IntroductionThe use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals.Materials and MethodsA set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed.ResultsNone of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count.DiscussionNo associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.
One hundred and twenty patients undergoing early legal termination of pregnancy by dilatation and suction curettage before 12 weeks of pregnancy were randomly allocated to receive total intravenous propofol anaesthesia either alone or supplemented with fentanyl 1.5 micrograms.kg-1 or alfentanil 15 micrograms.kg-1. Supplementation with fentanyl or alfentanil improved operating conditions (P < 0.01), reduced total propofol requirements (P < 0.01) and reduced postoperative pain intensity (P < 0.05). Immediate recovery, assessed by the time patients took to open the eyes, to give correct date of birth and by co-operation score, was more rapid in the alfentanil group compared to the control group (P < 0.05), whereas there was no significant difference between the alfentanil and fentanyl groups. The three anaesthetic techniques did not differ with regard to side effects. In conclusion, total intravenous propofol anaesthesia in patients undergoing early termination of pregnancy was improved by supplementation with either fentanyl 1.5 micrograms.kg-1 or alfentanil 15 micrograms.kg-1. The benefit was slightly greater with alfentanil than with fentanyl.
The effect of isocaloric (500 kcal) protein and carbohydrate ingestion was studied in a crossover study in nine healthy humans. Subjects were studied twice after overnight fasting, with an interval of 3 to 7 days. Blood was collected for 240 min after food ingestion. The initial reaction of growth hormone (GH) and thyroid stimulating hormone (TSH) to protein and carbohydrate was identical, with a reduction in both GH and TSH, and nadir occurring after 45-60 min and 120 min, respectively. During the next 120 min TSH returned to starting level after carbohydrate intake but was still reduced after protein intake (p less than 0.04). After both diets GH increased after the initial decline, the increase was greatest after protein intake and maximum was reached at 180 min (p less than 0.02). It has been reported that the 5'-deiodination of T4 is stimulated by insulin and inhibited by glucagon. The physiological increase in insulin after carbohydrate ingestion (p less than 0.05), and the physiological increase in glucagon after protein ingestion (p less than 0.05) was not associated with any changes in TT4, FT4, TT3, FT3, or rT3 that could indicate changes in the 5'-deiodinase activity.
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