Nutritional support during the hospital stay reduces mortality in patients with different types of cancers: secondary analysis of a prospective randomized trial.

BACKGROUND: Nutritional support in patients with cancer aims at improving quality of life. Whether use of nutritional support is also effective in improving clinical outcomes requires further study. PATIENTS AND METHODS: In this preplanned secondary analysis of patients with cancer included in a prospective, randomized-controlled, Swiss, multicenter trial (EFFORT), we compared protocol-guided individualized nutritional support (intervention group) to standard hospital food (control group) regarding mortality at 30-day (primary endpoint) and other clinical outcomes. RESULTS: We analyzed 506 patients with a main admission diagnosis of cancer, including lung cancer (n = 113), gastrointestinal tumors (n = 84), hematological malignancies (n = 108) and other types of cancer (n = 201). Nutritional risk based on Nutritional Risk Screening (NRS 2002) was an independent predictor for mortality over 180 days with an (age-, sex-, center-, type of cancer-, tumor activity- and treatment-) adjusted hazard ratio of 1.29 (95% CI 1.09-1.54; P = 0.004) per point increase in NRS. In the 30-day follow-up period, 50 patients (19.9%) died in the control group compared to 36 (14.1%) in the intervention group resulting in an adjusted odds ratio of 0.57 (95% CI 0.35-0.94; P = 0.027). Interaction tests did not show significant differences in mortality across the cancer type subgroups. Nutritional support also significantly improved functional outcomes and quality of life measures. CONCLUSIONS: Compared to usual hospital nutrition without nutrition support, individualized nutritional support reduced the risk of mortality and improved functional and quality of life outcomes in cancer patients with increased nutritional risk. These data further support the inclusion of nutritional care in cancer management guidelines.

Assessment of lateral line function: a potential technique for studies in ototoxicity.

In zebrafish neuromast hair cells, the process of programmed cell death ototoxic damage is strikingly similar to that of degenerating hair cells of the mammalian organ of Corti. Therefore, in vivo zebrafish assays involving the lateral line have been developed for drug ototoxicity screening. This is accomplished by examination of canal neuromast morphology in treated larvae using fluorescent dyes. To-date however, physiological confirmation of lateral line dysfunction resulting from such ototoxins has not been reported in the scientific literature--neither for larval nor adult zebrafish. Here we describe a rapid, non-invasive far-field electrophysiological method for assessing lateral line function. We suggest that ototoxic and otoprotective agents identified in larval studies may be assessed using this tool in adult fish. In this way, potential drug candidates can be further screened en route to testing in mammalian models, before potential clinical trials begin.

Evaluating the clinical utility of stereoscopic clinical photography.

Stereoscopic imaging during clinical evaluation can provide utility to physicians and medical educators by extending clinical photography with the provision of depth. A digital SLR camera body fitted with a stereoscopic lens and an autostereoscopic display are evaluated. This paper describes the image acquisition workflow and post-processing methods required to incorporate stereoscopic images into an electronic medical record for physician review.

Carbon accounting model for forests in Australia.

CAMFor (Carbon Accounting Model for Forests) is a sophisticated spreadsheet model developed to assist in carbon accounting and projection. This model can integrate information from a range of alternate sources including user input, default parameters and third party model outputs to calculate the carbon flows associated with a stand of trees and the wood products derived from harvests of that stand. Carbon is tracked in the following pools: * Biomass (stemwood, branches, bark, fine and coarse roots, leaves and twigs) * Soil (organic matter and inert charcoal) * Debris (coarse and fine litter, slash, below ground dead material) * Products (waste wood, sawn timber, paper, biofuel, reconstituted wood products). These pools can be tracked following thinning, fires and over multiple rotations. A sensitivity module has been developed to assist examination of the important assumptions and inputs. This paper reviews the functionality of CAMFor and reports on its use in a case study to explore the precision of estimates of carbon sequestration in a eucalypt plantation. Information on variability in unbiased models, measurement accuracy and other sources of error are combined in a sensitivity analysis to estimate the overall precision of sequestration estimates.

Pollution mitigation and carbon sequestration by an urban forest.

At the beginning of the 1900s, the Canberra plain was largely treeless. Graziers had carried out extensive clearing of the original trees since the 1820s leaving only scattered remnants and some plantings near homesteads. With the selection of Canberra as the site for the new capital of Australia, extensive tree plantings began in 1911. These trees have delivered a number of benefits, including aesthetic values and the amelioration of climatic extremes. Recently, however, it was considered that the benefits might extend to pollution mitigation and the sequestration of carbon. This paper outlines a case study of the value of the Canberra urban forest with particular reference to pollution mitigation. This study uses a tree inventory, modelling and decision support system developed to collect and use data about trees for tree asset management. The decision support system (DISMUT) was developed to assist in the management of about 400,000 trees planted in Canberra. The size of trees during the 5-year Kyoto Commitment Period was estimated using DISMUT and multiplied by estimates of value per square meter of canopy derived from available literature. The planted trees are estimated to have a combined energy reduction, pollution mitigation and carbon sequestration value of US$20-67 million during the period 2008-2012.

N-Acetyl-L-Cystein downregulates beta-amyloid precursor protein gene transcription in human neuroblastoma cells.

The causes for the sporadic form of Alzheimer's disease (AD) are still poorly understood, except from the fact that age is an important risk factor. The main component of the characteristic amyloid plaques in brains of AD patients are Abeta peptides, derivatives of the amyloid precursor protein APP. Oxidative stress may contribute to the aetiology of AD by dysregulation of APP metabolism. Overexpression of the APP gene could result in an increased secretion of neurotoxic Abeta peptides, while preventing the overexpression might be protective. We here report that the antioxidant N-Acetyl-L-Cystein (NAC) downregulates APP gene transcription in human neuroblastoma cells. The effect is reversible when cells are returned to NAC free medium. These results open up new possibilities for the development of therapeutic agents that intervene at the transcriptional level.

Change in rate-determining step in an E1cB mechanism during aminolysis of sulfamate esters in acetonitrile.

The kinetics of the reactions of the nitrogen-sulfur(VI) esters 4-nitrophenyl N-methylsulfamate (NPMS) with a series of pyridines and a series of alicyclic amines and of 4-nitrophenyl N-benzylsulfamate (NPBS) with pyridines, alicyclic amines, and a series of quinuclidines have been investigated in acetonitrile (ACN) in the presence of excess amine at various temperatures. Pseudo-first-order rate constants (k(obsd)) have been obtained by monitoring the release of 4-nitrophenol/4-nitrophenoxide. From the slope of a plot of k(obsd) vs [amine], second-order rate constants (k'(2)) have been obtained for the pyridinolysis of NPMS, and a Brønsted plot of log k'(2) vs pK(a) of pyridine gave a straight line with beta = 0.45. However, aminolysis with alicyclic amines of NPMS gave a biphasic Brønsted plot (beta(1) = 0.6, beta(2) approximately equal to 0). Pyridinolysis and aminolysis with alicyclic amines and quinuclidines of NPBS also gave similar biphasic Brønsted plots. This biphasic behavior has been explained in terms of a mechanistic change within the E1cB mechanism from an (E1cB)(irrev) (less basic amines) to an (E1cB)(rev) (more basic amines), and the change occurs at approximately the pK(a)'s (in ACN) of NPMS (17.94) and NPBS (17.68). The straight line Brønsted plot for NPMS with pyridines occurs because the later bases are not strong enough to substantially remove the substrate proton and initiate the mechanistic change observed in the reaction of NPMS with the strong alicyclic amines and quinuclidines. An entropy study supports the change from a bimolecular to a unimolecular mechanism. This is the first clear demonstration of this E1cB mechanistic changeover involving a nitrogen acid substrate.

N-acetyl-L-cysteine protects SHSY5Y neuroblastoma cells from oxidative stress and cell cytotoxicity: effects on beta-amyloid secretion and tau phosphorylation.

Redox changes within neurones are increasingly being implicated as an important causative agent in brain ageing and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD). Cells have developed a number of defensive mechanisms to maintain intracellular redox homeostasis, including the glutathione (GSH) system and antioxidant enzymes. Here we examine the effects of N-acetyl-L-cysteine (NAC) on beta-amyloid (A beta) secretion and tau phosphorylation in SHSY5Y neuroblastoma cells after exposure to oxidative stress inducing/cytotoxic compounds (H(2)O(2), UV light and toxic A beta peptides). A beta and tau protein are hallmark molecules in the pathology of AD while the stress factors are implicated in the aetiology of AD. The results show that H(2)O(2), UV light, A beta 1-42 and toxic A beta 25-35, but not the inactive A beta 35-25, produce a significant induction of oxidative stress and cell cytotoxicity. The effects are reversed when cells are pre-treated with 30 mM NAC. Cells exposed to H(2)O(2), UV light and A beta 25-35, but not A beta 35-25, secrete significantly higher amounts of A beta 1-40 and A beta 1-42 into the culture medium. NAC pre-treatment increased the release of A beta 1-40 compared with controls and potentiated the release of both A beta 1-40 and A beta 1-42 in A beta 25-35-treated cells. Tau phosphorylation was markedly reduced by H(2)O(2) and UV light but increased by A beta 25-35. NAC strongly lowered phospho-tau levels in the presence or absence of stress treatment.

Mercury induces cell cytotoxicity and oxidative stress and increases beta-amyloid secretion and tau phosphorylation in SHSY5Y neuroblastoma cells.

Concentrations of heavy metals, including mercury, have been shown to be altered in the brain and body fluids of Alzheimer's disease (AD) patients. To explore potential pathophysiological mechanisms we used an in vitro model system (SHSY5Y neuroblastoma cells) and investigated the effects of inorganic mercury (HgCl2) on oxidative stress, cell cytotoxicity, beta-amyloid production, and tau phosphorylation. We demonstrated that exposure of cells to 50 microg/L (180 nM) HgCl2 for 30 min induces a 30% reduction in cellular glutathione (GSH) levels (n = 13, p<0.001). Preincubation of cells for 30 min with 1 microM melatonin or premixing melatonin and HgCl2 appeared to protect cells from the mercury-induced GSH loss. Similarly, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assays revealed that 50 microg/L HgCl2 for 24 h produced a 50% inhibition of MTT reduction (n = 9, p<0.001). Again, melatonin preincubation protected cells from the deleterious effects of mercury, resulting in MTT reduction equaling control levels. The release of beta-amyloid peptide (Abeta) 1-40 and 1-42 into cell culture supernatants after exposure to HgCl2 was shown to be different: Abeta 1-40 showed maximal (15.3 ng/ml) release after 4 h, whereas Abeta 1-42 showed maximal (9.3 ng/ml) release after 6 h of exposure to mercury compared with untreated controls (n = 9, p<0.001). Preincubation of cells with melatonin resulted in an attenuation of Abeta 1-40 and Abeta 1-42 release. Tau phosphorylation was significantly increased in the presence of mercury (n = 9, p<0.001), whereas melatonin preincubation reduced the phosphorylation to control values. These results indicate that mercury may play a role in pathophysiological mechanisms of AD.

[Robot-assisted knee endoprosthesis]. / Roboterunterstützung in der Knieendoprothetik.

With the development of powerful computer systems, computer-assisted medical diagnosis and therapy have become common over the last 10 years. Even in the surgical field, computer- and robotic-assisted techniques are becoming practical but are not yet used on a daily basis. In the orthopaedic field, computer and robotic assistance is used in planning and performing demanding three-dimensional osteotomies, setting pedicle screws in the spine and milling the femoral medullary canal in total hip replacement. This article introduces a computer- and robotic-assisted system for performing arthroplasty in total knee replacement procedures.

Age-related changes in the mRNA expression of actin isoforms in Drosophila melanogaster.

In all organisms the process of aging is characterized by a gradual loss of homeostatic maintenance functions and physiological fitness. This might be caused-in part-by a down-regulation of important housekeeping and maintenance genes. In our previous work we have shown that in Drosophila melanogaster aging is accompanied by a decrease in steady-state levels of most RNA species. This includes structural genes and housekeeping genes, though at a different level. Here we have examined age-related changes in the mRNA levels of the gene family encoding the six Drosophila actin genes. Two actin isoforms code for cytoskeletal actins and represent housekeeping genes, whereas the four muscle actin genes are expressed tissue-specifically in differentiated muscles. The results suggest that the six actin genes are differentially regulated during aging as well. The two cytoskeletal actin genes show little changes in their steady-state mRNA levels. Drastic changes are observed, however, in the mRNAs coding for muscle actins, particularly the mRNAs coding for the jump and flight muscle actins.

N-acetylcysteine slows down ageing and increases the life span of Drosophila melanogaster.

Ageing can be defined as the time-dependent decline of physiological functions of an organism. The molecular causes for the ageing process are multiple, involving both genetic and environmental factors. It has been proposed that antioxidants may positively influence the ageing process, protecting the organism against free radical-induced damage. Here we show that the antioxidant N-acetylcysteine (NAC) has a life-extending effect on Drosophila melanogaster. Dietary uptake of NAC results in a dose-dependent increase in median and maximum life span. Flies fed on 1 mg/ml NAC food live 16.6% longer; at 10 mg/ml, life span increases by 26.6%. We have examined the effect of NAC treatment on protein and RNA levels: we observe an NAC-dependent increase in absolute amounts of total RNA and ribosomal RNA, but no differences in protein levels. The NAC effect on longevity may involve differential expression of specific mRNA genes, as suggested by RNA finger-printing experiments.

Wallaby serum amyloid A protein: cDNA cloning, sequence and evolutionary analysis.

A serum amyloid A (SAA) clone was isolated from a Tammar wallaby cDNA library, the most distantly related mammalian species for which an SAA has been described to date. The clone predicts a premolecule of 127 amino acids with good homology to other mammalian SAAs, and consists of an 18 residue leader peptide and a mature protein of 109 amino acids. Evolutionary analysis at both the protein and nucleotide level indicate that the wallaby SAA clone clusters with the acute phase SAAs. However, as the SAA superfamily has undergone concerted evolution it is not possible to determine at this point which acute phase SAA it is most like. The grouping of wallaby SAA inside the acute phase SAA cluster demonstrates that at least some of the duplication events giving rise to multiple acute phase genes occurred prior to the divergence of the eutherian and metatherian mammals.

Changes in the expression of genes involved in protein synthesis during Drosophila aging.

A characteristic feature of aging organisms is their loss in homeostatic functions, including the ability of protein synthesis and turnover. It has been proposed that in senescent Drosophila melanogaster the peptide synthesis elongation factor (EF) EF-1 alpha may become limiting and be responsible for the age-related decline in protein synthesis. We have determined the expression levels of EF genes in Drosophila and have compared them with the expression of several other genes involved in the protein synthesis pathway. Steady-state levels of mRNAs for EF-1 alpha F1 and F2, of mRNAs for four ribosomal proteins, of total poly A+ RNA, rRNA, and tRNA were measured. We show that most RNAs studied decrease immediately after eclosion. There is no evidence for EF-1 alpha mRNA becoming limiting in old flies. Our data suggest that down-regulation of RNA polymerase I-, II-, and III-mediated transcription may contribute to an age-related decrease in protein synthesis or other homeostatic functions.

Severe thrombosis during treatment with ethinylestradiol for tall stature.

High-dose estradiol therapy for reduction of final height may be complicated by severe side effects such as deep vein thrombosis. We report a 14.6-year-old girl with tall stature. In order to reduce final height she was treated with ethinylestradiol and medroxyprogesterone. After arthroscopy she suffered acute deep venous thrombosis of her left leg. Despite being monitored at short intervals, coagulation parameters such as AT III and protein C indicated no development of thrombosis. Medical height reduction with estrogen should be accompanied by heparinisation during longer-lasting periods of immobilisation.

Binding of thyroxine to pig transthyretin, its cDNA structure, and other properties.

Thyroxine binding to proteins in pig plasma during electrophoresis was observed in the albumin, but not in the prealbumin and post-albumin regions. Transthyretin could be identified in medium from in vitro pig choroid plexus incubations by size and number of subunits and a very high rate of synthesis and secretion. Its electrophoretic mobility was intermediate between that of thyroxine-binding globulin and albumin. It bound thyroxine, retinol-binding protein, anti-(rat transthyretin) antibodies and behaved similarly to transthyretins from other vertebrate species when plasma was extracted with phenol. Inhibition experiments with the synthetic flavonoid F 21388, analysing the binding of thyroxine, suggested that transthyretin is not a major thyroxine carrier in the bloodstream of pigs. Cloning and sequencing of transthyretin cDNA from both choroid plexus and liver showed that the same transthyretin mRNA is expressed in pig choroid plexus and liver. The amino acid sequence derived from the nucleotide sequence revealed that pig transthyretin differs from the transthyretins of all other studied vertebrate species by an unusual C-terminal extension consisting of the amino acids glycine, alanine and leucine. This extension results from the mutation of a stop codon into a codon for glycine. The unusual C-terminal extensions do not seem to interfere with the access of thyroxine to its binding site in the central channel of transthyretin.

The cerebral expression of plasma protein genes in different species.

The cerebrospinal fluid (CSF) contains the same proteins as blood plasma, but with a different pattern of concentrations. Protein concentrations in CSF are much lower than those in blood. CSF proteins are derived from blood or synthesized within the brain. The choroid plexus is an important source of CSF proteins. Transthyretin is the protein most abundantly synthesized and secreted by choroid plexus. It determines the distribution of thyroxine in the cerebral compartment. Synthesis of transthyretin first evolved in the brain, then later it became a plasma protein synthesized in the liver. Other proteins secreted by choroid plexus are serum retinol-binding protein, transferrin, caeruloplasmin, insulin-like growth factors, insulin-like growth factor binding proteins, cystatin C, alpha 1-antichymotrypsin, alpha 2-macroglobulin, prothrombin, beta 2-microglobulin and prostaglandin D synthetase. Species differences in expression of the genes for these proteins are outlined, and their developmental pattern, regulation and roles in the cerebral extracellular compartment are discussed.

Wallaby transthyretin.

A cDNA library was constructed from liver RNA of the Australian diprotodont marsupial Macropus eugenii, the Tammar wallaby. A cloned full-length transthyretin cDNA was sequenced. The derived amino-acid sequence showed 68% overall similarity to that of human transthyretin, with 86% similarity in the thyroxine binding site. Comparisons of nucleotide and amino acid sequences from several vertebrate species indicated that the greatest differences were in the region corresponding to the disordered N-terminus of mature human transthyretin. The evolutionary trees deduced from parsimony analyses of amino acid and nucleotide sequences of transthyretins, are consistent with that derived from fossil records.