Cardiovascular outcomes after simultaneous pancreas kidney transplantation compared to kidney transplantation alone: a propensity score matching analysis.

BACKGROUND: Coronary heart disease due to arteriosclerosis is the leading cause of death in type 1 diabetic patients with end-stage renal disease (ESRD). The aim of this study was to evaluate the effect of simultaneous pancreas kidney transplantation (SPKT) compared to kidney transplantation alone (KTA) on survival, cardiovascular function and metabolic outcomes. METHODS: A cohort of 127 insulin-dependent diabetes mellitus (IDDM) patients with ESRD who underwent either SPKT (n = 100) or KTA (n = 27) between 1998 and 2019 at the University Hospital of Leipzig were retrospectively evaluated with regard to cardiovascular and metabolic function/outcomes as well as survival rates. An additional focus was placed on the echocardiographic assessment of systolic and diastolic cardiac function pretransplant and during follow-up. To avoid selection bias, a 2:1 propensity score matching analysis (PSM) was performed. RESULTS: After PSM, a total of 63 patients were identified; 42 patients underwent SPKT, and 21 patients received KTA. Compared with the KTA group, SPKT recipients received organs from younger donors (p < 0.05) and donor BMI was higher (p = 0.09). The risk factor-adjusted hazard ratio for mortality in SPKT recipients compared to KTA recipients was 0.63 (CI: 0.49-0.89; P < 0.05). The incidence of pretransplant cardiovascular events was higher in the KTA group (KTA: n = 10, 47% versus SPKT: n = 10, 23%; p = 0.06), but this difference was not significant. However, the occurrence of cardiovascular events in the SPKT group (n = 3, 7%) was significantly diminished after transplantation compared to that in the KTA recipients (n = 6, 28%; p = 0.02). The cardiovascular death rate was higher in KTA recipients (19%) than in SPK recipients with functioning grafts (3.3%) and comparable to that in patients with failed SPKT (16.7%) (p = 0.16). In line with pretransplant values, SPKT recipients showed significant improvements in Hb1ac values (p = 0.001), blood pressure control (p = < 0.005) and low-density lipoprotein/high-density lipoprotein (LDL/HDL) ratio (p = < 0.005) 5 years after transplantation. With regard to echocardiographic assessment, SPKT recipients showed significant improvements in left ventricular systolic parameters during follow-up. CONCLUSIONS: Normoglycaemia and improvement of lipid metabolism and blood pressure control achieved by successful SPKT are associated with beneficial effects on survival, cardiovascular outcomes and systolic left ventricular cardiac function. Future studies with larger samples are needed to make predictions regarding cardiovascular events and graft survival.

Value of sarcopenia in the resection of colorectal liver metastases-a systematic review and meta-analysis.

Introduction: Sarcopenia is defined as a decline in muscle function as well as muscle mass. Sarcopenia itself and sarcopenic obesity, defined as sarcopenia in obese patients, have been used as surrogates for a worse prognosis in colorectal cancer. This review aims to determine if there is evidence for sarcopenia as a prognostic parameter in colorectal liver metastases (CRLM). Methods: PubMed, Embase, Cochrane Central, Web of Science, SCOPUS, and CINAHL databases were searched for articles that were selected in accordance with the PRISMA guidelines. The primary outcomes were overall survival (OS) and disease-free survival (DFS). A random effects meta-analysis was conducted. Results: After eliminating duplicates and screening abstracts (n = 111), 949 studies were screened, and 33 publications met the inclusion criteria. Of them, 15 were selected after close paper review, and 10 were incorporated into the meta-analysis, which comprised 825 patients. No significant influence of sarcopenia for OS (odds ratio (OR), 2.802 (95% confidence interval (CI), 1.094-1.11); p = 0.4) or DFS (OR, 1.203 (95% CI, 1.162-1.208); p = 0.5) was found, although a trend was defined toward sarcopenia. Sarcopenia significantly influenced postoperative complication rates (OR, 7.905 (95% CI, 1.876-3.32); p = 0.001) in two studies where data were available. Conclusion: Existing evidence on the influence of sarcopenia on postoperative OS as well as DFS in patients undergoing resection for CRLM exists. We were not able to confirm that sarcopenic patients have a significantly worse OS and DFS in our analysis, although a trend toward this hypothesis was visible. Sarcopenia seems to influence complication rates but prospective studies are needed.

pH-triggered aggregate shape of different generations lysine-dendronized maleimide copolymers with maltose shell.

Glycopolymers are promising materials in the field of biomedical applications and in the fabrication of supramolecular structures with specific functions. For tunable design of supramolecular structures, glycopolymer architectures with specific properties (e.g., controlled self-assembly) are needed. Using the concept of dendronized polymers, a series of H-bond active giant glycomacromolecules with maleimide backbone and lysine dendrons of different generations were synthesized. They possess different macromolecular size and functionality along the backbone. Their peripheral maltose units lead to solubility under physiological conditions and controlled aggregation behavior. The aggregation behavior was investigated depending on generation number, pH value, and concentration. A portfolio of complementary analytical tools give an insight into the influence of the different parameters in shaping a rod-, coil-, and worm-like molecular structure and their controlled aggregate formation. MD simulation helped us to understand the complex aggregation behavior of the linear polymer chain without dendritic units.

Preoperative pregabalin administration significantly reduces postoperative opioid consumption and mechanical hyperalgesia after transperitoneal nephrectomy.

BACKGROUND: Preoperative administration of pregabalin is proposed as a promising way of enhancing postoperative pain control. Whereas a few studies have investigated the effect of pregabalin on postoperative opioid consumption, no study has focused on the influence on postoperative hyperalgesia. In this randomized, triple-blinded, placebo-controlled study, we aimed to demonstrate that a single, preoperative dose of pregabalin reduces postoperative opioid consumption, mechanical hyperalgesia, and pain sensitivity. METHODS: Patients undergoing elective transperitoneal nephrectomy received 300 mg pregabalin or placebo 1 h before anaesthesia. After operation, patients received piritramide via a patient-controlled analgesia device. Pain levels and side-effects were documented. The area of hyperalgesia for punctuate mechanical stimuli around the incision was measured 48 h after the operation with a hand-held von Frey filament. Mechanical pain threshold was tested before and 48 h after surgery with von Frey filaments with increasing diameters. RESULTS: In each group, 13 patients were recruited. Total piritramide consumption [77 (16) vs 52 (16) mg, P=0.0004] and the normalized area of hyperalgesia [143 (87) vs 84 (54) cm(2), P=0.0497] were significantly decreased in the pregabalin group. There were no significant differences in mechanical pain threshold levels [1.20 (0.56) log(g) vs 1.05 (0.58) log(g), P=0.6738]. No case of severe sedation was reported in both groups. No other side-effects were observed. CONCLUSIONS: Our study has shown that preoperative administration of 300 mg pregabalin in patients undergoing transperitoneal nephrectomy reduces postoperative opioid consumption and decreases the area of mechanical hyperalgesia.

ERK phosphorylation drives cytoplasmic accumulation of hnRNP-K and inhibition of mRNA translation.

Heterogeneous nuclear ribonucleoprotein K (hnRNP-K) is one of a family of 20 proteins that are involved in transcription and post-transcriptional messenger RNA metabolism. The mechanisms that underlie regulation of hnRNP-K activities remain largely unknown. Here we show that cytoplasmic accumulation of hnRNP-K is phosphorylation-dependent. Mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) efficiently phosphorylates hnRNP-K both in vitro and in vivo at serines 284 and 353. Serum stimulation or constitutive activation of ERK kinase (MEK1) results in phosphorylation and cytoplasmic accumulation of hnRNP-K. Mutation at ERK phosphoacceptor sites in hnRNP-K abolishes the ability to accumulate in the cytoplasm and renders the protein incapable of regulating translation of mRNAs that have a differentiation-control element (DICE) in the 3' untranslated region (UTR). Similarly, treatment with a pharmacological inhibitor of the ERK pathway abolishes cytoplasmic accumulation of hnRNP-K and attenuates inhibition of mRNA translation. Our results establish the role of MAPK/ERK in phosphorylation-dependent cellular localization of hnRNP-K, which is required for its ability to silence mRNA translation.

[Pregabalin and postoperative hyperalgesia. A review]. / Pregabalin und postoperative Hyperalgesie. Ein Review.

Numerous studies support the theory that pregabalin causes an antihyperalgesic effect, which could be potentially beneficial in a perioperative setting. By binding to calcium channels pregabalin reduces the release of excitatory neurotransmitters and therefore inhibits central sensitization. Animal studies clearly demonstrated the antihyperalgesic potency of pregabalin but human experiments are, however, inconclusive. Clinical studies with quantitative sensory testing have not yet been published. Although strongly supported by theoretical considerations the routine preoperative application of pregabalin for the prevention of hyperalgesia cannot be recommended due to the lack of clinical studies. Future studies should incorporate secondary hyperalgesia and allodynia as primary parameters.

Transillumination and HDR Imaging for Proximal Caries Detection.

The purpose of this study was to develop an in vitro model for the validation of near-infrared transillumination (NIRT) for proximal caries detection, to enhance NIRT with high-dynamic-range imaging (HDRI), and to compare both methods, using micro-computed tomography (µCT) as a reference standard. Both proximal surfaces of 53 healthy or decayed permanent human teeth were examined using the Diagnocam (DC) (KaVo) and NIRT with HDRI (NIRT-HDRI). NIRT was combined with HDRI to improve the diagnostic performance by reducing under- and overexposed image areas. For NIRT-HDRI, an exposure series was captured and merged into a single HDR image. A classification was applied according to lesion depth. All surfaces were assessed twice by 2 trained examiners, and additionally with µCT for validation. The Kappa statistic was used to calculate inter-rater reliability and agreement between DC and NIRT-HDRI. Inter-rater reliability (weighted Kappa, wκ) showed very good agreement for the DC (0.90) and NIRT-HDRI (0.96). The overall agreement (wκ) was almost perfect (0.85). In the individual categories (0 to 4), the agreement (simple Kappa) ranged from almost perfect (category 4) to moderate (1 and 2) to substantial (categories 0 and 3). Sensitivity and specificity of sound surfaces, enamel, and dentin caries ranged from 0.57 to 0.99 and were similar for both methods in the different categories. NIRT-HDRI had a higher sensitivity for sound surfaces and enamel caries, as well as a higher specificity for dentin caries. Regarding the obtained images, HDRI allowed for the detection of caries within a greater range of luminance levels, resulting in a more detailed visualization of structures without under- or overexposure. However, HDRI this did not improve the diagnostics significantly. Distinguishing between a processed demineralized enamel and dentin lesions appears to be a problem specific to NIRT and cannot be balanced using HDRI.

Dehydropolymerisation of methylamine borane using a dinuclear 1,3-allenediyl bridged zirconocene complex.

The dinuclear zirconocene chloride complex 1 is a highly active precatalyst for the dehydropolymerisation of methylamine borane. Comparison with mononuclear Zr chlorides and related dinuclear complexes suggests that the nature of the bridging motif is essential for the unique reactivity of 1.

Bacterial expression, purification and partial characterization of recombinant rabbit reticulocyte 15-lipoxygenase.

The recombinant rabbit reticulocyte 15-lipoxygenase has been expressed in E. coli with a yield of about 50-70 micrograms pure lipoxygenase protein per 1 of liquid culture. The enzyme has been purified to apparent homogeneity from the bacteria lysis supernatant by ammonium sulfate precipitation, and two consecutive steps of anion exchange chromatography on a Mono Q column. As the native enzyme the recombinant lipoxygenase has a molecular mass of 75 kDa, an isoelectric point of 5.5 and oxygenates both linoleic acid (formation of 13S-hydroperoxy-9Z,13E-octadecadienoic acid) and arachidonic acid. With the latter substrate it exhibits a dual positional specificity (formation of 15S-hydroperoxy-5Z,8Z,11Z,13E-eicosatetranoic acid and 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid in a ratio of 12:1). Furthermore, the enzyme is capable of oxygenating biomembranes, as indicated by HPLC analysis of esterified oxygenated polyenoic fatty acids.

Human simulations of vocabulary learning.

The work reported here experimentally investigates a striking generalization about vocabulary acquisition: Noun learning is superior to verb learning in the earliest moments of child language development. The dominant explanation of this phenomenon in the literature invokes differing conceptual requirements for items in these lexical categories: Verbs are cognitively more complex than nouns and so their acquisition must await certain mental developments in the infant. In the present work, we investigate an alternative hypothesis; namely, that it is the information requirements of verb learning, not the conceptual requirements, that crucially determine the acquisition order. Efficient verb learning requires access to structural features of the exposure language and thus cannot take place until a scaffolding of noun knowledge enables the acquisition of clause-level syntax. More generally, we experimentally investigate the hypothesis that vocabulary acquisition takes place via an incremental constraint-satisfaction procedure that bootstraps itself into successively more sophisticated linguistic representations which, in turn, enable new kinds of vocabulary learning. If the experimental subjects were young children, it would be difficult to distinguish between this information-centered hypothesis and the conceptual change hypothesis. Therefore the experimental "learners" are adults. The items to be "acquired" in the experiments were the 24 most frequent nouns and 24 most frequent verbs from a sample of maternal speech to 18-24-month-old infants. The various experiments ask about the kinds of information that will support identification of these words as they occur in mother-to-child discourse. Both the proportion correctly identified and the type of word that is identifiable changes significantly as a function of information type. We discuss these results as consistent with the incremental construction of a highly lexicalized grammar by cognitively and pragmatically sophisticated human infants, but inconsistent with a procedure in which lexical acquisition is independent of and antecedent to syntax acquisition.

[Extrinsic allergic alveolitis in CT and HR-CT]. / Exogen allergische Alveolitis in CT und HR-CT.

The CT changes on conventional and high-resolution CT in 14 patients with exogenous allergic alveolitis (EAA) were analysed retrospectively. There were 8 patients with clinically subacute disease, 5 patients in a chronic stage and 1 patient with acute EAA. The appearances and their distribution were examined. Seven of the 8 patients in the subacute stage showed a ground glass pattern and multiple nodules of less than 2 mm. All patients in the chronic stage showed a combination of fine infiltrates, small nodules and irregular linear densities; distortion of the pulmonary pattern was present in 3 cases. The patient with acute EAA showed diffuse dense areas of consolidation in both lungs as well as multiple nodules and a ground glass pattern. The CT appearances of EAA correspond with the basic micropathology and, within the clinical context, permit diagnostic classification.

Expression of leukocyte-type 12-lipoxygenase and reticulocyte-type 15-lipoxygenase in rabbits.

From a rabbit reticulocyte library a full length cDNA was isolated which predicted a novel lipoxygenase (LOX) sharing 99% identical amino acids with the rabbit 15-lipoxygenase. HPLC product analysis of the bacterially expressed protein identified it as a leukocyte-type 12-lipoxygenase (1.12-LOX). This proves the co-expression of a 15-lipoxygenase and a 1.12-lipoxygenase in one mammalian species. Among the six amino acids that are different to rabbit 15-lipoxygenase, leucine 353 is shown to be the primary determinant for 12-positional specificity. In the 3'-untranslated region of the 12-LOX-mRNA a CU-rich, 20-fold repetitive element has been found, closely related to the differentiation control element (DICE) of the rabbit 15-LOX-mRNA which is organized by ten repeats of 19 bases. By genomic PCR the 3'-terminal part of the gene for the novel 12-lipoxygenase containing the introns 10-13 has been amplified and sequenced. The introns were very similar in length to the corresponding 15-lipoxygenase introns with 89% to 95% identical nucleotide sequences. By screening a rabbit reticulocyte library an alternative 15-lipoxygenase transcript of 3.6 kb has been detected containing a 1019 nucleotides longer 3'-untranslated region (UTR2) than the main 2.6 kb mRNA. The determination of the tissue distribution by Northern blotting showed that the 3.6 kb mRNA2 was only expressed in non-erythroid tissues, whereas the 2.6 kb mRNA1 was exclusively expressed in reticulocytes. The only cell type which has been found to express the 1.12-lipoxygenase abundantly are monocytes. The results indicate that the expression of 1.12-lipoxygenase and 15-lipoxygenase is highly regulated. The UTR2 of the 15-LOX-mRNA2 contained a novel eight-fold repetitive CU-rich motif of 23 bases length which is related but not identical to the DICE of 19 bases in the UTR1. The analysis of a genomic recombinant of the complete 9.0 kb Alox15 gene confirmed that UTR1 and UTR2 are not interrupted by an additional intron.

Meeting the challenges of information systems planning.

Strategic information systems planning (SISP) is the process of deciding the objectives of computing for an organization and then identifying the applications that the organization should computerize. SISP has become increasingly important as information systems have begun to play a more critical role in implementing business strategies. However, SISP is beset with problems that hinder organizations from determining their computing objectives and applications. This article identifies the impediments to SISP and offers some constructive actions for business planners to take to increase their chances of success. It also suggests that planners may face greater difficulties implementing their information systems plans than in initially creating them.

Guidelines for strategic information planning.

Developing a strategic information plan is an essential step for companies that want to realize the advantages of today's information technology. This article discusses ways to avoid the pitfalls that frequently occur during stages of information planning.

Caspase-3 cleaves hnRNP K in erythroid differentiation.

Post-transcriptional control of gene expression is crucial for the control of cellular differentiation. Erythroid precursor cells loose their organelles in a timely controlled manner during terminal maturation to functional erythrocytes. Extrusion of the nucleus precedes the release of young reticulocytes into the blood stream. The degradation of mitochondria is initiated by reticulocyte 15-lipoxygenase (r15-LOX) in mature reticulocytes. At that terminal stage the release of r15-LOX mRNA from its translational silenced state induces the synthesis of r15-LOX. Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a key regulator of r15-LOX mRNA translation. HnRNP K that binds to the differentiation control element (DICE) in the 3' untranslated region (UTR) inhibits r15-LOX mRNA translation initiation. During erythroid cell maturation, activation of r15-LOX mRNA translation is mediated by post-translational modifications of hnRNP K and a decrease of the hnRNP K level. To further elucidate its function in the post-transcriptional control of gene expression, we investigated hnRNP K degradation employing an inducible erythroid cell system that recapitulates both nuclear extrusion and the timely controlled degradation of mitochondria, mediated by the activation of r15-LOX synthesis. Interestingly, we detected a specific N-terminal cleavage intermediate of hnRNP K lacking DICE-binding activity that appeared during erythroid differentiation and puromycin-induced apoptosis. Employing mass spectrometry and enzymatic analyses, we identified Caspase-3 as the enzyme that cleaves hnRNP K specifically. In vitro studies revealed that cleavage by Caspase-3 at amino acids (aa) D334-G335 removes the C-terminal hnRNP K homology (KH) domain 3 that confers binding of hnRNP K to the DICE. Our data suggest that the processing of hnRNP K by Caspase-3 provides a save-lock mechanism for its timely release from the r15-LOX mRNA silencing complex and activation of r15-LOX mRNA synthesis in erythroid cell differentiation.