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: Galbeta1-4GlcNAcalpha2-6 sialyltransferase (ST6GalI) is an acute phase reactant whose release from cells can be induced by proinflammatory cytokines. Because patients with chronic renal failure have high circulating levels of proinflammatory cytokines, we hypothesized that patients on the renal transplant waiting list would have high circulating levels of ST6GalI, which might adversely affect post-transplant events.', 'Levels of ST6GalI were measured in the serum of 70 patients immediately before renal transplant; these were correlated with posttransplant events, such as delayed graft function and rejection.', 'The mean serum level of ST6GalI was significantly higher in the patients (3162+/-97 U) than in 19 controls (2569 +/- 125 U; P<0.003). Patients who required dialysis posttransplant for treatment of delayed graft function (n=20) had significantly higher levels of ST6GalI pretransplant (3735+/-228 U) than patients (n=50) who did not require dialysis (2933+/-83 U; P<0.0001). In a multivariate analysis the ST6GalI level and cold ischemic time were found to be independent risk factors for the development of delayed graft function.\Question: Do increased levels of GALbeta1-4GLCNACalpha2-6 sialyltransferase pretransplant predict delayed graft function in kidney transplant recipients?

SOLUTION: ST6GalI levels are high in renal failure patients awaiting a renal transplant and may be a risk factor for the development of delayed graft function. The assessment and perhaps modulation of a potential transplant recipient's ST6GalI systemic level may be beneficial.

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: HIV-1-infected and/or immune-activated microglia and macrophages are pivotal in the pathogenesis of HIV-1-associated neurocognitive disorders (HAND). Glutaminase, a metabolic enzyme that facilitates glutamate generation, is upregulated and may play a pathogenic role in HAND. Our previous studies have demonstrated that glutaminase is released to the extracellular fluid during HIV-1 infection and neuroinflammation. However, key molecular mechanisms that regulate glutaminase release remain unknown. Recent advances in understanding intercellular trafficking have identified microvesicles (MVs) as a novel means of shedding cellular contents. We posit that during HIV-1 infection and immune activation, microvesicles may mediate glutaminase release, generating excessive and neurotoxic levels of glutamate.', 'MVs isolated through differential centrifugation from cell-free supernatants of monocyte-derived macrophages (MDM) and BV2 microglia cell lines were first confirmed in electron microscopy and immunoblotting. As expected, we found elevated number of MVs, glutaminase immunoreactivities, as well as glutaminase enzyme activity in the supernatants of HIV-1 infected MDM and lipopolysaccharide (LPS)-activated microglia when compared with controls. The elevated glutaminase was blocked by GW4869, a neutral sphingomyelinase inhibitor known to inhibit MVs release, suggesting a critical role of MVs in mediating glutaminase release. More importantly, MVs from HIV-1-infected MDM and LPS-activated microglia induced significant neuronal injury in rat cortical neuron cultures. The MV neurotoxicity was blocked by a glutaminase inhibitor or GW4869, suggesting that the neurotoxic potential of HIV-1-infected MDM and LPS-activated microglia is dependent on the glutaminase-containing MVs.\Question: Do glutaminase-containing microvesicles from HIV-1-infected macrophages and immune-activated microglia induce neurotoxicity?

SOLUTION:
These findings support MVs as a potential pathway/mechanism of excessive glutamate generation and neurotoxicity in HAND and therefore MVs may serve as a novel therapeutic target.