Determinants of salivary evening alpha-amylase in a large sample free of psychopathology

Objective: Recently, salivary alpha-amylase (sAA) has been proposed as a suitable index for sympathetic activity and dysregulation of the autonomic nervous system (ANS). Although determinants of sAA have been described, they have not been studied within the same study with a large sample size without potential disturbances of psychopathology. In this paper, we report about correlates of evening sAA in saliva. Methods: In 487 participants (mean age = 42.9. years, 59.8% female) without lifetime psychiatric disorders from the Netherlands Study of Depression and Anxiety (NESDA), sociodemographic, health and sampling determinants of sAA levels were examined using multivariable linear regression analysis. sAA was measured in two saliva samples that participants collected in the late evening, at 22:00. h and 23:00. h, after which these were averaged. Results: In multivariate analysis, age (β= 0.20, p< 0.001) and daily alcohol intake (β= - 0.13, p= 0.01) were independent determinants of evening sAA levels. Gender, allergy or lung disease, and the use of oral contraceptives were univariate correlates, but no longer associated with sAA in the multivariate model. Conclusions: Age and alcohol use were identified as potential confounding factors that should be taken into account in epidemiologic studies that examine the ANS function using sAA. © 2012 Elsevier B.V

Paleoglaciology of the central East Antarctic Ice Sheet as revealed by blue-ice sediment

We present ∼100 cosmogenic surface exposure ages, including 75 new analyses, for a blue-ice moraine complex at Mt. Achernar, head of Law Glacier, in the central Transantarctic Mountains. The 10Be–3He–26Al ages along with previously-published boron concentrations chronicle past behavior of the East Antarctic Ice Sheet (EAIS) along the edge of the polar plateau since the sediments started to accumulate, around 0.5–1 Ma. Samples analyzed for 10Be from the Law Glacier surface record <100 years of exposure, indicating they likely have negligible inheritance when first exposed. The Law Glacier surface experienced relatively minor fluctuations in surface elevation throughout MIS 6 and 5, and likely during prior periods, as geomorphic features are intact and exposure ages are coherent on the moraine, ranging from ∼210 to ∼86 ka; respective means for MIS 5 till in two different areas are 106 ± 9.1 ka [n = 4 ages] and 106 ± 5.1 ka [n = 6]. Although we infer the Law Glacier has been relatively close to its current configuration generally since 0.5–1 Ma, disturbances to Achernar blue-ice moraine architecture seem apparent at times especially prior to the last two glacial cycles. The largest observed disturbance occurred when the nearby Lewis Cliffs Ice Tongue expanded either close to, or earlier than, 500-400 ka. A minimum ice thickness increase of 30 m is associated with the ∼20 ka blue-ice ridges, and a lateral moraine indicates the Law Glacier surface was ∼40–50 m higher at ∼9.2 ± 0.5 ka. Our findings support that lateral accretion over time formed the Mt. Achernar blue-ice moraine sequence, and by implication, other analogue Antarctic deposits. We interpret blue-ice moraines as representing, at times, relatively constant outlet glacier conditions and concur with prior studies that they reflect near-equilibrium forms. Blue-ice sediments are an underutilized and dateable paleoglaciologic and paleoclimate archive in Antarctica, including for former ice surface dynamics and possibly as a repository of old ice during periods such as MIS 5 and prior

A General Review Of Literature On Child's Occlusion

INTRODUCTION: Although HPA-axis activity has been studied extensively in relation to depression, there is no consensus whether HPA-axis parameters predicts major depressive disorder (MDD) recurrence. We investigated whether HPA-axis parameters (cortisol awakening response (CAR), the dexamethasone suppression test (DST) and evening cortisol) predict time to recurrence in remitted subjects with a history of MDD and whether childhood trauma and life events interact with HPA-axis parameters in increasing the risk for recurrence. METHOD: Data were derived from 549 subjects with a lifetime diagnosis of MDD in remission for at least six months preceding the baseline assessment of the Netherlands Study of Depression and Anxiety (NESDA). Subjects were followed up with two interviews over the course of four years to assess recurrence. DSM-IV based diagnostic interviews were used to assess time to recurrence of MDD. Seven salivary cortisol samples collected at baseline with information on CAR, evening cortisol and the DST. Hazard ratios were calculated using Cox regression analysis, adjusted for covariates. RESULTS: A higher CAR was associated with time to recurrence of MDD (HR=1.03, 95%CI 1.003-1.060, p=0.03) whereas evening cortisol and DST were not. No interactions between HPA-axis parameters and stress-related factors were found. CONCLUSIONS: Our data support previous studies reporting that subjects with a higher CAR are more vulnerable to recurrence of MDD

Twist-1 is upregulated by NSD2 and contributes to tumour dissemination and an epithelial-mesenchymal transition-like gene expression signature in t(4;14)-positive multiple myeloma

Approximately 15% of patients with multiple myeloma (MM) harbour the t(4;14) chromosomal translocation, leading to the overexpression of the histone methyltransferase NSD2. Patients with this translocation display increased tumour dissemination, accelerated disease progression and rapid relapse. Using publicly available gene expression profile data from NSD2(high) (n=135) and NSD2(low) (n=878) MM patients, we identified 39 epithelial-mesenchymal transition (EMT)-associated genes which are overexpressed in NSD2(high) MM plasma cells. In addition, our analyses identified Twist-1 as a key transcription factor upregulated in NSD2(high) MM patients and t(4;14)-positive cell lines. Overexpression and knockdown studies confirmed that Twist-1 is involved in driving the expression of EMT-associated genes in the human MM cell line KMS11 and promoted the migration of myeloma cell lines in vitro. Notably, Twist-1 overexpression in the mouse MM cell line 5TGM1 significantly increased tumour dissemination in an intratibial tumour model. These findings demonstrate that Twist-1, downstream of NSD2, contributes to the induction of an EMT-like signature in t(4;14)-positive MM and enhances the dissemination of MM plasma cells in vivo, which may, in part, explain the aggressive disease features associated with t(4;14)-positive MM.Chee Man Cheong, Krzysztof M. Mrozik, Duncan R. Hewett, Elyse Bell, Vasilios Panagopoulos, Jacqueline E. Noll, Jonathan D. Licht, Stan Gronthos, Andrew C.W. Zannettino, Kate Vandyk

Efficacy of consolidation high-dose chemotherapy with ifosfamide, carboplatin and etoposide (HD-ICE) followed by autologous peripheral blood stem cell rescue in chemosensitive patients with metastatic soft tissue sarcomas.

Prognosis of patients with metastatic soft tissue sarcomas (MSTS) is poor even after response to doxorubicin-based chemotherapy. We report phase II data of high-dose chemotherapy and peripheral blood stem cell (PBSC) rescue in patients with MSTS responding to AI-G chemotherapy. PATIENTS AND METHODS: From 1997 to 2002, 55 patients with MSTS were prospectively treated with 4 cycles of AI-G (doxorubicin 75 mg/m(2), ifosfamide 6 g/m(2) with G-CSF support). Responders received 2 further cycles of AI-G with collection of PBSCs. High-dose chemotherapy consisted of ifosfamide 12 g/m(2), carboplatin 1.2 g/m(2) and etoposide 1.2 g/m(2) (HD-ICE) followed by reinfusion of PBSCs. RESULTS: Twenty-one of 55 patients (38%) were assessed as responders (3 complete response, 18 partial response). All but 2 patients refusing treatment received high-dose chemotherapy with PBSC rescue leading to grade IV hematologic toxicity without severe infections in all patients. No toxic death occurred. After a median follow-up time of 30 months, the median progression-free time was 12 months and survival time was 22 months for the entire group. By intent-to-treat analysis the probability of 5-year progression-free survival was significantly higher for patients allocated to HD-ICE compared to patients receiving second-line chemotherapy after failure of AI-G (14 vs. 3%; p = 0.003). The estimated 5-year overall survival between the 2 groups was different (27% vs. not reached) but did not reach significance (p = 0.08). CONCLUSION: HD-ICE is feasible and promising in patients with chemosensitive MSTS. A randomized phase III trial is warranted to further define the role of HD-ICE as consolidation treatment in these patients

Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies

Contains fulltext : 155154.pdf (Publisher’s version ) (Open Access)Atypical hemolytic uremic syndrome (aHUS) is a rare, possibly life-threatening disease characterized by platelet activation, hemolysis and thrombotic microangiopathy (TMA) leading to renal and other end-organ damage. We originally conducted two phase 2 studies (26 weeks and 1 year) evaluating eculizumab, a terminal complement inhibitor, in patients with progressing TMA (trial 1) and those with long duration of aHUS and chronic kidney disease (trial 2). The current analysis assessed outcomes after 2 years (median eculizumab exposure 100 and 114 weeks, respectively). At all scheduled time points, eculizumab inhibited terminal complement activity. In trial 1 with 17 patients, the platelet count was significantly improved from baseline, and hematologic normalization was achieved in 13 patients at week 26, and in 15 patients at both 1 and 2 years. The estimated glomerular filtration rate (eGFR) was significantly improved compared with baseline and year 1. In trial 2 with 20 patients, TMA event-free status was achieved by 16 patients at week 26, 17 patients at year 1, and 19 patients at year 2. Criteria for hematologic normalization were met by 18 patients at each time point. Improvement of 15 ml/min per 1.73 m(2) or more in eGFR was achieved by 1 patient at week 26, 3 patients at 1 year, and 8 patients at 2 years. The mean change in eGFR was not significant compared with baseline, week 26, or year 1. Eculizumab was well tolerated, with no new safety concerns or meningococcal infections. Thus, a 2-year analysis found that the earlier clinical benefits achieved by eculizumab treatment of aHUS were maintained at 2 years of follow-up