Notes

Chronotype changes as they age; seven-year follow-up in the Holland examine associated with depression and anxiety cohort.
The importance of drug dosing time in pharmacokinetics, pharmacodynamics and toxicity is receiving increasing attention from the scientific community. In spite of mounting evidence that circadian oscillations affect drug absorption, distribution, metabolism and excretion (ADME), there are yet many unanswered questions in this field and occasionally conflicting experimental results. Such data arise not only from translational difficulties caused by interspecies differences, but also from variability in study design and a lack of understanding of how the circadian clock affects physiological factors that strongly influence ADME, namely the expression and activity of drug transporters. Hence, the main goal of this review is to provide an updated analysis of the role of the circadian rhythm in drug absorption, distribution across blood-tissue barriers, metabolism in hepatic and extra-hepatic tissues, and hepatobiliary and renal excretion. It is expected that the research suggestions herein proposed will contribute to a tissue-targeted and time-targeted pharmacotherapy. This article is protected by copyright. All rights reserved.OBJECTIVE To study the profile of children with Hemophagocytic Lymphohistiocytosis (HLH) in a tertiary care hospital for children. METHODS A retrospective analysis of case records of 52 children diagnossed with HLH was performed. RESULTS Of the 52 children 13% (n = 7) had Familial HLH and 87% (n = 45) had secondary HLH (sHLH). Common manifestations were fever (100%), organomegaly (87%), respiratory distress (54%), neurological symptoms (31%) and skin rashes (26.2%). Anemia and thrombocytopenia were present in 51% and 73% respectively. Hyperferritinemia was present in 96% and hypofibrinogenemia in 42% and high lactate dehydrogenase (LDH) in 91%. Bone marrow examination showed hemophagocytosis in 80%. Most common etiology among infections was viral infections (67%), of which Dengue was the most common (52%). Among children with sHLH 51% received supportive care only. Ala-Gln manufacturer Thirty-seven percent (n = 17) received intravenous (IV) immunoglobulin and steroids. Of these 77% (n = 35) recovered completely. Children with familial HLH were initiated on HLH 2004 protocol but all of them expired due to disease progression. CONCLUSIONS Identifying HLH early and managing it, poses a significant challenge. Prompt recognition and initiation of immunosuppressive therapy is extremely important for the better outcome; hence high clinical suspicion and structured work up including immunological, and genetic studies is required. It may be difficult to differentiate primary and secondary HLH in many instances unless genetic analysis is done. Identification of familial HLH is necessary for early referral to Hematopoietic Stem Cell Transplantation (HSCT). Hence screening for primary HLH needs to be considered in all children with HLH.Outcome of childhood cancer in low middle-income countries continues to be poor. One of the proposed reasons for this poor outcome is increased time spent in diagnosis and initiation of treatment. The present study was done to quantify the magnitude and types of time intervals in management of childhood cancer. Parents of 111 children with newly diagnosed cancer were interviewed. Median total time interval for entire cohort was 58 d. The most important contributor to this total interval was Referral interval. Gender and use of alternative medicine significantly affected the total interval. Increased primary care physician sensitization for quicker referral to specialized centers may mitigate the delay and improve outcome.The advent of next gene sequencing technology has led to the publication of a profusion of papers on monogenic contributions to pediatric kidney disorders. It started with the discovery of mutations in the podocin gene in steroid resistant nephrotic syndrome (SRNS). It is realized now that genetic disorders contribute to about 30% of chronic renal diseases in children, and significantly to many other kidney disorders. This paper covers briefly the new genetic technologies, the benefits of genetic testing, and the indication for genetic testing in various kidney disorders. It covers SRNS, congenital anomalies of the kidney, cystic kidney disease, tubulopathies, nephronophthisis, Fabry disease, Alport and Lowe syndrome. Atypical hemolytic uremic syndrome, renal tubular acidosis and nephrolithiasis are also covered briefly. It is hoped that this paper will encourage the pediatricians to investigate monogenic disorders of the kidney as it helps in their proper classification, informs prognosis, suggests specific treatment and aids in genetic and reproductive counseling.OBJECTIVE To evaluate the effect of maternal/ neonatal vitamin D levels on culture positive neonatal sepsis. METHODS This prospective cohort study was conducted in the NICU of a tertiary care teaching hospital in Odisha, Eastern India from January 2015 through December 2016. Forty (40) neonates with culture positive sepsis were included in the study group. Forty (40) healthy neonates admitted for evaluation of neonatal jaundice who are similar in gender, gestational age, postnatal age and without any clinical signs of sepsis were recruited as control group after informed consent. Vitamin D level (25 OH D) was assessed in the neonates and their mothers in both the groups. RESULTS Neonatal 25 OH vitamin D level in the study group (12.71 ± 2.82 ng/ml) was significantly lower than in the control group (25.46 ± 7.02 ng/ml). The Odds ratio was 273 (95% CI 30.39-2451.6) for culture positive sepsis in neonates with vitamin D deficiency/insufficiency. Mothers of septic neonates had significantly lower 25 OH vitamin D level (20.92 ± 3.92 ng/ml) than the mothers of healthy neonates in control group (27.31 ± 6.83 ng/ml). The Odds ratio was 4.71 (95% CI 1.69-13.1) for culture positive sepsis in babies born to mothers with vitamin D deficiency/insufficiency. CONCLUSIONS Neonates with vitamin D deficiency/insufficiency are at higher risk for developing sepsis than those with sufficient vitamin D levels. Lower vitamin D levels in mothers is also associated with increased risk of sepsis in the neonates.
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