Impact of ß-hydroxy-ß-methylbutyrate (HMB) on muscle loss and protein metabolism in critically ill patients: A RCT.

PURPOSE: Muscle wasting deteriorates life quality after critical illness and increases mortality. Wasting starts upon admission to intensive care unit (ICU). We aimed to determine whether ß-hydroxy-ß-methylbutyrate (HMB), a metabolite of leucine, can attenuate this process. METHODS: Prospective randomized, placebo-controlled double blind trial. INCLUSION CRITERIA: ICU patients depending on mechanical ventilation on day 3 having a functional gastrointestinal tract. They were randomized to HMB (3 g/day) or placebo (maltodextrin) from day 4 on for 30 days. PRIMARY OUTCOME: magnitude of loss of skeletal muscle area (SMA) of the quadriceps femoris measured by ultrasound at days 4 and 15. SECONDARY OUTCOMES: body composition, change in protein metabolism assessed by amino acids tracer pulse, and global health at 60 days. Data are mean [95% CI]. Statistics by ANCOVA with correction for confounders sex, age and/or BMI. RESULTS: Thirty patients completed the trial, aged 65 [59, 71] years, SAPS2 score 48 [43, 52] and SOFA 8.5 [7.4, 9.7]. The loss of total SMA was 11% between days 4 and 15 (p < 0.001), but not different between the groups (p = 0.86). In the HMB group, net protein breakdown (Δ Estimate HMB-Placebo: -153 [-242, -63]; p = 0.0021) and production of several amino acid was significantly reduced, while phase angle increased more (0.66 [0.09, 1.24]; p = 0.0247), and SF-12 global health improved more (Δ Estimate HMB-Placebo: 27.39 [1.594, 53.19], p = 0.04). CONCLUSION: HMB treatment did not significantly reduce muscle wasting over 10 days of observation (primary endpoint), but resulted in significantly improved amino acid metabolism, reduced net protein breakdown, a higher phase angle and better global health. CLINICALTRIALS. GOV IDENTIFIER: NCT03628365.

A novel 384-multiwell microelectrode array for the impedimetric monitoring of Tau protein induced neurodegenerative processes.

Over the last decades, countless bioelectronic monitoring systems were developed for the analysis of cells as well as complex tissues. Most studies addressed the sensitivity and specificity of the bioelectronic detection method in comparison to classical molecular biological assays. In contrast, the up scaling as a prerequisite for the practical application of these novel bioelectronic monitoring systems is mostly only discussed theoretically. In this context, we developed a novel 384-multiwell microelectrode array (MMEA) based measurement system for the sensitive label-free real-time monitoring of neurodegenerative processes by impedance spectroscopy. With respect to the needs of productive screening systems for robust and reproducible measurements on high numbers of plates, we focused on reducing the critical contacting of more than 400 electrodes for a 384-MMEA. Therefore, we introduced an on top array of immersive counter electrodes that are individually addressed by a multiplexer and connected all measurement electrodes on the 384-MMEA to a single contact point. More strikingly, our novel approach provided a comparable signal stability and sensitivity similar to an array with integrated counter electrodes. Next, we optimized a SH-SY5Y cell based tauopathy model by introducing a novel 5-fold Tau mutation eliminating the need of artificial tauopathy induction. In combination with our novel 384-MMEA based measurement system, the concentration and time dependent neuroregenerative effect of the kinase inhibitor SRN-003-556 could be quantitatively monitored. Thus, our novel screening system could be a useful tool to identify and develop potential novel therapeutics in the field of Tau-related neurodegenerative diseases.

Spatiotemporal variation of dissolved (238)U in the Gironde fluvial-estuarine system (France).

Dissolved uranium ((238)U(D)) was measured within the Gironde fluvial-estuarine system (France), which is well known for its heavy metal pollution and its subsequent environmental effects. Dissolved (238)U activities exhibit the highest levels and variability in the small watersheds of the Isle and Riou-Mort rivers, ascribed to low discharges and the occurrence of peculiar features (local U ore deposits; Permian layers). The major tributaries of the Gironde Estuary: Garonne, Lot and Dordogne, show rather stable (238)U(D), higher than the global mean riverine uranium activity. In the Gironde Estuary (238)U(D) behaves conservatively along the river-estuary-ocean transect. Dissolved (238)U distribution in the Gironde fluvial-estuarine system can be explained by the characteristics of considered drainage basins. There is no evidence of anthropogenic pollution.

Children's environment in Central Europe: threats and chances.

Many of the "classical" environmental hazards and risks (such as anthropogenic chemical and physical factors, e.g., asbestos, dioxin, electromagnetic fields and "pesticides") are in our countries not major determinants of children's health and well being; however, there may exist unseen or unrecognized causal contexts. Some hazards, such as UV light, noise, fine particles, tobacco smoke, legal and illegal drugs, and radon, are considered important by experts, but are still largely ignored by the public. In our society, despite of, or maybe because of the multitude of information and disinformation, adequate risk perception continues to be a problem. Furthermore, ever-new environmental toxicants will come to the surface and occupy medial interest, and thus, continuing attention is warranted. Of our children's environment, yet other facets are of prime importance: nutrition, housing and traffic and public media. Most important, however, is the fact that society (governments, administration, industry and consumers) are disregarding the long-term sustainability of their actions and behaviour, thus endangering the future of our children and grandchildren. This is in contrast with the existing declarations and official action plans. In future, ranking of priorities for research and actions will be necessary, taking into account costs and effectiveness since resources to be invested into these issues certainly will remain limited.

Potential impact of former Zn ore extraction activities on dissolved uranium distribution in the Riou-Mort watershed (France).

The industrial basin of Decazeville (Riou-Mort watershed, South-West France) is well known for its heavy metal pollution and its subsequent environmental effects on the Lot-Garonne River system. The source of this pollution is the Riou-Mort River, which drains smelting waste areas. A first survey after remediation works has revealed elevated dissolved uranium (U(D)) concentrations in the outlet of the Riou-Mort River. The objective of this research is to identify the origin of U(D) in the Riou-Mort watershed and to evaluate the impact of industrial activities on this element. Uranium was measured at 10 water sampling sites, located upstream and downstream the industrial basin, and in three smelting waste deposits. Uranium concentrations in the smelting waste deposits reach up to 14.4 mg kg(-1) and (234U/238U) activity ratios (AR) are near unity. Dissolved U concentrations in the Riou-Mort River and its main tributaries ranges over two orders of magnitude from 0.02 to 6.1 microg L(-1). The highest levels were measured in a site with no anthropogenic pollution, upstream from the industrial area. This observation suggests that U(D) is mainly linked to weathering; the elevated U concentrations originate from the naturally occurring radioactive materials (NORM) located in the Permian bedrock and no significant U pollution exists, at present, in the Riou-Mort watershed. This work demonstrates that spatial monitoring coupled with a long time-series are an essential prerequisite in assessment of spatiotemporal variations of U(D), prior to a diagnostic of pollution in a small watershed.

Liver metastases in rats: chemoembolization combined with interstitial laser ablation for treatment.

PURPOSE: To assess the effect of transcatheter arterial chemoembolization (TACE) combined with laser-induced thermotherapy (LITT) for treatment of liver metastases in an animal model. MATERIALS AND METHODS: All experiments were approved by the German government and the institutional animal research review board. After subcapsular liver implantation of colorectal cancer cells in 30 WAG rats (on day 0), the animals were randomly assigned to three interventional treatment groups. In the 10 rats in group A, TACE was performed: Fourteen days after cancer cell implantation and within 20 minutes after laparotomy and retrograde placement of a microcatheter into the gastroduodenal artery, these rats were injected with mitomycin (0.1 mg), iodized oil (0.1 mL), and degradable starch microspheres (5.0 mg). In the 10 rats in group B, LITT was performed: Also on day 14, the tumors in these animals were exposed to Nd:YAG laser light of 1064 nm at 2 W for 5 minutes. In the 10 rats in group C, combined treatment was administered: TACE was performed on day 14, and LITT was performed on day 21. Tumor volumes were measured before (on day 13) and after (on day 28) treatment with magnetic resonance (MR) imaging, and the mean tumor growth ratio (day 13 tumor volume divided by day 28 tumor volume) was calculated. RESULTS: The mean tumor volumes measured before and after the treatments were, respectively, 0.11 and 0.60 cm(3) in group A, 0.11 and 0.68 cm(3) in group B, and 0.11 and 0.35 cm(3) in group C. The mean tumor growth ratio was 5.42 in group A, 6.14 in group B, and 3.15 in group C. According to Bonferroni test results, compared with the rats in groups A and B (controls), the group C rats had significantly inhibited tumor growth (P < .01 for both comparisons). CONCLUSION: Use of combined TACE-LITT treatment, compared with the use of TACE or LITT alone, significantly inhibits tumor growth.

Investigation of dissolved uranium content in the watershed of Seine River (France).

A systematic survey of dissolved uranium activity was carried out in the Seine and the Marne over one year. A small watershed, the Grand Morin, included in the Seine one, was also investigated from stream to medium-sized rivers. The Melarchez stream exhibits low but variable dissolved 238U levels (3.3 +/- 2.0 mBq l(-1)). Thereafter, uranium activities show a rapid increase to reach, from the Grand Morin River, a rather constant range (8-11 mBq l(-1)). On the Marne before the confluence with the Seine, dissolved 238U is nearly invariable (9.1 +/- 0.8 mBq l(-1)), for flow rates comprised between 60 and 423 m3 s(-1). Dissolved 238U in the Seine corresponds to almost triple the global mean riverine uranium concentration. In the estuary of the Seine, uranium shows a gradual increase, resulting from conservative mixing of river with sea waters.

Prospective comparison of MR enteroclysis with multidetector spiral-CT enteroclysis: interobserver agreement and sensitivity by means of "sign-by-sign" correlation.

Our objective was a prospective comparison of MR enteroclysis (MRE) with multidetector spiral-CT enteroclysis (MSCTE). Fifty patients with various suspected small bowel diseases were investigated by MSCTE and MRE. The MSCTE was performed using slices of 2.5 mm, immediately followed by MRE, obtaining T1- and T2-weighted sequences, including gadolinium-enhanced acquisition with fat saturation. Three radiologists independently evaluated MSCTE and MRE searching for 12 pathological signs. Interobserver agreement was calculated. Sensitivities and specificities resulted from comparison with pathological results ( n=29) and patient's clinical evolution ( n=21). Most pathological signs, such as bowel wall thickening (BWT), bowel wall enhancement (BWE) and lymphadenopathy (ADP), showed better interobserver agreement on MSCTE than on MRE (BWT: 0.65 vs 0.48; BWE: 0.51 vs 0.37; ADP: 0.52 vs 0.15). Sensitivity of MSCTE was higher than that of MRE in detecting BWT (88.9 vs 60%), BWE (78.6 vs 55.5%) and ADP (63.8 vs 14.3%). Wilcoxon signed-rank test revealed significantly better sensitivity of MSCTE than that of MRE for each observer ( p=0.028, p=0.046, p=0.028, respectively). Taking the given study design into account, MSCTE provides better sensitivity in detecting lesions of the small bowel than MRE, with higher interobserver agreement.