Metabolic balance studies and dietary protein requirements in patients undergoing continuous ambulatory peritoneal dialysis

Metabolic balance studies and dietary protein requirements in patients undergoing continuous ambulatory peritoneal dialysis. Balance studies for nitrogen, potassium, magnesium, phosphorus, and calcium were carried out in eight men undergoing continuous ambulatory peritoneal dialysis (CAPD) to determine dietary protein requirements and mineral balances. Patients were fed high energy diets for 14 to 33 days which provided either 0.98 (seven studies) or 1.44g (six studies) of primarily high biological value protein/kg body wt/day. Mean nitrogen balance was neutral with the lower protein diet (+0.35 ± 0.83SEMg/day) and strongly positive with the higher protein diet (+2.94 ± 0.54g/day). With the higher protein diet the balances for potassium, magnesium, and phosphorus were strikingly positive, there was an increase in body weight in all patients, and a rise in mid-arm muscle circumference in five of the six patients. The relation between protein intake and nitrogen balance suggests that the daily protein requirement for clinically stable CAPD patients should be at least 1.1g/kg/day; to account for variability among subjects 1.2 to 1.3g protein/kg/day is probably preferable. Potassium balance correlated directly with nitrogen balance (r = 0.81). High fecal potassium losses (19 ± 1.2 mEq/day) in all patients probably helped maintain normal serum potassium concentrations. Mean serum magnesium was increased (3.1 ± 0.1 mg/dl), and magnesium balances were positive suggesting that the dialysate magnesium of 1.85 mg/dl is excessive. The netgain of calcium from dialysate was 84 ± 18 mg/day; this correlated inversely with serum calcium levels (r = -0.90).Bilans métaboliques et besoins protéiques alimentaires de malades en dialyse péritonéale continue ambulatoire. Des études de bilan de l'azote, du potassium, du magnésium, du phosphore et du calcium, étaient fait en sept hommes en dialyse péritonéale continue ambulatoire (CAPD), pour déterminer leurs besoins protéiques alimentaires et leur bilan minéral. Les malades ont reçu pendant 14 à 33 jours des régimes hautement énergétiques, apportant soit 0,98 (sept études), soit 1,44g (six études) de protéines de haute valeur biologique par kg de poids et par jour. Le bilan azoté moyen etait nul avec le régime comportant la plus faibie teneur protéique (+ 0,35 ± 0,88g/jSEM) et était fortement positive avec le régime à plus forte teneur protéique (+2,94 ± 0,54g/j). Avec le régime à haute teneur en protéine, les bilans potassique, magnésien et phosphoré étaient fortement positifs; le poids corporel s'est élevé chez tous les malades; la circonférence musculaire mesurée du milieu du bras a augmenté chez cinq sur six malades. La relation existant entre l'apport protéique et le bilan azoté suggère que les besoins journaliers en protéines pour des malades cliniquement stables en CAPD devraient être au moins de 1,1g/kg/j; 1,2 à 1,3g de protéines/kg/j sont sans doute préférables pour tenir compte de la variabilité entre les sujets. Le bilan potassique était directement corrélé avec la balance azotée (r = 0,81). De fortes pertes potassiques fécales (19 ± 1,2 mEq/j) chez tous les malades ont probablement contribué à maintenir normales les concentrations sériques du potassium. La magnésémie moyenne était élevée (3,1 ± 0,1 mg/dl), et les bilans magnésiens aient positifs suggérant que le magnésium du dialysat (1,85 18 mg/dl) était trop élevé. Le gain net en calcium à partir du dialysat était de 84 ± 18 mg/j; ce gain était inversement corrélé avec la calcémie (r = 0,90)

Glucose absorption during continuous ambulatory peritoneal dialysis

Glucose absorption during continuous ambulatory peritoneal dialysis. Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are exposed to a continuous infusion of glucose via their peritoneal cavity. We performed studies to quantitate the amount of energy derived from dialysate glucose. Net glucose absorption averaged 182 ± (SD) 61 g/day in 19 studies with a dialysate dextrose concentration of 1.5 or 4.25 g/dl. The amount of glucose absorbed per liter of dialysate (y) varied with the concentration of glucose in dialysate (x), (y = 11.3x - 10.9, r = 0.96), The amount of glucose absorbed per day during a given dialysis regimen was constant. Energy intake from dialysate glucose was 8.4 ± 2.8 kcal/kg of body wt per day, or 12 to 34% of total energy intake. This additional energy may contribute to the anabolic effect reported during CAPD. The ability to vary glucose absorption by altering the dialysate glucose concentration may prove a useful tool to modify energy intake.Absorption de glucose au cours de la dialyse péritonéale continue ambulatoire. Les malades soumis à la dialyse péritonéale continue ambulatoire (CAPD) sont exposés à une administration continue de glucose via leur cavité péritonéale. La quantité d'énergie qui dérive du glucose du dialysat a été quantifiée. L'absorption nette de glucose est en moyenne de 182 ± (SD) 61 g/jour au cours de 19 études avec un dialysat contenant du dextrose, 1,5 ou 4,25 g/dl. La quantité de glucose absorbée par litre de dialysat (y) varie avec la concentration de glucose dans le dialysat (x), (y = 11,3x - 10,9, r = 0,96). La quantité de glucose absorbée par jour pour un type donné de dialyse a été constante. L'entrée d'énergie à partir du glucose du dialysat était de 8,4 ± 2,8 kcal/kg de poids par jour, soit 12 à 34% de l'entrée totale d'énergie. Cette énergie supplémentaire peut contribuer à l'effet anabolique rapporté au cours de CAPD. La possibilité de faire varier l'absorption de glucose en modifiant la concentration de glucose dans le dialysat peut être un moyen utile pour influencer l'entrée d'énergie

In vivo T1ρ and T2 mapping of articular cartilage in osteoarthritis of the knee using 3T MRI

SummaryObjectiveEvaluation and treatment of patients with early stages of osteoarthritis (OA) is dependent upon an accurate assessment of the cartilage lesions. However, standard cartilage dedicated magnetic resonance (MR) techniques are inconclusive in quantifying early degenerative changes. The objective of this study was to determine the ability of MR T1rho (T1ρ) and T2 mapping to detect cartilage matrix degeneration between normal and early OA patients.MethodSixteen healthy volunteers (mean age 41.3) without clinical or radiological evidence of OA and 10 patients (mean age 55.9) with OA were scanned using a 3Tesla (3T) MR scanner. Cartilage volume and thickness, and T1ρ and T2 values were compared between normal and OA patients. The relationship between T1ρ and T2 values, and Kellgren–Lawrence scores based on plain radiographs and the cartilage lesion grading based on MR images were studied.ResultsThe average T1ρ and T2 values were significantly increased in OA patients compared with controls (52.04±2.97ms vs 45.53±3.28ms with P=0.0002 for T1ρ, and 39.63±2.69ms vs 34.74±2.48ms with P=0.001 for T2). Increased T1ρ and T2 values were correlated with increased severity in radiographic and MR grading of OA. T1ρ has a larger range and higher effect size than T2, 3.7 vs 3.0.ConclusionOur results suggest that both in vivo T1ρ and T2 relaxation times increase with the degree of cartilage degeneration. T1ρ relaxation time may be a more sensitive indicator for early cartilage degeneration than T2. The ability to detect early cartilage degeneration prior to morphologic changes may allow us to critically monitor the course of OA and injury progression, and to evaluate the success of treatment to patients with early stages of OA

Characterisation of chilean hazelnut (gevuina avellana) tissues : light microscopy and cell wall polysaccharides

By applying several differential staining techniques and light microscopy, the structure and composition of Chilean hazelnut (Gevuina avellana) seeds were analysed. The structure of the G avellana seed is very simple, with a thin, heavily lignified seed coat and two voluminous cotyledons. The embryo food reserves are uniformly distributed over the cotyledon cells. The cell wall polysaccharides were recovered from the alcohol-insoluble residue by mild treatment with warm chlorite solution and sequential extraction with alkali solutions of increasing concentration. FT-IR spectra in the 1200–850 cm-1 region were used together with chemometric techniques to distinguish the hemicellulosic and pectic polysaccharides in the extracts. The most abundant extracts were fractionated by graded precipitation in ethanol. A xyloglucan was identified by 1H and 13C NMR as the major hemicellulosic polysaccharide, with a sugar composition of 4Glc:3.5Xyl:1Gal:0.5Fuc. The hazelnut cell walls are composed of equivalent amounts of pectic polysaccharides, xyloglucans and cellulose.Fundação para a Ciência e Tecnologia (FCT) - PRAXIS XXI/BPD/18824/99. Research Unit 62/94, QOPNA (Aveiro, Portugal). INCO-DC 96-2205 (OLNOCO)

Accumulation of human-adapting mutations during circulation of A(H1N1)pdm09 influenza virus in humans in the United Kingdom

The influenza pandemic that emerged in 2009 provided an unprecedented opportunity to study adaptation of a virus recently acquired from an animal source during human transmission. In the United Kingdom, the novel virus spread in three temporally distinct waves between 2009 and 2011. Phylogenetic analysis of complete viral genomes showed that mutations accumulated over time. Second- and third-wave viruses replicated more rapidly in human airway epithelial (HAE) cells than did the first-wave virus. In infected mice, weight loss varied between viral isolates from the same wave but showed no distinct pattern with wave and did not correlate with viral load in the mouse lungs or severity of disease in the human donor. However, second- and third-wave viruses induced less alpha interferon in the infected mouse lungs. NS1 protein, an interferon antagonist, had accumulated several mutations in second- and third-wave viruses. Recombinant viruses with the third-wave NS gene induced less interferon in human cells, but this alone did not account for increased virus fitness in HAE cells. Mutations in HA and NA genes in third-wave viruses caused increased binding to alpha-2,6-sialic acid and enhanced infectivity in human mucus. A recombinant virus with these two segments replicated more efficiently in HAE cells. A mutation in PA (N321K) enhanced polymerase activity of third-wave viruses and also provided a replicative advantage in HAE cells. Therefore, multiple mutations allowed incremental changes in viral fitness, which together may have contributed to the apparent increase in severity of A(H1N1)pdm09 influenza virus during successive waves. IMPORTANCE: Although most people infected with the 2009 pandemic influenza virus had mild or unapparent symptoms, some suffered severe and devastating disease. The reasons for this variability were unknown, but the numbers of severe cases increased during successive waves of human infection in the United Kingdom. To determine the causes of this variation, we studied genetic changes in virus isolates from individual hospitalized patients. There were no consistent differences between these viruses and those circulating in the community, but we found multiple evolutionary changes that in combination over time increased the virus's ability to infect human cells. These adaptations may explain the remarkable ability of A(H1N1)pdm09 virus to continue to circulate despite widespread immunity and the apparent increase in severity of influenza over successive waves of infection

MRI texture analysis of subchondral bone at the tibial plateau

OBJECTIVES: To determine the feasibility of MRI texture analysis as a method of quantifying subchondral bone architecture in knee osteoarthritis (OA).   METHODS: Asymptomatic subjects aged 20-30 (group 1, n = 10), symptomatic patients aged 40-50 (group 2, n = 10) and patients scheduled for knee replacement aged 55-85 (group 3, n = 10) underwent high spatial resolution T1-weighted coronal 3T knee MRI. Regions of interest were created in the medial (MT) and lateral (LT) tibial subchondral bone from which 20 texture parameters were calculated. T2 mapping of the tibial cartilage was performed in groups 1 and 2. Mean parameter values were compared between groups using ANOVA. Linear discriminant analysis (LDA) was used to evaluate the ability of texture analysis to classify subjects correctly.   RESULTS: Significant differences in 18/20 and 12/20 subchondral bone texture parameters were demonstrated between groups at the MT and LT respectively. There was no significant difference in mean MT or LT cartilage T2 values between group 1 and group 2. LDA demonstrated subject classification accuracy of 97 % (95 % CI 91-100 %).   CONCLUSION: MRI texture analysis of tibial subchondral bone may allow detection of alteration in subchondral bone architecture in OA. This has potential applications in understanding OA pathogenesis and assessing response to treatment.   KEY POINTS: • Improved techniques to monitor OA disease progression and treatment response are desirable • Subchondral bone (SB) may play significant role in the development of OA • MRI texture analysis is a method of quantifying changes in SB architecture • Pilot study showed that this technique is feasible and reliable • Significant differences in SB texture were demonstrated between individuals with/without OA

Stability of the Influenza Virus Hemagglutinin Protein Correlates with Evolutionary Dynamics

ABSTRACT Protein thermodynamics are an integral determinant of viral fitness and one of the major drivers of protein evolution. Mutations in the influenza A virus (IAV) hemagglutinin (HA) protein can eliminate neutralizing antibody binding to mediate escape from preexisting antiviral immunity. Prior research on the IAV nucleoprotein suggests that protein stability may constrain seasonal IAV evolution; however, the role of stability in shaping the evolutionary dynamics of the HA protein has not been explored. We used the full coding sequence of 9,797 H1N1pdm09 HA sequences and 16,716 human seasonal H3N2 HA sequences to computationally estimate relative changes in the thermal stability of the HA protein between 2009 and 2016. Phylogenetic methods were used to characterize how stability differences impacted the evolutionary dynamics of the virus. We found that pandemic H1N1 IAV strains split into two lineages that had different relative HA protein stabilities and that later variants were descended from the higher-stability lineage. Analysis of the mutations associated with the selective sweep of the higher-stability lineage found that they were characterized by the early appearance of highly stabilizing mutations, the earliest of which was not located in a known antigenic site. Experimental evidence further suggested that H1N1 HA stability may be correlated with in vitro virus production and infection. A similar analysis of H3N2 strains found that surviving lineages were also largely descended from viruses predicted to encode more-stable HA proteins. Our results suggest that HA protein stability likely plays a significant role in the persistence of different IAV lineages. IMPORTANCE: One of the constraints on fast-evolving viruses, such as influenza virus, is protein stability, or how strongly the folded protein holds together. Despite the importance of this protein property, there has been limited investigation of the impact of the stability of the influenza virus hemagglutinin protein—the primary antibody target of the immune system—on its evolution. Using a combination of computational estimates of stability and experiments, our analysis found that viruses with more-stable hemagglutinin proteins were associated with long-term persistence in the population. There are two potential reasons for the observed persistence. One is that more-stable proteins tolerate destabilizing mutations that less-stable proteins could not, thus increasing opportunities for immune escape. The second is that greater stability increases the fitness of the virus through increased production of infectious particles. Further research on the relative importance of these mechanisms could help inform the annual influenza vaccine composition decision process

Laser-induced modification of the patellar ligament tissue: comparative study of structural and optical changes

The effects of non-ablative infrared (IR) laser treatment of collagenous tissue have been commonly interpreted in terms of collagen denaturation spread over the laser-heated tissue area. In this work, the existing model is refined to account for the recently reported laser-treated tissue heterogeneity and complex collagen degradation pattern using comprehensive optical imaging and calorimetry toolkits. Patella ligament (PL) provided a simple model of type I collagen tissue containing its full structural content from triple-helix molecules to gross architecture. PL ex vivo was subjected to IR laser treatments (laser spot, 1.6 mm) of equal dose, where the tissue temperature reached the collagen denaturation temperature of 60 ± 2°C at the laser spot epicenterin the first regime, and was limited to 67 ± 2°C in the second regime. The collagen network was analyzed versus distance from the epicenter. Experimental characterization of the collagenous tissue at all structural levels included cross-polarization optical coherence tomography, nonlinear optical microscopy, light microscopy/histology, and differential scanning calorimetry. Regressive rearrangement of the PL collagen network was found to spread well outside the laser spot epicenter (>2 mm) and was accompanied by multilevel hierarchical reorganization of collagen. Four zones of distinct optical and morphological properties were identified, all elliptical in shape, and elongated in the direction perpendicular to the PL long axis. Although the collagen transformation into a random-coil molecular structure was occasionally observed, it was mechanical integrity of the supramolecular structures that was primarily compromised. We found that the structural rearrangement of the collagen network related primarily to the heat-induced thermo-mechanical effects rather than molecular unfolding. The current body of evidence supports the notion that the supramolecular collagen structure suffered degradation of various degrees, which gave rise to the observed zonal character of the laser-treated lesion

Developmental Localization and Methylesterification of Pectin Epitopes during Somatic Embryogenesis of Banana (Musa spp. AAA)

The plant cell walls play an important role in somatic embryogenesis and plant development. Pectins are major chemical components of primary cell walls while homogalacturonan (HG) is the most abundant pectin polysaccharide. Developmental regulation of HG methyl-esterification degree is important for cell adhesion, division and expansion, and in general for proper organ and plant development.Developmental localization of pectic homogalacturonan (HG) epitopes and the (1→4)-β-D-galactan epitope of rhamnogalacturonan I (RG-I) and degree of pectin methyl-esterification (DM) were studied during somatic embryogenesis of banana (Musa spp. AAA). Histological analysis documented all major developmental stages including embryogenic cells (ECs), pre-globular, globular, pear-shaped and cotyledonary somatic embryos. Histochemical staining of extracellularly secreted pectins with ruthenium red showed the most intense staining at the surface of pre-globular, globular and pear-shaped somatic embryos. Biochemical analysis revealed developmental regulation of galacturonic acid content and DM in diverse embryogenic stages. Immunodots and immunolabeling on tissue sections revealed developmental regulation of highly methyl-esterified HG epitopes recognized by JIM7 and LM20 antibodies during somatic embryogenesis. Cell walls of pre-globular/globular and late-stage embryos contained both low methyl-esterified HG epitopes as well as partially and highly methyl-esterified ones. Extracellular matrix which covered surface of early developing embryos contained pectin epitopes recognized by 2F4, LM18, JIM5, JIM7 and LM5 antibodies. De-esterification of cell wall pectins by NaOH caused a decrease or an elimination of immunolabeling in the case of highly methyl-esterified HG epitopes. However, immunolabeling of some low methyl-esterified epitopes appeared stronger after this base treatment.These data suggest that both low- and highly-methyl-esterified HG epitopes are developmentally regulated in diverse embryogenic stages during somatic embryogenesis. This study provides new information about pectin composition, HG methyl-esterification and developmental localization of pectin epitopes during somatic embryogenesis of banana

Genetic improvement of tomato by targeted control of fruit softening

Controlling the rate of softening to extend shelf life was a key target for researchers engineering genetically modified (GM) tomatoes in the 1990s, but only modest improvements were achieved. Hybrids grown nowadays contain 'non-ripening mutations' that slow ripening and improve shelf life, but adversely affect flavor and color. We report substantial, targeted control of tomato softening, without affecting other aspects of ripening, by silencing a gene encoding a pectate lyase