Sample carryover and cleaning procedures for asymmetrical flow field-flow fractionation instrument.

Asymmetrical flow field-flow (AF4) fractionation aims in separation of sample components to yield elution of homogenous fractions identified as well-defined peaks in the chromatograms. Separation that occurs in matrix-free open channel potentiates high recovery that can be close to 100%. However, sample properties and separation conditions may induce carryover of sample components during AF4 analysis and in sample sequences. This compromises the quality of the data collected from the online detectors and the downstream offline analytics of the collected fractions. In this study, we followed sample carryover in AF4 using model viruses and analyzed various cleaning solutions and rinse methods to reduce carryover. We introduce an SDS-NaOH -based rinsing and decontamination protocol for the AF4 instrument enabling high-quality data collection.

Posterior Spinal Fusion Extended to Stable Vertebra Provides Similar Outcome in Juvenile Idiopathic Scoliosis Patients Compared with Adolescents with Fusion to the Touched Vertebra.

BACKGROUND AND AIMS:: To compare outcomes between posterior spinal fusion of juvenile idiopathic scoliosis and adolescent idiopathic scoliosis patients with a minimum of 2-year follow-up. The juvenile idiopathic scoliosis patients were fused to the stable vertebra and adolescent idiopathic scoliosis to the touched vertebra. We hypothesized that extending the spinal fusion to the stable vertebra in juvenile patients would provide similar outcomes compared with fusion to the touched vertebra in adolescents. MATERIALS AND METHODS:: A prospective comparative study of 21 consecutive children with juvenile (Risser 0) and 84 adolescent (Risser ⩾2) idiopathic scoliosis (1:4 ratio) undergoing bilateral segmental pedicle screw instrumentation and direct vertebral derotation with a minimum of 2-year follow-up. RESULTS:: Juvenile patients had a significantly larger main curve (58° vs 53°, p = 0.003), more fused levels (p = 0.012) and posterior column osteotomies (p = 0.014) than adolescent patients. Distal adding-on (>10°) was observed in one (4.7%) juvenile and three (3.6%) adolescent patients (p = 0.80), without the need for revisions. Scoliosis Research Society 24 total score averaged 101 in juvenile and 97 in adolescent group at 2-year follow-up (p = 0.047). CONCLUSION:: Posterior spinal fusion with bilateral segmental pedicle screw instrumentation to the stable vertebra provides similar clinical and radiographic outcomes in juvenile patients as compared with adolescents with fusion to the touched vertebra in idiopathic scoliosis. Health-related quality of life as measured using the Scoliosis Research Society 24 questionnaire at the end of follow-up was better in the juvenile as compared with the adolescent group.

Membrane-containing virus particles exhibit the mechanics of a composite material for genome protection.

The protection of the viral genome during extracellular transport is an absolute requirement for virus survival and replication. In addition to the almost universal proteinaceous capsids, certain viruses add a membrane layer that encloses their double-stranded (ds) DNA genome within the protein shell. Using the membrane-containing enterobacterial virus PRD1 as a prototype, and a combination of nanoindentation assays by atomic force microscopy and finite element modelling, we show that PRD1 provides a greater stability against mechanical stress than that achieved by the majority of dsDNA icosahedral viruses that lack a membrane. We propose that the combination of a stiff and brittle proteinaceous shell coupled with a soft and compliant membrane vesicle yields a tough composite nanomaterial well-suited to protect the viral DNA during extracellular transport.

Outcomes of growing rod surgery for severe compared with moderate early-onset scoliosis: a matched comparative study.

Aims: The aim of this study was to compare the outcomes of surgery using growing rods in patients with severe versus moderate early-onset scoliosis (EOS). Patients and Methods: A review of a multicentre EOS database identified 107 children with severe EOS (major curve ≥ 90°) treated with growing rods before the age of ten years with a minimum follow-up of two years and three or more lengthening procedures. From the same database, 107 matched controls with moderate EOS were identified. Results: The mean preoperative major curve was 101° (90 to 139) in the severe group and 67° (33° to 88°) in the moderate group (p < 0.001), which was corrected at final follow-up to 57° (10° to 96°) in the severe group and 40° (3° to 85°) in the moderate group (p < 0.001). T1-S1 height increased by a mean of 54 mm (-8 to 131) in the severe group and 27 mm (-4 to 131) in the moderate group at the initial surgery (p < 0.001), and by 50 mm (-17 to 200) and 54 mm (-11 to 212), respectively, during distraction (p = 0.84). The mean number of complications per patient was 2.6 (0 to 14) in the severe group and 1.9 (0 to 10) in the moderate group (p = 0.040). Five patients (4.7%) in the severe group and three (2.8%) in the moderate group developed a neurological deficit postoperatively (p = 0.47). Conclusion: Severe EOS can be treated effectively using growing rods, but the risk of complications is high. Cite this article: Bone Joint J 2018;100-B:772-9.

Electrophysiological evidence of enhanced distractibility in ADHD children.

Abnormal involuntary attention leading to enhanced distractibility may account for different behavioral and cognitive problems in children with attention deficit hyperactivity disorder (ADHD). This was investigated in the present experiment by recording event-related brain potentials (ERPs) to distracting novel sounds during performance of a visual discrimination task. The overall performance in the visual task was less accurate in the ADHD children than in the control children, and the ADHD children had a higher number of omitted responses following novel sounds. In both groups, the distracting novel sounds elicited a biphasic P3a ERP component and a subsequent frontal Late Negativity (LN). The early phase of P3a (180-240 ms) had significantly smaller amplitudes over the fronto-central left-hemisphere recording sites in the ADHD children than in the control group presumably due to an overlapping enhanced left-hemisphere dominant negative ERP component elicited in the ADHD group. Moreover, the late phase of P3a (300-350 ms) was significantly larger over the left parietal scalp areas in the ADHD children than in the controls. The LN had a smaller amplitude and shorter latency over the frontal scalp in the ADHD group than in the controls. In conclusion, the ERP and behavioral effects caused by the novel sounds reveal deficient control of involuntary attention in ADHD children that may underlie their abnormal distractibility.

Endothelial cell damage in piglet coronary artery after intravenous administration of E. coli endotoxin. A scanning and transmission electron-microscopic study.

E. Coli endotoxin was administered to 6 piglets from a litter of 10. Three days after the endotoxin stimulus 3 piglets showed definitive morphological evidence of endothelial damage to their left coronary artery. The proximal parts of the coronary artery were severely damaged. In scanning electron microscopy, the changes varied from disappearance of the microvilli to complete exfoliation of the endothelial cells. In cases of severe endothelial cell damage transmission electron microscopy revealed severe changes or even signs of cell death in the inner medial smooth muscle cells. Only of the piglets died prematurely. We are sufficiently encouraged to continue testing the theory that repeated endothelial cell damage initiates stenosing lesions in the coronary arteries.

Effect of repeated endotoxin treatment and hypercholesterolemia on preatherosclerotic lesions in weaned pigs. Part II. Lipid and glycosaminoglycan analysis of intima and inner media.

We compared the effects of mild hypercholesterolemia and repeated endotoxin infusions on the biochemical composition of aortic intima and inner media of 24 piglets divided into 4 groups 5 days after weaning: controls on normal diet (group I); normal diet and endotoxin (group II); fat-supplemented diet (group III); and fat-supplemented diet and endotoxin (group IV). It was found that mild hypercholesterolemia increased the concentration of arterial esterified cholesterol and the relative amount of the fraction containing chondroitin sulphates A and C in total glycosaminoglycans. Endotoxin infusions partly prevented the increase of serum cholesterol caused by the fat-supplemented diet but had no independent effect on the arterial biochemical composition; nor did they affect the biochemical changes caused by hypercholesterolemia. When the results of all groups were combined, chondroitin sulphates A and C showed a significant positive correlation with the concentration of arterial esterified cholesterol and the percentage of linoleic acid in arterial cholesteryl esters. Serum total cholesterol did not correlate with arterial cholesterol fractions, but the ratio of high density lipoprotein-cholesterol to total serum cholesterol showed a negative association with arterial esterified cholesterol. The present findings indicate that (1) mild hypercholesterolemia is atherogenic in young piglets, and (2) changes in arterial glycosaminoglycan composition might be one of the earliest biochemical alterations in atherogenesis.

Effect of repeated endotoxin treatment and hypercholesterolemia on preatherosclerotic lesions in weaned pigs. Part 1. Scanning and transmission electron microscopic study.

Endothelial cell damage is considered to be the primary event in atherogenesis. In this study we compared the effects of mild hypercholesterolemia and repeated E. coli endotoxin infusions on the endothelial cells of the coronary arteries of the pig. We divided 24 pigs into 4 groups: I: controls on normal diet; II: normal diet and endotoxin treatment; III: fat-supplemented diet; IV: fat-supplemented diet and endotoxin treatment. The animals on a fat-supplemented diet showed the most frequent and most severe endothelial cell damage. The damage was less when this diet was combined with endotoxin treatment. Endotoxin reduced the serum total cholesterol level (P less than 0.01). The cholesterol level correlated very significantly (P less than 0.001) with endothelial damage of the coronary arteries. Mild hypercholesterolemia (s-cholesterol 5.68 mmol/l, controls 2.28 mmol/l) was thus associated with toxic effects in the endothelial cells. The E. coli endotoxin infusions did not have any cumulative effect on the lesions.

A practical prognostic index for inoperable non-small-cell lung cancer.

Radical radiotherapy is widely used to treat inoperable non-small-cell lung cancer (NSCLC) although only a small number of patients benefit in the long run from this intensive treatment. There is a small proportion of long-term survivors who might derive advantage from even more aggressive radiotherapy combined with chemotherapy. In order to support optimal treatment selection we have carried out univariate and multivariate analyses of possible prognostic variables in the retrospective data of 502 NSCLC patients treated at one institute with external radiotherapy, both with curative and palliative intent. To obtain more accurate tools for a rational treatment decision, we identified, by using Cox's proportional-hazards model, the five most powerful determinants of overall survival and combined them to a prognostic index. On the basis of only the number of these risk factors (advanced stage, general or metastatic symptoms, poor performance status, anemia and tumor size of at least 7 cm), the patient falls into one of the six possible prognostic groups and these groups turned out to be identifiable as separate prognostic clusters. Thirty-one per cent of the patients have three or more risk factors and a median survival of 5-7 months compared with 18 months for patients without any non-favorable factor. Furthermore, the prognostic factors were so strong that multivariate analyses did not reveal the treatment selection to have any significant influence on survival. As each of the five variables have the advantage of being routinely available, our index is simple enough to be used in daily clinical practice. The clinical value of the prognostic index should be verified by using independent data.

Metabolic responses to exercise in the racehorse: changes in plasma alanine concentration.

Previous studies in humans have shown that alanine is released from the skeletal muscle in proportion to the work load. We have measured plasma alanine and urea concentrations in well-trained Standardbred and Finnish-bred (cold-blooded) trotters after a graded-intensity exercise and during recovery to study metabolic responses to exercise in this animal model. As controls we measured blood lactate, pyruvate, and glucose concentrations as well as hematocrit values. Metabolic responses to exercise were closely reflected in all these parameters. Plasma alanine increased relatively more than plasma lactate at moderate-intensity exercise near anaerobic threshold. The linear correlation between the intensity of exercise and plasma alanine was similar to that observed earlier in humans. Interestingly, plasma alanine concentrations remained elevated long after the submaximal exercise, whereas the concentration of lactate, pyruvate, and glucose decreased more rapidly. No significant changes were found in plasma urea concentration under these conditions. The most significant differences in the metabolic responses to exercise of the two breeds studied were the higher lactate-to-pyruvate ratios achieved during the high-intensity exercise and the more sensitive increases of plasma alanine even during low-intensity exercise in the Finnish-bred horses. These differences probably reflect different compositions of muscle fiber types in the two breeds. The findings together indicate that plasma alanine is greatly increased in the racehorse during and after a high-intensity exercise and thus is an important vehicle in transporting ammonia and carbon skeletons of products of anaerobic glycolysis out of the muscle tissue.

Dissemination of endometrial cells during carbon dioxide hysteroscopy and chromotubation among infertile patients.

The presence of endometrial cells in PF before and after diagnostic CO2 hysteroscopy and after liquid chromotubation was studied with 51 infertile patients. Cytological samples of PF or washings did not reveal endometrial cells in any case before hysteroscopy. Endometrial cells were found in PF in 16% after CO2 hysteroscopy and in 65% of cases after chromotubation. All (100%) patients with and 49% of those without endometriosis had endometrial cells in PF after liquid chromotubation. We conclude that endometrial cells are disseminated into the peritoneal cavity in a minor degree during CO2 hysteroscopy, whereas more remarkable dissemination of endometrial cells occurs during liquid chromotubation.

Astrocytes as targets for CNS effects of organic solvents in vitro.

The aim of the study was to evaluate astrocytes in vitro as a model for studies of solvent neurotoxicity. Primary astrocyte cultures were established from newborn rat cerebella. The cells were cultured in the modified Minimum Essential Medium (MEM), and the neural membranes isolated from cultures were exposed to solvents in incubation mixtures containing different solvent concentrations (3, 6, and 9 mM) for one hour. The activity of membrane-bound total ATPase was determined after exposure to aromatic hydrocarbons (benzene, toluene, xylene, styrene and ethylbenzene), and to n-hexane and cyclohexane. The enzyme activities were decreased by aromatic hydrocarbons linearly according to the log dose and in order to the log lipid/water partition coefficients, benzene having the smallest and ethylbenzene the greatest effect in all concentrations studied. Cyclohexane caused much smaller enzyme inhibition (18% of control activity in 9 mM concentration) than ethylbenzene (67% in 9 mM), in spite of very similar partition coefficients. N-hexane had clearly slighter enzyme inhibiting effect than aromatic hydrocarbons, in spite of its markedly greater lipophilicity. In addition to lipophilicity, the structure of solvent molecule seems to be important when considering the CNS toxicity. These results suggest that organic solvents exert their toxic effects on CNS, at least in part, by disturbing ATPase-dependent astrocytic regulatory functions.

Limited value of ultrasound measured skin thickness in predicting bone mineral density in peri- and postmenopausal women.

Measurement of skin thickness has been proposed to be capable of predicting low bone mineral density and the risk of osteoporosis in postmenopausal women. In order to investigate the association between the two factors, we measured skin thickness on the leg, lower abdomen and forearm by ultrasound scanning, and bone mineral density at the lumbar spine, femoral neck and distal radius by dual-energy X-ray absorptiometry in 60 peri- and postmenopausal women. Only a loose association was found between skin thickness and bone mineral density at any site, the highest correlation being between lumbar bone mineral density and abdominal skin thickness. The results of our study confirm that there is some association between the two factors, but the measurement of skin thickness, although easy and reliable, is not a clinically sufficient method to predict bone mineral density.

Dexmedetomidine alleviates ethanol withdrawal symptoms in the rat.

The effect of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on ethanol withdrawal symptoms was studied in chronically ethanol-fed rats. After a 4-day ethanol intoxication period the rats were given s.c. injections of dexmedetomidine (3, 10, or 30 micrograms/kg) or saline (control group) at 10, 16, 22, and 39 h after the last dose of ethanol. The severity of ethanol withdrawal symptoms (rigidity, tremor, irritability, hypoactivity) was rated up to 58 h, blind to the treatments. The results showed that dexmedetomidine at doses 10 and 30 micrograms/kg significantly diminished the severity of the ethanol withdrawal reaction as measured by the sum score of the three most specific withdrawal signs (rigidity, tremor, and irritability). Dexmedetomidine at 10 micrograms/kg was the most effective dose, especially in the latter half of the withdrawal period (23-58 h after last dose of ethanol). The results suggest that dexmedetomidine in the treatment of ethanol withdrawal symptoms should be further studied.

Changing strategies in the surgical management of acute necrotizing pancreatitis.

During 1982-90 we changed the surgical treatment of acute necrotizing pancreatitis twice. The operative strategy consisted of early formal resection (n = 13) during 1982-84, early lavational surgery (n = 15) during 1985-87 and late necrosectomy (n = 17) during 1988-90. The mortality rate decreased from 54% to 40% and to 24%, respectively. The pattern of complications changed from bleeding in resections to pseudocysts and fistulas in late necrosectomy. Sepsis and multiorgan failure were still main problems. These results led us to begin a prospective study of planned repeated debridement by open packing after delayed necrosectomy.

Postoperative signs in 96 dogs undergoing soft tissue surgery.

The signs shown by 96 dogs recovering at home after day-case soft tissue operations were assessed by their owners for three days. On the day of the operation there were behavioural changes in all the animals, but by two days after the operation changes in behaviour were detected in only 85 per cent of them. The most common changes were in the dogs' demeanour and their way of moving; there were decreases in overall activity and playfulness, and increases in contact seeking. The dogs also showed signs of pain: the highest ratings were observed on the day of the operation, when the median value on a visual analogue scale from 0 to 100 mm was 43 mm, with a range from 0 to 95 mm. The type of operation significantly affected the signs observed.

[The "hyena disease" of cattle in Finland]. / Die "Hyänenkrankheit" des Rindes in Finnland.

The first occurrence of "Hyena disease" in cattle in Finland is described. The affected beef bulls consumed very high doses of vitamins A, D and E. Some of them developed to "Hyena" bulls and some to "Hyena/dwarf"-bulls. The radiological signs in the skeleton were similar to those which can occur in connection with vitamin A and D overdoses.

Acute pancreatitis in patients over 80 years.

OBJECTIVE: To evaluate the occurrence, aetiology and outcome of acute pancreatitis (AP) in patients over 80 years of age, compared with those between 61 and 79 years old. DESIGN: Retrospective analysis. SETTING: University hospital, Finland. SUBJECTS: Subgroups of 22 patients 80 years old or over and 139 patients 61-79 years old out of 1058 episodes of AP between 1982 and 1990. MAIN OUTCOME MEASURES: Mortality, morbidity, and hospital stay. RESULTS: The percentage of patients aged 80 or more varied from 0 in 1982 to 3% in 1990; 13 (59%) were women compared with 47 (34%) in the 61-79 year old group (p = 0.03). AP in the older group was more likely to be necrotising 9/22 (41%) compared with 23/139 (17%), p = 0.02) and to have been caused by biliary disease 15/22 (68%) compared with 54/139 (39%), (p = 0.01). The overall mortality was 9/22 (41%) in the 80 years and over group and 24/139 (17%) in patients aged 61-79 years (p = 0.02). All 9 patients in their eighties with necrotising pancreatitis died. Neither the mode of treatment nor the Glasgow prognostic scoring had any relation to mortality in the older group. CONCLUSIONS: AP in patients of 80 or more is a serious disease with a high mortality irrespective of standard treatment.