ProTherm and ProNIT are two thermodynamic databases that contain experimentally determined thermodynamic parameters of protein stability and protein–nucleic acid interactions, respectively. The current versions of both the databases have considerably increased the total number of entries and enhanced search interface with added new fields, improved search, display and sorting options. As on September 2005, ProTherm release 5.0 contains 17 113 entries from 771 proteins, retrieved from 1497 scientific articles (∼20% increase in data from the previous version). ProNIT release 2.0 contains 4900 entries from 273 research articles, representing 158 proteins. Both databases can be queried using WWW interfaces. Both quick search and advanced search are provided on this web page to facilitate easy retrieval and display of the data from these databases. ProTherm is freely available online at and ProNIT at .
BackgroundEndoplasmic reticulum (ER) stress generated unfolded stress response (UPR) is a basic survival mechanism which protects cell under unfavourable conditions. Leishmania parasite modulates host macrophages in various ways to ensure its survival. Modulation of PI3K-Akt pathway in delayed apoptotic induction of host; enables parasite to stabilize the infection for further propagation.MethodologyInfected RAW macrophages were exposed to campothecin or thagsigargin and phosphorylation status of PERK, Akt, BAD and Cyt-C was determined through western blotting using phospho specific antibody. Expression at transcriptional level for cIAP1 &2, ATF4, CHOP, ATF3, HO-1 and sXBP1 was determined using real time PCR. For inhibition studies, RAW macrophages were pre-treated with PERK inhibitor GSK2606414 before infection.FindingsOur studies in RAW macrophages showed that induction of host UPR against L.donovani infection activates Akt mediated pathway which delays apoptotic induction of the host. Moreover, Leishmania infection results in phosphorylation and activation of host PERK enzyme and increased transcription of genes of inhibitor of apoptosis gene family (cIAP) mRNA. In our inhibition studies, we found that inhibition of infection induced PERK phosphorylation under apoptotic inducers reduces the Akt phosphorylation and fails to activate further downstream molecules involved in protection against apoptosis. Also, inhibition of PERK phosphorylation under oxidative exposure leads to increased Nitric Oxide production. Simultaneously, decreased transcription of cIAP mRNA upon PERK phosphorylation fates the host cell towards apoptosis hence decreased infection rate.ConclusionOverall the findings from the study suggests that Leishmania modulated host UPR and PERK phosphorylation delays apoptotic induction in host macrophage, hence supports parasite invasion at early stages of infection.
Objectives: We investigated the association of fluid overload and oxygenation in critically sick children, and their correlation with various outcomes (duration of ventilation, ICU stay, and mortality). We also assessed whether renal angina index (RAI) at admission can predict mortality or acute kidney injury (AKI) on day 3 after admission.Design and setting: Prospective study, pediatric intensive care in a tertiary hospital.Duration: June 2013-June 2014.Patients: Patients were included if they needed invasive mechanical ventilation for >24 h and had an indwelling arterial catheter. Patients with congenital heart disease or those who received renal replacement therapy (RRT) were excluded.Methods: Oxygenation index, fluid overload percent (daily, cumulative), RAI at admission and pediatric logistic organ dysfunction (PELOD) score were obtained in all critically ill children. KDIGO classification was used to define AKI, using both creatinine and urine output criteria. Admission data for determination of RAI included the use of vasopressors, invasive mechanical ventilation, percent fluid overload, and change in kidney function (estimated creatinine clearance). Univariable and multivariable approaches were used to assess the relations between fluid overload, oxygenation index and clinical outcomes. An RAI cutoff >8 was used to predict AKI on day 3 of admission and mortality.Results: One hundred and two patients were recruited. Fluid overload predicted oxygenation index in all patients, independent of age, gender and PELOD score (p < 0.05). Fluid overload was associated with longer duration of ventilation (p < 0.05), controlled for age, gender, and PELOD score. Day-3 AKI rates were higher in patients with a RAI of 8 or more, and higher areas under the RAI curve had better prediction rates for Day-3 AKI. An RAI <8 had high negative predictive values (80–95%) for Day-3 AKI. RAI was better than traditional markers of pediatric severity of illness (PELOD) score for prediction of AKI on day 3.Conclusions: This study emphasizes that positive fluid balance adversely affects intensive care in critically ill children. Further, the RAI prediction model may help optimize treatment and improve clinical prediction of AKI.
The triad of pancreatitis, hypertriglyceridemia, and diabetic ketoacidosis and its treatment has not been extensively discussed in the pediatric literature. We report a 4-year-old child with severe hypertriglyceridemia, pancreatitis, and diabetic ketoacidosis. Hypertriglyceridemia and pancreatitis with diabetic ketoacidosis can be successfully managed with insulin and hydration therapy in children. Early recognition of this triad is important as insulin requirements, recovery duration, and prognosis can be altered.
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