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The Multi-Ion Reflection Apparatus for Collinear Laser Spectroscopy (MIRACLS), currently under development at ISOLDE/CERN, aims to combine the high resolution of fluorescence-based collinear laser spectroscopy (CLS) with a high sensitivity. This will be achieved by confining 30-keV ion bunches in a Multi-Reflection Time-of-Flight (MR-ToF) device which allows laser spectroscopic probing for several thousand times. An MR-ToF setup operating at ∼ 1.5keV beam energy has been adapted for a proof-of-principle experiment. Thus, efforts had to be undertaken to reduce the laser stray light as the leading source of background of this apparatus, not originally designed for CLS. These measures enabled CLS of 24,26Mg+ ions in single-path mode, i.e. without ion trapping, which is the reference point to gauge the gain in sensitivity of the MIRACLS technique. [ABSTRACT FROM AUTHOR]

BACKGROUND The Nav1.8 voltage-gated sodium channel, expressed in peripheral nociceptive neurons, plays a role in transmitting nociceptive signals. The effect of VX-548, an oral, highly selective inhibitor of Nayl.8, on control of acute pain is being studied. METHODS After establishing the selectivity of VX-548 for Na,!.8 inhibition in vitro, we conducted two phase 2 trials involving participants with acute pain after abdominoplasty or bunionectomy. In the abdominoplasty trial, participants were randomly assigned in a 1:1:1:1 ratio to receive one of the following over a 48-hour period: a 100-mg oral loading dose of VX-548, followed by a 50-mg maintenance dose every 12 hours (the high-dose group); a 60-mg loading dose of VX-548, followed by a 30-mg maintenance dose every 12 hours (the middle-dose group); hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. In the bunionectomy trial, participants were randomly assigned in a 2:2:1:2:2 ratio to receive one of the following over a 48-hour treatment period: oral high-dose VX-548; middle-dose VX-548; low-dose VX-548 (a 20-mg loading dose, followed by a 10-mg maintenance dose every 12 hours); oral hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. The primary end point was the time-weighted sum of the pain-intensity difference (SPID) over the 48-hour period (SPID48), a measure derived from the score on the Numeric Pain Rating Scale (range, 0 to 10; higher scores indicate greater pain) at 19 time points after the first dose of VX-548 or placebo. The main analysis compared each dose of VX-548 with placebo. RESULTS A total of 303 participants were enrolled in the abdominoplasty trial and 274 in the bunionectomy trial. The least-squares mean difference between the high-dose VX-548 and placebo groups in the time-weighted SPID48 was 37.8 (95% confidence interval [CI], 9.2 to 66.4) after abdominoplasty and 36.8 (95% CI, 4.6 to 69.0) after bunionectomy. In both trials, participants who received lower doses of VX-548 had results similar to those with placebo. Headache and constipation were common adverse events with VX-548. CONCLUSIONS As compared with placebo, VX-548 at the highest dose, but not at lower doses, reduced acute pain over a period of 48 hours after abdominoplasty or bunionectomy. VX-548 was associated with adverse events that were mild to moderate in severity. (Funded by Vertex Pharmaceuticals; VX21-548-101 and VX21-548-102 ClinicalTrials.gov numbers, NCT04977336 and NCT05034952.). [ABSTRACT FROM AUTHOR]

Increased plasma free fatty acid (FFA) levels are a feature of insulin resistance and type 2 diabetes. The aim of the present study was to assess the effect of L-carnitine supplementation on plasma lipids and the expression of enzymes in peripheral mononucleated cells (PMNC) involved in the regulation of fatty acid and glucose oxidation. L-Carnitine supplementation of 2 g/day resulted in a significant decrease in plasma FFA and in a less pronounced diminution of the plasma triacylglycerols. In addition, a concomitant increase in the relative mRNA abundances of carnitine acyltransferases (5- to 10-fold) and of the carnitine carrier OCTN2 (12-fold) in PMNC of pregnant women was found. The results of the present study provide evidence that L-carnitine supplementation in pregnancy (2 g/day) avoids a striking increase in plasma FFA, which are thought to be the main cause of insulin resistance and consequently gestational diabetes mellitus. Copyright © 2010 S. Karger AG, Basel Erhöhte Konzentrationen an freien Fettsäuren (FFS) im Plasma sind für eine Insulinresistenz und eine diabetische Stoffwechsellage charakteristisch. In der vorliegenden Studie sollte der Effekt einer Carnitinsupplementation auf die Konzentration von Plasmalipiden und auf die Expression von Enzymen in den peripheren mononukleären Blutzellen (PMNC), die an der Regulation der Fettsäure- und Glukoseoxidation beteiligt sind, untersucht werden. Die Supplementation von L-Carnitin (2 g/Tag) resultierte in einer signifikanten Verminderung der Konzentration der Plasma-FFS und einer weniger starken Reduzierung der Plasma-Triacylglycerol-Konzentrationen. Zusätzlich kam es zu einer gleichzeitigen Zunahme der relativen mRNS-Menge von Carnitinacyltransferasen (CPT1A 5-fach, CPT1B 10-fach, CRAT 5-fach) und des spezifischen Carnitin-Transportproteins OCTN2 (12-fach) in den PMNC von Schwangeren. Die Ergebnisse der vorliegenden Studie belegen, dass 2 g L-Carnitin-Supplementation täglich bei Schwangeren den starken Anstieg der Plasma-FFS verhindert, welche eine Insulinresistenz und in weiterer Folge einen Schwangerschaftsdiabetes induzieren könnten. Des taux élevés d'acides gras libres caractérisent l'insulino-résistance et le diabète du type 2. Le but de cette étude était la détermination de l'effet de la L-carnitine supplémentée sur les lipides plasmatiques et l'expression des enzymes dans les cellules périphériques mononucléées (CPMN) qui sont impliquées dans le réglage de l'oxydation des acides gras et du glucose. La supplémentation de L-carnitine (2 g/jour) aboutit à une diminution significative des acides gras libres plasmatiques et une diminution moins marquée des triacylglycérols plasmatiques. En plus, il y avait une augmentation parallèle de l'abondance relative d'ARNm des acyltransférases de carnitine (5- 10 fois plus) et du vecteur de carnitine spécifique OCTN2 (12 fois plus) dans les CPMN de femmes enceintes. Les résultats de l'étude ci-dessous sont la preuve qu'une supplémentation de L-carnitine (2 g/jour) pendant la grossesse prévient l'augmentation marquée des acides gras libres plasmatiques qui sont considérés la cause principale de l'insulino-résistance et par conséquent du diabète gestationnel. [ABSTRACT FROM AUTHOR]

In this case study, we present two Holocaust survivors who appeared to have adapted well post-trauma, but developed severe PTSD symptomatology following the onset of neurologic illness in later life. These individuals were referred for neuropsychological evaluations by their treating neurologists to assess their levels of cognitive functioning. We present the neuropsychological findings, and discuss possible mechanisms for the emergence of PTSD symptoms. These case studies demonstrate the need for systematic research to further investigate the potential relationship between aging, degenerative disease, and PTSD symptoms in elderly trauma survivors. [ABSTRACT FROM AUTHOR]

This study examined the success of titanium (Ti) removable partial dentures (RPDs) compared with that of cobalt–chromium (Co–Cr) RPDs using a randomized controlled clinical trial. Thirty-eight RPD patients were provided with either Co–Cr (20 patients) or Ti (18 patients) RPDs. The total numbers of dentures was 31 (13 maxillary, 18 mandibular) for Co–Cr and 23 (11 maxillary, 12 mandibular) for Ti. Patients were reviewed for 24 months following denture issue. After the initial 12 months, 20 clinical problems were recorded and became the criteria for subsequent assessment. Incidence of failure was analysed using both Fisher's exact test and the chi square test at a significance level of P<0·05. Fracture of retainers in both metals occurred only in the first 12 months. Some failure types presented at significantly higher levels in the first 12 months but there were no significant differences between the two in all the criteria examined between the 12- and the 24-month reviews. Although differences existed in failure types between Co–Cr and Ti RPDs during the early review stages, the overall success rate of Ti RPDs was comparable with that of Co–Cr RPDs after 24 months. The higher incidence of failures in Ti RPDs prior to the 12-month review suggests the importance of taking its lower rigidity into account when designing RPDs. [ABSTRACT FROM AUTHOR]

Titanium (Ti) is a relatively new metal in prosthodontics. As a possible material for removable partial dentures (REDs), it was used in its pure form to make 10 RPDs which were compared with 10 identical cobalt-chromium (Co-Cr) alloy RPDs in a clinical trial. The dentures were used alternately for four weeks, the subjects were asked to answer a questionnaire and then the Co-Cr dentures were withdrawn, The Ti dentures were then followed up for 2 years and another standardized questionnaire administered. A survival rate of rests and retainers of 91% was recorded and the dentures were found to be more comfortable (55%) and preferred (64%) than the Co-Cr dentures. Factors to increase the success rates are discussed. [ABSTRACT FROM AUTHOR]

A case involving a 67 year old man with an immunocytoma initially presenting as Waldenström's macroglobulinemia which transformed into a high grade malignant lymphoma of immunoblastic type after treatment with cyclophosphamide and corticosteroids over 5 months is presented. IgM (kappa) present in the serum in the phase of immunocytoma was demonstrated also on the less differentiated cells of the high grade lymphoma. The permanent production of the same immunoglobuline molecule suggests that both morphologically different malignancies derived from one B cell clone. [ABSTRACT FROM AUTHOR]

Introduction La pathogénie de la néphropathie à IgA (NIgA) implique la présence d’une forme soluble du récepteur des IgA, le CD89s dans les dépôts mésangiaux. Nous avons préalablement montré que la transglutaminase 2 (TG2) est nécessaire à la formation des dépôts d’IgA1. Cette enzyme ubiquitaire présente diverses fonctions dont la régulation de certaines métalloprotéases (MMP). L’objectif est de déterminer le rôle de la TG2 dans l’induction d’une MMP responsable du clivage du CD89 et la formation des complexes circulants d’IgA1-CD89s. Matériels et méthodes Des souris α1KI-CD89Tg ont été comparées à des souris invalidées pour TG2. Les complexes ont été dosés par Elisa et l’expression du CD89 mesurée par cytométrie. L’activité des gélatinasses a été mesurée par zymographie. Des inhibiteurs de protéase ont été testés pour bloquer le clivage du CD89. Les MMP ont été dosées chez les patients. Résultats L’invalidation de TG2 chez la souris α1KI-CD89Tg entraîne une diminution des complexes circulants CD89s-pIgA1 associée à une augmentation de l’expression du CD89 membranaire des monocytes circulants. In vitro, une augmentation significative de la liaison des pIgA1 aux macrophages dérivés de la moelle osseuse (MMO) a été observée en absence de TG2. Pour déterminer la protéase impliquée, nous avons d’abord montré sur la lignée U937 que le clivage du CD89 est induit par le PMA et qu’il peut être bloqué par un inhibiteur de large spectre des protéases, le GM6001. Pour identifier une protéase contrôlée par la TG2, nous avons montré que MMP9 est présente uniquement dans le mésangium des α1KI-CD89Tg et active dans les surnageant des MMO de ces souris. De plus, les taux sériques de MMP9 ont été significativement plus élevés chez les patients atteints de NIgA. Nous avons également analysé PP2A une sérine phosphatase connue pour réprimer MMP9 et activer le CD89. En effet, en absence de TG2, PP2A est très fortement augmentée dans les MMO des α1KI-CD89Tg. Discussion Nos résultats suggèrent que MMP9 monocytaire soit impliqué dans la formation des complexes pIgA1-sCD89, et que le clivage du CD89 est régulé par l’axe TG2-PP2A. Conclusion La dérégulation de l’axe TG2-PP2A-MMP9 pourrait jouer un rôle crucial dans la pathogenèse de la N-IgA. [ABSTRACT FROM AUTHOR]

The Smith-Lemli-Opitz syndrome (SLOS) is a phenotypically variable metabolic malformation and mental retardation syndrome for which more than 80 mutations in the DHCR7 disease-causing gene have been described. The DHCR7 mutational spectra differ significantly in different areas of Europe, and several common putative founder mutations account for a substantial fraction of all mutations in some ethnic groups. Here we have analysed 47 SLOS patients and describe 14 newly identified mutations in 18 SLOS patients of Ashkenazi Jewish, Austrian, British, German, Italian, Irish, Polish, Portuguese, and Spanish origins. Half of the new mutations are in the transmembrane domains of the protein. In addition, there were two null mutations, one mutation in the 4th cytoplasmic loop, two mutations in the first and last codons, and three mutations in other regions such as the second cytoplasmic loop and the first endoplasmic loop. The analysis included 20 Spanish and 12 Italian SLOS patients and revealed very different mutation spectra in these patients compared to previously described patients from Czechoslovakia, Germany, Poland, and the UK and implicated p.Thr93Met on the J haplotype as the most frequent Mediterranean founder mutation. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Inflammation and social adversity have been linked to poorer long-term outcomes in breast cancer (BCa) patients, whereas greater social and family well-being (sfwb) relates to less inflammation and longer disease-free interval in BCa. S100A8A9 is a RAGE-related ligand that can up-regulate inflammatory and pro-metastatic processes and has been associated with increased risk of BCa metastasis. Here we examined associations between sfwb, s100A8A9 levels, and pro-inflammatory cytokines in 50 (M age = 53.65) distressed BCa patients in the weeks post-surgery (T1) and at 12-months (T2). Regression analyses controlling for age and disease stage showed lower S100A8A9 levels related to greater FACTsfwb at T1 (β = -.353, p =.001) and T2 (β = -.398, p =.01). S100A8A9 significantly related to T1 levels of IL6 (β =.412, p =.008) and IL1 β (β =.588, p =.001), and T2 levels of IL6 (β =.486, p =.001) and IL-1 β (β =.548, p =.001). Additionally, 12-month change in S100A8A9 was significantly related to 12-month change in IL6 (β =.279, p =.001) and IL1 β (β =.164, p =.001). These findings demonstrate that greater social and family well-being during BCa primary treatment is associated with lower levels of upstream and downstream inflammatory markers and point to the potential value of psychosocial interventions that target enhancement of social and family well-being during this time.. [ABSTRACT FROM AUTHOR]