[Effectiveness and Cost-Effectiveness of Daily School Sport in the Primary School--Project: "fit for pisa"]. / Effektivität und Kosteneffektivität täglichen Schulsports in der Grundschule--das Projekt "fit für pisa".

The "fit for pisa" intervention implemented daily physical education at five primary schools in Göttingen. The results of the evaluation show an increase in physical activity among the students participating in the programme. At the same time sedentary behaviour, like watching television, decreased remarkably. In the long run the promotion of an active lifestyle had improved the body mass index. The study emphasises the need for government funding to implement the programme across the country.

[Implementing daily physical education in primary school - potentials and barriers from the involved actor's point of view]. / Täglichen Schulsport in der Grundschule implementieren - Potenziale und Barrieren aus Sicht der beteiligten Akteure.

OBJECTIVE: The objective was to determine to what extent daily physical education can be implemented in primary schools, what barriers exist and how to overcome the mentioned barriers. Moreover, it was analysed to what extent daily physical education is accepted by teachers, external trainers, parents and students. METHODS: Semi-structured interviews with parents (n=7), teachers (n=5) and external trainers (n=6) of the intervention schools. The intervention students (n=44) were surveyed within focus groups. RESULTS: All surveyed groups appraised the implementation of daily school sports as successful. The cooperation between the schools and the sports club should be maintained during a comprehensive implementation of daily physical education. Besides an improved lessons quality teachers and external trainers reported an improved social behaviour of the children. Parents perceived positive effects on the child development. All groups believe that daily physical education increases the enjoyment of children in sports. As a certain barrier a lack of resources (e. g., facilities, equipment, financial resources) in the schools were mentioned. CONCLUSIONS: The cooperation between the schools and the sports club proved to be an applicable model to implement daily physical education. The combination of teachers and external trainers can contribute to a higher lesson quality. Considering the perceived potentials of daily physical education by all surveyed groups, a comprehensive implementation of systematic daily physical activity promotion in the primary school setting should be tapped more strongly in future.

[Health economic evaluation of health promotion - the example "fit for pisa"]. / Gesundheitsökonomische Evaluation der Gesundheitsförderung - am Beispiel "fit für pisa"

The increasing prevalence of risk factors associated with physical inactivity lead to an economic burden on society. The article uses the example of the prevention measure "fit for pisa" to investigate to what extent a full economic evaluation can provide a basis for decision-makers. The intervention integrated the daily physical education at 5 primary schools in Göttingen for the entire school term. The study is intended to provide information on short- and long-term potential savings. A process analysis identified the prevention performance from a societal perspective. Resource consumption was recorded in (partly) standardisedform and evaluated and also revealed the need for investment in sports halls with capacity to expand the programme to all primary schools in Göttingen. In the routine the implementation costs of half-day schools are 619 € per student year; for all-day schools 236 € per student year. The consideration of the short-term outcomes shows that TV viewing has decreased and physical activity has been strongly encouraged. The active life style promotion has shown an improvement on BMI in the medium-term. On the basis of a decision analytical model, a cost-benefit analysis of the program over the life course will be undertaken.

P-gp substrate-induced neurotoxicity in an Abcb1a knock-in/Abcb1b knock-out mouse model with a mutated canine ABCB1 targeted insertion.

Certain dog breeds, especially Collies, are observed to exhibit neurotoxicity to avermectin drugs, which are P-glycoprotein (P-gp) substrates. This neurotoxicity is due to an ABCB1 gene mutation (ABCB1-1Δ) that results in non-functional P-gp expression. A developed Abcb1a knock-in/Abcb1b knock-out mouse model expressing the ABCB1-1Δ canine gene was previously reported and mice exhibited sensitivity upon ivermectin administration. Here, model and wild-type mice were administered P-gp substrates doramectin, moxidectin, and digoxin. While knock-in/knock-out mice exhibited ataxia, lethargy and tremor, wild-type mice remained unaffected. In addition, no neurotoxic clinical signs were observed in either mouse type administered domperidone, a P-gp substrate with no reported neurotoxicity in ABCB1-1Δ Collies. Overall, neurotoxic signs displayed by model mice closely paralleled those observed in ivermectin-sensitive Collies. This model can be used to identify toxic P-gp substrates with altered safety in dog populations and may reduce dog use in safety studies that are part of the drug approval process.

Array CGH in patients with developmental delay or intellectual disability: are there phenotypic clues to pathogenic copy number variants?

Array comparative genomic hybridization (array CGH) is now widely adopted as a first-tier clinical diagnostic test in individuals with unexplained developmental delay/intellectual disability (DD/ID) and congenital anomalies. Our study aimed at enlarging the phenotypic spectrum associated with clinically relevant copy number variants (CNVs) as well as delineating clinical criteria, which may help separating patients with pathogenic CNVs from those without pathogenic CNVs. We performed a retrospective review of clinical and array CGH data of 342 children with unexplained DD/ID. The phenotypic features of patients with clinically significant CNV were compared with those without pathogenic CNVs. Array CGH detected pathogenic CNVs in 13.2% of the patients. Congenital anomalies, especially heart defects, as well as primary microcephaly, short stature and failure to thrive were clearly more frequent in children with pathogenic CNVs compared with children with normal array CGH results. Thus, we assume that in patients with unexplained DD/ID, array CGH will more probably detect a significant CNV if any of these features is part of the patient's phenotype.

Obese boys at increased risk for nonalcoholic liver disease: evaluation of 16,390 overweight or obese children and adolescents.

OBJECTIVE: Comorbidities of childhood obesity challenge health-care systems in Europe. Further, there is a lack of population-specific prevalence data and diagnostic strategies available, especially for obesity-related disturbances of liver function. Therefore, the prevalence of elevated liver enzymes and their relationship to biological parameters were studied in a large pediatric obesity cohort. METHODS: In 111 specialized pediatric obesity centers in Germany, Austria and Switzerland, 16,390 children and adolescents (age 12.4±2.6 years, 58% boys) were categorized as overweight (body mass index (BMI) >90th percentile) and obese (>97th percentile) and studied for related comorbidities, especially nonalcoholic fatty liver disease (NAFLD; as defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >50 U l(-1)). Data were collected using a standardized software program (APV) for longitudinal multicenter documentation. Pseudonymized data were transmitted for central statistical analysis. RESULTS: In this pediatric cohort, 16% of the study population was overweight, 46% obese and 35% extremely obese (>99.5th percentile extreme obesity (Xob)). NAFLD was present in 11% of the study population, but predominantly in boys (boys vs girls; 14.4:7.4%; P<0.001), in Xob (obese vs Xob; 9.5:17.0%; P<0.001) and in older age (< 12 vs ≥12 years; 8:12%; P<0.001; adjusted for BMI). ALT >50 U l(-1) was significantly associated with fasting insulin and BMI-SDS. In multiple logistic regression models, Xob and male gender were strongly associated with NAFLD (odds ratio Xob vs normal weight=3.2; boys vs girls OR=2.3). CONCLUSION: In a large cohort of overweight and obese European children and adolescents, markers of nonalcoholic liver disease, especially ALT, are frequent and predicted by Xob and male gender. The results underline the epidemiological dimension of this obesity-related morbidity even in childhood. Therefore, at least ALT is recommended as a screening parameter in basic care.

[Obesity in children and adolescents and their parents. Correlation of standardized body mass index between patients, their parents and siblings from the multicentre APS data]. / Adipositas bei Kindern, Jugendlichen und ihren Eltern. Assoziation des standardisierten BMI zwischen Patienten, Eltern und Geschwistern anhand multizentrischer APV-Daten.

BACKGROUND: Obesity in children and adolescents is moving into the focus of public interest. Genetic as well as environmental factors are important in the etiology of obesity. The aim of this multicentre study was to correlate the weight of overweight or obese children and adolescents with that of their parents and siblings. PATIENTS AND METHODS: Anthropometric and other data - comorbidities, various influencing factors and treatment - were collected from the adiposity data acquisition system for prospective surveillance (APS). Currently 125 medical centers and pediatric care clinics in Germany, Austria and Switzerland use the APS documentation. Until February 2008 data on a total of 37,062 children and adolescents had been collected. RESULTS: Data to calculate the Body Mass Index (BMI) were obtained from both parents of 11,074 (29,9%) children and adolescents. The mean BMI Standard Deviation Score (SDS) of these children and adolescents was 2.46. Their mean age was 11.9 years; 46% were males. The mean BMI-SDS of these children and adolescents correlated significantly with the BMI-SDS of both the mother (r=0.29 [Spearman's rank correlation coefficient]) and the father (r=018, both p<0.0001). The correlation with the father's BMI was closer in adolescents (15-20 years, r=0.20) than in young children (<10 years: r=0.12). The correlation with the mother's BMI was independent of age. A multivariate model including the BMI of the parents as well as age and sex of the children and adolescents explained 10.0% of the variance. Significant influencing factors were BMI of the mother, sex and the relationship between BMI of mother, age and sex. Data for the BMI of siblings were available of 3,933 (10.6 %) children and adolescents. The correlation of the BMI of the children and adolescents with that of their siblings was +0.17 (p<0.0001). This correlation was highest in adolescence (<10 years.: r=0.17, 15-20 years.: r=0.24, both p<0.0001). CONCLUSION: The patient's weight correlated more strongly with the mother's than the father's weight or that of the siblings.

[Physical (in)activity in childhood and adolescence]. / Körperliche (In)Aktivität in Kindheit und Jugend.

In the last two decades in Germany and other countries physical activity of children and adolescents declined while sedentary lifestyle increased. Physical inactivity in childhood and youth is related with coronary heart disease risk factors and higher prevalence of obesity. International recommendations suggest daily 60 minutes or more moderate to vigorous physical activity and less than 2 hours sedentary activity in leisure.

Inactivation of Cryptosporidium parvum oocysts in fresh apple cider by UV irradiation.

This study evaluated the efficacy of UV irradiation on the inactivation of Cryptosporidium parvum oocysts in fresh apple cider. Cider was inoculated with oocysts and exposed to 14.32 mJ of UV irradiation/cm(2). Oocyst viability was assessed with the gamma interferon gene knockout (GKO) mouse and infant BALB/cByJ mouse models. All GKO mice challenged with UV-treated cider demonstrated no morbidity or mortality, and infant BALB/c mice challenged with treated cider were negative for the presence of C. parvum. In contrast, the GKO mice challenged with non-UV-treated inoculated cider died and the parasite was detected in the ileums of all challenged infant mice. This study shows that UV irradiation can be used to inactivate C. parvum in fresh apple cider.

New Zealand white rabbit as a nonsurgical experimental model for Salmonella enterica gastroenteritis.

Rabbits orally challenged with Salmonella enterica developed a dose-dependent diarrheal disease comparable to human salmonellosis. Viable Salmonella organisms recovered from the intestine and deep tissues indicate local and systemic infections. Therefore, results show that the rabbit can be used as a model for diarrheal disease and sequelae associated with salmonellosis.

Attempts to establish experimental Cyclospora cayetanensis infection in laboratory animals.

Attempts were made to develop an animal model for Cyclospora cayetanensis to identify a practical laboratory host for studying human cyclosporiasis. Oocysts collected from stool of infected humans in the United States, Haiti, Guatemala, Peru, and Nepal were held in potassium dichromate solution to allow development of sporozoites. The following animal types were inoculated: 9 strains of mice, including adult and neonatal immunocompetent and immune-deficient inbred and outbred strains, rats, sandrats, chickens, ducks, rabbits, jirds, hamsters, ferrets, pigs, dogs, owl monkeys, rhesus monkeys, and cynomolgus monkeys. Most animals were inoculated by gavage, although some of the primates were fed oocysts on food items. The animals were examined for signs of infection, particularly diarrhea, and stool samples were examined for 4-6 wk after inoculation. None of the animals developed patent infections or signs of infection. We conclude that none of the animals tested is susceptible to infection with C. cayetanensis.

The effects of an alpha hydroxy acid (glycolic acid) on hairless guinea pig skin permeability.

The barrier integrity of hairless guinea pig skin after treatment with an alpha hydroxy acid was assessed through in vivo topical application of an oil-in-water emulsion containing 5 or 10% glycolic acid at pH 3.0. The control was a commercial moisturizing lotion, pH 7.8. A dosing regimen for the glycolic acid formulations that was tolerated by the hairless guinea pigs and significantly decreased stratum corneum turnover time was determined using the dansyl chloride staining technique. Once-daily dosing of hairless guinea pig skin for 3 weeks with the glycolic acid formulations resulted in approximately a 36-39% decrease in stratum corneum turnover time compared with the control lotion. After this treatment, hairless guinea pigs were sacrificed for the in vitro measurement of the percutaneous absorption of [14C]hydroquinone and [14C]musk xylol. No significant differences in the 24-hour absorption of either test compound were found for skin treated with the control lotion or the glycolic acid formulations. There were also no significant differences found in the absorption of [3H]water through skin from the different treatment groups. Although no increase in skin penetration occurred after treatment with the glycolic acid formulations, histology revealed approximately a twofold increase in epidermal thickness. Also the number of nucleated cell layers nearly doubled in skin treated with 5% and 10% glycolic acid compared with the control lotion and untreated skin. These studies demonstrate that substantial changes in the structure of hairless guinea pig epidermis can occur without significant effect on skin permeability of two model compounds.

Light microscopic observations on the reproductive tract of the male sand rat, Psammomys obesus.

The anatomy of the reproductive tract of the male sand rat, Psammomys obesus, was examined by light microscopy. Histologically, the reproductive tract is similar to other rodent species. Seminiferous tubules in the 1-month-old sand rat do not contain a tubular lumen but Sertoli cells, spermatogonia and spermatocytes are present. A full complement of germ cells is present in the seminiferous tubules by 2.5 months and spermatogenesis is well established. The interstitial space is not well defined until 2.5 months when cell types typical of most rodent species are observed. The epididymis is not noticeably segmented into lobules. An epididymal lumen is not observed until 2.5 months. Cauda epididymal sperm are not observed in the 1 or 2.5-month-old animals and cauda epididymal sperm counts from the 7.5 and 12.5-month-old animals are highly variable. The epididymis, proximal and middle regions of the vas deferens, seminal vesicles and prostate display morphological and histological characteristics similar to other rodent species. The distal end of the vas deferens is not expanded to form an ampulla.

Monitoring brevetoxins during a Gymnodinium breve red tide: comparison of sodium channel specific cytotoxicity assay and mouse bioassay for determination of neurotoxic shellfish toxins in shellfish extracts.

In October of 1996, a Gymnodinium breve bloom occurred in shellfish harvesting waters of Alabama, Mississippi and Louisiana, Gulf of Mexico, USA. Bloom densities reached 5.6x10(5) cells liter(-1) and bloom residence at shellfish sampling stations ranged from 3 to 28 days. Brevetoxin-2 dominated G. breve toxin profiles in bloom seawater extracts. Shellfish toxicity, assessed by mouse bioassay, exceeded the guidance level for up to 75 days after the bloom had dissipated. Cytotoxicity assays and mouse bioassays showed similar temporal patterns of shellfish toxicity, but the two methods differed in estimations of brevetoxin-3 equivalent toxicity by a factor of 93 to 1. LC-ESI-MS showed the temporal patterns in shellfish toxicity reflected metabolism of G. breve toxins. The molecular ions m/z 1004, 1017 and 1033 dominated LC-ESI-MS spectra of toxic chromatographic fractions from the extracts and were identified as brevetoxin metabolites on the basis of LC-APCI-MS-MS. The discrepancy between cytotoxicity and mouse bioassay estimates of brevetoxin-3 equivalent toxicity resulted from the difference in extraction efficiency of solvents used in the respective methods and the relative sensitivity of the assays to toxin metabolite mixtures present in the extracts. The normalized cytotoxicity assay showed 75% agreement with mouse bioassay positive test samples and 64% agreement with mouse bioassay negative test samples. Published in 1999 by John Wiley & Sons, Ltd.

Histopathological evaluation of liver, pancreas, spleen, and heart from iron-overloaded Sprague-Dawley rats.

The effects of increasing dietary levels of Fe on the histopathology of liver, pancreas, spleen, and heart were examined in a rat model for iron overload. Sprague-Dawley rats were fed diets containing 35, 350, 3,500, or 20,000 micrograms Fe/g, and, after 12 wk, there was a direct correlation between increased liver nonheme Fe and lipid peroxidation measured by the lipid-conjugated diene assay. Histopathological examination of tissues revealed the following: (a) hepatocellular hemosiderosis in all groups of rats, with a dose-related accumulation of cytoplasmic Fe-positive material predominantly in hepatocytes located in the periportal region (Zone 1), (b) myocardial degeneration and necrosis (cardiomyopathy) with hemosiderin in interstitial macrophages or in myocardial fibers of animals with heart damage, (c) splenic lymphoid atrophy affecting the marginal zone of the white pulp and hemosiderin deposition in the sinusoidal macrophages, and (d) pancreatic atrophy with loss of both the endocrine and exocrine pancreatic tissue in those animals receiving 3,500 and 20,000 micrograms Fe/g of diet. The toxic effects of Fe overload in this rat model include cellular apoptosis or necrosis in heart, spleen, and pancreas and, when coupled with the findings on lipid peroxidation, suggests that oxidative stress is involved in the pathogenesis of the lesions.

Neurobehavioral dysfunctions associated with dietary iron overload.

Excessive dietary Fe is known to be toxic, but the extent of neurobiological involvement is not clear. In the present study male weanling rats were fed diets containing Fe at 35 (control), 350, 3500, or 20000 ppm for 12 wk. An Fe-deficient group (4 ppm) was included for comparison. Rats were tested for behavioral and body weight changes at various times after initiation of diets, and liver and brain nonheme Fe were measured at term. Excess dietary Fe, primarily at 20000 ppm, significantly decreased activity, habituation, reflex startle, and conditioned avoidance response performance, and enhanced prepulse modulation of startle. Body weights were also markedly decreased. Fe-deficient animals showed similar behavioral effects but more moderate body weight changes. Liver nonheme Fe varied directly with dietary levels. Whole-brain nonheme Fe was significantly reduced in Fe-deficient animals but increased only at the 20000-ppm level. Homeostatic mechanisms appear to regulate whole-brain Fe more effectively under conditions of dietary Fe overload than under conditions of Fe deficiency. The behavioral changes associated with dietary Fe overload may represent secondary consequences of systemic toxicity.

Epidemiology of Potomac horse fever: an investigation into the possible role of non-equine mammals.

A serological study of antibodies to Ehrlichia risticii was carried out on 10 species of wild and domestic mammals found on or near 21 horse farms in an area of the USA in which Potomac horse fever is endemic. No antibodies were found in 133 peridomestic rodents (Norway rats and house mice), nor in 108 wild rodents (white-footed mice and meadow voles) captured on farms. Three of the six domestic animal species examined, cats, pigs and a goat, showed serological evidence of exposure to E risticii. Seropositive animals were detected on three of the 21 premises. The eight seropositive cats (of 48 cats tested) were on two farms, and the three seropositive pigs (of 14 tested) were all on one farm which lay some 3 km from where the one seropositive goat (of three tested) was found. None of the 79 dogs, 75 cattle and seven sheep tested had antibodies to E risticii. The significance of these findings is discussed in the light of current understanding of the transmission of Potomac horse fever and of the epidemiology of other related ehrlichial diseases.

Disease features in horses with induced equine monocytic ehrlichiosis (Potomac horse fever).

Fifty-five horses were inoculated IV and/or SC with materials containing Ehrlichia risticii, ie, infected whole blood, buffy coat cells, or cell culture, to study clinical and hematologic features of equine monocytic ehrlichiosis (Potomac horse fever). Major clinical and hematologic features of induced E risticii infection were biphasic increase in rectal temperature with peak increases of 38.9 C and 39.3 C on postinoculation days (PID) 5 and 12, respectively; depression; anorexia; decreased WBC count (maximal decrease of 47% on PID 12); and diarrhea from PID 14 to PID 18. Increased WBC count was an inconsistent feature, with a maximal increase of 51.5% on PID 20. During times of decreased and increased WBC counts, lymphocyte/neutrophil ratios remained fairly constant. However, not all horses had all clinical and hematologic features, and these features were present in different degrees among horses. Increased rectal temperature, depression, anorexia, and decreased WBC count were more consistent features, whereas diarrhea developed in 73% of the horses. Of 55 horses, 39 (71%) had all clinical and hematologic features of the disease (classic disease), whereas 16 (29%) horses did not have greater than or equal to 1 of these features (nonclassic disease). The E risticii titer in the blood (ehrlichemia) was maximum during the peak increase in rectal temperature. In 55 horses, mortality was 9%. Significant differences (P greater than 0.5) in clinical and hematologic features were not detected between horses that survived and those that died of E risticii infection.

Attempted transmission of Ehrlichia risticii by field-captured Dermacentor variabilis (Acari: Ixodidae).

The capability of field-collected American dog ticks, Dermacentor variabilis, to infect horses with Ehrlichia risticii, causative agent of Potomac horse fever (PHF), was examined by allowing adult ticks collected from horse farms with a history of PHF to feed on susceptible horses. More than 500 male and female ticks attached and fed on 3 test horses; however, no clinical or serologic evidence of PHF was observed in treated or control horses. All horses were challenge exposed with E risticii-infective blood by inoculation at 60 to 65 days after ticks fed, and all developed clinical PHF with subsequent seroconversion. The data, therefore, indicated that adult D variabilis, a common parasite of horses on Maryland premises where PHF is enzootic, may not serve as a vector of E risticii.

Comparison of the serum bactericidal activity of ceftriaxone/piperacillin and ceftriaxone/netilmicin.

The serum bactericidal activities of ceftriaxone, netilmicin, piperacillin and the combinations of ceftriaxone with each of the two other antibiotics were compared 1, 4 and 24 h after i.v. infusion in six volunteers. One hundred and one clinical isolates were used, including Staphylococcus aureus, Pseudomonas aeruginosa and various Enterobacteriaceae. The highest bactericidal titers were found against the Enterobacteriaceae, geometric means of 1:741 and 1:851 being obtained for ceftriaxone/netilmicin and ceftriaxone/piperacillin respectively. Against Staphylococcus aureus the geometric mean bactericidal titers of ceftriaxone/piperacillin (1:105) were markedly higher than ceftriaxone/netilmicin (1:35). Low bactericidal activity was exhibited by all drugs and combinations tested against Pseudomonas aeruginosa; a geometric mean bactericidal titer of 1:4.6 was achieved. The serum bactericidal activity of the double beta-lactam combinations was found to be at least equal to that of the combination containing a cephalosporin and an aminoglycoside.