Rosette-forming glioneuronal tumor of the cerebellum in statu nascendi: an incidentally detected diminutive example indicates derivation from the internal granule cell layer

Rosette-forming glioneuronal tumor (RGNT) is a recently introduced, indolent neoplasm composed of diminutive circular aggregates of neurocytic-like cells on a noninfiltrative astrocytic background, typically located in the cerebellar midline The traded concept of RGNT being derived from site-specific periventricular precursors may be questioned in the face of extracerebellar examples as well as ones occurring in combination with other representatives of the glioneuronal family. We describe a hitherto not documented example of asymptomatic RGNT discovered during autopsy of a 74-year-old male. Located in the tuberal vermis, this lesion of 6 mm diameter consisted of several microscopic nests of what were felt to represent nascent stages of RGNT, all of them centered on the internal granular layer, and ranging from mucoid dehiscences thereof to fully evolved - if small - tumor foci. Molecular genetic analysis revealed a missense mutation in Exon 20 of the PIK3CA gene involving an A→G transition at Nucleotide 3140. On the other hand, neither codeletion of chromosomes 1p/19q nor pathogenic mutations of IDH1/2 were detected. By analogy with in situ paradigms in other organs, we propose that this tumor is likely to have arisen from the internal granular layer, rather than the plate of the 4th ventricle. A suggestive departure from the wholesale argument of "undifferentiated precursors", this finding also indirectly indicates that a subset of non-classical RGNTs - in particular extracerebellar examples, whose origin cannot be mechanistically accounted for by either of the above structures - may possibly reflect an instance of phenotypic convergence, rather than a lineage-restricted entity.

Body salt and water balances in cardiothoracic surgery patients with intensive care unit-acquired hyponatremia

PURPOSE Hyponatremia is frequently observed in intensive care unit (ICU) patients, but there is still lack information on the physiological mechanisms of development. MATERIALS AND METHODS In this retrospective analysis we performed tonicity balances in 54 patients with ICU acquired hyponatremia. We calculated fluid and solute in and outputs during 24 hours in 106 patient days with decreasing serum-sodium levels. RESULTS We could observe a positive fluid balance as a single reason for hyponatremia in 25% of patients and a negative solute balance in 57%. In 18% both factors contributed to the decrease in serum-sodium. Hyponatremic patients had renal water retention, measured by electrolyte free water clearance calculation in 79% and positive input of free water in 67% as reasons for decline of serum-sodium. The theoretical change of serum sodium during 24 hours according to the calculations of measured balances correlated well with the real change of serum sodium (r = 0.78, P < .01). CONCLUSIONS Balance studies showed that renal water retention together with renal sodium loss and high electrolyte free water input are the major contributors to the development of hyponatremia. Control of renal water and sodium handling by urine analysis may contribute to a better fluid management in the ICU population.

Optical imaging of postsynaptic odor representation in the glomerular layer of the mouse olfactory bulb.

Olfactory glomeruli are the loci where the first odor-representation map emerges. The glomerular layer comprises exquisite local synaptic circuits for the processing of olfactory coding patterns immediately after their emergence. To understand how an odor map is transferred from afferent terminals to postsynaptic dendrites, it is essential to directly monitor the odor-evoked glomerular postsynaptic activity patterns. Here we report the use of a transgenic mouse expressing a Ca(2+)-sensitive green fluorescence protein (GCaMP2) under a Kv3.1 potassium-channel promoter. Immunostaining revealed that GCaMP2 was specifically expressed in mitral and tufted cells and a subpopulation of juxtaglomerular cells but not in olfactory nerve terminals. Both in vitro and in vivo imaging combined with glutamate receptor pharmacology confirmed that odor maps reported by GCaMP2 were of a postsynaptic origin. These mice thus provided an unprecedented opportunity to analyze the spatial activity pattern reflecting purely postsynaptic olfactory codes. The odor-evoked GCaMP2 signal had both focal and diffuse spatial components. The focalized hot spots corresponded to individually activated glomeruli. In GCaMP2-reported postsynaptic odor maps, different odorants activated distinct but overlapping sets of glomeruli. Increasing odor concentration increased both individual glomerular response amplitude and the total number of activated glomeruli. Furthermore, the GCaMP2 response displayed a fast time course that enabled us to analyze the temporal dynamics of odor maps over consecutive sniff cycles. In summary, with cell-specific targeting of a genetically encoded Ca(2+) indicator, we have successfully isolated and characterized an intermediate level of odor representation between olfactory nerve input and principal mitral/tufted cell output.

Characterization and differentiation of body fluids, putrefaction fluid, and blood using Hounsfield unit in postmortem CT

The purpose of the present study was to evaluate the ranges of Hounsfield unit (HU) found in body fluids, putrefaction fluids, and blood on postmortem CT and how these ranges are affected by postmortem interval, temperatures, and CT beam energy. Body fluids, putrefaction fluids, and blood from a total of 53 corpses were analyzed to determine the ranges of HU values from postmortem CT images that were taken prior to autopsy. The fluids measured in CT images were obtained at autopsy and examined in terms of macroscopic and microscopic appearances. Body fluids and blood were also collected in plastic bottles, which were subjected to CT scans at different beam energies (80-130 kV) and at various fluid temperatures (4 to 40 °C). At a postmortem interval of 1 to 4 days, the ranges of HU values of the serous fluids (13-38 HU) and the nonsedimented blood (40-88 HU) did not overlap. In the sedimented blood, the upper serum layer exhibited HU value ranges that overlapped with those of the serous fluids. The putrefaction fluids exhibited a range of HU values between 80 and -130 HU. Elevated HU values were observed in fluids with accretive cell impurities. HU values decreased slightly with increasing temperature and CT beam energy. We concluded that serous fluids and blood in fresh corpses can be characterized and differentiated from each other based on HU value ranges. In contrast, body fluids in decomposed corpses cannot be differentiated by their HU value ranges. Different beam energies and corpse temperatures had only minor influences on HU value ranges and therefore should not be obstacles to the differentiation and characterization of body fluids and blood.

Precision of fit of implant-supported screw-retained 10-unit computer-aided-designed and computer-aided-manufactured frameworks made from zirconium dioxide and titanium: an in vitro study

OBJECTIVE To analyze the precision of fit of implant-supported screw-retained computer-aided-designed and computer-aided-manufactured (CAD/CAM) zirconium dioxide (ZrO) frameworks. MATERIALS AND METHODS Computer-aided-designed and computer-aided-manufactured ZrO frameworks (NobelProcera) for a screw-retained 10-unit implant-supported reconstruction on six implants (FDI positions 15, 13, 11, 21, 23, 25) were fabricated using a laser (ZrO-L, N = 6) and a mechanical scanner (ZrO-M, N = 5) for digitizing the implant platform and the cuspid-supporting framework resin pattern. Laser-scanned CAD/CAM titanium (TIT-L, N = 6) and cast CoCrW-alloy frameworks (Cast, N = 5) fabricated on the same model and designed similar to the ZrO frameworks were the control. The one-screw test (implant 25 screw-retained) was applied to assess the vertical microgap between implant and framework platform with a scanning electron microscope. The mean microgap was calculated from approximal and buccal values. Statistical comparison was performed with non-parametric tests. RESULTS No statistically significant pairwise difference was observed between the relative effects of vertical microgap between ZrO-L (median 14 μm; 95% CI 10-26 μm), ZrO-M (18 μm; 12-27 μm) and TIT-L (15 μm; 6-18 μm), whereas the values of Cast (236 μm; 181-301 μm) were significantly higher (P < 0.001) than the three CAD/CAM groups. A monotonous trend of increasing values from implant 23 to 15 was observed in all groups (ZrO-L, ZrO-M and Cast P < 0.001, TIT-L P = 0.044). CONCLUSIONS Optical and tactile scanners with CAD/CAM technology allow for the fabrication of highly accurate long-span screw-retained ZrO implant-reconstructions. Titanium frameworks showed the most consistent precision. Fit of the cast alloy frameworks was clinically inacceptable.

4-year clinical outcomes and predictors of repeat revascularization in patients treated with new-generation drug-eluting stents: a report from the RESOLUTE All-Comers trial (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention)

OBJECTIVES The aim of the study was to investigate 4-year outcomes and predictors of repeat revascularization in patients treated with the Resolute zotarolimus-eluting stent (R-ZES) (Medtronic, Minneapolis, Minnesota) and XIENCE V everolimus-eluting stent (EES) (Abbott Vascular, Abbott Park, Illinois) in the RESOLUTE (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention) All-Comers trial. BACKGROUND Data on long-term outcomes of new-generation drug-eluting stents are limited, and predictors of repeat revascularization due to restenosis and/or progression of disease are largely unknown. METHODS Patients were randomly assigned to treatment with the R-ZES (n = 1,140) or the EES (n = 1,152). We assessed pre-specified safety and efficacy outcomes at 4 years including target lesion failure and stent thrombosis. Predictors of revascularization at 4 years were identified by Cox regression analysis. RESULTS At 4 years, the rates of target lesion failure (15.2% vs. 14.6%, p = 0.68), cardiac death (5.4% vs. 4.7%, p = 0.44), and target vessel myocardial infarction (5.3% vs. 5.4%, p = 1.00), clinically-indicated target lesion revascularization (TLR) (7.0% vs. 6.5%, p = 0.62), and definite/probable stent thrombosis (2.3% vs. 1.6%, p = 0.23) were similar with the R-ZES and EES. Independent predictors of TLR were age, insulin-treated diabetes, SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score, treatment of saphenous vein grafts, ostial lesions, and in-stent restenosis. Independent predictors of any revascularization were age, diabetes, previous percutaneous coronary intervention, absence of ST-segment elevation myocardial infarction, smaller reference vessel diameter, SYNTAX score, and treatment of left anterior descending, right coronary artery, saphenous vein grafts, ostial lesions, or in-stent restenosis. CONCLUSIONS R-ZES and EES demonstrated similar safety and efficacy throughout 4 years. TLR represented less than one-half of all repeat revascularization procedures. Patient- and lesion-related factors predicting the risk of TLR and any revascularization showed considerable overlap. (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention [RESOLUTE-AC]; NCT00617084).

Treatment of exudative age-related macular degeneration with a designed ankyrin repeat protein that binds vascular endothelial growth factor: a phase I/II study

PURPOSE To evaluate the safety, tolerability and bioactivity of ascending doses of MP0112, a designed ankyrin repeat protein (DARPin) that binds with high affinity to vascular endothelial growth factor-A (VEGF-A), in treatment-naive patients with exudative age-related macular degeneration (AMD). DESIGN Phase I/II, open-label, multicenter, dose-escalation study. METHODS Patients were to receive a single intravitreal injection of MP0112 at doses ranging from 0.04 to 3.6 mg and be monitored for 16 weeks for safety, efficacy, pharmacokinetics, and dose response. RESULTS Altogether, 32 patients received a single injection of MP0112. The maximum tolerated dose was 1.0 mg because of a case of endophthalmitis in the 2.0 mg cohort. Drug-related adverse events were reported by 13 (41%) of 32 patients; they included ocular inflammation in 11 patients (7 mild, 4 moderate in severity). Visual acuity scores were stable or improved compared with baseline for ≥4 weeks following injection; both retinal thickness and fluorescein angiography leakage decreased in a dose-dependent manner. Rescue therapy was administered to 20 (91%) of 22 patients who received 0.04-0.4 mg MP0112 compared with 4 of 10 (40%) patients who received 1.0 or 2.0 mg. Of patients in the higher-dose cohorts who did not require rescue treatment, 83% (5/6) maintained reductions in central retinal thickness through week 16. CONCLUSIONS A single injection of 1.0 or 2.0 mg MP0112 resulted in mean decreases in retinal thickness and leakage area despite ocular inflammation. Larger-scale studies are warranted to confirm these observations.

Crystal structures of isotypic poly[bis(benzimidazolium) [tetra-μ-iodido-stannate(II)]] and poly[bis(5,6-difluorobenzimidazolium) [tetra-μ-iodido-stannate(II)]]

The isostructural title compounds, {(C7H7N2)2[SnI4]}n, (1), and {(C7H5F2N2)2[SnI4]}n, (2), show a layered perovskite-type structure composed of anionic {[SnI4]2-}n sheets parallel to (100), which are decorated on both sides with templating benzimidazolium or 5,6-di­fluoro­benzimidazolium cations, respectively. These planar organic heterocycles mainly form N-H...I hydrogen bonds to the terminal I atoms of the corner-sharing [SnI6] octa­hedra (point group symmetry 2) from the inorganic layer, but not to the bridging ones. This is in contrast to most of the reported structures of related compounds where ammonium cations are involved. Here hydrogen bonding to both types of iodine atoms and thereby a distortion of the inorganic layers to various extents is observed. For (1) and (2), all Sn-I-Sn angles are linear and no out-of-plane distortions of the inorganic layers occur, a fact of relevance in view of the material properties. The arrangement of the aromatic cations is mainly determined through the direction of the N-H...I hydrogen bonds. The coherence between organic bilayers along [100] is mainly achieved through van der Waals inter­actions.

All-ceramic or metal-ceramic tooth-supported fixed dental prostheses (FDPs)? A systematic review of the survival and complication rates. Part II: Multiple-unit FDPs.

OBJECTIVE To assess the 5-year survival of metal-ceramic and all-ceramic tooth-supported fixed dental prostheses (FDPs) and to describe the incidence of biological, technical and esthetic complications. METHODS Medline (PubMed), Embase and Cochrane Central Register of Controlled Trials (CENTRAL) searches (2006-2013) were performed for clinical studies focusing on tooth-supported FDPs with a mean follow-up of at least 3 years. This was complemented by an additional hand search and the inclusion of 10 studies from a previous systematic review [1]. Survival and complication rates were analyzed using robust Poisson's regression models to obtain summary estimates of 5-year proportions. RESULTS Forty studies reporting on 1796 metal-ceramic and 1110 all-ceramic FDPs fulfilled the inclusion criteria. Meta-analysis of the included studies indicated an estimated 5-year survival rate of metal-ceramic FDPs of 94.4% (95% CI: 91.2-96.5%). The estimated survival rate of reinforced glass ceramic FDPs was 89.1% (95% CI: 80.4-94.0%), the survival rate of glass-infiltrated alumina FDPs was 86.2% (95% CI: 69.3-94.2%) and the survival rate of densely sintered zirconia FDPs was 90.4% (95% CI: 84.8-94.0%) in 5 years of function. Even though the survival rate of all-ceramic FDPs was lower than for metal-ceramic FDPs, the differences did not reach statistical significance except for the glass-infiltrated alumina FDPs (p=0.05). A significantly higher incidence of caries in abutment teeth was observed for densely sintered zirconia FDPs compared to metal-ceramic FDPs. Significantly more framework fractures were reported for reinforced glass ceramic FDPs (8.0%) and glass-infiltrated alumina FDPs (12.9%) compared to metal-ceramic FDPs (0.6%) and densely sintered zirconia FDPs (1.9%) in 5 years in function. However, the incidence of ceramic fractures and loss of retention was significantly (p=0.018 and 0.028 respectively) higher for densely sintered zirconia FDPs compared to all other types of FDPs. CONCLUSIONS Survival rates of all types of all-ceramic FDPs were lower than those reported for metal-ceramic FDPs. The incidence of framework fractures was significantly higher for reinforced glass ceramic FDPs and infiltrated glass ceramic FDPs, and the incidence for ceramic fractures and loss of retention was significantly higher for densely sintered zirconia FDPs compared to metal-ceramic FDPs.

Graphics Processor Unit Based Parallelization of Optimized Baseline Wander Filtering Algorithms for Long-term Electrocardiography

Long-term electrocardiogram (ECG) often suffers from relevant noise. Baseline wander in particular is pronounced in ECG recordings using dry or esophageal electrodes, which are dedicated for prolonged registration. While analog high-pass filters introduce phase distortions, reliable offline filtering of the baseline wander implies a computational burden that has to be put in relation to the increase in signal-to-baseline ratio (SBR). Here we present a graphics processor unit (GPU) based parallelization method to speed up offline baseline wander filter algorithms, namely the wavelet, finite, and infinite impulse response, moving mean, and moving median filter. Individual filter parameters were optimized with respect to the SBR increase based on ECGs from the Physionet database superimposed to auto-regressive modeled, real baseline wander. A Monte-Carlo simulation showed that for low input SBR the moving median filter outperforms any other method but negatively affects ECG wave detection. In contrast, the infinite impulse response filter is preferred in case of high input SBR. However, the parallelized wavelet filter is processed 500 and 4 times faster than these two algorithms on the GPU, respectively, and offers superior baseline wander suppression in low SBR situations. Using a signal segment of 64 mega samples that is filtered as entire unit, wavelet filtering of a 7-day high-resolution ECG is computed within less than 3 seconds. Taking the high filtering speed into account, the GPU wavelet filter is the most efficient method to remove baseline wander present in long-term ECGs, with which computational burden can be strongly reduced.

Long-term results of a prospective randomised trial assessing the impact of readaptation of the dorsolateral peritoneal layer following extended pelvic lymph node dissection and cystectomy.

OBJECTIVE To evaluate the long term oncological and functional outcomes after readaptation of the dorsolateral peritoneal layer following pelvic lymph node dissection (PLND) and cystectomy . PATIENTS AND METHODS A randomised, single-center, single-blinded, two-arm trial was conducted on 200 consecutive cystectomy patients who underwent PLND and cystectomy for bladder cancer (

On the seasonal variations of salinity of the tropical Atlantic mixed layer

The physical processes controlling the mixed layer salinity (MLS) seasonal budget in the tropical Atlantic Ocean are investigated using a regional configuration of an ocean general circulation model. The analysis reveals that the MLS cycle is generally weak in comparison of individual physical processes entering in the budget because of strong compensation. In evaporative regions, around the surface salinity maxima, the ocean acts to freshen the mixed layer against the action of evaporation. Poleward of the southern SSS maxima, the freshening is ensured by geostrophic advection, the vertical salinity diffusion and, during winter, a dominant contribution of the convective entrainment. On the equatorward flanks of the SSS maxima, Ekman transport mainly contributes to supply freshwater from ITCZ regions while vertical salinity diffusion adds on the effect of evaporation. All these terms are phase locked through the effect of the wind. Under the seasonal march of the ITCZ and in coastal areas affected by river (7°S:15°N), the upper ocean freshening by precipitations and/or runoff is attenuated by vertical salinity diffusion. In the eastern equatorial regions, seasonal cycle of wind forced surface currents advect freshwaters, which are mixed with subsurface saline water because of the strong vertical turbulent diffusion. In all these regions, the vertical diffusion presents an important contribution to the MLS budget by providing, in general, an upwelling flux of salinity. It is generally due to vertical salinity gradient and mixing due to winds. Furthermore, in the equator where the vertical shear, associated to surface horizontal currents, is developed, the diffusion depends also on the sheared flow stability.

Three-State Single-Molecule Naphthalenediimide Switch: Integration of a Pendant Redox Unit for Conductance Tuning

We studied charge transport through core-substituted naphthalenediimide (NDI) single-molecule junctions using the electrochemical STM-based break-junction technique in combination with DFT calculations. Conductance switching among three well-defined states was demonstrated by electrochemically controlling the redox state of the pendent diimide unit of the molecule in an ionic liquid. The electrical conductances of the dianion and neutral states differ by more than one order of magnitude. The potential-dependence of the charge-transport characteristics of the NDI molecules was confirmed by DFT calculations, which account for electrochemical double-layer effects on the conductance of the NDI junctions. This study suggests that integration of a pendant redox unit with strong coupling to a molecular backbone enables the tuning of charge transport through single-molecule devices by controlling their redox states.

The outer mucus layer hosts a distinct intestinal microbial niche

The overall composition of the mammalian intestinal microbiota varies between individuals: within each individual there are differences along the length of the intestinal tract related to host nutrition, intestinal motility and secretions. Mucus is a highly regenerative protective lubricant glycoprotein sheet secreted by host intestinal goblet cells; the inner mucus layer is nearly sterile. Here we show that the outer mucus of the large intestine forms a unique microbial niche with distinct communities, including bacteria without specialized mucolytic capability. Bacterial species present in the mucus show differential proliferation and resource utilization compared with the same species in the intestinal lumen, with high recovery of bioavailable iron and consumption of epithelial-derived carbon sources according to their genome-encoded metabolic repertoire. Functional competition for existence in this intimate layer is likely to be a major determinant of microbiota composition and microbial molecular exchange with the host.

Impact of a communication strategy on family satisfaction in the intensive care unit.

BACKGROUND Family satisfaction of critically ill patients has gained increased interest as important indicator to evaluate the quality of care in the intensive care unit (ICU). The family satisfaction in the ICU questionnaire (FS-ICU 24) is a well-established tool to assess satisfaction in such settings. We tested the hypothesis that an intervention, aiming at improved communication between health professionals and patients' next of kin in the ICU improves family satisfaction, as assessed by FS-ICU 24. METHODS Using a multicenter before-and-after study design, we evaluated medium-term effectiveness of VALUE, a recently proposed strategy aiming at improved communication. Satisfaction was assessed using the FS-ICU 24 questionnaire. Performance-importance plots were generated in order to identify items highly correlated with overall satisfaction but with low individual score. RESULTS A total of 163 completed family questionnaires in the pre-intervention and 118 in the post-intervention period were analyzed. Following the intervention, we observed: (1) a non-significant increase in family satisfaction summary score and sub-scores; (2) no decline in any individual family satisfaction item, and (3) improvement in items with high overall impact on satisfaction but quoted with low degree of satisfaction. CONCLUSION No significant improvement in family satisfaction of critically ill adult patients could be found after implementing the VALUE strategy. Whether these results are due to insufficient training of the new strategy or a missing effect of the strategy in our socio-economic environment remains to be shown.