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Background: Spinal cord compression is a rare presentation of non-Hodgkin lymphoma (NHL) in children. We aimed to describe the prevalence, histological subtypes, clinical presentation, therapy, and outcome of those children in a population-based cohort. The chemotherapy regimen remained comparable over time., Methods: We retrospectively identified all children and adolescents with paresis as initial manifestations of the NHL between January 1990 and December 2020 from the NHL-BFM database. Characteristics, therapy, and outcome data were gathered from the database and patient files., Results: Fifty-seven of 4779 children (1.2%) presented with initial paresis due to spinal cord compression. The median age was 10.3 years (range, 3.1-18.0 years), and 33% were female. Initial symptoms were paresis/weakness (n = 50, 88%), back pain (n = 33, 58%), paresthesia (n = 23, 40%), and bladder dysfunction and/or constipation (n = 22, 39%), persisting for a median of 14 days before diagnosis. Subtype distribution was mature B-NHL (n = 41, 72%), precursor B-lymphoblastic lymphoma (LBL) (n = 12, 21%), anaplastic large cell lymphoma (ALCL) (n = 3, 5%), and T-LBL (n = 1, 2%). Initial emergency therapy included surgery (70%) and/or chemotherapy/steroids (63%). Five-year event-free survival and overall survival (80% ± 5% and 82% ± 5%, respectively) were comparable with all other NHL patients. Neurological symptoms persisted in approximately one-third of surviving patients at the last follow-up., Conclusion: 1.2% of pediatric NHL patients presented with paresis from spinal cord compression mainly due to B-cell lymphomas. Neurological sequelae were observed in one-third of surviving patients., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Minimally processed vegetables (MPVs) are marketed as convenient and healthy choices for consumers. However, the absence of post-commercialization treatments raises concerns about their microbiological safety. This study investigated the processing practices of 28 Brazilian MPV plants and compared the microbiological quality of these products with fresh counterparts in the city of Sao Paulo, Brazil. Through cluster analysis, the processing plants were categorized into two groups: group 1 (nineteen plants) primarily uses chemical substances in the washing step, while group 2 (nine plants) avoids chemical use but employs similar rinsing practices. Microbiological analysis of 100 samples (49 unprocessed and 51 MPVs) revealed no significant differences in microbial group counts (Enterobacteriaceae, coliforms, and E. coli) between the in natura (unprocessed) and MPV products. However, the prevalence of E. coli was higher in natura vegetables than in MPVs. The results indicated the presence of Salmonella DNA (from either dead or live cells or residual DNA) in 4 samples (3 in natura and 1 MPV) using conventional PCR, suggesting the presence of the pathogen in these samples. Listeria monocytogenes was absent, but Listeria innocua was found in two unprocessed products. The study suggests that certain MPVs have microbial loads similar to unprocessed vegetables, potentially serving as carriers for pathogen transmission. These findings emphasize the importance of understanding practices in Brazilian MPV processing plants, informing the implementation of control measures to improve MPV safety and shelf-life, thus ensuring microbiological safety., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

While survival has improved for Burkitt lymphoma patients, potential differences in outcome between pediatric and adult patients remain unclear. In both age groups, survival remains poor at relapse. Therefore, we conducted a comparative study in a large pediatric cohort, including 191 cases and 97 samples from adults. While TP53 and CCND3 mutation frequencies are not age related, samples from pediatric patients showed a higher frequency of mutations in ID3, DDX3X, ARID1A and SMARCA4, while several genes such as BCL2 and YY1AP1 are almost exclusively mutated in adult patients. An unbiased analysis reveals a transition of the mutational profile between 25 and 40 years of age. Survival analysis in the pediatric cohort confirms that TP53 mutations are significantly associated with higher incidence of relapse (25 ± 4% versus 6 ± 2%, p-value 0.0002). This identifies a promising molecular marker for relapse incidence in pediatric BL which will be used in future clinical trials., (© 2022. The Author(s).)

Sporadic Burkitt lymphoma (BL) is the most frequent tumour of children and adolescents but a rare subtype of lymphomas in adults. To date most molecular data have been obtained from lymphomas arising in the young. Recently, Epstein-Barr virus (EBV) positive and negative BL in young patients was shown to differ in molecular features. In the present study, we present a large age-overarching cohort of sporadic BL (n = 162) analysed by immunohistochemistry, translocations of MYC proto-oncogene, basic helix-loop-helix transcription factor (MYC), B-cell leukaemia/lymphoma 2 (BCL2) and B-cell leukaemia/lymphoma 6 (BCL6) and by targeted sequencing. We illustrate an age-associated inter-tumoral molecular heterogeneity in this disease. Mutations affecting inhibitor of DNA binding 3, HLH protein (ID3), transcription factor 3 (TCF3) and cyclin D3 (CCND3), which are highly recurrent in paediatric BL, and expression of sex determining region Y-box transcription factor 11 (SOX11) declined with patient age at diagnosis (P = 0·0204 and P = 0·0197 respectively). In contrast, EBV was more frequently detected in adult patients (P = 0·0262). Irrespective of age, EBV-positive sporadic BL showed significantly less frequent mutations in ID3/TCF3/CCND3 (P = 0·0088) but more often mutations of G protein subunit alpha 13 (GNA13; P = 0·0368) and forkhead box O1 (FOXO1; P = 0·0044) compared to EBV-negative tumours. Our findings suggest that among sporadic BL an EBV-positive subgroup of lymphomas increases with patient age that shows distinct pathogenic features reminiscent of EBV-positive endemic BL., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Aims: This study evaluated the microbiological quality and safety of minimally processed parsley sold in southeastern Brazilian food markets., Methods and Results: One hundred samples were submitted to the enumeration of Enterobacteriaceae by plating on MacConkey agar. Colonies of Enterobacteriaceae were randomly selected and identified by MALDI-TOF MS. Samples were also tested for Listeria monocytogenes and Salmonella sp. The mean count of Enterobacteriaceae was 6·0 ± 1·0 log CFU per gram, while 18 genera (including 30 species) of bacteria belonging to this family were identified. Salmonella and L. monocytogenes were not detected, while L. innocua was found in two samples and L. fleischmannii was found in one sample. Moreover generic Escherichia coli was found in three samples, all from different brands of minimally processed parsley., Conclusions: Even though microbial pathogens were not isolated, a variety of indicator micro-organisms were identified, including vegetable spoilers and species capable of causing human opportunistic infections. These results suggest hygienic failures and/or lack of temperature control during processing and storage of these ready-to-eat products., Significance and Impact of Study: This study highlights the need for control measures during the production chain of minimally processed parsley in order to reduce microbial contamination and the risks of foodborne diseases., (© 2020 The Society for Applied Microbiology.)

Food Microbiology is included in majors such as Food Engineering, Food Science and Technology, Nutrition, Veterinary Medicine, Gastronomy, Pharmaceutical Sciences, among others. Food safety and hygiene are usually the focus, but the technological applications of microbes through fermentations are also covered. During an education symposium at the Brazilian Congress of Microbiology in 2017, a group of professors expressed their difficulties associated with teaching to new generations, the use of technology in the classroom, and the application of new learning tools. The objective of this study was to gather information about the educational practices among Brazilian professors who teach Food Microbiology throughout the country. The results indeed confirmed the diversity of careers in which food microbiology is taught. We verified that professors mixed traditional teaching strategies with modern active learning methods, even though some difficulties associated with lack of time, pedagogical training, and low adherence of students for adopting these modern methods were commonly highlighted. The preferred teaching approaches were dialogued or discussed lectures, seminars, homework, case studies, and field visits. It is noteworthy that most professors still use traditional teaching methods. It is crucial that awareness concerning the educational needs in different careers and the challenges and dilemmas facing education for the new generations should be dealt with by using effective teaching approaches in food microbiology education. We suggest that a more permanent discussion forum among faculty members dealing with food microbiology in the country should be launched and this work is a step towards this goal.

This study aims to quantify the extent of electrolyte (potassium, magnesium, and phosphorus) and blood glucose changes during targeted temperature management (TTM), with insight on electrolyte replacements and insulin administration. This was a 3-year retrospective study of patients who underwent TTM via Arctic Sun. Electrolyte and blood glucose values in addition to electrolyte replacements and insulin administrations were collected before, during, and post-TTM. The primary analysis assessed changes in electrolyte and blood glucose values during and after TTM, and the secondary analysis assessed changes before and during, and before and after TTM. The secondary analysis also incorporated amount of electrolyte replacements and insulin administrations patients received before, during, and post-TTM. Sixty patients were included for analysis. Comparing levels during to after TTM, there was a significant increase in potassium (3.7 [0.7]-4.4 [0.7] mmol/L, p  < 0.001) and decrease in blood glucose (192 [135]-134 [55] mg/dL, p  = 0.001). Comparing levels before to during TTM, there was a significant decrease in potassium (4.3 [0.7]-3.7 [0.7] mmol/L, p  < 0.001) and phosphorus (4.8 [3.2]-3.4 [1.5] mg/dL, p  = 0.003). Comparing levels before to after TTM, there was a significant decrease in phosphorus (4.5 [2.9]-3.3 [1.2] mmol/L, p  = 0.026) and blood glucose (219 [35]-134 [55] mg/dL, p  < 0.001). Patients received on average potassium 102 mEq, magnesium 1.9 g, phosphorus 9 mmol, and insulin 94 units. Potassium significantly decreased during and significantly increased after TTM. Phosphorus significantly decreased during TTM and blood glucose significantly decreased after TTM. There were no significant changes in magnesium during the defined time period.

This study aimed at estimating the prevalence in adults of complying with the aerobic physical activity (PA) recommendation through transportation-related walking and cycling. Furthermore, potential determinants of transportation-related PA recommendation compliance were investigated. 10,872 men and 13,144 women aged 18 years or older participated in the cross-sectional 'German Health Update 2014/15 - EHIS' in Germany. Transportation-related walking and cycling were assessed using the European Health Interview Survey-Physical Activity Questionnaire. Three outcome indicators were constructed: walking, cycling, and total active transportation (≥600 metabolic equivalent, MET-min/week). Associations were analyzed using multilevel regression analysis. Forty-two percent of men and 39% of women achieved ≥600 MET-min/week with total active transportation. The corresponding percentages for walking were 27% and 28% and for cycling 17% and 13%, respectively. Higher population density, older age, lower income, higher work-related and leisure-time PA, not being obese, and better self-perceived health were positively associated with transportation-related walking and cycling and total active transportation among both men and women. The promotion of walking and cycling among inactive people has great potential to increase PA in the general adult population and to comply with PA recommendations. Several correlates of active transportation were identified which should be considered when planning public health policies and interventions.

Thrombosis within the membrane oxygenator (MO) during extracorporeal membrane oxygenation (ECMO) can lead to sudden oxygenator dysfunction with deleterious effects to the patient. The purpose of this study was to identify predictors of circuit exchange during ECMO. This is a single-center, retrospective study of all patients who received ECMO at our institution from January 2010 to December 2015. Changes in potential markers were compared on Day 3 vs. Day 0 before MO exchange. Of the 150 patients who received ECMO, there were 58 MO exchanges in 35 patients. Mean ECMO duration was 21.1 (±12.7) days. D-dimer (DD) (μg/mL) (mean difference -2.6; 95% confidence interval [CI]: -4.2 to -1.1; p = .001) increased significantly in the 3 days leading up to MO exchange, whereas fibrinogen (mg/dL) (mean difference 90.7; 95% CI: 41.8-139.6; p = .001), platelet (PLT) count (1,000/μL) (mean difference 23.3; 95% CI: 10.2-36.4; p = .001), and heparin dose (units/h) (mean difference 261.7; 95% CI: 46.3-477.1; p = .02) decreased. Increasing DD or decreasing fibrinogen, PLT count, or heparin dose may indicate an impending need for MO exchange in patients receiving ECMO. Early identification of these changes may help prevent sudden MO dysfunction.

GSK2982772 is a highly selective inhibitor of receptor-interacting protein kinase 1 (RIPK1) being developed to treat chronic inflammatory diseases. This first-in-human study evaluated safety, tolerability, pharmacokinetics (PK), and exploratory pharmacodynamics (PD) of GSK2982772 administered orally to healthy male volunteers. This was a Phase I, randomized, placebo-controlled, double-blind study. In Part A, subjects received single ascending doses of GSK2982772 (0.1-120 mg) or placebo in a crossover design during each of 4 treatment periods. In Part B, subjects received repeat doses of GSK2982772 (20 mg once daily [QD] to up to 120 mg twice daily [BID]) or placebo for 14 days. Part C was an open-label relative bioavailability study comparing 20-mg tablets vs capsules. Safety, tolerability, pharmacokinetics (PK), RIPK1 target engagement (TE), and pharmacodynamics (PD) were assessed. The most common adverse events (AEs) were contact dermatitis and headache. Most AEs were mild in intensity, and there were no deaths or serious AEs. The PK of GSK2982772 was approximately linear over the dose range studied (up to 120 mg BID). There was no evidence of drug accumulation upon repeat dosing. Greater than 90% RIPK1 TE was achieved over a 24-hour period for the 60-mg and 120-mg BID dosing regimens. Single and repeat doses of GSK2982772 were safe and well tolerated. PK profiles showed dose linearity. The high levels of RIPK1 TE support progression into Phase II clinical trials for further clinical development., (© 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Background: This methodological paper describes the integration of the 'European Health Interview Survey wave 2' (EHIS 2) into the 'German Health Update' 2014/2015 (GEDA 2014/2015-EHIS)., Methods: GEDA 2014/2015-EHIS is a cross-sectional health survey. A two-stage stratified cluster sampling approach was used to recruit persons aged 15 years and older with permanent residence in Germany. Two different modes of data collection were used, self-administered web questionnaire and self-administered paper questionnaire. The survey instrument implemented the EHIS 2 modules on health status, health care use, health determinants and social background variables and additional national questions. Data processing was conducted according to the quality and validation rules specified by Eurostat., Results: In total, 24,824 questionnaires were completed. The response rate was 27.6%. The two-stage cluster sample method seems to have been successful in achieving a sample with high representativeness. The final micro data file was inspected, approved and certified by Eurostat. Access to micro data of the EHIS 2 can be provided by Eurostat via research contract and to the GEDA 2014/2015-EHIS public use file by the Research Data Centre of the Robert Koch Institute. First EHIS 2 results are available at the Eurostat website., Conclusions: Integrating a multinational health survey into an existing national health monitoring system was a challenge in Germany. The national survey methodology for conducting the survey had to be further developed in order to meet the overarching goal of harmonizing the health information from national statistical offices and public health research institutes across the European Union. The harmonized EHIS 2 data source will profoundly impact international public health research in the near future. The next EHIS wave 3 will be conducted around 2019.

Background and Purpose: Intracerebral hemorrhage leads to disability or death with few established treatments. Adverse outcomes after intracerebral hemorrhage result from irreversible damage to neurons resulting from primary and secondary injury. Secondary injury has been attributed to hemoglobin and its oxidized product hemin from lysed red blood cells. The aim of this study was to identify the underlying cell death mechanisms attributable to secondary injury by hemoglobin and hemin to broaden treatment options., Methods: We investigated cell death mechanisms in cultured neurons exposed to hemoglobin or hemin. Chemical inhibitors implicated in all known cell death pathways were used. Identified cell death mechanisms were confirmed using molecular markers and electron microscopy., Results: Chemical inhibitors of ferroptosis and necroptosis protected against hemoglobin- and hemin-induced toxicity. By contrast, inhibitors of caspase-dependent apoptosis, protein or mRNA synthesis, autophagy, mitophagy, or parthanatos had no effect. Accordingly, molecular markers of ferroptosis and necroptosis were increased after intracerebral hemorrhage in vitro and in vivo. Electron microscopy showed that hemin induced a necrotic phenotype. Necroptosis and ferroptosis inhibitors each abrogated death by >80% and had similar therapeutic windows in vitro., Conclusions: Experimental intracerebral hemorrhage shares features of ferroptotic and necroptotic cell death, but not caspase-dependent apoptosis or autophagy. We propose that ferroptosis or necroptotic signaling induced by lysed blood is sufficient to reach a threshold of death that leads to neuronal necrosis and that inhibition of either of these pathways can bring cells below that threshold to survival., (© 2017 American Heart Association, Inc.)

Background: Only few studies have focused on the cognitive processes of the respondents that are involved when answering physical activity questionnaires (PAQs). This study aimed at examining whether two PAQs work as intended with different segments of the survey population in different cultural settings in Europe., Methods: The International Physical Activity Questionnaire - Short Form (IPAQ-SF) and the US National Health Interview Survey - Adult Core Physical Activity Questionnaire (NHIS-PAQ) were tested in Belgium, Estonia, Germany and the UK using a standardized cognitive interviewing procedure. IPAQ-SF measures total vigorous physical activity (PA), moderate PA, walking and sitting. NHIS-PAQ measures leisure-time vigorous PA, light and moderate PA and muscle-strengthening PA. In total 62 persons completed cognitive interviews, at least 15 interviews were conducted in each country., Results: Both PAQs performed as intended with young and high-skilled persons and those having a regular exercise schedule. For the others, however, the testing revealed that problems occurred with both PAQs relating to understanding the concepts of '(light and) moderate' and 'vigorous' PA, classifying activities into the provided answer options of different PA intensities, recalling instances of 'normal' activities such as walking and sitting, and calculating the total duration of more than one activity or instance of an activity. The revealed problems with the questionnaires were quite similar in different countries; profound cultural differences were not observed., Conclusions: Both questionnaires were difficult to answer for many respondents and rather user-unfriendly. They are designed to measure an exactness of PA quantity (frequency and duration) and intensity which would be desirable to obtain from a scientific point of view; however, respondents can hardly provide this information for cognitive reasons. Studies investigating the respondents' perspective are useful for improving physical activity information based on self-reports.

CARMA-BCL10-MALT1 signalosomes play important roles in antigen receptor signaling and other pathways. Previous studies have suggested that as part of this complex, MALT1 functions as both a scaffolding protein to activate NF-κB through recruitment of ubiquitin ligases, and as a protease to cleave and inactivate downstream inhibitory signaling proteins. However, our understanding of the relative importance of these two distinct MALT1 activities has been hampered by a lack of selective MALT1 protease inhibitors with suitable pharmacologic properties. To fully investigate the role of MALT1 protease activity, we generated mice homozygous for a protease-dead mutation in MALT1. We found that some, but not all, MALT1 functions in immune cells were dependent upon its protease activity. Protease-dead mice had defects in the generation of splenic marginal zone and peritoneal B1 B cells. CD4+ and CD8+ T cells displayed decreased T cell receptor-stimulated proliferation and IL-2 production while B cell receptor-stimulated proliferation was partially dependent on protease activity. In dendritic cells, stimulation of cytokine production through the Dectin-1, Dectin-2, and Mincle C-type lectin receptors was also found to be partially dependent upon protease activity. In vivo, protease-dead mice had reduced basal immunoglobulin levels, and showed defective responses to immunization with T-dependent and T-independent antigens. Surprisingly, despite these decreased responses, MALT1 protease-dead mice, but not MALT1 null mice, developed mixed inflammatory cell infiltrates in multiple organs, suggesting MALT1 protease activity plays a role in immune homeostasis. These findings highlight the importance of MALT1 protease activity in multiple immune cell types, and in integrating immune responses in vivo.

Receptor-interacting protein kinase 3 (RIP3 or RIPK3) has emerged as a central player in necroptosis and a potential target to control inflammatory disease. Here, three selective small-molecule compounds are shown to inhibit RIP3 kinase-dependent necroptosis, although their therapeutic value is undermined by a surprising, concentration-dependent induction of apoptosis. These compounds interact with RIP3 to activate caspase 8 (Casp8) via RHIM-driven recruitment of RIP1 (RIPK1) to assemble a Casp8-FADD-cFLIP complex completely independent of pronecrotic kinase activities and MLKL. RIP3 kinase-dead D161N mutant induces spontaneous apoptosis independent of compound, whereas D161G, D143N, and K51A mutants, like wild-type, only trigger apoptosis when compound is present. Accordingly, RIP3-K51A mutant mice (Rip3(K51A/K51A)) are viable and fertile, in stark contrast to the perinatal lethality of Rip3(D161N/D161N) mice. RIP3 therefore holds both necroptosis and apoptosis in balance through a Ripoptosome-like platform. This work highlights a common mechanism unveiling RHIM-driven apoptosis by therapeutic or genetic perturbation of RIP3., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We report on the effect of pulse to pulse interactions during percussion drilling of steel using high power ps-laser radiation with repetition rates of up to 10 MHz and high average powers up to 80 W. The ablation rate per pulse is measured as a function of the pulse repetition rate for four fluences ranging from 500 mJ/cm2 up to 1500 mJ/cm2. For every investigated fluence an abrupt increase of the ablation rate per pulse is observed at a distinctive repetition rate. The onset repetition rate for this effect is strongly dependent on the applied pulse fluence. The origin of the increase of the ablation rate is attributed to the emergence of a melt based ablation processes, as Laser Scanning Microscopy (LSM) images show the occurrence of melt ejected material surrounding the drilling holes. A semi empirical model based on classical heat conduction including heat accumulation as well as pulse-particle interactions is applied to enable quantitative conclusions on the origin of the observed data. In agreement with previous studies, the acquired data confirm the relevance of these two effects for the fundamental description of materials processing with ultra-short pulsed laser radiation at high repetition rates and high average power.

Physical activity during childhood and adolescence has numerous health benefits, while sedentary behavior, especially electronic media use, is associated with the development of overweight. Therefore, the promotion of physical activity during childhood and adolescence is an integral part of national public health efforts. The aim of this article is to describe the physical activity behavior of German children and adolescents based on the nationwide data of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS wave 1). Furthermore, the association between physical activity and sports participation and use of screen-based media in youth aged 11 to 17 years was analyzed. The analyses included data from 10,426 children and adolescents aged 3-17 years collected by telephone interviews. Children older than 11 years answered the questions by themselves, whereas a parent was interviewed for younger children. The descriptive analyses were performed under consideration of social and demographic factors. According to the results of KiGGS wave 1 a total of 77.5% (95% Cl 76.0-78.9 %) of the children and adolescents participated in sports activities, and 59.7% (58.1-61.3 %) were members of a sports club. The recommendation of the World Health Organization (WHO) to be physically active at least 60 min per day was achieved by 27.5% (26.0-28.9 %). Children and adolescents with a low socioeconomic status (SES) participated less in sports activities than children of higher SES groups. Excessive use of screen-based media was more likely to be associated with lack of sports participation than with a lack of physical activity. In the future, preventive measures should promote the daily physical activity of children and adolescents and additionally encourage children and adolescents with low SES to participate in sports activities.

RIP1 (RIPK1) kinase is a key regulator of TNF-induced NF-κB activation, apoptosis, and necroptosis through its kinase and scaffolding activities. Dissecting the balance of RIP1 kinase activity and scaffolding function in vivo during development and TNF-dependent inflammation has been hampered by the perinatal lethality of RIP1-deficient mice. In this study, we generated RIP1 kinase-dead (Ripk1(K45A)) mice and showed they are viable and healthy, indicating that the kinase activity of RIP1, but not its scaffolding function, is dispensable for viability and homeostasis. After validating that the Ripk1(K45A) mice were specifically protected against necroptotic stimuli in vitro and in vivo, we crossed them with SHARPIN-deficient cpdm mice, which develop severe skin and multiorgan inflammation that has been hypothesized to be mediated by TNF-dependent apoptosis and/or necroptosis. Remarkably, crossing Ripk1(K45A) mice with the cpdm strain protected against all cpdm-related pathology. Together, these data suggest that RIP1 kinase represents an attractive therapeutic target for TNF-driven inflammatory diseases., (Copyright © 2014 by The American Association of Immunologists, Inc.)

Regular physical activity can have a positive effect on health at any age. Today's lifestyles, however, can often be characterised as sedentary. Therefore, the promotion of physical activity and sports has become an integral part of public health measures. The representative data of adults aged 18 to 79 years in Germany obtained from the "German Health Interview and Examination Survey for Adults" (DEGS1) provide an overview of self-estimated current physical activity behaviour. The results show that one third of the adult population claims to pay close attention to reaching a sufficient level of physical activity and one fourth participates in sports for at least 2 h/week on a regular basis. Thus, the percentage of adults regularly engaged in sports has increased compared to the previous "German National Health Interview and Examination Survey 1998". Still, four out of five adults do not achieve at least 2.5 h/week of moderate-intensity physical activity as recommended by the World Health Organisation. Consequently, future individual-level and population-level interventions should focus on target group-specific measures while continuing to promote regular physical activity in all segments of the population. An English full-text version of this article is available at SpringerLink as supplemental.

A high level of fitness is an indicator for a good health state. Therefore, cardiorespiratory fitness was examined in the cross-sectional German Health Interview Survey for Adults (DEGS1). Data from 3030 test-qualified adults between 18 and 64 years old were assessed by means of a standardized submaximal cycle ergometer test. Test-qualified participants were significantly younger, more often men, less often obese and showed a better health state than those who were not test-qualified. The calculated physical work capacity at 75 % of the age-predicted maximum heart rate (PWC75%) in watts per kg bodyweight was among men 1.52 and among women 1.15. PWC75% declines by 4.2 % per age decade for men and 4.8 % for women. A higher socioeconomic status (SES) is associated with better fitness among women. No significant association was observed between SES and fitness among men. These findings can be used to develop target-group specific health-promotion interventions in order to enhance cardiorespiratory fitness. It is planned to calculate updated PWC reference values based on the DEGS1 data. An English full-text version of this article is available at SpringerLink as supplemental.

A state of good fitness is related to a better health state and a lower mortality risk. In the German Health Interview and Examination Survey for Adults (DEGS1), aerobic fitness was measured among adults between 18 and 64 years old using a submaximal cycle ergometry test. The total sample comprised 5,263 persons, amongst those 3,111 were categorized as being test-qualified according to the Physical Activity Readiness-Questionnaire. There were 3,030 persons who absolved a submaximal exercise test according to the exercise protocol of the WHO (25/25/2). The test-participation rate was 57.2 % in relation to the total sample and 97.4 % among test-qualified persons. Apart from the continuous heart-rate monitoring, capillary blood was taken prior to starting the test and at the end of each workload stage for performing blood lactate analyses. The test ended when 85 % of the age-predicted maximal heart rate was exceeded. In all 11.9 % of the tests were terminated earlier, the mean exercise duration was 10.8 min, and the anticipated submaximal exertion in the highest workload stage was on average achieved with a mean of 15 on the 20-point RPE scale. The nationwide data can now be used for the national health monitoring system, epidemiological research and for the calculation of reference values. An English full-text version of this article is available at SpringerLink as supplemental.

New product development involves people with different backgrounds. Designers, engineers, and consumers all have different criteria, and these criteria interact. Early concepts evolve in this kind of collaborative context, and there is a need for dynamic visualization of the interaction between design shape and other shape-related design criteria. In this paper, a Morphable Model is defined from simplified representations of suitably chosen real cars, providing a continuous shape space to navigate, manipulate, and visualize. Physical properties and consumer-provided scores for the real cars (such as 'weight' and 'sportiness') are estimated for new designs across the shape space. This coupling allows one to manipulate the shape directly while reviewing the impact on estimated criteria, or conversely, to manipulate the criterial values of the current design to produce a new shape with more desirable attributes.

Many studies have reported quantitative trait loci on chromosome 6 that affect milk production traits in dairy cattle. Osteopontin (OPN) and peroxisome proliferator activated receptor gamma coactivator 1 alpha (PPARGC1A) are located in the middle of chromosome 6 about 6 Mb apart, which is approximately 12 cM. The objective of this study was to investigate the association of OPN and PPARGC1A variants with milk production traits in 2 independent Holstein cattle populations: the University of Wisconsin (UW) daughter design and the Cooperative Dairy DNA Repository (CDDR) granddaughter design resource populations. For OPN, 891 cows from the UW resource population were genotyped for the C/T polymorphism reported previously in the CDDR population. Additive effects were significant for fat percentage, protein percentage, and fat yield in the UW resource population. These results are consistent with previous studies that have shown significant association of OPN variants with milk composition traits. The association between PPARC1A variants was investigated in UW and CDDR resource populations using 2 single nucleotide polymorphisms. For the UW resource population, additive effects were significantly increased for protein percentage and decreased for milk yield. Dominance effects were not significant for any of the examined traits. For the CDDR population, PPARGC1A was associated with a significant increase in milk protein percentage and in SCS. Thus, in UW and CDDR populations, PPARGC1A was associated with a significant increase in milk protein percentage in contrast to association results previously reported for the German Holstein population.

Objective: To evaluate the efficacy of epidural morphine in treating heroin withdrawal in patients who failed to detoxify by the other methods., Design: Prospective study., Setting: Department of Psychiatry of a general hospital., Patients: 8 ASA physical status I patients, aged 26 to 42 years, not having concurrent diseases requiring medication, and who had previously failed other methods of detoxification., Interventions: Epidural catheters were inserted at the L(3)-L(4) interspace. Bolus injections of morphine sulfate, 3.0 mg in normal saline, were administered epidurally at 24-hour intervals. Treatment continued for 10 to 12 days., Measurements: Withdrawal symptoms, such as mydriasis, insomnia, rhinorrhea, arthralgia, muscular pain, tooth pain, vomiting, diarrhea, dysphoria, and drug craving were monitored., Main Results: Withdrawal symptoms ceased within 10 days. Withdrawal symptoms were diminished or entirely abolished by the treatment, and no patient requested to drop out of the program. Discontinuation of the epidural injections did not cause relapse of withdrawal. All patients reported that withdrawal with epidural morphine was considerably easier compared to other methods that they had previously experienced., Conclusions: A preliminary evaluation of epidural morphine in addicts that failed previous detoxifications showed high effectiveness of this method in reducing withdrawal symptoms.

Sphingosine-1-phosphate (SPP) can constrict isolated intrarenal blood vessels in vitro and reduce renal blood flow in vivo. The present study has investigated the role of extracellular Ca2+ and dihydropyridine-sensitive Ca2+ channels in SPP-induced renovascular contraction. In isolated intrarenal microvessels, cumulative addition of SPP (0.1-100 microM) caused concentration-dependent vasoconstriction (maximum effect 5.0 +/- 1.1 mN). In the presence of nifedipine (300 nM, added 30 min before SPP) or EGTA (5 mM, added 1 min before SPP), SPP-induced vasoconstriction was almost completely abolished. In thiobutabarbitone-anaesthetized rats, i.v. bolus injections of SPP (1-100 microg/kg) dose-dependently lowered renal blood flow from basal values of approximately 4.8 ml/min by up to 2.2 +/- 0.2 ml/min but had only little effect on mean arterial pressure. Pretreatment with nifedipine (10-100 microg/kg per min, i.v.) dose-dependently attenuated SPP-induced renal blood flow reductions. We conclude that SPP-induced renovascular contraction requires the influx of extracellular Ca2+ which may occur largely via nifedipine-sensitive L-type Ca2+ channels.

To evaluate patients with gallbladder polyps and to compare them with patients with chronic acalculous cholecystitis, 301 patients with chronic acalculous disease of the gallbladder, of which 45 had polyp disease of the gallbladder, were reviewed out of 7181 cholecystectomies performed from June 1985 through June 1995. Of the 45 patients, 30 (Group A) were diagnosed preoperatively by ultrasound and 15 (Group B) postoperatively on pathologic examination. In each group, the most common polyp was cholesterol type (19/45) with multiple lesions in 10 of these 19 patients. Chronic cholecystitis was present elsewhere in the gallbladder in 40 per cent of Group A and 80 per cent of Group B patients (P = 0.02). Forty-three patients had polyps less than 5 mm in diameter, one a 1.5-cm gallbladder cholesterol polyp, and one a 1.3-cm tubulovillous polyp with a focus of carcinoma in situ. During this same period, 17 patients had primary malignancy of the gallbladder, none of which were found in polypoid lesions. In Group A patients there were significantly fewer preoperative tests than in typical acalculous patients [2.3 versus 3.8 (P<0.03)], including upper endoscopy (P<0.02) and hepatobiliary scintigraphy (P<0.00001). Of the patients with polyps, 42 of 45 (93.3%) had resolution of symptoms postoperatively with a mean follow-up of 178.9+/-505.0 days (range 1-2438 days). Most patients with biliary tract symptoms and a small (<5-mm) gallbladder polyp underwent fewer preoperative diagnostic tests than patients with chronic acalculous cholecystitis. This abbreviated preoperative workup appears warranted in view of the high incidence of symptom resolution.

Three radiation-induced alleles of the mouse p locus, p6H, p25H, and pbs, cause defects in growth, coordination, fertility, and maternal behavior in addition to p gene-related hypopigmentation. These alleles are associated with disruption of the p gene plus an adjacent gene involved in the disorders listed. We have identified this adjacent gene, previously named rjs (runty jerky sterile), by positional cloning. The rjs cDNA is very large, covering 15,264 nucleotides. The predicted rjs-encoded protein (4,836 amino acids) contains several sequence motifs, including three RCC1 repeats, a structural motif in common with cytochrome b5, and a HECT domain in common with E6-AP ubiquitin ligase. On the basis of sequence homology and conserved synteny, the rjs gene is the single mouse homolog of a previously described five- or six-member human gene family. This family is represented by at least two genes, HSC7541 and KIAA0393, from human chromosome 15q11-q13. HSC7541 and KIAA0393 lie close to, or within, a region commonly deleted in most Prader-Willi syndrome patients. Previous work has suggested that the multiple phenotypes in rjs mice might be due to a common neuroendocrine defect. In addition to this proposed mode of action, alternative functions of the rjs gene are evaluated in light of its known protein homologies.

The recessive mutation at the pale ear (ep) locus on mouse chromosome 19 was found to be the homologue of human Hermansky-Pudlak syndrome (HPS). A positional cloning strategy using yeast artificial chromosomes spanning the HPS locus was used to identify the HPS gene and its murine counterpart. These genes and their predicted proteins are highly conserved at the nucleotide and amino acid levels. Sequence analysis of the mutant ep gene revealed the insertion of an intracisternal A particle element in a protein-coding 3' exon. Here we demonstrate that mice with the ep mutation exhibit abnormalities similar to human HPS patients in melanosomes and platelet-dense granules. These results establish an animal model of HPS and will facilitate biochemical and molecular analyses of the functions of this protein in the membranes of specialized intracellular organelles.

Background and Objectives: The aim of the study was to determine the effect of epidural bupivacaine block on midazolam hypnotic requirements., Methods: Sixty unpremedicated, ASA physical status I or II male patients, aged 45-65 years and scheduled for elective lower abdominal, pelvic, or lower limb surgery participated in this randomized, double-blind, placebo-controlled study. The study population was composed of three groups: Before administration of midazolam, patients in the first group received an intramuscular injection of 15 mL saline (M), those in the second group an intramuscular injection of 15 mL 0.5% bupivacaine (MIB), and those in the third group an epidural injection of 15 mL 0.5% bupivacaine at the L3-L4 level (MEB). Loss of the ability to respond to verbal command was used as an endpoint for the effect of midazolam injected intravenously in predetermined doses (five patients per dose) 30 minutes after a bupivacaine (or saline) injection. Midazolam dose-response curves were obtained by probit analysis., Results: The midazolam median effective dose values for the hypnotic effect were 0.20 mg/kg (95% confidence limit, 0.10-0.27 mg/kg) in the M group; 0.10 mg/kg (0.06-0.22 mg/kg) in the MIB group; and 0.04 mg/kg (0.03-0.07 mg/kg) in the MEB group. The differences between the midazolam median effective dose values had high levels of significance: P < .00001 for MEB versus M, P < .002 for MEB versus MIB, and P < .01 for MIB versus M., Conclusions: Epidural bupivacaine block profoundly decreases midazolam hypnotic requirements. The most likely explanation for this effect is the reduction in afferent input induced by the block.

Study Objective: To test the hypothesis that subarachnoid bupivacaine blockade decreases hypnotic requirements for thiopental sodium and midazolam., Design: Randomized, double-blind, placebo-controlled study., Setting: Teaching hospital., Patients: 53 nonpremedicated ASA physical status I and II adult male patients scheduled for elective lower abdominal, pelvic, or lower limb surgery., Interventions: Intravenous injections of midazolam or thiopental were administered with or without subarachnoid bupivacaine blockade (12.5 mg) at the L3-L4 level. Thiopental or midazolam hypnotic requirements were determined using loss of ability to open eyes in response to verbal command as an endpoint. The thiopental requirements were determined by titration; the midazolam requirements were determined from dose-response curves obtained with bolus injections of predetermined doses of the drug., Measurements and Main Results: Subarachnoid bupivacaine blockade decreased the hypnotic dose of thiopental from 3.40 +/- 0.68 mg/kg (mean +/- SD) with a dose range of 2.3 to 4.5 mg/kg (intramuscular saline) to 2.17 +/- 0.48 mg/kg with a dose range of 1.3 to 2.8 mg/kg (p < 0.005 for the difference). The ED50 value of midazolam decreased with the bupivacaine blockade, from 0.23 mg/kg (95% confidence limits: 0.08 to 0.38 mg/kg) to 0.06 mg/kg (0.01 to 0.14 mg/kg), with p < 0.0001 for the difference., Conclusion: Subarachoid bupivacaine blockade decreases hypnotic requirements for both thiopental and midazolam. The results suggest that the reduction in hypnotic requirements is due to the decrease in afferent input induced by spinal anesthesia.

The aim of this study was to test the hypothesis that the induction and maintenance of anesthesia with the use of fentanyl or ketamine reduces postoperative pain and wound hyperalgesia beyond the period when these effects can be explained by the direct analgesic action of these drugs. Twenty-seven patients scheduled for elective hysterectomy were investigated in a double-blind, randomized study. Patients were divided into three groups. In the fentanyl group, anesthesia was induced with fentanyl 5 micrograms/kg combined with thiopental 3 mg/kg and maintained with isoflurane and fentanyl 0.02 microgram.kg-1.min-1. In the ketamine group, anesthesia was induced with ketamine 2 mg/kg in combination with thiopental 3 mg/kg and maintained with isoflurane and ketamine 20 micrograms.kg-1.min-1. In the control group, anesthesia was induced with thiopental 5 mg/kg and maintained with isoflurane only. Patients in all three groups received identical postoperative pain treatment. The intensity of spontaneous incisional pain and movement-associated pain was measured with a visual analog self-rating method. The surgical wound hyperalgesia was assessed by measuring pain threshold to pressure on the wound by using an algometer, and also by measuring the intensity of pain to suprathreshold pressure on the wound with the visual analog self-rating method. Forty-eight hours after surgery, the pain threshold was 0.90 +/- 0.06 kg in controls, 1.69 +/- 0.19 kg (P < 0.001) in the fentanyl group, and 1.49 +/- 0.15 kg (P < 0.01) in the ketamine group.(ABSTRACT TRUNCATED AT 250 WORDS)

The induction dose-response of propofol was compared with the dose-response of its combination with fentanyl and with that of fentanyl alone in three groups of 60 women undergoing minor gynaecological surgery. Dose-response curves were determined for each group using bootstrap and isobolographic analyses. Propofol was found to act additively with fentanyl for induction of anaesthesia. Twenty-three percent of the ED50 of fentanyl was required in combination with 75% of the ED50 for propofol to achieve the ED50 of the combination. This indicates that, for induction of anaesthesia, propofol and fentanyl are not synergistic.

Many studies (several even before American Heart Association recommended in 1973 that lay public be trained in cardiopulmonary resuscitation (CPR] have documented that retention of CPR skills is poor, unaffected by modifications in curriculum or whether the students are lay or professional. We chose to investigate what actually occurs during a CPR course, and gained the following insights: despite clearly defined curricula, we found that instructors did not teach in a standardized way. Practice time was limited and errors in performance were not corrected. Instructors consistently rated the students' overall performance as acceptable; at the same time, using the same checklist, we consistently rated performance as unacceptable. The checklist is an inaccurate tool for evaluating CPR performance. Despite the poor performance that we documented, students and instructors were satisfied with the courses and believed that the level of performance was high. As a result of these studies, we discovered that the problem of poor retention of CPR skills may lie not with the learner or the curriculum, but with the instructor. But, since lives are being saved with bystander CPR, does this documented poor retention matter? Perhaps the solution is not only to improve instructor training to make certain that students receive adequate practice time and accurate skill evaluation, but also to modify the criteria for correct performance when testing for retention. These criteria should be based on the minimum CPR skills that are required to sustain life for the critical 4-8 min before defibrillation and other advanced cardiac life support are delivered.

Recent studies have demonstrated that parenteral deferroxamine can prolong life in patients with iron overload. We have developed a non-human primate model of iron overload and have accurately determined negative iron balance in parenteral and oral studies of deferroxamine and a new chelator, desferrithiocin. Cebus monkeys were loaded with iron dextran (10 mg/kg twice weekly) until their serum contained a transferrin saturation greater than 75%, and (in two animals) liver biopsies showed iron loading. When complete iron balance studies were performed at this time, basal iron balance was -53 +/- 11 micrograms (N = 4), providing a low background for provocative studies. Iron balance was determined for intramuscular (N = 2) and oral (N = 3) deferroxamine, as well as intramuscular (N = 1) and oral (N = 4) desferrithiocin. The pattern of iron excretion after parenteral deferroxamine strongly resembled that of the iron-loaded, transfused human. Desferrithiocin was found to have significant activity as an oral chelator. This Cebus monkey model accurately determines negative iron balance and readily permits precise comparison of iron chelators given parenterally or orally. This model may offer an important step between rodent and human trials of promising new iron chelators.

We present an operation model in rats, which according to our opinion prevents duodenogastric reflux effectively. The duodenum is divided distally from the pylorus and a pyloro-jejunostomy performed combined with a Roux-en-Y anastomosis. Rats operated this way and submitted to restraint stress developed significantly less stress lesions than operated control under same conditions. However, operated rats submitted to the operation and offered a 5 mMol/l drinking solution of crude taurocholic acid during 20 days before submitted to stress had significantly more stress lesions than operated animals with tap water before restraint stress.

The stress ulcer formation is enhanced significantly in rats operated with pyloro-jejunostomy and Roux-en-Y anastomosis by taurocholic acid or a mixture of taurocholic and glycocholic acid. However, the incidence of stress ulcers is significantly reduced by adding lysolecithin to the drinking solution containing these bile acids in the same concentration, though lysolecithin alone induces significantly more stress ulcers than tap water in rats with the same operation submitted to immobilisation stress.

For the purpose of studying the significance of the bile and duodenal reflux into the stomach in rats we present an experimental animal model which--in contrast to the procedures reported until now--can exactly be reproduced due to the advantage of microsurgical techniques, thus reducing the operative trauma and accidental results during experimentation. The surgical procedure consists of a pylorojejunostomy with a Roux-en-y loop. This experimental model offers the possibility to discern a great deal of the problems and conditions which may be responsible in the adverse effect of bile and/or duodenal juice on the gastric mucosa.

Unlabelled: Cysteamine induces duodenal ulcers in rats, but bile diversion inhibits ulcer formation. Since lysolecithin inhibits stress ulceration in rats, it is assessed now whether lysolecithin inhibits cysteamine-induced ulcers, too. Male rats were operated: division of the duodenum distally to the pylorus, duodenojejunostomy. Roux-en-Y duodenojejunostomy. 4 groups comprising 10 animals. Drinking solution for group 1, 3 and 4: Na taurocholate and glycocholic acid (5 mmol/l). For group 2 addition of 0.2 mmol/l lysolecithin. Cysteamine-HCl (10%) twice subcutaneously on the 19th day in group 1, 3 and 4, isotonic NaCl in group 2. In group four 1 ml lysolecithin per gastric tube 1 h before cysteamine., Results: Group 1: 8 animals with 16 ulcers, group 2: 7 with 10 ulcers, group 3: no ulcers, group 4: 3 with 5 ulcers (p less than 0.05/p less than 0.02)., Conclusion: Lysolecithin, a substance produced during fat digestion, exerted an ulceroprotective property (lyso-protection) under experimental conditions, as shown here for the first time, to the author's knowledge. The enhancement of cysteamine-induced duodenal ulcer development by bile salts is again documented.

The induction dose-response of midazolam was compared with the dose-response of its combination with methohexitone sodium and with that of methohexitone alone. Three groups of 60 unpremedicated ASA physical state I or II women undergoing minor gynaecological interventions were studied. The end-point of induction of anaesthesia was inability to open eyes upon command. Dose-response curves were determined for each group with a probit procedure and compared with an isobolographic analysis. Midazolam was found to act in synergism with methohexitone for induction of anaesthesia. Twenty-seven percent ED50 for methohexitone was required in combination with 33% of ED50 for midazolam to achieve the ED50 of the combination. This degree of synergism is in agreement with that described in animal research.

The method of two-dimensional polyacrylamide gel electrophoresis has been used to investigate the post mortem stability of protein and mRNA in human liver. The electrophoretic mobility of proteins and of the in vitro translation products of the mRNA were found to be essentially unaffected by incubation of the liver at 37 degrees C for up to 2 h or at 4 degrees C for up to 16 h. This study indicates that the major protein and mRNA species in liver are stable enough following death to allow meaningful studies on tissue collected under standard autopsy conditions.

The effect of basic and advanced cardiac life support (BLS and ACLS) on long-term survival is dependent upon both the response time and the quality of intervention. Retention research using the results of classroom testing as indirect indicators has shown that performance of BLS and ACLS skills is poor. This suggests that BLS and ACLS courses do not teach the knowledge and skills well, the information is too difficult to retain, testing procedures are faulty, and/or the performance standards are unrealistic. To maximize the likelihood of successful resuscitation from cardiac arrest, we propose the following: (a) simplify the BLS procedures; (b) simplify the BLS and ACLS curricula; (c) simplify teaching strategies; (d) simplify testing based on what steps are required to sustain life; (e) define objective criteria for knowledge acquisition and skill performance; (f) base refresher training on diagnosed deficiencies and evaluate innovative ways to improve retention; (g) develop a resuscitation record to provide accurate documentation of patient status, dysrhythmias, therapy, and responses to therapy; (h) develop a process evaluation tool to evaluate individual and group performances during actual resuscitation; and (i) form an international consortium of BLS and ACLS investigators.

Reductive methylation has been used to radioactively label crude-extract proteins with 3H or 14C. The procedure achieved good isotope incorporation and resolution of proteins on two-dimensional polyacrylamide gels. It allows high-precision comparison of tissue samples by double-labelling and should facilitate the study of tissue proteins by two-dimensional gel electrophoresis.