Quantification of Epstein-Barr virus DNA load, interleukin-6, interleukin-10, transforming growth factor-β1 and stem cell factor in plasma of patients with nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common epithelial neoplasm among the Chinese populations in Southern China and South East Asia. Epstein-Barr virus (EBV) is known to be an important etiologic agent of NPC and the viral gene products are frequently detected in NPC tissues along with elevated antibody titres to the viral proteins (VCA and EA) in a majority of patients. Elevated plasma EBV DNA load is regarded as an important marker for the presence of the disease and for the monitoring of disease progression. However, other serum/plasma parameters such as the levels of certain interleukins and growth factors have also been implicated in NPC. The objectives of the present study are, 1) to investigate the correlations between plasma EBV DNA load and the levels of interleukin (IL)-6, IL-10, TGF-β1 and SCF (steel factor) and 2) to relate these parameters to the stages of NPC and the effect of treatment. METHODS: A total of 78 untreated NPC patients were enrolled in this study. Of these, 51 were followed-up after treatment. The remaining patients had irregular or were lost to follow-up. Plasma EBV DNA was quantified using real-time quantitative PCR. The levels of plasma interleukins and growth factors were quantified using ELISA. RESULTS: A significant decrease in EBV DNA load was detected in plasma of untreated NPC patients (1669 ± 637 copies/mL; n = 51) following treatment (57 ± 37 copies/mL, p < 0.05); n = 51). Plasma EBV DNA load was shown to be a good prognosticator for disease progression and clinical outcome in five of the follow-up patients. A significant difference in IL-6 levels was noted between the untreated patients (164 ± 37 pg/mL; n = 51) and following treatment (58 ± 16 pg/mL, p < 0.05; n = 51). Positive correlations between EBV DNA load and IL-10 (r(49) = 0.535, p < 0.01), between IL6 and IL-10 (r(49) = 0.474, p < 0.01) and between TGF and SCF (r(49) = 0.464, p < 0.01) were observed in patients following treatment. None of the parameters tested including IgA-VCA were associated with tumour stages. CONCLUSION: We conclude that among the parameters investigated, EBV DNA load and IL-6 levels were promising markers for the presence of NPC and for the assessment of treatment outcome

Selective Interaction of Syntaxin 1A with KCNQ2: Possible Implications for Specific Modulation of Presynaptic Activity

KCNQ2/KCNQ3 channels are the molecular correlates of the neuronal M-channels, which play a major role in the control of neuronal excitability. Notably, they differ from homomeric KCNQ2 channels in their distribution pattern within neurons, with unique expression of KCNQ2 in axons and nerve terminals. Here, combined reciprocal coimmunoprecipitation and two-electrode voltage clamp analyses in Xenopus oocytes revealed a strong association of syntaxin 1A, a major component of the exocytotic SNARE complex, with KCNQ2 homomeric channels resulting in a ∼2-fold reduction in macroscopic conductance and ∼2-fold slower activation kinetics. Remarkably, the interaction of KCNQ2/Q3 heteromeric channels with syntaxin 1A was significantly weaker and KCNQ3 homomeric channels were practically resistant to syntaxin 1A. Analysis of different KCNQ2 and KCNQ3 chimeras and deletion mutants combined with in-vitro binding analysis pinpointed a crucial C-terminal syntaxin 1A-association domain in KCNQ2. Pull-down and coimmunoprecipitation analyses in hippocampal and cortical synaptosomes demonstrated a physical interaction of brain KCNQ2 with syntaxin 1A, and confocal immunofluorescence microscopy showed high colocalization of KCNQ2 and syntaxin 1A at presynaptic varicosities. The selective interaction of syntaxin 1A with KCNQ2, combined with a numerical simulation of syntaxin 1A's impact in a firing-neuron model, suggest that syntaxin 1A's interaction is targeted at regulating KCNQ2 channels to fine-tune presynaptic transmitter release, without interfering with the function of KCNQ2/3 channels in neuronal firing frequency adaptation

Maternal and neonatal outcomes after caesarean delivery in the African Surgical Outcomes Study: a 7-day prospective observational cohort study.

BACKGROUND: Maternal and neonatal mortality is high in Africa, but few large, prospective studies have been done to investigate the risk factors associated with these poor maternal and neonatal outcomes. METHODS: A 7-day, international, prospective, observational cohort study was done in patients having caesarean delivery in 183 hospitals across 22 countries in Africa. The inclusion criteria were all consecutive patients (aged ≥18 years) admitted to participating centres having elective and non-elective caesarean delivery during the 7-day study cohort period. To ensure a representative sample, each hospital had to provide data for 90% of the eligible patients during the recruitment week. The primary outcome was in-hospital maternal mortality and complications, which were assessed by local investigators. The study was registered on the South African National Health Research Database, number KZ_2015RP7_22, and on ClinicalTrials.gov, number NCT03044899. FINDINGS: Between February, 2016, and May, 2016, 3792 patients were recruited from hospitals across Africa. 3685 were included in the postoperative complications analysis (107 missing data) and 3684 were included in the maternal mortality analysis (108 missing data). These hospitals had a combined number of specialist surgeons, obstetricians, and anaesthetists totalling 0·7 per 100 000 population (IQR 0·2-2·0). Maternal mortality was 20 (0·5%) of 3684 patients (95% CI 0·3-0·8). Complications occurred in 633 (17·4%) of 3636 mothers (16·2-18·6), which were predominantly severe intraoperative and postoperative bleeding (136 [3·8%] of 3612 mothers). Maternal mortality was independently associated with a preoperative presentation of placenta praevia, placental abruption, ruptured uterus, antepartum haemorrhage (odds ratio 4·47 [95% CI 1·46-13·65]), and perioperative severe obstetric haemorrhage (5·87 [1·99-17·34]) or anaesthesia complications (11·47 (1·20-109·20]). Neonatal mortality was 153 (4·4%) of 3506 infants (95% CI 3·7-5·0). INTERPRETATION: Maternal mortality after caesarean delivery in Africa is 50 times higher than that of high-income countries and is driven by peripartum haemorrhage and anaesthesia complications. Neonatal mortality is double the global average. Early identification and appropriate management of mothers at risk of peripartum haemorrhage might improve maternal and neonatal outcomes in Africa. FUNDING: Medical Research Council of South Africa.Medical Research Council of South Africa