Paediatric high-grade osteosarcoma and its prognostic factors: a 10-year retrospective study.

INTRODUCTION: This retrospective study was conducted to identify the characteristics of paediatric high-grade osteosarcoma and define its prognostic factors. METHODS: We identified paediatric patients (aged <19 years at diagnosis) diagnosed with high-grade osteosarcoma from 1 January 2009 to 31 December 2018 in two hospitals in Hong Kong, then retrospectively evaluated their medical records to identify prognostic factors. RESULTS: In total, 52 patients were included in this study (22 girls, 42.3%). Femoral tumour was the most common form of osteosarcoma. Most patients (78.8%) had localised disease at diagnosis. The lung was the most common site of metastasis. Almost half (n=23, 46.9%) of the patients showed a good response to chemotherapy (ie, chemonecrosis >90%). Most patients (n=40, 80%) underwent limb-salvage surgery. The event-free survival and overall survival rates were 55.8% and 71.2%, respectively. Prognostic factors independently associated with poor event-free survival and poor overall survival were the presence of metastasis at diagnosis, poor tumour chemonecrosis, and the need for amputation. CONCLUSION: This multicentre review of paediatric high-grade osteosarcoma showed that the baseline patient demographics, event-free survival, and overall survival in Hong Kong were similar to previous findings in other countries. Patients with metastatic disease at diagnosis and poor chemonecrosis had worse survival outcomes. Molecular analyses of genetic abnormalities may help to identify targeted therapies in future studies.

Fatty acid profile differs between organic and conventionally produced cow milk independent of season or milking time.

Differing amounts of fresh forage and concentrates fed, and level of input contributes to the differences reported in fatty acid (FA) composition of organic and conventionally produced cow milk. In many previous studies designed to investigate this phenomenon, comparisons were made between grazed organic cows and housed conventional cows. In the present study, we have investigated differences between organic and conventional milk produced using year-round pasture grazing, as practiced in New Zealand. The FA composition was determined in milk sampled at morning and evening milking in both spring and autumn. Samples were taken from 45 cows from the Massey University organic herd and compared with 50 cows from the corresponding conventional herd grazed and managed similarly at the same location. Forty-three out of 51 analyzed FA were influenced by season, whereas 28 were different between production systems. In addition, one-half were also different due to time of milking. Levels of linoleic acid and α-linolenic acid were higher in organic milk, whereas conjugated linoleic acid (CLA) and vaccenic acid were higher in conventional milk. The first 3 FA (linoleic acid, α-linolenic acid, and CLA) were more abundant in milk harvested during autumn, and the CLA concentration was also significantly influenced by time of milking. Our results confirm reports that the FA profile is affected by season and time of milking, and we also showed an effect due to the production system, when both sets of cows were kept continuously on pasture, even after taking milking time and seasonal effect into account.

Pathological Internet use and associated factors among university students in Hong Kong.

1. Among university entrants, the prevalence of pathological Internet use (PIU) increased more than three-fold (from 5.0 to 15.7%) after 18 months of university life. Psycho-social factors such as depression, life dissatisfaction, and use of the Internet for recreational purposes were associated with the development of PIU. 2. University health workers should be aware that PIU is associated with inferior mental well-being, increased sleeping disorders, and deterioration of family relationships. Special attention should be given to Mainland Chinese students and those with pre-existing psychological problems, as they are more prone to developing PIU. 3. Most university students with PIU were unaware of the health implications of the condition and thus not motivated to seek help. Health workers must take a pro-active approach.

Self-Cognizant Bionic Liquid Sensor for Pathogen Diagnosis.

As observed in the outbreaks of SARS and swine flu, as well as many other infectious diseases, the huge volume of human traffic across numerous enclosed public venues has posed immense challenges to preventing the spread of communicable diseases. There is an urgent need for effective disease surveillance management in public areas under pandemic outbreaks. The physicochemical properties associated with ionic liquids make them particularly suited for molecular communications in sensing networks where low throughput is quite adequate for pathogen detection. This paper presents a self-cognizant system for rapid diagnosis of infectious disease using a bionic sensor such that testing can be supported without collecting a fluid sample from a subject through any invasive methods. The system is implemented for testing the performance of the proposed bionic liquid sensing network.

Comparative Analysis of Gait Speed Estimation Using Wideband and Narrowband Radars, Thermal Camera, and Motion Tracking Suit Technologies.

Research has shown that cognitive and physical functioning of older adults can be reflected in indicators such as walking speed. While changes in cognition, mobility, or health cause changes in gait speed, often gradual variations in walking speed go undetected until severe problems arise. Discrete clinical assessments during clinical consultations often fail to detect changes in day-to-day walking speeds and do not reflect walking speeds in everyday environments, where most of the mobility issues happen. In this paper, we compare four walking speed measurement technologies to a GAITRite mat (gold standard): (1) an ultra wideband radar (covering the band from 3.3 GHz to 10 GHz), (2) a narrow band 24-GHz radar (with a bandwidth of 250 MHz), (3) a perception Neuron Motion Tracking suit, and (4) a thermal camera. Data were collected in parallel using all sensors at the same time for 10 healthy adults for normal and slow walking paces. A comparison of the sensors indicates better performance at lower gait speeds, with offsets (when compared to GAITRite) between 0.1 and 20% for the ultra wideband radar, 1.9 and 17% for the narrowband radar, 0.1 and 38% for the thermal camera, and 1.7 and 38% for the suit. This paper supports the potential of unobtrusive radar-based sensors and thermal camera technologies for ambient autonomous gait speed monitoring for contextual, privacy-preserving monitoring of participants in the community.

(D-Ala2)-Met-enkephalinamide: a potent, long-lasting synthetic pentapeptide analgesic.

[D-Ala2]-Met-enkephalinamide (DALA), a synthetic enkephalin analog designed by in vitro analysis, binds to opiate receptors almost as tightly as methionine-enkephalin. Since it is not susceptible to degradation by brain enzymes, low doses (5 to 10 micrograms) cause profound, long-lasting, morphine-like analgesia when microinjected into rat brain.

Characterization of high density lipoprotein binding to human adipocyte plasma membranes.

Freshly isolated human adipocytes showed specific uptake of 125I-labeled human high density lipoprotein (HDL2 and HDL3), a portion of which could be released by subsequent incubation with excess unlabeled ligand. To study the mechanism of HDL binding, sucrose gradient-purified adipocyte plasma membranes were incubated with radioiodinated lipoprotein particles under equilibrium conditions in the absence (total binding) or presence (nonspecific binding) of 100-fold excess unlabeled ligand. Specific binding of HDL2 and HDL3, calculated by subtracting nonspecific from total binding, was Ca++ independent, unaffected by EDTA, and not abolished by pronase treatment of the membranes. Modification of HDL3 by reductive methylation or cyclohexanedione treatment also failed to affect its binding to adipocyte plasma membranes. High salt concentration (200 mM NaCl) inhibited specific binding of HDL2 and HDL3 but had no effect on LDL binding. A significant portion of 125I-HDL2 or 125I-HDL3 binding was consistently inhibited by adding excess unlabeled LDL, but this inhibition was incomplete as compared with a similar molar excess of unlabeled HDL2 or HDL3. The role of apoproteins (apo) in HDL binding to adipocyte membranes was examined by comparing binding of HDL2 and HDL3 isolated from normal, abetalipoproteinemic (abeta) and apo E-deficient (apo E0) plasma. Specific binding was observed with all normal and mutant HDL particles. Furthermore, a significant portion (61-78%) of abeta-HDL2, apo E0-HDL2, and apo E0-HDL3 binding was inhibited by adding 100-fold excess of unlabeled low density lipoproteins (LDL). The cross-competition of LDL and HDL binding was confirmed by the ability of normal, abeta, and apo E0-HDL2 to completely inhibit 125I-LDL binding. These data suggest that HDL binding is independent of apo E and that the responsible apoprotein(s) of HDL complete with LDL-apo B for binding to the same or closely related site in the adipocyte plasma membrane. Normal and apo E0-HDL3 binding was also completely inhibited by normal HDL2, which suggested that HDL2 and HDL3 probably bind to the same site. Scatchard analysis of normal HDL2, normal HDL3, and apo E0-HDL3 binding data best fitted a one-component binding profile with similar equilibrium dissociation constants (40-96 nM). HDL3 binding was found to be effectively inhibited by anti-human apo AI or anti-human apo AII, but not by anti-human apo B antisera. This binding was also unaffected by monoclonal anti-human apo B or E antibodies known to inhibit binding of apo B or apo E containing lipoprotein to the LDL receptor of cultured fibroblasts. These findings, taken together, suggest that human fat cells possess HDL binding sites with apo AI and /or apo AII specificity. The significant but partial inhibition of HDL2 and HDL3 binding by LDL along with the complete inhibition of LDL binding by HDL2 and HDL3 tends to exclude a single binding site that interacts both lipoproteins and favors the interpretation that LDL and HDL particles bind to multiple recognition sites or to different conformation of the same lipoprotein binding domain on the human fat cell.

Composition, morphology and distribution of high-density lipoproteins in plasma and peripheral lymph: effect of feeding cholesterol and saturated fat.

In euthyroid dogs fed a diet rich in cholesterol and saturated fat, the cholesterol concentration in both plasma and peripheral lymph increased progressively with the appearance of HDLc (d 1.006-1.063). This HDLc fraction was heterogeneous and could be separated into 'slow' and 'fast' migrating fractions by Pevikon block electrophoresis. On SDS-polyacrylamide gel electrophoresis, plasma 'slow' HDLc was appreciably enriched in apolipoprotein (apo) E, while plasma and lymph 'fast' HDLc were apo E-poor. In contrast, no apo E was visible in lymph 'slow' HDLc in either plasma or lymph HDL2 fractions (d 1.087-1.21). The interstitial HDL fractions containing apo A-IV ('fast' HDLc and HDL2) were also rich in free cholesterol, implying that apo A-IV-containing particles are involved in reverse cholesterol transport. Plasma and peripheral lymph HDL2 and 'fast' HDLc cholesterol/protein ratios were not different, whereas lymph 'slow' HDLc was 24% that of plasma, indicating that interstitial 'slow' HDLc was poor in cholesterol compared to plasma. This marked reduction in lymph 'slow' HDLc cholesterol suggests that this particle was either selectively retarded from egress by the endothelial barrier, or that interstitial 'slow' HDLc represents a depleted particle involved in the delivery of cholesterol to peripheral tissues. These findings taken together support the hypothesis that interstitial 'slow' HDLc may represent a particle involved in cholesterol ester delivery, in contrast with HDL2 and 'fast' HDLc, which could serve as an efflux acceptor of tissue free cholesterol. This study demonstrates significant heterogeneity of interstitial peripheral lymph lipoproteins compared to plasma lipoproteins, and indicates selective distribution of these particles in the extravascular space.

Transfer of free and esterified cholesterol from low-density lipoproteins and high-density lipoproteins to human adipocytes.

Cholesterol stored in human adipose tissue is derived from circulating lipoproteins. To delineate the cholesterol transport function of LDL and HDL, the movement of radiolabelled esterified cholesterol and free cholesterol from labelled LDL and HDL to human adipocytes was examined in the present study. LDL and HDL were enriched and labelled in esterified cholesterol with [14C]cholesterol by the action of plasma lipid transfer proteins and lecithin-cholesterol acyltransferase. Doubly labelled (3H,14C) LDL and HDL were prepared by exchanging free [3H]cholesterol into the 14C-labelled lipoproteins. 14C-labelled lipoprotein and 3H-labelled lipoprotein were also prepared separately and mixed to yield a mixed doubly labelled lipoprotein. Relative to the total amount added, proportionally more free than esterified cholesterol was transferred to the adipocytes upon incubation with any doubly labelled LDL and HDL. The calculated mass of free and esterified cholesterol transferred, however, varied with different labelled lipoproteins. 3H- and 14C-labelled LDL or HDL transferred 2-3-fold more esterified than free cholesterol while the reverse occurred with the mixed doubly labelled LDL or HDL. Thus, free cholesterol-depleted particles preferentially transferred cholesterol ester to the fat cells. In the presence of the homologous unlabelled native lipoprotein, the transfers of free and esterified cholesterol from labelled LDL or HDL were specifically inhibited. Selective transfer of esterified cholesterol relative to apoprotein was also observed when esterified cholesterol uptake from both LDL and HDL was assayed along with the binding of 125I-labelled lipoprotein. The cellular accumulation of cholesterol ether-labelled HDL (a non-hydrolyzable analogue of cholesterol ester) exceeded that of cholesterol ester consistent with significant hydrolysis of the latter physiological substrate. These results demonstrate preferential transfer of free cholesterol and esterified cholesterol over apoprotein for both LDL and HDL in human adipocytes. Furthermore, the data suggest that the cholesterol ester transport function of LDL and HDL can be enhanced by free cholesterol depletion and cholesterol ester enrichment of the particles, and affirms a role for adipose tissue in the metabolism of lipid-modified lipoproteins.

Asymmetric distribution of phosphatidylethanolamine fatty acyl chains in the membrane of vesicular stomatitis virus.

The membrane of vesicular stomatitis virus (VSV) contains two distinct pools of phosphatidylethanolamine molecules which reside in the inner and outer phospholipid monolayers, respectively. 36% of the total membrane phosphatidylethanolamine is found in the outer monolayer while 64% is found in the inner. The two pools of VSV phosphatidylethanolamine can be distinguished operationally by the fact that only outer phosphatidylethanolamine is reactive in intact virions with the membrane-impermeable reagent trinitrobenzenesulfonate (TNBS). We have made use of this property to separate inner from outer VSV phosphatidylethanolamine and to determine the fatty acyl chain compositions of the two phosphatidylethanolamine pools separately. The results show that compared to outer phosphatidylethanolamine, inner phosphatidylethanolamine molecules contain a significantly higher proportion of unsaturated fatty acyl chains. Furthermore, whereas the proportion of unsaturated fatty acyl chains was found to be quite similar at the 1 and 2 glycerol carbon atoms in inner phosphatidylethanolamine, a marked dissimilarity was observed in outer phosphatidylethanolamine; outer phosphatidylethanolamine was enriched in saturated fatty acyl chains at the 1 position and in unsaturated fatty acyl chains at the 2 position. The differential fatty acyl chain composition of inner compared to outer phosphatidylethanolamine indicates that rapid, random transmembrane migration (flip-flop) of phosphatidylethanolamine does not occur in the VSV membrane. The nature of the fatty acyl chain asymmetry observed in VSV phosphatidylethanolamine does not support the view that the identity of the fatty acyl chains can uniquely specify or determine which side of the membrane individual phosphatidylethanolamine molecules come to occupy. Although fatty acyl chain asymmetry and phosphatidylethanolamine asymmetry are correlated in VSV, no simple rules can be discerned which uniquely relate the two paramaters.

The role of apolipoprotein A-I and apolipoprotein A-II in high-density lipoprotein binding to human adipocyte plasma membranes.

Adipocyte plasma membranes purified from omental fat tissue biopsies of massively obese subjects possess specific binding sites for high-density lipoprotein (HDL3). This binding was independent of apolipoprotein E as HDL3 isolated from plasma of an apolipoprotein E-deficient individual was bound to a level comparable to that of normal HDL3. To examine the importance of apolipoprotein A-I, the major HDL3 apolipoprotein, in the specific binding of HDL3 to human adipocytes, HDL3 modified to contain varying proportions of apolipoproteins A-I and A-II was prepared by incubating normal HDL3 particles with different amounts of purified apolipoprotein A-II. As the apolipoproteins A-I-to-A-II ratio in HDL3 decreased, the binding of these particles to adipocyte plasma membranes was reduced. Compared to control HDL3, a 92 +/- 3.1% reduction (mean +/- S.E., n = 3) in maximum binding capacity was observed along with an increased binding affinity for HDL3 particles in which almost all of the apolipoprotein A-I had been replaced by A-II. The uptake of HDL cholesteryl ester by intact adipocytes as monitored by [3H]cholesteryl ether labeled HDL3, was also significantly reduced (about 35% reduction, P less than 0.005) by substituting apolipoprotein A-II for A-I in HDL3. These data suggest that HDL binding to human adipocyte membranes is mediated primarily by apolipoprotein A-I and that optimal delivery of cholesteryl ester from HDL to human adipocytes is also dependent on apolipoprotein A-I.

The effects of acute and chronic diabetes on myocardial metabolism in rats.

This study examined how the duration of experimentally induced diabetes affects myocardial metabolism. Both acutely (2-day) and chronically (30-day and 90-day) streptozocin (STZ)-diabetic rats exhibited hyperglycemia and hyperketonemia, while hyperlipemia was evident only in the chronically diabetic rats. The activity of succinate dehydrogenase was lower, whereas that of 3-hydroxyacyl-CoA-dehydrogenase was higher in the hearts of chronically diabetic rats. Although myocardial concentrations of glucose-6-phosphate, glycogen, and triacylglycerols were elevated in diabetes, the patterns of alterations differed between acute and chronic diabetes. The fructose-1,6-diphosphate/fructose-6-phosphate ratio declined progressively after STZ administration, which was not accompanied by a reciprocal increase in citrate levels, although citrate concentrations were elevated. Impaired glucose oxidation was more severe in the freshly isolated heart cells from 30-day than from 2-day diabetic rats. For a given substrate concentration, the oxidation rates of palmitate and 3-hydroxybutyrate were markedly reduced in myocytes from 30-day diabetic rats. However, they were similar to or even higher than the rates found in their control counterparts under conditions that reflected the respective in vivo concentrations of the substrates. Incubating isolated myocytes from 2-day diabetic rats in the presence of insulin only partially restored the impaired glucose oxidation. Insulin administered to the animals 4 h before the experiments restored the impaired glucose oxidation by the cells. Insulin in vitro or single injection in vivo had little or no effect on glucose oxidation in isolated myocytes from 30-day diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Preoperative evaluation of laparoscopic living renal donors with computerized tomography and its effect on donor morbidity and graft function.

OBJECTIVE: To assess the efficacy of CT angiography (CTA) in evaluating the renovascular anatomy in 50 patients who underwent laparoscopic donor nephrectomy, and to correlate results with donor morbidity and recipient outcome. METHODS: Forty-eight patients were evaluated by CTA prior to laparoscopy. Donors with aberrant renovasculature and their respective recipients were divided into: 1) accurate preoperative CTA ("predictive group", PG), 2) inaccurate CTA ("non-predictive group", NPG). Warm ischemia times (WIT), estimated blood loss (EBL), operative time (OT), and the open conversion rate were compared. Recipient creatinine values on post-operative day 1 and 3 months were recorded with the rate of delayed graft function (DGF) and ureteral complication. Statistical significance was calculated using the student's T-test. RESULTS: Among patients with aberrant vasculature (48%, 23/48) at laparoscopy, 14 were accurately predicted by CT angiography (11 arterial, 3 venous). NPG consisted of 5 duplicated arteries, 1 early arterial branching, and 3 anomalous veins. CT accuracy was 85%. The sensitivity and specificity of the arterial imaging were 65% and 100% respectively, while those of venous imaging were 50% and 100%. EBL, WIT, OT, number of open conversions, and ureteral complications were statistically insignificant between groups (p= 0.05, 95% C.I.). The mean decreases in creatinine between NPG and PG on post-operative day 1 and at 3 months were 45.4% and 54.8%, and 71.5% and 79.1% respectively, both statistically insignificant. Two of 8 in the NPG experienced DGF as compared to 1/8 in the PG. CONCLUSIONS: Despite the lower sensitivity of this study, the discordance between imaging and laparoscopy did not augment donor morbidity or increase adverse recipient outcomes. This may indicate that regardless of the shortcomings of 2-D CTA for living donors, it represents a safe and effective imaging modality when coupled with meticulous laparoscopic dissection and central intraoperative involvement of the transplant surgeon.

Synergistic regulation of fetal rat liver nicotinamide adenine dinucleotide phosphate (reduced form) cytochrome c reductase activity: effects of L-triiodothyronine and hydrocortisone.

The activity of hepatic NADPH cytochrome c reductase, an enzyme important in drug and steroid metabolism, increases rapidly during the perinatal period in rats. However, the regulation of this increase is not well understood. To investigate the role of hormones in the development of NADPH cytochrome c reductase activity, fetal rat livers in organ culture were used in the present study. Explants from 20-day-old fetal rat liver could be maintained for up to 96 h in a serum-free medium with or without added hormones. When the explants were exposed to 50 nM L-T3 for 72 h, they had 74% greater NADPH cytochrome c reductase activity than controls. In contrast, 1 microM hydrocortisone (HC) stimulated reductase activity by only 20%. However, when T3 was added with HC there was a synergistic effect, resulting in a 167% elevation in NADPh cytochrome c reductase activity. The response to T3 plus HC was detectable after 24 h and maximal after 72 h. Control activity rose slightly during the first 48 h in culture and was stable thereafter. Stimulation of reductase activity by T3 was detectable at 0.1 nM, half maximal at 2 nM, and maximal between 10 nM and 100 nM. T4 also stimulated NADPh cytochrome c reductase activity in explants but was only 3-4% as potent as T3. The effect of steroids was specific for glucocorticoids. Neither glucagon nor insulin had any measurable effect on reductase activity. Electron micrographs revealed that hepatic ultrastructure was well preserved for at least 72 h of incubation in the presence or absence of hormones. The data suggest, therefore, that the normal perinatal development of hepatic NADPH cytochrome c reductase activity in rats is regulated at least in part by thyroid hormones acting synergistically with glucocorticoids.

Dietary polyunsaturated fatty acids enhance the uptake of high-density lipoprotein cholesterol ester by rat adipocytes.

Compared with diets high in saturated and monounsaturated fatty acids (20% lard by weight), diets high in polyunsaturated fatty acids (20% sunflower oil) alter the fatty acid composition of rat adipocyte plasma membranes and enhance HDL2 binding. We examined the effect of these two diets on HDL1 and HDL2 apolipoprotein and cholesterol uptake by adipocytes isolated from perirenal and epididymal adipose tissue of male Wistar rats. Consistent with selective cellular uptake. HDL esterified cholesterol uptake was 3-10-fold higher than predicted from HDL apolipoproteins associated with adipocytes. Dietary polyunsaturated fatty acids significantly enhanced apolipoprotein and esterified-cholesterol uptakes from HDL2 by perirenal adipocytes. This effect of dietary fat composition was adipose-region (perirenal greater than epididymal) and HDL-subfraction (HDL2 greater than HDL1) specific. Thus, diet-induced changes known to alter membrane phospholipid composition and increase HDL2 binding are also associated with enhanced HDL2-esterified-cholesterol uptake by adipocytes.