An ovine model of hyperdynamic endotoxemia and vital organ metabolism

BACKGROUND: Animal models of endotoxemia are frequently used to understand the pathophysiology of sepsis and test new therapies. However, important differences exist between commonly used experimental models of endotoxemia and clinical sepsis. Animal models of endotoxemia frequently produce hypodynamic shock in contrast to clinical hyperdynamic shock. This difference may exaggerate the importance of hypoperfusion as a causative factor in organ dysfunction. This study sought to develop an ovine model of hyperdynamic endotoxemia and assess if there is evidence of impaired oxidative metabolism in the vital organs. METHODS: Eight sheep had microdialysis catheters implanted into the brain, heart, liver, kidney and arterial circulation. Shock was induced with a 4hr escalating dose infusion of endotoxin. After 3hrs vasopressor support was initiated with noradrenaline and vasopressin. Animals were monitored for 12hrs after endotoxemia. Blood samples were recovered for haemoglobin, white blood cell count, creatinine and proinflammatory cytokines (IL-1Beta, IL-6 & IL-8). RESULTS: The endotoxin infusion was successful in producing distributive shock with the mean arterial pressure decreasing from 84.5 ± 12.8 mmHg to 49 ± 8.03 mmHg (p < 0.001). Cardiac index remained within the normal range decreasing from 3.33 ± 0.56 l/min/m to 2.89l ± 0.36 l/min/m (p = 0.0845). Lactate/pyruvate ratios were not significantly abnormal in the heart, brain, kidney or arterial circulation. Liver microdialysis samples demonstrated persistently high lactate/pyruvate ratios (mean 37.9 ± 3.3). CONCLUSIONS: An escalating dose endotoxin infusion was successful in producing hyperdynamic shock. There was evidence of impaired oxidative metabolism in the liver suggesting impaired splanchnic perfusion. This may be a modifiable factor in the progression to multiple organ dysfunction and death

Interwell coupling effect in Si/SiGe quantum wells grown by ultra high vacuum chemical vapor deposition

Si/Si0.66Ge0.34coupled quantum well (CQW) structures with different barrier thickness of 40, 4 and 2 nm were grown on Si substrates using an ultra high vacuum chemical vapor deposition (UHV-CVD) system. The samples were characterized using high resolution x-ray diffraction (HRXRD), cross-sectional transmission electron microscopy (XTEM) and photoluminescence (PL) spectroscopy. Blue shift in PL peak energy due to interwell coupling was observed in the CQWs following increase in the Si barrier thickness. The Si/SiGe heterostructure growth process and theoretical band structure model was validated by comparing the energy of the no-phonon peak calculated by the 6 + 2-bandk·pmethod with experimental PL data. Close agreement between theoretical calculations and experimental data was obtained

Povezanost između polimorfizama XRCC1 ARG399GLN i P53 ARG72PRO s rizikom od raka želuca i debeloga crijeva u turskoj populaciji

Gastric cancer is one of the most common cancers of the gastrointestinal system, and its overall fi ve-year survival rate is still 15 % to 20 %, as it can mostly be diagnosed at an advanced stage. On the other hand, although colorectal cancer has a rather good prognosis, mortality is one half that of the incidence. As carcinogenesis is believed to involve reactive radicals that cause DNA adduct formation, impaired repair activity, and weakened tumour suppression, it would help to understand the role of the polymorphisms of nucleotide excision repair enzyme XRCC1 and of tumour suppressor gene p53 in gastric and colorectal cancers. Our study included 94 gastric cancer patients, 96 colorectal cancer patients, and 108 cancer-free individuals as control with the aim to see if there was an association between XRCC1 Arg399Gln and p53 Arg72Pro polymorphisms and cancer susceptibility. DNA was extracted from peripheral blood cells and genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism. Polymorphism p53 Arg72Pro was not associated with either gastric or colorectal carcinoma, while XRCC1 Arg399Gln was not associated with the increased risk of colorectal cancer. However, XRCC1 homozygous Gln allele at codon 399 was associated with 2.54 times higher risk of gastric cancer.Rak želuca najčešći je oblik karcinoma probavnoga sustava, a ukupno mu je preživljenje i dalje 15 % do 20 %, budući da se većinom dijagnosticira u poodmakloj fazi razvoja. S druge pak strane, premda rak debeloga crijeva ima prilično dobru prognozu, smrtnost je i dalje 50 %. Vjeruje se da je nastanak karcinoma povezan s reaktivnim radikalima koji uzrokuju stvaranje DNA-adukata, onemogućavaju popravak DNA te slabe supresiju tumora. Stoga bi bilo korisno razumjeti ulogu polimorfi zama gena za enzim XRCC1 koji sudjeluje u popravku isjecanjem nukleotida i tumor-supresorskoga gena p53 u nastanku raka želuca i debeloga crijeva. Naše je ispitivanje obuhvatilo 94 bolesnika s rakom želuca, 96 bolesnika s rakom debeloga crijeva te 108 kontrolnhih ispitanika (koji nisu oboljeli od bilo kojeg oblika raka) s ciljem da se utvrdi povezanost između polimorfi zama XRCC1 Arg399Gln i p53 Arg72Pro i sklonosti nastanku raka. DNA je dobiven iz stanica periferne krvi, a genotip utvrđen s pomoću metode lančane reakcije polimerazom - polimorfi zma restrikcijskih fragmenata na osnovi dužine (PCRRLFP). Polimorfi zam p53 Arg72Pro nije se pokazao povezanim s povećanim rizikom od raka želuca ili debeloga crijeva niti je XRCC1 Arg399Gln bio povezan s povećanim rizikom od raka debeloga crijeva, ali je zato rizik od raka želuca u homozigotnih nositelja ovoga polimorfi zma bio 2,54 puta veći

Act In case of Depression: The evaluation of a care program to improve the detection and treatment of depression in nursing homes. Study Protocol

Contains fulltext : 95616.pdf (publisher's version ) (Open Access)BACKGROUND: The aim of this study is evaluating the (cost-) effectiveness of a multidisciplinary, evidence based care program to improve the management of depression in nursing home residents of somatic and dementia special care units. The care program is an evidence based standardization of the management of depression, including standardized use of measurement instruments and diagnostical methods, and protocolized psychosocial, psychological and pharmacological treatment. METHODS/DESIGN: In a 19-month longitudinal controlled study using a stepped wedge design, 14 somatic and 14 dementia special care units will implement the care program. All residents who give informed consent on the participating units will be included. Primary outcomes are the frequency of depression on the units and quality of life of residents on the units. The effect of the care program will be estimated using multilevel regression analysis. Secondary outcomes include accuracy of depression-detection in usual care, prevalence of depression-diagnosis in the intervention group, and response to treatment of depressed residents. An economic evaluation from a health care perspective will also be carried out. DISCUSSION: The care program is expected to be effective in reducing the frequency of depression and in increasing the quality of life of residents. The study will further provide insight in the cost-effectiveness of the care program. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR1477

Twin's Birth-Order Differences in Height and Body Mass Index From Birth to Old Age : A Pooled Study of 26 Twin Cohorts Participating in the CODATwins Project

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first-and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.Peer reviewe

The importance of Real-Life research in Respiratory Medicine: Manifesto of the Respiratory Effectiveness Group:Endorsed by the International Primary Care Respiratory Group and the World Allergy Organization

status: publishe

Genetic and environmental influences on human height from infancy through adulthood at different levels of parental education

Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis.Peer reviewe

Parental Education and Genetics of BMI from Infancy to Old Age : A Pooled Analysis of 29 Twin Cohorts

Objective The objective of this study was to analyze how parental education modifies the genetic and environmental variances of BMI from infancy to old age in three geographic-cultural regions. Methods A pooled sample of 29 cohorts including 143,499 twin individuals with information on parental education and BMI from age 1 to 79 years (299,201 BMI measures) was analyzed by genetic twin modeling. Results Until 4 years of age, parental education was not consistently associated with BMI. Thereafter, higher parental education level was associated with lower BMI in males and females. Total and additive genetic variances of BMI were smaller in the offspring of highly educated parents than in those whose parents had low education levels. Especially in North American and Australian children, environmental factors shared by co-twins also contributed to the higher BMI variation in the low education level category. In Europe and East Asia, the associations of parental education with mean BMI and BMI variance were weaker than in North America and Australia. Conclusions Lower parental education level is associated with higher mean BMI and larger genetic variance of BMI after early childhood, especially in the obesogenic macro-environment. The interplay among genetic predisposition, childhood social environment, and macro-social context is important for socioeconomic differences in BMI.Peer reviewe