p> <p>Background</p> <p>Much environmental health research depends on human volunteers participating with biological samples. The perception study explores why and how people participate in a placenta perfusion study in Copenhagen. The participation implies donation of the placenta after birth and some background information but no follow up.</p> <p>Methods</p> <p>Nineteen semi-structured qualitative interviews were conducted with participants in the placenta perfusion study after donation of placenta. Observation studies were made of recruitment sessions.</p> <p>Results</p> <p>The interviewed participants are generally in favour of medical research. They participated in the placenta perfusion study due to a belief that societal progress follows medical research. They also felt that participating was a way of giving something back to the Danish health care system. The participants have trust in medical science and scientists, but trust is something which needs to be created through "trust-work". Face-to-face interaction, written information material and informed consent forms play important parts in creating trusting relationships in medical research.</p> <p>Conclusion</p> <p>Medical research ethics do not only amount to specific types of written information material but should also be seen as a number of trust making performances involving researchers as well as research participants.</p

SynthEx: a synthetic-normal-based DNA sequencing tool for copy number alteration detection and tumor heterogeneity profiling

TCGA head and neck squamous cell carcinoma clinical information of tumors used in comparisons (n = 100). (XLSX 55 kb

Perbandingan Analgesia Epidural Menggunakan Bupivakain 0,125% dengan Kombinasi Bupivakain 0,0625% dan Fentanil 2 μg/mL terhadap Nyeri dan Blok Motorik pada Persalinan Normal

Analgesia epidural merupakan standar emas untuk memfasilitasi persalinan normal tanpa nyeri. Tujuan penelitian ini adalah untuk membandingkan analgesia epidural bupivakain 0,125% dengan bupivakain 0,0625% ditambah fentanil 2 μg/mL yang diukur dengan numeric rating scale (NRS) dan blok motorik yang dinilai dengan skala bromage selama persalinan normal. Penelitian dilakukan sebagai uji klinis acak terkontrol buta ganda terhadap 34 parturien primigravida dengan status fisik ASA II yang direncanakan melahirkan normal di ruang bersalin Rumah Sakit Dr. Hasan Sadikin Bandung pada Desember 2011–Juni 2012. Subjek dikelompokkan menjadi 2, kelompok bupivakain (B) dan kelompok bupivakain fentanil (BF). Hasil penelitian dianalisis memakai uji chi-kuadrat dan uji t-independent dengan tingkat kepercayaan 95% dan dianggap bermakna bila p0,05. Nilai bromage kelompok B vs BF berbeda bermakna dengan nilai p0.05. Bromage score B vs BF group significantly different with p value <0.05 at 90 minutes. This study concluded that the combination of 0.0625% bupivacaine + fentanyl 2 μg/mL produce analgesia similar to that provided by infusion of 0.125% bupivacaine and reduce the incidence of motor block during labor.Key words: Bupivacaine, bromage score, epidural, fentanyl, numeric rating scale (NRS), parturien, primigravida DOI: http://dx.doi.org/10.15851/jap.v1n2.12

Hemodynamic changes during aortic valve surgery among patients with aortic stenosis

Introduction. Patients with severe aortic stenosis (AS) undergoing surgery are at increased risk of hypotension and hypoperfusion. Although treatable with inotropic agents or fluid, little is known about how these therapies affect central hemodynamics in AS patients under general anesthesia. We measured changes in central hemodynamics after dobutamine infusion and fluid bolus among patients with severe AS and associated these changes with preoperative echocardiography. Methods. We included 33 patients with severe AS undergoing surgical AVR. After induction of general anesthesia, hemodynamic measurements were obtained with a pulmonary artery catheter, including Cardiac index (CI), stroke volume index (SVi) and pulmonary capillary wedge pressure (PCWP). Measurements were repeated during dobutamine infusion, after fluid bolus and lastly after sternotomy. Results. General anesthesia resulted in a decrease in CI and SVi compared to preoperative values. During dobutamine infusion CI increased but mean SVi did not (38 ± 12 vs 37 ± 13 ml/m², p = .90). Higher EF and SVi before surgery and a larger decrease in SVi after induction of general anesthesia were associated with an increase in SVi during dobutamine infusion. After fluid bolus both CI, SVi (48 ± 12 vs 37 ± 13 ml/min/m², p < .0001) and PCWP increased. PCWP increased mostly among patients with a larger LA volume index. Conclusion. In patients with AS, CI can be increased with both dobutamine and fluid during surgery. Dobutamine’s effect on SVI was highly variable and associated with baseline LVEF, and an increase in CI was mostly driven by an increase in heart rate. Fluid increased SVi at the cost of an increase in PCWP