958 resultados para Early feeding


Relevância:

20.00% 20.00%

Publicador:

Resumo:

Aims: To gain insight on the immunological processes behind cow’s milk allergy (CMA) and the development of oral tolerance. To furthermore investigate the associations of HLA II and filaggrin genotypes with humoral responses to early oral antigens. Methods: The study population was from a cohort of 6209 healthy, full-term infants who in a double-blind randomized trial received supplementary feeding at maternity hospitals (mean duration 4 days): cow’s milk (CM) formula, extensively hydrolyzed whey formula or donor breast milk. Infants who developed CM associated symptoms that subsided during elimination diet (n=223) underwent an open oral CM challenge (at mean age 7 months). The challenge was negative in 112, and in 111 it confirmed CMA, which was IgE-mediated in 83. Patients with CMA were followed until recovery, and 94 of them participated in a follow-up study at age 8-9 years. We investigated serum samples at diagnosis (mean age 7 months, n=111), one year later (19 months, n=101) and at follow-up (8.6 years, n=85). At follow-up, also 76 children randomly selected from the original cohort and without CM associated symptoms were included. We measured CM specific IgE levels with UniCAP (Phadia, Uppsala, Sweden), and β-lactoglobulin, α-casein and ovalbumin specific IgA, IgG1, IgG4 and IgG levels with enzyme-linked immunosorbent assay in sera. We applied a microarray based immunoassay to measure the binding of IgE, IgG4 and IgA serum antibodies to sequential epitopes derived from five major CM proteins at the three time points in 11 patients with active IgE-mediated CMA at age 8-9 years and in 12 patients who had recovered from IgE-mediated CMA by age 3 years. We used bioinformatic methods to analyze the microarray data. We studied T cell expression profile in peripheral blood mononuclear cell (PBMC) samples from 57 children aged 5-12 years (median 8.3): 16 with active CMA, 20 who had recovered from CMA by age 3 years, 21 non-atopic control subjects. Following in vitro β-lactoglobulin stimulation, we measured the mRNA expression in PBMCs of 12 T-cell markers (T-bet, GATA-3, IFN-γ, CTLA4, IL-10, IL-16, TGF-β, FOXP3, Nfat-C2, TIM3, TIM4, STIM-1) with quantitative real time polymerase chain reaction, and the protein expression of CD4, CD25, CD127, FoxP3 with flow cytometry. To optimally distinguish the three study groups, we performed artificial neural networks with exhaustive search for all marker combinations. For genetic associations with specific humoral responses, we analyzed 14 HLA class II haplotypes, the PTPN22 1858 SNP (R620W allele) and 5 known filaggrin null mutations from blood samples of 87 patients with CMA and 76 control subjects (age 8.0-9.3 years). Results: High IgG and IgG4 levels to β-lactoglobulin and α-casein were associated with the HLA (DR15)-DQB1*0602 haplotype in patients with CMA, but not in control subjects. Conversely, (DR1/10)-DQB1*0501 was associated with lower IgG and IgG4 levels to these CM antigens, and to ovalbumin, most significantly among control subjects. Infants with IgE-mediated CMA had lower β -lactoglobulin and α-casein specific IgG1, IgG4 and IgG levels (p<0.05) at diagnosis than infants with non-IgE-mediated CMA or control subjects. When CMA persisted beyond age 8 years, CM specific IgE levels were higher at all three time points investigated and IgE epitope binding pattern remained stable (p<0.001) compared with recovery from CMA by age 3 years. Patients with persisting CMA at 8-9 years had lower serum IgA levels to β-lactoglobulin at diagnosis (p=0.01), and lower IgG4 levels to β-lactoglobulin (p=0.04) and α-casein (p=0.05) at follow-up compared with patients who recovered by age 3 years. In early recovery, signal of IgG4 epitope binding increased while that of IgE decreased over time, and binding patterns of IgE and IgG4 overlapped. In T cell expression profile in response to β –lactoglobulin, the combination of markers FoxP3, Nfat-C2, IL-16, GATA-3 distinguished patients with persisting CMA most accurately from patients who had become tolerant and from non-atopic subjects. FoxP3 expression at both RNA and protein level was higher in children with CMA compared with non-atopic children. Conclusions: Genetic factors (the HLA II genotype) are associated with humoral responses to early food allergens. High CM specific IgE levels predict persistence of CMA. Development of tolerance is associated with higher specific IgA and IgG4 levels and lower specific IgE levels, with decreased CM epitope binding by IgE and concurrent increase in corresponding epitope binding by IgG4. Both Th2 and Treg pathways are activated upon CM antigen stimulation in patients with CMA. In the clinical management of CMA, HLA II or filaggrin genotyping are not applicable, whereas the measurement of CM specific antibodies may assist in estimating the prognosis.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Jarvis et al. (Research Articles, 12 December 2014, p. 1320) presented molecular clock analyses that suggested that most modern bird orders diverged just after the mass extinction event at the Cretaceous-Paleogene boundary (about 66 million years ago). We demonstrate that this conclusion results from the use of a single inappropriate maximum bound, which effectively precludes the Cretaceous diversification overwhelmingly supported by previous molecular studies.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Currently, we live in an era characterized by the completion and first runs of the LHC accelerator at CERN, which is hoped to provide the first experimental hints of what lies beyond the Standard Model of particle physics. In addition, the last decade has witnessed a new dawn of cosmology, where it has truly emerged as a precision science. Largely due to the WMAP measurements of the cosmic microwave background, we now believe to have quantitative control of much of the history of our universe. These two experimental windows offer us not only an unprecedented view of the smallest and largest structures of the universe, but also a glimpse at the very first moments in its history. At the same time, they require the theorists to focus on the fundamental challenges awaiting at the boundary of high energy particle physics and cosmology. What were the contents and properties of matter in the early universe? How is one to describe its interactions? What kind of implications do the various models of physics beyond the Standard Model have on the subsequent evolution of the universe? In this thesis, we explore the connection between in particular supersymmetric theories and the evolution of the early universe. First, we provide the reader with a general introduction to modern day particle cosmology from two angles: on one hand by reviewing our current knowledge of the history of the early universe, and on the other hand by introducing the basics of supersymmetry and its derivatives. Subsequently, with the help of the developed tools, we direct the attention to the specific questions addressed in the three original articles that form the main scientific contents of the thesis. Each of these papers concerns a distinct cosmological problem, ranging from the generation of the matter-antimatter asymmetry to inflation, and finally to the origin or very early stage of the universe. They nevertheless share a common factor in their use of the machinery of supersymmetric theories to address open questions in the corresponding cosmological models.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Objective: To describe the prevalence and demographic, clinical and functional correlates of childhood trauma in patients attending early psychosis clinics. Method: Participants were recruited from outpatients attending four early psychosis services. Exposure to childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Psychopathology was measured using the Positive and Negative Syndrome Scale and the Depression, Anxiety and Stress Scale. Social and vocational functioning and substance use were also assessed. Results: Over three-quarters of the 100 patients reported exposure to any childhood trauma. Emotional, physical and sexual abuse were reported by 54%, 23% and 28% of patients, respectively, while 49% and 42% of patients reported emotional and physical neglect, respectively. Female participants were significantly more likely to be exposed to emotional and sexual abuse. Exposure to childhood trauma was correlated with positive psychotic symptoms and higher levels of depressive, anxiety and stress symptoms; however, it had no impact on social or vocational functioning or recent substance use. Conclusion: Exposure to childhood trauma was common in patients with early psychosis, and associated with increased symptomatology. Existing recommendations that standard clinical assessment of patients with early psychosis should include inquiry into exposure to childhood trauma are supported.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

New stars form in dense interstellar clouds of gas and dust called molecular clouds. The actual sites where the process of star formation takes place are the dense clumps and cores deeply embedded in molecular clouds. The details of the star formation process are complex and not completely understood. Thus, determining the physical and chemical properties of molecular cloud cores is necessary for a better understanding of how stars are formed. Some of the main features of the origin of low-mass stars, like the Sun, are already relatively well-known, though many details of the process are still under debate. The mechanism through which high-mass stars form, on the other hand, is poorly understood. Although it is likely that the formation of high-mass stars shares many properties similar to those of low-mass stars, the very first steps of the evolutionary sequence are unclear. Observational studies of star formation are carried out particularly at infrared, submillimetre, millimetre, and radio wavelengths. Much of our knowledge about the early stages of star formation in our Milky Way galaxy is obtained through molecular spectral line and dust continuum observations. The continuum emission of cold dust is one of the best tracers of the column density of molecular hydrogen, the main constituent of molecular clouds. Consequently, dust continuum observations provide a powerful tool to map large portions across molecular clouds, and to identify the dense star-forming sites within them. Molecular line observations, on the other hand, provide information on the gas kinematics and temperature. Together, these two observational tools provide an efficient way to study the dense interstellar gas and the associated dust that form new stars. The properties of highly obscured young stars can be further examined through radio continuum observations at centimetre wavelengths. For example, radio continuum emission carries useful information on conditions in the protostar+disk interaction region where protostellar jets are launched. In this PhD thesis, we study the physical and chemical properties of dense clumps and cores in both low- and high-mass star-forming regions. The sources are mainly studied in a statistical sense, but also in more detail. In this way, we are able to examine the general characteristics of the early stages of star formation, cloud properties on large scales (such as fragmentation), and some of the initial conditions of the collapse process that leads to the formation of a star. The studies presented in this thesis are mainly based on molecular line and dust continuum observations. These are combined with archival observations at infrared wavelengths in order to study the protostellar content of the cloud cores. In addition, centimetre radio continuum emission from young stellar objects (YSOs; i.e., protostars and pre-main sequence stars) is studied in this thesis to determine their evolutionary stages. The main results of this thesis are as follows: i) filamentary and sheet-like molecular cloud structures, such as infrared dark clouds (IRDCs), are likely to be caused by supersonic turbulence but their fragmentation at the scale of cores could be due to gravo-thermal instability; ii) the core evolution in the Orion B9 star-forming region appears to be dynamic and the role played by slow ambipolar diffusion in the formation and collapse of the cores may not be significant; iii) the study of the R CrA star-forming region suggests that the centimetre radio emission properties of a YSO are likely to change with its evolutionary stage; iv) the IRDC G304.74+01.32 contains candidate high-mass starless cores which may represent the very first steps of high-mass star and star cluster formation; v) SiO outflow signatures are seen in several high-mass star-forming regions which suggest that high-mass stars form in a similar way as their low-mass counterparts, i.e., via disk accretion. The results presented in this thesis provide constraints on the initial conditions and early stages of both low- and high-mass star formation. In particular, this thesis presents several observational results on the early stages of clustered star formation, which is the dominant mode of star formation in our Galaxy.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The evolutionary success of beetles and numerous other terrestrial insects is generally attributed to co-radiation with flowering plants but most studies have focused on herbivorous or pollinating insects. Non-herbivores represent a significant proportion of beetle diversity yet potential factors that influence their diversification have been largely unexamined. In the present study, we examine the factors driving diversification within the Scarabaeidae, a speciose beetle family with a range of both herbivorous and non-herbivorous ecologies. In particular, it has been long debated whether the key event in the evolution of dung beetles (Scarabaeidae: Scarabaeinae) was an adaptation to feeding on dinosaur or mammalian dung. Here we present molecular evidence to show that the origin of dung beetles occurred in the middle of the Cretaceous, likely in association with dinosaur dung, but more surprisingly the timing is consistent with the rise of the angiosperms. We hypothesize that the switch in dinosaur diet to incorporate more nutritious and less fibrous angiosperm foliage provided a palatable dung source that ultimately created a new niche for diversification. Given the well-accepted mass extinction of non-avian dinosaurs at the Cretaceous-Paleogene boundary, we examine a potential co-extinction of dung beetles due to the loss of an important evolutionary resource, i.e., dinosaur dung. The biogeography of dung beetles is also examined to explore the previously proposed "out of Africa" hypothesis. Given the inferred age of Scarabaeinae as originating in the Lower Cretaceous, the major radiation of dung feeders prior to the Cenomanian, and the early divergence of both African and Gondwanan lineages, we hypothesise that that faunal exchange between Africa and Gondwanaland occurred during the earliest evolution of the Scarabaeinae. Therefore we propose that both Gondwanan vicariance and dispersal of African lineages is responsible for present day distribution of scarabaeine dung beetles and provide examples.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

There is increasing evidence that the origins of poor adult health and health inequalities can be traced back to circumstances preceding current socioeconomic position and living conditions. The life-course approach to examining the determinants of health has emphasised that exposure to adverse social and economic circumstances in earlier life or concurrent adverse circumstances due to unfavourable living conditions in earlier life may lead to poor health, health-damaging behaviour, disease or even premature death in adulthood. There is, however, still a lack of knowledge about the contribution of social and economic circumstances in childhood and youth to adult health and health inequalities, and even less is known about how environmental and behavioural factors in adulthood mediate the effects of earlier adverse experiences. The main purpose of this study was to deepen our understanding of the development of poor health, health-damaging behaviours and health inequalities during the life-course. Its aim was to find out which factors in earlier and current circumstances determine health, the most detrimental indicators of health behaviour (smoking, heavy drinking and obesity as a proxy for the balance between nutrition and exercise), and educational health differences in young adults in Finland. Following the ideas of the social pathway theory, it was assumed that childhood environment affects adult health and its proximal determinants via different pathways, including educational, work and family careers. Early adulthood was studied as a significant phase of life when many behavioural patterns and living conditions relevant to health are established. In addition, socioeconomic health inequalities seem to emerge rapidly when moving into adulthood; they are very small or non-existent in childhood and adolescence, but very marked by early middle age. The data of this study were collected in 2000 2001 as part of the Health 2000 Survey (N = 9,922), a cross-sectional and nationally representative health interview and examination survey. The main subset of data used in this thesis was the one comprising the age group 18 29 years (N = 1,894), which included information collected by standardised structured computer-aided interviews and self-administered questionnaires. The survey had a very high participation rate at almost 90% for the core questions. According to the results of this study, childhood circumstances predict the health of young adults. Almost all the childhood adversities studied were found to be associated with poor self-rated health and psychological distress in early adulthood, although fewer associations were found with the somatic morbidity typical of young adults. These effects seemed to be more or less independent of the young adult s own education. Childhood circumstances also had a strong effect on smoking and heavy drinking, although current circumstances and education in particular, played a role in mediating this effect. Parental smoking and alcohol abuse had an influence on the corresponding behaviours of offspring. Childhood circumstances had a role in the development of obesity and, to a lesser extent, overweight, particularly in women. The findings support the notion that parental education has a strong effect on early adult obesity, even independently of the young adult s own educational level. There were marked educational differences in self-rated health in early adulthood: those in the lowest educational category were most likely to have average or poorer health. Childhood social circumstances seemed to explain a substantial part of these educational differences. In addition, daily smoking and heavy drinking contributed substantially to educational health differences. However, the contribution of childhood circumstances was largely shared with health behaviours adopted by early adulthood. Employment also shared the effects of childhood circumstances on educational health differences. The results indicate that childhood circumstances are important in determining health, health behaviour and health inequalities in early adulthood. Early recognition of childhood adversities followed by relevant support measures may play an important role in preventing the unfortunate pathways leading to the development of poor health, health-damaging behaviour and health inequalities. It is crucially important to recognise the needs of children living in adverse circumstances as well as children of substance abusing parents. In addition, single-parent families would benefit from support. Differences in health and health behaviours between different sub-groups of the population mean that we can expect to see ever greater health differences when today s generation of young adults grows older. This presents a formidable challenge to national health and social policy as well as health promotion. Young adults with no more than primary level education are at greatest risk of poor health. Preventive policies should emphasise the role of low educational level as a key determinant of health-damaging behaviours and poor health. Keywords: health, health behaviour, health inequalities, life-course, socioeconomic position, education, childhood circumstances, self-rated health, psychological distress, somatic morbidity, smoking, heavy drinking, BMI, early adulthood

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Moudgal and co-workers1-3 recently reported that the administration to intact pregnant rats of rabbit antiserum ovine interstitial cell stimulating hormone (ICSH) on any one day between the eighth and twelfth days of pregnancy resulted in resorption of foetuses and termination of pregnancy. This effect was readily reversed by the simultaneous administration of progesterone but not by oestradiol-17β. These observations suggested that ICSH was involved in progesterone synthesis and as such is a luteotropic factor in the rat.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

This thesis describes current and past n-in-one methods and presents three early experimental studies using mass spectrometry and the triple quadrupole instrument on the application of n-in-one in drug discovery. N-in-one strategy pools and mix samples in drug discovery prior to measurement or analysis. This allows the most promising compounds to be rapidly identified and then analysed. Nowadays properties of drugs are characterised earlier and in parallel with pharmacological efficacy. Studies presented here use in vitro methods as caco-2 cells and immobilized artificial membrane chromatography for drug absorption and lipophilicity measurements. The high sensitivity and selectivity of liquid chromatography mass spectrometry are especially important for new analytical methods using n-in-one. In the first study, the fragmentation patterns of ten nitrophenoxy benzoate compounds, serial homology, were characterised and the presence of the compounds was determined in a combinatorial library. The influence of one or two nitro substituents and the alkyl chain length of methyl to pentyl on collision-induced fragmentation was studied, and interesting structurefragmentation relationships were detected. Two nitro group compounds increased fragmentation compared to one nitro group, whereas less fragmentation was noted in molecules with a longer alkyl chain. The most abundant product ions were nitrophenoxy ions, which were also tested in the precursor ion screening of the combinatorial library. In the second study, the immobilized artificial membrane chromatographic method was transferred from ultraviolet detection to mass spectrometric analysis and a new method was developed. Mass spectra were scanned and the chromatographic retention of compounds was analysed using extract ion chromatograms. When changing detectors and buffers and including n-in-one in the method, the results showed good correlation. Finally, the results demonstrated that mass spectrometric detection with gradient elution can provide a rapid and convenient n-in-one method for ranking the lipophilic properties of several structurally diverse compounds simultaneously. In the final study, a new method was developed for caco-2 samples. Compounds were separated by liquid chromatography and quantified by selected reaction monitoring using mass spectrometry. This method was used for caco-2 samples, where absorption of ten chemically and physiologically different compounds was screened using both single and nin- one approaches. These three studies used mass spectrometry for compound identification, method transfer and quantitation in the area of mixture analysis. Different mass spectrometric scanning modes for the triple quadrupole instrument were used in each method. Early drug discovery with n-in-one is area where mass spectrometric analysis, its possibilities and proper use, is especially important.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The status of the TOTEM experiment is described as well as the prospects for the measurements in the early LHC runs. The primary goal of TOTEM is the measurement of the total p-p cross section, using a method independent of the luminosity. A final accuracy of 1% is ex- pected with dedicated β∗ = 1540 m runs, while at the beginning a 5% resolution is achievable with a β∗ = 90 m optics. Accordingly to the running scenarios TOTEM will be able to measure the elastic scattering in a wide range of t and to study the cross-sections and the topologies of diffractive events. In a later stage, physics studies will be extended to low-x and forward physics collaborating with CMS as a whole experimental apparatus.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Our finding that the inhibitors of DNA methylation, 5-azacytidine, 5-azadeoxycytidine or adenosine dialdehyde, given after a carcinogen all potentiated initiation suggested that hypomethylation of DNA during repair synthesis of DNA might play a role in the initiation of the carcinogenic process. To examine this aspect further, we have asked the question, do the nodules which develop from initiated cells after promotion with 1% orotic acid exhibit an altered methylation pattern in their DNA? The methylation status of the DNA from nodules has been examined using the restriction endonucleases HpaII/MspI and HhaI which distinguish between methylated and unmethylated cytosines in their nucleotide recognition DNA 5'-CCGG and 5'-GCGC respectively. The proto-oncogenes, c-myc, c-fos and c-Ha-ras, in the DNA were primarily studied in this investigation because of their possible involvement in cell proliferation and/or in cell transformation and tumorigenesis. The results indicate that in the nodule DNA, c-myc and c-fos are hypomethylated in the sequence of CCGG while the c-Ha-ras shows hypomethylation in the alternating GCGC sequence. This methylation pattern seen in the nodule DNA is not found in the DNA of the non-nodular surrounding liver or liver tissue after exposure to promoter or carcinogen alone. It is also not found in the DNA of regenerating liver. It is particularly significant that the methylation patterns in the c-myc and c-Ha-ras regions are similar to those found in several cancer tissues. The results suggest that this methylation pattern is acquired early in the carcinogenic process and raises the question whether it has any bearing on the process.