Combining supervised and unsupervised named entity recognition to detect psychosocial risk factors in occupational health checks.

INTRODUCTION: In occupational health checks the information about psychosocial risk factors, which influence work ability, is documented in free text. Early detection of psychosocial risk factors helps occupational health care to choose the right and targeted interventions to maintain work capacity. In this study the aim was to evaluate if we can automate the recognition of these psychosocial risk factors in occupational health check electronic records with natural language processing (NLP). MATERIALS AND METHODS: We compared supervised and unsupervised named entity recognition (NER) to detect psychosocial risk factors from health checks' documentation. Occupational health nurses have done these records. RESULTS: Both methods found over 60% of psychosocial risk factors from the records. However, the combination of BERT-NER (supervised NER) and QExp (query expansion/paraphrasing) seems to be more suitable. In both methods the most (correct) risk factors were found in the work environment and equipment category. CONCLUSION: This study showed that it was possible to detect risk factors automatically from free-text documentation of health checks. It is possible to develop a text mining tool to automate the detection of psychosocial risk factors at an early stage.

Expected shifts in Fusarium species' composition on cereal grain in Northern Europe due to climatic change.

In Northern Europe, changes in climate may result in better growing conditions for many crops. However, the expected warmer and more humid conditions are favourable for Fusarium head blight infections on cereals. The Fusarium species prevalent in Nordic areas to date are the same as in Central Europe: F. avenaceum, F. culmorum, F. graminearum and F. poae. The prevalence of F. graminearum in cereal grain has already increased in Central Europe and is likely to increase in the North due to the expected changes in weather conditions, reduced tillage and the predicted increase in maize cultivation in Nordic countries. The possible weather extremes predispose cereals to Fusarium infections by increasing the populations of insect pests injuring plants. Adverse conditions may even create conditions suitable for F. subglutinans or F. verticilloides to infect maize and possibly other cereals in rotation in southern parts of Scandinavia. The importance of the species that infect in relatively dry conditions, F. langsethiae and F. poae, may also increase on winter cereals which are predicted to be more prevalent in future farming. If the number of crop species cultivated will increase and non-cereal crops are included in rotations effects of reduced tillage on Fusarium infections in grain could be limited. The predicted changes in climate towards 2050 are expected to slightly change Fusarium species composition in Northern Europe. An increase in F. graminearum and possibly the invasion of northern parts of Central Europe and Denmark by fumonisin producers is expected.

Sensitivity of barley varieties to weather in Finland.

Global climate change is predicted to shift seasonal temperature and precipitation patterns. An increasing frequency of extreme weather events such as heat waves and prolonged droughts is predicted, but there are high levels of uncertainty about the nature of local changes. Crop adaptation will be important in reducing potential damage to agriculture. Crop diversity may enhance resilience to climate variability and changes that are difficult to predict. Therefore, there has to be sufficient diversity within the set of available cultivars in response to weather parameters critical for yield formation. To determine the scale of such 'weather response diversity' within barley (Hordeum vulgare L.), an important crop in northern conditions, the yield responses of a wide range of modern and historical varieties were analysed according to a well-defined set of critical agro-meteorological variables. The Finnish long-term dataset of MTT Official Variety Trials was used together with historical weather records of the Finnish Meteorological Institute. The foci of the analysis were firstly to describe the general response of barley to different weather conditions and secondly to reveal the diversity among varieties in the sensitivity to each weather variable. It was established that barley yields were frequently reduced by drought or excessive rain early in the season, by high temperatures at around heading, and by accelerated temperature sum accumulation rates during periods 2 weeks before heading and between heading and yellow ripeness. Low temperatures early in the season increased yields, but frost during the first 4 weeks after sowing had no effect. After canopy establishment, higher precipitation on average resulted in higher yields. In a cultivar-specific analysis, it was found that there were differences in responses to all but three of the studied climatic variables: waterlogging and drought early in the season and temperature sum accumulation rate before heading. The results suggest that low temperatures early in the season, delayed sowing, rain 3-7 weeks after sowing, a temperature change 3-4 weeks after sowing, a high temperature sum accumulation rate from heading to yellow ripeness and high temperatures (⩾25°C) at around heading could mostly be addressed by exploiting the traits found in the range of varieties included in the present study. However, new technology and novel genetic material are needed to enable crops to withstand periods of excessive rain or drought early in the season and to enhance performance under increased temperature sum accumulation rates prior to heading.

Influence of adenosine triphosphate and ABCB1 (MDR1) genotype on the P-glycoprotein-dependent transfer of saquinavir in the dually perfused human placenta.

BACKGROUND: The ATP-dependent drug-efflux pump, P-glycoprotein (P-gp) encoded by ABCB1 (MDR1), plays a crucial role in several tissues forming blood-tissue barriers. Absence of a normally functioning P-gp can lead to a highly increased tissue penetration of a number of clinically important drugs. METHODS: We have studied the dose-response effect of exogenous ATP on the placental transfer of the well-established P-gp substrate saquinavir in 17 dually perfused human term placentas. We have also studied the influence of the ABCB1 polymorphisms 2677G>T/A and 3435C>T on placental P-gp expression (n = 44) and the transfer (n = 16) of saquinavir. RESULTS: The present results indicate that the addition of exogenous ATP to the perfusion medium does not affect the function of P-gp as measured by saquinavir transfer across the human placenta. The variant allele 3435T was associated with significantly higher placental P-gp expression than the wild-type alleles. However, neither polymorphism affected placental transfer of saquinavir nor there was any correlation between P-gp expression and saquinavir transfer. CONCLUSIONS: Our results indicate that addition of exogenous ATP is not required for ATP-dependent transporter function in a dually perfused human placenta. Although the ABCB1 polymorphism 3435C>T altered the expression levels of P-gp in the human placenta, this did not have any consequences on P-gp-mediated placental transfer of saquinavir.

APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex.

In mitosis, the anaphase-promoting complex (APC) regulates the onset of sister-chromatid separation and exit from mitosis by mediating the ubiquitination and degradation of the securin protein and mitotic cyclins. With the use of a baculoviral expression system, we have reconstituted the ubiquitin ligase activity of human APC. In combination with Ubc4 or UbcH10, a heterodimeric complex of APC2 and APC11 is sufficient to catalyze the ubiquitination of human securin and cyclin B1. However, the minimal APC2/11 ubiquitin ligase module does not possess substrate specificity, because it also ubiquitinates the destruction box deletion mutants of securin and cyclin B1. Both APC11 and UbcH10 bind to the C-terminal cullin homology domain of APC2, whereas Ubc4 interacts with APC11 directly. Zn(2+)-binding and mutagenesis experiments indicate that APC11 binds Zn(2+) at a 1:3 M ratio. Unlike the two Zn(2+) ions of the canonical RING-finger motif, the third Zn(2+) ion of APC11 is not essential for its ligase activity. Surprisingly, with Ubc4 as the E2 enzyme, Zn(2+) ions alone are sufficient to catalyze the ubiquitination of cyclin B1. Therefore, the Zn(2+) ions of the RING finger family of ubiquitin ligases may be directly involved in catalysis.

Reactions of N,N-bis(2-chloroethyl)-p-aminophenylbutyric acid (chlorambucil) with 2'-deoxyguanosine.

N,N-Bis(2-chloroethyl)-p-aminophenylbutyric acid (chlorambucil, 1) was allowed to react in the presence of 2'-deoxyguanosine (16 mM) at physiological pH (cacodylic acid, 50% base), and the reactions were followed by HPLC/MS/MS techniques. Although the predominant reaction observed was chlorambucil hydrolysis, ca. 24% of 1 reacted with different heteroatoms of the nucleoside. As expected, the principal site of 2'-deoxyguanosine alkylation was N7. Alkylation of N7 caused spontaneous depurination, and N-(7-guaninylethyl)-N-hydroxyethyl-p-aminophenylbutyric acid (5) and the corresponding N7,N7-bis-adduct (6) were the major stable dGuo derivatives. Also several other adducts were detected and tentatively identified by means of MS/MS and UV. From them, the O(6-), N1-, N(2-), and O5'-derivatives can be biologically significant. Our results shed new light on DNA modifications caused by chlorambucil, which is an important chemotherapeutic drug and a known carcinogen.

Effects of weight loss on peak flow variability, airways obstruction, and lung volumes in obese patients with asthma.

STUDY OBJECTIVES: To clarify the pathophysiologic features of the relation between asthma and obesity, we measured the effects of weight reduction on peak expiratory flow (PEF) variability and airways obstruction, compared to simultaneous changes in lung volumes and ventilatory mechanics in obese patients with stable asthma. METHODS: Fourteen obese asthma patients (11 women and 3 men; aged 25 to 62 years) were studied before and after a very-low-calorie-diet period of 8 weeks. PEF variability was determined as diurnal and day-to-day variations. FEV(1) and maximal expiratory flow values were measured with a flow-volume spirometer. Lung volumes, airways resistance (Raw), and specific airways conductance were measured using a constant-volume body plethysmograph. Minute ventilation was monitored in patients in supine and standing positions. RESULTS: As patients decreased their body mass index (SD) from 37.2 (3.7) to 32.1(4.2) kg/m(2) (p < 0. 001), diurnal PEF variation declined from 5.5% (2.4) to 4.5% (1.5) (p = 0.01), and day-to-day variation declined from 5.3% (2.6) to 3. 1% (1.3) (p < 0.005). The mean morning PEF, FEV(1), and FVC increased after weight loss (p = 0.001, p < 0.005, and p < 0.05, respectively). Flow rate at the middle part of FVC (FEF(25-75)) increased even when related to lung volumes (FEF(25-75)/FVC; p < 0. 05). Functional residual capacity and expiratory reserve volume were significantly higher after weight loss (p < 0.05 and p < 0.005, respectively). A significant reduction in Raw was found (p < 0.01). Resting minute ventilation decreased after weight loss (p = 0.01). CONCLUSION: Weight loss reduces airways obstruction as well as PEF variability in obese patients with asthma. The results suggest that obese patients benefit from weight loss by improved pulmonary mechanics and a better control of airways obstruction.

Recognition of misfolding proteins by PA700, the regulatory subcomplex of the 26 S proteasome.

The 26 S proteasome is a large protease complex that catalyzes the degradation of both native and misfolded proteins. These proteins are known to interact with PA700, the regulatory subcomplex of the 26 S proteasome, via a covalently attached polyubiquitin chain. Here we provide evidence for an additional ubiquitin-independent mode of substrate recognition by PA700. PA700 prevents the aggregation of three incompletely folded, nonubiquitinated substrates: the DeltaF-508 mutant form of cystic fibrosis transmembrane regulator, nucleotide binding domain 1, insulin B chain, and citrate synthase. This function does not require ATP hydrolysis. The stoichiometry required for this function, the effect of PA700 on the lag phase of aggregation, and the temporal specificity of PA700 in this process all indicate that PA700 interacts with a subpopulation of non-native conformations that is either particularly aggregation-prone or nucleates misassociation reactions. The inhibition of off-pathway self-association reactions is also reflected in the ability of PA700 to promote refolding of citrate synthase. These results provide evidence that, in addition to binding polyubiquitin chains, PA700 contains a site(s) that recognizes and interacts with misfolded or partially denatured polypeptides. This feature supplies an additional level of substrate specificity to the 26 S proteasome and a means by which substrates are maintained in a soluble state until refolding or degradation is complete.

Upright body position and weight loss improve respiratory mechanics and daytime oxygenation in obese patients with obstructive sleep apnoea.

To determine whether upright body position and weight loss would improve daytime gas exchange in moderately obese patients with obstructive sleep apnoea (OSAS), 13 patients with mild or moderate OSAS were studied before and after weight loss. Pulmonary function tests, arterial blood gases and respiratory gas analysis were measured prior to and after a very low calorie diet (VLCD) period of six weeks. Arterial blood gases were measured in supine and standing positions and closing volume in supine and sitting positions before and after weight loss. In the upright position, there was a significant increase in PaO2 (P<0.005) accompanied by a significant decrease in alveolar-arterial PO2 difference (P<0.005) and closing volume (P<0.05). The median weight loss was 11 kg (range 5-18). The number of desaturation episodes (four percentage units or more per hour during sleep) (ODI4) decreased (P<0.01) after weight loss. The change in PaO2 with weight loss correlated with the decrease in ODI4 (r=0.73, P<0.01). The increase in expiratory reserve volume (ERV) was closely related to the amount of weight lost (r=0.895, P<0.01). The results indicate that weight loss and upright body position improved daytime respiratory mechanics and gas exchange in obese patients with OSAS. The findings suggest that obesity plays an important role in the pathogenesis of daytime gas exchange disturbances in obese OSAS patients. The adoption of a more upright sleep posture might improve nocturnal oxygenation in obese patients with OSAS.

Mass spectrometric (HPLC/ESI--MS/MS) quantification of pyrimido[1,3-a]purin-10(3H)-one, a guanine adduct formed by reaction of malondialdehyde with DNA.

A high performance liquid chromatography/electrospray ionization tandem mass spectrometric (HPLC/ESI MS/MS) method has been developed for quantification of pyrimido[1,2-a]purin-10(3H)-one adducts from DNA. The method is based on acid-catalyzed cleavage of the adducts from DNA and the use of [2,3a,10-13C3]pyrimido[1,2-a]purin-10(3H)-one as an internal standard in the analysis. For this purpose the latter compound was prepared. Rate constants for the acid-catalyzed cleavage of pyrimido[1,2-a]purin-10(3H)-one from the corresponding 2'-deoxyribonucleoside were determined, and its hydrolytic stability and possible formation by a cross reaction between guanine and [2,3a,10]pyrimido[1,2-a]purin-10(3H)-one were studied.

Long-term treatment of ulcerative colitis with ciprofloxacin: a prospective, double-blind, placebo-controlled study.

BACKGROUND & AIMS: Although bacterial bowel flora may be one of the contributing factors in the pathogenesis of chronic mucosal inflammation, antibiotic treatment has no established role in ulcerative colitis. The aim of the study was to evaluate the role of ciprofloxacin in the induction and maintenance of remission in ulcerative colitis in patients responding poorly to conventional therapy with steroids and mesalamine. METHODS: Ciprofloxacin (n = 38; 500-750 mg twice a day) or placebo (n = 45) was administered for 6 months in a double-blind, randomized study with a high but decreasing dose of prednisone and maintenance treatment with mesalamine including follow-up for the next 6 months. Clinical assessment and colonoscopic evaluation were performed at 0, 3, 6, and 12 months. Treatment failure, the primary end point, was defined as both symptomatic and endoscopic failure to respond. RESULTS: During the first 6 months, the treatment-failure rate was 21% in the ciprofloxacin-treated group and 44% in the placebo group (P = 0.02). Endoscopic and histological findings were used as secondary end points and showed better results in the ciprofloxacin group at 3 months but not at 6 months. CONCLUSIONS: Addition of a 6-month ciprofloxacin treatment for ulcerative colitis improved the results of conventional therapy with mesalamine and prednisone.

Cholesterol metabolism and non-cholesterol sterols in patients with ileal pouch anastomosis.

BACKGROUND: Previous studies suggest only minor changes in bile acid metabolism after panproctocolectomy with ileal pouch construction. AIMS/METHODS: To investigate these changes further, we studied cholesterol absorption and serum, biliary and fecal non-cholesterol sterols and lipids in 12 ileal pouch patients and 10 controls. RESULTS: In patients, cholesterol absorption was markedly reduced and was associated with low serum total and LDL cholesterol and LDL triglyceride levels, but surprisingly, cholesterol synthesis, as indicated by sterol-balance data or serum cholesterol precursor levels, was within low normal limits. The high proportions of serum plant sterol to cholesterol, particularly that of campesterol, were not related to cholesterol absorption, but were attributable to a markedly reduced biliary cholesterol secretion. Interestingly, in these patients the fractional absorption of campesterol was normal, whereas that of sitosterol, like cholesterol, was reduced and was positively related to the intestinal influx of cholesterol. The patients' serum cholestanol proportion was normal, but the proportion of the cholestanol formed during intestinal passage was significantly reduced (17.9% vs 65.2% in controls). CONCLUSIONS: Thus ileal pouch patients are characterized by sterol malabsorption, lowered serum total and LDL-cholesterol levels, but unexpectedly without any increase in cholesterol synthesis. The lack of high serum cholestanol, shown earlier frequently in unoperated patients with ulcerative colitis, may indicate reversible cholestasis, a finding deserving further exploration.

Impaired absorption of cholesterol and bile acids in patients with an ileoanal anastomosis.

BACKGROUND: No data exist on cholesterol absorption in patients with an ileoanal anastomosis (IAA). AIMS: To study cholesterol absorption and its effects on cholesterol and bile acid metabolism in patients with an IAA. PATIENTS AND METHODS: Cholesterol absorption, and serum, biliary, and faecal lipids were studied in 24 patients with an IAA and 20 controls. RESULTS: Fractional cholesterol absorption was significantly lower in the patients (36% versus 47% in controls). Surprisingly, the calculated intestinal influx of endogenous cholesterol was reduced so that the absolute absorption of cholesterol was decreased; elimination of cholesterol as faecal neutral steroids remained normal. Thus, the slightly increased cholesterol synthesis was mainly due to increased faecal bile acid excretion, which, in turn, was associated with reduced absorption and biliary secretion of bile acids. Serum total and low density lipoprotein (LDL) cholesterol and LDL triglycerides were lower in the patients. Molar percentage and saturation index of biliary cholesterol were slightly higher in patients with an IAA. Proportions of secondary bile acids in bile and faeces were diminished, and faecal unidentified bile acids were higher in patients. CONCLUSIONS: Cholesterol absorption is significantly impaired in patients with an IAA, and is closely related to changes in serum and biliary lipids observed in these patients.

Improved gas exchange during exercise after weight loss in morbid obesity.

The aim of this study was to determine the effect of weight loss induced by 6 weeks very-low-calorie-diet (VLCD) and behavioural intervention on pulmonary gas exchange during exercise in non-smoking morbid obese (BMI>40 kg/m2) otherwise healthy patients. Seven obese patients underwent a maximal bicycle ergometer test with continuous analysis of expired air and arterial blood sampling before and after a mean weight loss of 18% (25.7 kg, range: 10-50 kg). Body mass index (BMI) decreased with weight loss from 46.6 (6.3) kg/m2 to 38.0 (4.7) kg/m2 (P<0.01). Oxygen consumption (VO2) at low and submaximal exercise levels decreased after weight reduction, but the change was not statistically significant. The peak oxygen consumption related to body weight (VO2/kg) increased 22% from the initial 16.2 (3.6) ml/min/kg to 19.8 (3.1) ml/min/kg (P<0.05). Decrease in VCO2 was significant at submaximal exercise level. Ventilatory equivalent for CO2 increased significantly after weight reduction (P<0.05). Standing up and light exercise resulted in a significant increase in the mean arterial oxygen tension (PaO2) (P<0.05) and a significant decrease in the mean alveolar-arterial difference P(A-a)O2 (P<0.05) when compared to supine values. The mean increase in PaO2 with weight loss was not significant. The peak P(A-a)O2 decreased significantly after weight reduction. In conclusion, weight reduction induced by VLCD and behavioural intervention without exercise therapy can improve gas exchange during exercise in morbid obesity. Increased wasted ventilation, and a tendency to alveolar hyperventilation, after weight loss may reflect a delay in the adaptation of regulation of breathing to rapid weight loss.

Serum cholesterol, cholesterol precursors and plant sterols in different inflammatory bowel diseases.

The role of cholestasis and ileal dysfunction on sterol metabolism was studied in 79 patients with inflammatory bowel diseases (IBDs) and in 23 irritable bowel syndrome (IBS) controls by determining serum sterol/cholesterol proportions. The sterols included cholesterol precursors (delta 8-cholestenol, desmosterol and lathosterol), markers of cholesterol synthesis, cholestanol and plant sterols (campesterol and sitosterol), markers of cholesterol absorption and biliary secretion. The IBD patients were subgrouped into distal ulcerative colitis (dUC, n = 21), pancolitis (pUC, n = 29), ileal Crohn's disease (iCD, n = 20) and colonic Crohn's disease (cCD, n = 9). The cholestanol proportions were increased in the 3 colonic IBD groups, up to two times in cCD patients and seven times in a case with clinically overt primary sclerosing cholangitis, but were within the control IBS levels in the patients with iCD. The sitosterol, but not campesterol, proportion was significantly increased only in the pUC group. In the iCD group only the serum precursor sterol proportions, especially those for delta 8-cholestenol and lathosterol, were elevated probably due to ileal dysfunction induced bile acid malabsorption and compensatorily increased cholesterol synthesis. In conclusion, the findings suggest that the increased cholestanol proportion in colonic IBD is determined mainly by impaired biliary elimination of this sterol, while in ileal affision the dominating change in sterol balance is activated cholesterol synthesis. Thus increased serum cholestanol is a novel finding in colonic IBD, apparently indicating the presence of subclinical cholestasis in a marked number (20-50%) of IBD patients.

Effect of weight loss and body position on pulmonary function and gas exchange abnormalities in morbid obesity.

OBJECTIVE: To determine, whether behavioral management of obesity including very-low-calorie-diet would produce weight loss enough to improve pulmonary mechanics and gas exchange in morbid obesity. DESIGN: Pulmonary function and arterial oxygenation were studied before and after weight loss in 11 patients attending a group therapy with the program of VLCD for 6 weeks and 16 weeks' behavioral intervention. MEASUREMENTS: Spirometry, diffusing capacity, body plethysmograph, closing volume and arterial blood gas analyses. RESULTS: The mean initial BMI was 45.4 kg/m2 (range 39.8-58.7 kg/m2) and decreased to 39.4 kg/m2 (range 31-49.8 kg/m2) (P < 0.01). Expiratory reserve volume (ERV) and functional residual capacity (FRC) improved significantly with weight loss. Closing capacity (CC) exceeded FRC in 10 cases of 11 at the initial stage, but after weight loss only in three patients. The mean arterial oxygen tension with the patients in supine position did not change after weight loss, but standing up improved PaO2 significantly before and after weight loss. CONCLUSION: The dietary treatment of morbid obesity was sufficient to induce improvement in lung volumes, but not enough to improve arterial oxygenation, although ventilatory mechanics was improved significantly and the tendency to early small airway closure was decreased. Hypoxemia was significantly relieved by standing up both before and after weight loss.

Triple therapy of Helicobacter pylori infection in peptic ulcer. A 12-month follow-up study of 93 patients.

This study was undertaken to evaluate the success of triple therapy in peptic ulcer patients and ulcer relapses. One hundred and one consecutive Helicobacter pylori-positive peptic ulcer patients were assigned to an open trial with 2 weeks of treatment with colloidal bismuth subcitrate, amoxicillin, and metronidazole. At the 6-week follow-up only 1 duodenal ulcer was unhealed of 57 active ulcers, and H. pylori was found to be eradicated in 84% of the 100 subjects. The sensitivity to metronidazole was determined from 71 pretreatment strains of H. pylori. Eradication of H. pylori succeeded in 89% of the patients with metronidazole-susceptible strains and in 61% of patients with metronidazole-resistant strains (p < 0.03). All 16 patients in whom the treatment failed to eradicate the organism had metronidazole-resistant strains after treatment. The ulcer relapse rate was low. At the 12-month follow-up of 93 patients only 1 of the 84 H. pylori-negative patients (including 4 patients after new successful therapy) had relapsing ulcers (2 asymptomatic episodes), and 1 had H. pylori reinfection, whereas 3 of the 9 bacteria-positive patients relapsed (p = 0.002); at the 2-year control 2 more patients had ulcer relapses. The eradication of H. pylori infection clearly prevents relapses of peptide ulcer, but the success of triple therapy depends on the frequency of pretreatment metronidazole-resistant H. pylori strains.

Metered-dose aerosolized bronchodilators in prehospital care: a feasibility study.

The prehospital use of aerosolized bronchodilators was studied in 50 adult patients with bronchospasm. The specific beta 2-agonist, albuterol, was discharged from a metered-dose inhaler (MDI) into the Inhal-aid reservoir-delivery device. No serious adverse effects were encountered, although a substantial proportion of the patients (36%) had difficulty utilizing the device. Ability to use the system properly correlated with improvement in symptoms; inability to use the device was most clearly related to severity of clinical presentation. It is concluded that the use of aerosolized bronchodilators is feasible in prehospital care and most useful in patients with mild or moderately severe symptoms.