TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Ventriculo-peritoneal shunting is the most commonly used method for the treatment of paediatric hydrocephalus. The programmable valve with the ability to adjust the opening pressure non-invasively has made it easier to find exactly the right opening pressure for each child and reduce the risk of over- or under-drainage. The aim of this investigation was to study our clinical experience with the adult Codman Hakim programmable valve in children, with reference to complications and economic impact.', 'A seven-year retrospective study of 122 hydrocephalic children (aged from children born prematurely to 15 years old) shunted with the adult Codman Hakim programmable valve was performed.', 'The programmable valve was the first shunt in 76 children and in 14 after prior ventricular drainage. The remaining 46 had different non-programmable systems as their first shunt. The most common reason for changing to a programmable valve was over-drainage. With the programmable valve, catheter-related complications, e.g. proximal (36%) or distal obstructions (30%), were the main reasons for surgical revision. Non-invasive pressure adjustment was performed in 73% of the children. Among the children with the programmable valve as their first shunt, 57 (75%) were adjusted, 12 (21%) had severe symptoms of over-drainage and would have required urgent surgical change of the valve if it had not been adjustable. A resetting of the opening pressure after MRI was found in 38% and accidental resetting occurred in 4%. Programmable valves are about twice as expensive as non-programmable valves. We estimated the increased cost of the valve and compared it with the savings from a reduction in the number of re-operations. The total cost for the programmable valve (as the primary shunt) in our study was less than that for expected re-operations due to over- or under-drainage when using non-programmable valves.\Question: Is the programmable adult Codman Hakim valve useful even in very small children with hydrocephalus . A 7-year retrospective study with special focus on cost/benefit analysis?

SOLUTION: The programmable valve was easy to handle; only one size was required and the adjustment made it possible to achieve an optimal intraventricular pressure with a lower total cost, reduced hospital stay as well as an increased quality of life for the children.

PROBLEM: Context: Talin-1 is a cytoskeleton protein that participates in cell migration and plays a role in tumor formation, migration, and metastasis in different types of cancer. Chinese investigators have observed that the levels of Talin-1 protein and mRNA expression in HCC tissues are significantly lower than in the adjacent non-cancerous tissue. However, Japanese investigators have reported that Talin-1 is upregulated in HCC. Tln2 as homologous gene of Tln-1, which encodes a very similar protein, but the role of Talin-2 is very little known in primary liver cancer (PLC). We investigated whether the expression of Talin-1 in PLC may be associated with the histological subtype as well as the role of Talin-1 in tumor cell invasion and migration using human hepatocellular carcinoma cell lines.', 'We measured the mRNA expression levels of Talin-1 and Talin-2 in five human liver cancer cell lines and normal human liver cell (LO2 cell line) by real-time PCR and the protein expression levels of Talin-1 by Western blot. Migration and invasion of the cells were assessed using transwell assays and cell scratch experiments, respectively, and proliferation was assessed by soft AGAR colony formation.', 'Talin-1 and Talin-2 expression differed significantly between the five human liver cancer cell lines and LO2 cell line (p<0.05). Compared with the LO2 cell line, the invasion and migration capabilities of the five cancer cell lines differed significantly (p<0.05). Similarly, the colony-forming ability differed (p<0.05).\Question: Does talin-1 correlate with reduced invasion and migration in human hepatocellular carcinoma cells?

SOLUTION: High levels of Talin-1 expression are correlated with reduced invasion and migration as well as decreased malignancy in human liver cancer cell lines; the suppression of Talin-1 promotes invasion and migration. In addition, Talin-2 may be correlated with invasion and migration in human hepatocellular carcinoma.

PROBLEM: Context: Isotretinoin is effective in the treatment of severe acne and rosacea. Both parent drug and its main metabolite 4-oxo-isotretinoin are potentially teratogenic compounds and contain a carboxylic acid moiety. In the presence of ethanol, naturally occurring as well as synthetic retinoids also containing a carboxylic acid moiety are capable of undergoing an ethyl esterification with the metabolic formation of more lipophilic compounds with a much longer terminal half-life.', 'To determine if isotretinoin (13-cis-RA), its main metabolite 4-oxo-isotretinoin (4-oxo-13-cis-RA), and other possible metabolites in the presence or absence of ethanol are converted to their corresponding ethyl derivatives in patients with severe acne or rosacea after multiple isotretinoin dosing. In addition, pharmacokinetic parameters of the parent drug and its 4-oxo metabolite were determined.', 'Eleven patients with severe acne or rosacea were treated with isotretinoin daily for 3 months and investigated pharmacokinetically during 24 h after 1 month of treatment and for up to 28 days after discontinuation of therapy. A possible influence of ethanol was evaluated using a simple self-administered questionnaire and by measuring serum ethanol levels during treatment. The concentrations of isotretinoin, 4-oxo-isotretinoin and possible ethylated and nonethylated metabolites were measured by reverse-phase high-performance liquid chromatography.', "Although seven of 11 patients had a considerable weekly alcohol intake, no endogenous synthesis of ethyl derivatives of isotretinoin, the main 4-oxo metabolite or the all-trans compounds was chromatographically detectable in any of the patients' plasma samples during the treatment period. Multiple dose pharmacokinetic data for the parent drug and its main metabolite were comparable to previous studies.\Question: Are the metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea influenced by ethanol?

SOLUTION:
The metabolism and pharmacokinetics of isotretinoin and its main metabolites are not influenced by ethanol during long-term isotretinoin treatment. After ceasing long-term isotretinoin therapy the recommended period of 1 month for using anticonceptive measures in fertile women seems adequate.