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.

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.

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.

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.

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.

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.

[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.

On-line preferential solvation studies of polymers by coupled chromatographic-Fourier transform infrared spectroscopic flow-cell technique.

Qualitative and quantitative comparison between liquid chromatography (LC) and LC coupled with Fourier transform infrared spectroscopy (LC-FTIR) to evaluate preferential solvation phenomenon of polymers in a mixed solvent has been performed. These studies show that LC-FTIR technique leads to detailed structural information without the requirement for determination of additional parameters for quantitative analysis except calibration. Appropriate experimental conditions for preferential solvation study have been established by variation of polymer concentration, molar mass and eluent content.

Ex-Utero Intrapartum Treatment (EXIT) in a giant case of Congenital Cystic Adenomatoid Malformation (CCAM) of the lung.

Congenital Cystic Adenomatoid Malformations (CCAM) of the lung are a relatively rare anomaly. The majority of cases do not require any antenatal or perinatal interventions. However, selected cases need special and intensified management. This article discusses a case of a CCAM of the left pulmonary lobe covering 2/3 to 3/4 of the thoracic volume, causing mediastinal shift and hydrops. The enormous size required the planning of an EXIT (Ex Utero-Intrapartum Treatment) procedure, which was performed when the trial of intraoperative ventilation of the lungs was unsuccessful. A thoracotomy and resection of the left upper lobe were performed with the fetus on feto-placental circulation. After resection and closure of the thoracotomy, improvement of lung ventilation allowed the delivery of the child. The child and mother were discharged in a healthy condition. We conclude that the EXIT procedure is a feasible and potentially life-saving method for select cases of prenatally detected CCAM.

[Feasibility of fetal echocardiography at 11-14 weeks scan]. / Durchführbarkeit der fetalen Echokardiographie im Rahmen des 11-14 Wochen-Ultraschalls.

PURPOSE: Sonographic diagnostics are increasingly brought forward into the first trimenon. Lately, more and more expert studies have been published on echocardiography in the context of the Nuchal Translucency (NT) screening (gestational age 11-14 weeks). The aim of this study has been to evaluate the feasibility of early echocardiography on the occasion of first trimenon screening in the context of routine operation. MATERIALS AND METHODS: From February 2003 to March 2004, an echocardiography was prospectively sought in 130 assigned, unselected pregnant women during the first trimenon screening. Three doctors with different OGUM/DEGUM (Austrian and German societies for ultrasound in medicine) qualifications at our ward tried to represent the four-chamber view (4CV) and the outflow tracts (OFT), each via B-mode and color Doppler. The study conditions were "routine", in particular they were temporally limited. In case no sufficient visual representation was achievable with the transabdominal examination, transvaginal sonography was also used. RESULTS: Via B-mode, 4CV was indicated as successful in 86/130, and OFTs in 37/130. Via color Doppler, on the other hand, it was possible to sufficiently represent 4CV in 75/130 and OFTs in 87/130. CONCLUSION: In routine screening, early heart examination is a big challenge and in many cases even with good equipment no complete diagnostic echocardiography can be achieved. The utilisation of the color Doppler is helpful particularly for the representation of the outflow tracts.

Chest sonography in the diagnosis of pulmonary embolism: a comparison with MRI angiography and ventilation perfusion scintigraphy.

AIM: To compare the diagnostic performance of chest sonography, MRI angiography and ventilation/perfusion intigraphy in pulmonary embolism (PE). METHOD: In a prospective clinical study, 55 patients (41 women, 14 men, age 23 - 91 years) with clinical signs of PE were investigated within 48 hours of the onset of symptoms. The final diagnosis was made by MRI angiography (reference method). RESULTS: PE was diagnosed in a total of 36 patients. Chest sonography revealed rounded or wedge-shaped hypoechoic lesions in 30 patients. On ventilation/perfusion (V/P) scintigraphy, 41 patients had positive V/P scans, but only 23 were of high probability. Chest ultrasound had a positive predictive value of 97 % to diagnose PE. The sensitivity, specificity, the negative predictive value and accuracy were 81 %, 84 %, 84 % and 82 %, respectively. As 18 patients had inconclusive scans, the diagnostic performance of ventilation/perfusion scintigraphy was poor. The positive predictive value, sensitivity and specificity were 58 %, 42 % and 91 %, respectively. Patients in whom PE was excluded mainly suffered from congestive heart failure, bronchopulmonary infections or pulmonary hypertension. CONCLUSION: A negative sonographic study cannot rule out PE with certainty. However, a chest sonography is of acceptable diagnostic value in patients with suspected PE and may be used as an adjunct or guide to more established methods.

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.

Evidence that fragile X mental retardation protein is a negative regulator of translation.

Fragile X syndrome is a common form of inherited mental retardation. Most fragile X patients exhibit mutations in the fragile X mental retardation gene 1 (FMR1) that lead to transcriptional silencing and hence to the absence of the fragile X mental retardation protein (FMRP). Since FMRP is an RNA-binding protein which associates with polyribosomes, it had been proposed to function as a regulator of gene expression at the post-transcriptional level. In the present study, we show that FMRP strongly inhibits translation of various mRNAs at nanomolar concentrations in both rabbit reticulocyte lysate and microinjected Xenopus laevis oocytes. This effect is specific for FMRP, since other proteins with similar RNA-binding domains, including the autosomal homologues of FMRP, FXR1 and FXR2, failed to suppress translation in the same concentration range. Strikingly, a disease-causing Ile-->Asn substitution at amino acid position 304 (I304N) renders FMRP incapable of interfering with translation in both test systems. Initial studies addressing the underlying mechanism of inhibition suggest that FMRP inhibits the assembly of 80S ribosomes on the target mRNAs. The failure of FMRP I304N to suppress translation is not due to its reduced affinity for mRNA or its interacting proteins FXR1 and FXR2. Instead, the I304N point mutation severely impairs homo-oligomerization of FMRP. Our data support the notion that inhibition of translation may be a function of FMRP in vivo. We further suggest that the failure of FMRP to oligomerize, caused by the I304N mutation, may contribute to the pathophysiological events leading to fragile X syndrome.

Lipoxygenase mRNA silencing in erythroid differentiation: The 3'UTR regulatory complex controls 60S ribosomal subunit joining.

15-lipoxygenase (LOX) expression is translationally silenced in early erythroid precursor cells by a specific mRNA-protein complex formed between the differentiation control element in the 3' untranslated region (UTR) and hnRNPs K and E1. The 3'UTR regulatory complex prevents translation initiation by an unknown mechanism. We demonstrate that the 40S ribosomal subunit can be recruited and scan to the translation initiation codon even when the silencing complex is bound to the 3'UTR. However, the joining of the 60S ribosomal subunit at the AUG codon to form a translation competent 80S ribosome is inhibited, unless initiation is mediated by the IGR-IRES of the cricket paralysis virus. These findings identify the critical step at which LOX mRNA translation is controlled and reveal that 60S subunit joining can be specifically regulated.

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.

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.