Background: Diffusion tensor imaging (DTI) allows the analysis of changes in microstructure, through the quantification of the spread and direction of water molecules in tissues. We used fractional anisotropy (FA) maps to compare the integrity of WM between patients and controls. The objective of the present study was to investigate WM abnormalities in patients with frontal lobe epilepsy secondary to focal cortical dysplasia (FCD). Materials and Methods: We included 31 controls  and 22 patients , recruited from our outpatient clinic. They had clinical and EEG diagnosis of frontal lobe epilepsy, secondary to FCD detected on MRI. Patients and controls underwent 3T MRI, including the DTI sequence, obtained in 32 directions and b value of 1000 s/mm2. To process the DTI we used the following softwares: MRIcroN and FSL/TBSS . We used a threshold-free cluster enhancement with significance at p < 0.05, fully corrected for multiple comparisons across space. Results: Areas with FA reduction in patients were identified in both hemispheres, mainly in the frontal lobes, cingulum, and forceps minor (p = 0.014), caudate e anterior thalamic radiation (p = 0.034), superior longitudinal fasciculus (p = 0.044), uncinate fasciculus, and inferior fronto-occipital fasciculus (p = 0.042). Conclusion: Our results showed a widespread pattern of WM microstructural abnormalities extending beyond the main lesion seen on MRI , which may be related to frequent seizures or to the extent of MRI-invisible portion of FCD. Epilepsy secondary to focal cortical dysplasia (FCD) usually begins early in life, is often refractory to antiepileptic drug (AED) therapy, and a frequent cause of focal motor status or focal epilepsy, which may be life-threatening  is a non-invasive imaging technique that can examine molecular diffusion of water within the brain by applying gradients in at least six non-collinear directions. DTI can evaluate white matter integrity and may detect abnormalities in earlier stages than conventional T2- or T1-weighted imaging  and 22 patients  with MRI defined FCD, recruited from our outpatient clinic at our University Hospital from May 2009 to April 2010. Informed consent was obtained for participation in the studies, approved by the Internal Review Board of our institution.®, release 2.6.1.0. The DTI acquisition was performed in axial plane obtained in 32 directions; 2 mm thickness, with echo time 60, factor-b 1000, reconstructed matrix 128 × 127, field of view (FOV), 232 × 232. In addition, all patients had a 3T MRI epilepsy protocol that included 3 mm coronal T1-weighted inversion recovery, 3 mm coronal T2-weighted multi-echo sequence, 3 mm coronal and axial FLAIR, volumetric T1-weighted sequence with 1 mm isotropic voxels, and volumetric T2-weighted sequence with 1 mm × 1 mm × 1.5 mm voxels. All images were analyzed in a workstation with high resolution widescreen monitor. Multiplanar reconstructions on T1 and T2 volumetric sequences were performed for all patients. The neuroimaging characteristics for diagnosing probable FCD were based on a recent proposal for classification by Blümcke et al. .For processing the DTI, all imaging data were transferred to a cluster of Linux workstations. The structural images were visually inspected for any structural abnormalities by a neuroimaging expert. First DICOM images were converted to 4D-Nifti file using the MRIcroN program. Preprocessing and analyses of diffusion data was done with an in-house protocol using FSL. For voxelwise analysis of FA values we applied TBSS , with threshold-free cluster enhancement with significance at n = 11; female n = 11).Of all patients included in the study, 12 had right-sided lesions and 10 had left-sided MRI lesions , ipsilateral hemisphere, forceps minor (p = 0.042), and cingulum (p = 0.048) in the contralateral hemisphere , left corticospinal tract and right corticospinal (p = 0.022), right inferior fronto-occipital fasciculus (p = 0.022), left cingulum e forceps minor (p = 0.014), anterior thalamic radiation, fasciculus uncinatus, left inferior fronto-occipital fasciculus (p = 0.036), left superior and inferior longitudinal fasciculus, and forceps major , left inferior longitudinal fasciculus (p = 0.032), inferior fronto-occipital fasciculus (p = 0.038), right and left anterior thalamic radiation , left corticospinal tract (p = 0.042), cingulum and left forceps major (p = 0.048), left inferior fronto-occipital fasciculus  demonstrated bilateral and widespread FA changes; however, these were slightly more extensive in the group with left-sided FCD. Perhaps this could be related to the fact that the dominant hemisphere for language may be more vulnerable to damage.In one study : degradation of both axonal membranes and myelin (Beaulieu et al., Unfortunately, we were not able to perform correlations between EEG abnormalities and FA abnormalities, or between the extent of visible FCD and the degree of FA abnormalities, because this was a group analysis. Another limitation of this paper is that we had confirmation of FCD on histopathology in only four patients, since the others are still waiting or refused surgery.Diffusion tensor imaging and tractography in patients with FCD may be useful in the detection and delineation of MRI-invisible structural abnormalities, and in determining both the connectivity of a given area of the cortex and the spatial relationship between the lesion and major white matter tracts.Further studies need to be conducted to evaluate the usefulness of DTI for the delineation of white matter abnormalities in patients with epilepsy.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Heracleum persicum was introduced to Norway as an ornamental in the 1830′s. Towards the end of the 19th century, it started spreading outside gardens, later to become a frequent sight in the major towns and settlements of North Norway – and a veritable pest plant. During the last 100 years or so, a substantial ethnobotanical tradition related to the species has evolved, demonstrating that folk knowledge is not only forgotten and lost, but also charting new terrain.H. persicum in Norway has been extracted from my own, substantial archive of interviews, questionnaires, and correspondence related to the ethnobotany of Norway.This survey is based on data extracted from all relevant publications, including botanical literature, travel accounts, newspaper notes, etc., as far as they have come to my attention. In addition, information on vernacular names and various uses of the H. persicum tends to be known to everyone, even by city dwellers who otherwise generally neglect plants. People tend to love or hate it, and in Tromsø, the largest town of northern Norway, the species has become more or less emblematic of the city. Both here and in other areas of northern Norway, it is referred to by a variety of vernacular names, partly borrowed from other species, partly derived from the Latin genus name, and partly coined for this species only. In the latter group, tromsøpalme  has proved by far the most popular invention. It was seemingly first used (and coined) by German soldiers during the World War II occupation of Norway, but now largely replaces other vernacular names. The plant is still popular with children, who frequently play in and with it, whereas adults have been more prone to speculate on its origins – and how to get rid of it. Salt is the most popular “herbicide” for this purpose.Where extant, H. persicum has accumulated at least twenty different vernacular names in Norway, and a variety of other traditions. By necessity, all these traditions are less than 180 years old, showing that even modern and urban societies may produce a substantial body of plant lore, which certainly merits ethnobotanical attention.Over the years,  Linnaea borealis L. )ealis L. , and col Harmaja .Restricting the scope of ethnobotany to traditional lifestyles and the past presents a strictly limited view of what the field should cover. In some ways, it is rather similar to the (mainly) American notion, as expressed e.g. by Richards Evan Schultes when visiting Britain, “The British Isles have no ethnobotany” (see : vii), iAnyone, no matter their ethnicity, has some relationship with plants and animals, which is bound to produce at least some knowledge or tradition worthy of ethnobiological interest. Modern city and town dwellers may have much less contact with nature than their ancestors, but they are still bound to meet, eat, like and dislike a substantial number of plants. In doing so, they will obviously use a number of vernacular names, coining new ones as needed, and frequently accumulating a variety of other lore in the process.Heracleum persicum Desf. ex Fisch. in Norway. It was introduced as an ornamental to the far north of the country in 1836 ” (EBATA 2009:27). Literature sources sometimes make the same assumption: “It was supposedly imported from somewhere in northern Russia” . Their introduction is comparatively recent, and mostly related to the experiments with growing plants transferred from other parts of Russia, carried out in the botanical garden at Kirovsk from the 1930′s onwards  used herakleum. And all of us said herakleum, we had not even heard of tromsøpalme.” (EBATA 2005:32). “We said herakleum when I was a child.” (…) “At least until after the war. Then, the tromsøpalme name became common.” (EBATA 2006:133). Some believed the latter name had gained support through the newspapers (EBATA 2005:19), which may well be correct.Even in Tromsø, other names previously predominated ,76: “We tromsøpalme has been so successful that it is now largely supplanting all other vernacular names. Some of those I have interviewed could only remember that the plant previously went by some other, now forgotten name .As a vernacular name, Heracleum mantegazzianum, H. persicum was introduced to Europe as an ornamental. Old photographs from coastal North Norway frequently show large stands adorning gardens and summer houses . Cuowing.” (: 100).tromsøpalmen was planted around the houses, as an ornamental and to provide shelter. As there is such a lot growing at the parsonage, it is assumed that the vicar’s family has planted herakla in the garden, which was established around 1870.” (EBATA 2005:38).Interviews provide some further glimpses of its use in gardens, e.g. at Dverberg in Andøy, Nordland: “According to what people said, Heracleum persicum was still popular, and being introduced to new gardens, about 1900, e.g. at Reinøya in Karlsøy, Troms: “My grandma (…) had it in a garden there, at Reinøya. I believe it was introduced from Tromsø about 1900.” (EBATA 1995:1). A similar date was suggested at Honningsvåg in Nordkapp (Finnmark): “We’ve got it in the garden here, and it is about a hundred years old” (EBATA 2006:100). As is often the case on the outer coast, it was used to provide shelter: “There are perhaps twenty or thirty meters of it, as a sheltering wall” (EBATA 2006:100). It was put to similar use at Andøy in Nordland: “Araklia was used to provide shelter” (EBATA 2005:47).H. persicum has been planted as an ornamental at some graveyards in comparatively recent times, e.g. at Laukvik in Lenvik, Troms (EBATA 2007:88).Nowadays, cultivation is much less frequent, and primarily seen in some coastal villages of the high north, where trees and shrubs fail to grow. Exceptions occur, and Heracleum persicum remain a favourite motive among photographers in Tromsø, especially in late autumn and winter. Such pictures are featured by the local newspapers every winter. The decorative, dried-out umbels have also frequently been brought indoors, e.g. in Målselv, Troms: “In the seventies, my aunt had dried flowering stems” – as a decoration. She kept them for years, but in the end, “they were thrown in the sea” (EBATA 2007:50). The umbels have also been used as topics for jewellery and similar small, decorative objects.The stout, dry stems and umbels of Log by Stuart Frost, which is made entirely of rings cut from the hollow stem  where we lived until 1968 there was a lof of tromsøpalmer along the road, almost like a hedge. It was a fine place for hiding when we played hide and seek.” (EBATA 2006:69). Similar games were played in nearby Andøy: “The children used to run about there in the autumn.” (EBATA 2005:39); “We pretended to be Indians, making huts in the araklia jungle” (EBATA 2005:47).Despite these useful properties, the large and dense stands as such were perhaps the most valued aspect of Heracleum forest”  “There were lots of tromsøpalme here in the old days. A jungle.” (EBATA 2006:40). ”Above the city center, we had a veritable “forest” [of H. persicum] at hand. Here, Robin Hood roamed with his men, and Tarzan, the king of apes. In the cinema, we had seen Indians and cowboys ride across the prairie with the dust raising high behind them. Deprived of horses, even they  would fit under the leaves.” (…) “And last, but not least, quite a few small outlaws have bided their time here, searched for by their family, while the storm abated.” , and would hide there.” (EBATA 2005:34).Children in Finnmark utilized the iding.” (: 105). Stromsøpalme. And since its juice is somewhat caustic, they had [sore] raccoon-like rings around the eyes” (EBATA 2005:31). Others would hardly believe that the plants could be dangerous, commenting that the children in Nordkapp, Finnmark “had fought and ravaged and torn apart and hit each other with these [plants], and never suffered [any harm]” (EBATA 2006:100).The hollow stems could also serve as a kind of telescope – or rather, a telescope look-a-like, as noted in Lenvik, Troms: “I remember my grandfather told me that they made binoculars of Heracleum persicum was no exception. At least by children in Tromsø, the young umbels were considered edible: “Yes, we ate the bud.” (EBATA 2006:26). “We ate them. They tasted like cauliflower.” “And I have spoken with several others who ate them. We never got ill.” (EBATA 2005:32). “We even ate rogna  of one»  was as fine as before” (EBATA 2005:43). Some would first dissolve the salt in water, and sometimes even heat it to boiling before applying it .A popular remedy or “herbicide” along the coast was salt, easily available e.g. from the many fish-handling plants -103. PeoH. persicum by digging it up – at least in one case with the help of local boys looking for earthworms as bait (EBATA 2005:46) – although some suggest that bait from such soils catch no fish [Others tried to combat  no fish . Others  no fish ,100, gas no fish , or para no fish . At MåsøThe control measures invented locally show some similarity with those tried and tested in a number of scientific studies. In both cases, grazing and herbicides -30 are tH. persicum has become more or less emblematic of the city. It is frequently photographed, and has been used in art and jewellery. The city’s activity center for the elderly (Heracleum) , and one of the major prizes of the city’s annual international film festival  have all gained their names from it. Heracleum persicum or tromsøpalmen has become emblematic to such an extent that attempts at eradicating the species has met considerable opposition among locals. People are prone to defend the plant, contributing newspaper comments opposing any such action  at Tromsøya [Heracleum persicum[In Tromsø, ) Figure , an annuon e.g. -110). So. SoH. peon . ItTromsøya . Others  persicum-122.bunad) are popular garments for festive occasions throughout the country, despite being traditionally used only in some district. Areas with no traditional pattern have solved the problem by inventing new ones, and the one for Tromsø of course incorporates Heracleum umbels in its design. At the crown prince’s wedding in 2001, several suggested using a tromsøpalme as the city of Tromsø’s wedding gift, either a live plant specimen, or a glass engraving of it [tromsøpalmen is now deeply engraved in local lore and tradition.Norwegian folk costumes  and the three northernmost counties .With the earliest documented introduction of a large H. persicum has also become one of the few plants almost everyone in the north has heard of, gaining more than twenty different vernacular names, and a solid position in the childhood memories of many of those who have grown up here [Within less than two centuries,  up here . By doinH. persicum has been duly black-listed in Norway [H. persicum may seem less dangerous in this respect than H. mantegazzianum.Disregarding local sentiments, n Norway , being sn Norway -126, cf.n Norway , and then Norway -131. SucH. persicum are so large and widely distributed that eradication is inconceivable, and the cost alone would be prohibitive. Thus, new generations of children will certainly be able to use it in their games, probably adding more local lore in the process. Perhaps the species will even turn out to be useful (from an adult perspective) after all. Known as golpar in Iran, it is utilized there as a food plant. The fruits are commonly used as a spice, and young stems are harvested for making pickles [In terms of attempts of eradication, people need not worry. The stands of  pickles . In Iran pickles -134.The author declares that he has no competing interests.Decoding EBATA, or some notes on my own material.Click here for file


Its role in human fetal growth has remained ambiguous, as it has only been studied in term tissues. Conversely the maternally expressed growth suppressor, PHLDA2, has a significant negative correlation between its term placental expression and birth weight.Fetal growth involves highly complex molecular pathways. IGF2 is a key paternally expressed growth hormone that is critical for IGF1, IGF2, their receptors IGF1R and IGF2R, and PHLDA2 on term birth weight.The aim of this study is to address the role in early gestation of expression of IGF1, IGF2, IGF1R, IGF2R and PHLDA2 in chorionic villus samples (CVS) (n = 260) collected at 11–13 weeks' gestation. Expression was correlated with term birth weight using statistical package R including correction for several confounding factors.Real-time quantitative PCR was used to investigate mRNA expression of IGF2 and IGF2R revealed a significant positive correlation with birth weight . No effect was observed for IGF1, IGF1R or PHLDA2 and birth weight. Critically, small for gestational age (SGA) neonates had significantly lower IGF2 levels than appropriate for gestational age neonates (p = 3·6×10−7).Transcript levels of IGF2 mRNA levels at 12 weeks gestation could provide a useful predictor of future fetal growth to term, potentially predicting SGA babies. SGA babies are known to be at a higher risk for type 2 diabetes. This research reveals an imprinted, parentally driven rheostat for in utero growth.Our findings show that  Fetal growth involves a complex interaction between genes and the environment, with such significant complexity that many of the molecular pathways remain to be elucidated. Normal fetal growth depends on the successful nutrient exchange between the mother and the fetus via the placenta. When this critical balance is impaired it can result in a small for gestational age (SGA) baby Igf2) and its chelating receptor Igf2rIgf2 results in a 40% reduction in birth weight which contrasts with loss of the maternally-expressed Igf2r, resulting in a 30% increase in birth weight IGF2 has been implicated in two imprinted human growth disorders, the overgrowth, Beckwith-Wiedemann syndrome (BWS) One group of growth genes of particular interest are the imprinted genes that are found almost exclusively in Eutherian  mammals. Genomic imprinting defines allele-specific, differential expression of a gene, according to its parent of origin. If the paternal allele is expressed, the maternal allele is imprinted (silenced) and vice versa. The “parental conflict hypothesis” is still the most widely accepted explanation for the evolution of genomic imprinting PHLDA2) is maternally expressed, paternally imprinted, in both humans and mice Phlda2 in growth and development of the placenta was demonstrated by knockout mouse models that were associated with a significant increase in placental size during mid to late gestation PHLDA2 report increased expression in SGA pregnancies and a negative association with birth weight Pleckstrin homology-like domain family A member 2 (IGF1) and its primary binding receptor IGF1R are not imprinted. IGF1 exerts its growth properties on almost every cell in the body. A homozygous partial deletion of Igf1r in mice stunted height and weight, as well as disrupted the pubertal growth spurt. A complete inactivation of Igf1r is lethal in the neonatal period Igf2 deficient mice, restriction of growth was seen to continue into the postnatal period in the Igf1 mutants Insulin-like growth factor 1  was performed at 11–13 weeks of gestation in 260 singleton pregnancies that subsequently resulted in normal live births at term. The samples were collected from women undergoing CVS for prenatal diagnosis of chromosomal defects at King's College Hospital London. The excess tissue samples used for this study were obtained from women agreeing to participate in research, which was approved by the King's College Hospital Ethics Committee.th percentile, large (LGA) with birth weight >90th percentile and appropriate (AGA).Demographic characteristics were recorded including maternal age, racial origin, smoking status, parity and body mass index as well as pregnancy outcomes such as gestational age at delivery, sex and birth weight. Other birth parameters such as placental weight were not available, nor were blood or tissue samples from the newborn baby. The pregnancies were subdivided according to the birth weight of neonates into small for gestational age (SGA) with birth weight <10DNA and RNA were extracted using the iPrep Purification Instrument (Invitrogen), either by use of the iPrep™ ChargeSwitch® gDNA Tissue Kit, or iPrep™ PureLink™ Total RNA and Trizol® Plus RNA kit including DNAse treatment, according to the manufacturer's instructions.β-actin (ACTB) were used to check the integrity of the cDNA and ensure no DNA contamination. The forward (F) and reverse (R) primers spanned an intron and the sequences are: β-actin.F- gtcttcccctccatcgtg and β-actin.R- ggtcatcttctcgcggttg.Reverse transcriptase (RT) methodology was based on a standard protocol using M-MLV reverse transcriptase and random primer hexamers (Promega). Primers for the housekeeping gene aacaccccacaaaagctcag; IGF2.R- tgcatggattttggttttca; IGF2R.F- gaaacacaaaacctacgacc; IGF2R.R- agaacccaaaagagccaacc; PHLDA2.F- caaaccccgcacgccatgag and PHLDA2.R- ctgtgcccattgcaaataaatc. The same primers were used for cDNA with the exception of IGF2R.R- cctttggagtacgtgacaac. 20 ul reactions were set up and thermal cycling conditions were 94°C for 5 min, 94°C for 30 sec, 60°C for 30 sec, 72°C for 30 sec for 35 cycles, and 72°C for 2 min.Genomic DNA and cDNA from CVS were amplified by PCR before sequencing. Primers (5′ to 3′ sequence) used for genomic DNA are IGF2.F- IGF2, IGF2R and PHLDA2 in CVS was carried out by DNA sequence analysis of expressed single nucleotide polymorphisms (SNP) in CVS gDNA after amplification using specific primers . Corresponding cDNA samples were screened in patients heterozygous for the IGF2 A/G (rs680), IGF2R A/G (rs1805075) and PHLDA2 A/G (rs1056819) SNPs (http://www.ncbi.nlm.nih.gov/projects /SNP/). Sequencing reactions were prepared according to the manufacturer's instructions (Applied Biosystems) using the ABI Prism Big Dye terminator cycle sequencing ready reaction kit (BDT v1.1). Sequencing products were run on an ABI Prism 3730 DNA analyzer, and the read-out was analysed with Sequencher™ v4.8 (Gene Codes Corporation).Imprinting analysis of IGF1, IGF2, IGF1R, IGF2R and PHLDA2 as well as the endogenous control gene L19 (a housekeeping gene ubiquitously expressed in the placenta) ggaggctggagatgtattgc; IGF1.R- acttgcttctgtcccctcct; IGF2.F- cgagagggacgtgtcgacc; IGF2.R- ggactgcttccaggtgtcata; IGF2R.F- ccggcgtgctctgga; IGF2R.R- ccagagggtcacagtggaaga; IGF1R.F- ccaagggtgtggtgaaagat; IGF1R.R- tccatgatgaccagtgttgg; PHLDA2.F- ccatccccgcagcccaaacc; PHLDA2.R- ccacgtcctagcctgggtcc; L19.F- gcggaagggtacagccaat and L19.R- caggctgtgatacatgtggcg. All primer sets were free of primer-dimer products. The RTqPCR assays were run in triplicate for each sample, with the gene of interest and housekeeping gene run on the same 96-well plates. A control pool of CVS cDNA was also included on each plate. Amplification conditions include initial incubation at 95°C for 10 min and repetitive denaturation at 95°C for 15 sec and annealing at 60°C for 1 min for 40 cycles.The quantitative expression analysis of the genes of interest, T) values were within 1 CT of each other. The quantitative values for each triplicate were averaged and the relative expression of the genes of interest was determined by a ratio of their expression to that of the L19 housekeeping gene for the same sample.After amplification, quantitative expression levels were obtained using the StepOne software (version 2.1). All triplicate cycle threshold  was used to compare the gene expression means between the three different categorical birth weight groups  taking into consideration any confounding factors. Statistical package “R” (version 2.13.0) was used for the analyses and for calculating adjusted R-squared (R2) values. Significance was defined as p<0.05.Standard multiple linear regression models were used to examine the correlation of IGF1, IGF2, IGF2R, IGF1R and PHLDA2 mRNA levels in first-trimester placental tissue with the birth weight of the resultant term new born babies. We correlate this data taking into account the carefully recorded birth parameters that may have a confounding effect  and IGF2R (p = 0.04) between CVS tissue and birth weight , IGF1 (p = 0.48) or IGF1R (p = 0.08) between CVS tissue and birth weight (Significant associations were observed for expression of h weight . Importah weight .IGF2 to IGF1R (p = 0.005) was significantly associated with birth weight but no association was found for the ratio of IGF1 to IGF1R (p = 0.76) or the ratio of IGF2 to IGF2R (p = 0.93) between CVS tissue and birth weight  with birth weight >90th percentile and appropriate . In the SGA group compared to the AGA group, IGF2 expression was reduced by statistically significant amounts (p = 3.6×10−7), despite no significant differences in the expression levels of individual receptors . In the LGA group IGF2R expression was found to be higher than in the AGA group (p = 0.02) and IGF1R expression was lower than in the SGA group (p = 0.05)  with birth weight <10 = 0.05) .IGF2 and PHLDA2 are both known to be imprinted in mouse and human IGF2R in the human population is reported to be monoallelically expressed (i.e. imprinted) in only 10% of individuals, which is in contrast to the mouse, where it is fully imprinted IGF2), rs1805075 (IGF2R) and rs1056819 (PHLDA2) were used to report on allele-specific expression and thus determine imprinting status of IGF2, IGF2R and PHLDA2. Genomic DNA extracted from the CVS from 200 patients were tested for heterozygosity at these SNPs, with 40 samples found to be informative at rs680 for IGF2, 24 samples at rs1805075 for IGF2R and 21 samples at rs1056819 for PHLDA2. The 40 informative IGF2 individuals and the 21 informative PHLDA2 individuals were all found to be monoallelically expressed. For the 24 samples informative for IGF2R, 21 (88%) were biallellically expressed for IGF2R and 3 (12%) were monoallelic, which is similar to the expected population frequency , this narrow window might not be the best to investigate IGF1 expression, as IGF1 does not appear in the fetal circulation until later In this study, expression of PHLDA2 expression is negatively associated with birth weight PHLDA2 expression levels in CVS and birth weight. This suggests that maternally expressed PHLDA2 is suppressing the baby's growth later in pregnancy rather than early on. Previous studies investigating term placental IGF2 expression have shown inconclusive results. However, in our study a statistically significant association was observed between IGF2 expression levels in CVS and birth weight, suggesting that the paternal genome is promoting the baby's growth earlier in pregnancy. Therefore, the two parental genomes appear to be acting at different times during pregnancy to control the fetal weight. This supports the idea that whilst increased fetal growth is important early on, it must still require careful regulation by the mother to ensure a successful birth.Although previous studies have shown that placental IGF2 expression levels compared to AGA neonates, but no differences were observed between the levels of the receptors IGF2R and IGF1R. This highlights the importance of the IGF2 ligand rather than the receptor level in determining size of the neonate in SGA pregnancies. This is in agreement with previous studies investigating IGF2 mRNA levels in the placentas from growth-restricted pregnancies In our study, SGA neonates had significantly lower in utero growth potential. We used a larger sample size and we investigated the whole growth spectrum including not only SGA but also LGA neonates. We reasoned that extending the investigation of these genes to samples displaying macrosomic birth weight would also reveal further correlations between growth parameters and gene expression. In this study, LGA neonates had higher IGF2R expression levels compared to AGA neonates and lower IGF1R levels compared to SGA babies. Similar results have been reported in placenta tissue for IGF1R mRNA levels alone IGF2R and correspondingly less IGF1R, which could remove IGF2. This balance may represent another important compensatory mechanism in response to fetal overgrowth. This is also supported by the fact that a significant association was observed between the ratio of IGF2 to IGF1R and birth weight, suggesting that the levels of IGF1R in LGA neonates decrease as their IGF2 levels increase, to avoid any further increase in size.To better understand the causes and consequences of fetal growth restriction as a human pregnancy complication, we focused on available tissue from the first trimester, as this time window is more likely to accurately reflect the in uteroIGF2 paternal haplotypes are linked to higher maternal glucose levels that increase the risk of gestational diabetes The “small baby syndrome hypothesis” proposed by Barker et al., (1993) suggests that there is an inverse linear relation between birth weight and T2D in utero. Understanding the developmental role, function and parent-of-origin effect of critical imprinted genes during human fetal growth will make an important contribution to effective clinical evaluation of growth disorders and their association with longer term, metabolically related, health risks such as T2D. Determination of paternal IGF2 expression in the first trimester, potentially in maternal blood, may act as a predictor of fetal growth trajectory for later in the pregnancy. An early growth biomarker could be invaluable to alert Obstetricians and Neonatologists towards closer ‘at risk’ pregnancy surveillance.An important aim for antenatal care is the prediction, detection and treatment of anomalous fetal growth. We know that variation in size at birth results from interaction between fetal genetic factors and the maternal genetic and uterine environment. In this study we also implicate the important role of the father's genes in fetal growth Figure S1Confounding factors. Correlation of birth weight with gestational age at term Click here for additional data file.


Poorly spaced pregnancies have been documented worldwide to result in adverse maternal and child health outcomes. The World Health Organization (WHO) recommends a minimum inter-birth interval of 33 months between two consecutive live births in order to reduce the risk of adverse maternal and child health outcomes. However, birth spacing practices in many developing countries, including Tanzania, remain scantly addressed.Longitudinal data collected in the Rufiji Health and Demographic Surveillance System (HDSS) from January 1999 to December 2010 were analyzed to investigate birth spacing practices among women of childbearing age. The outcome variable, non-adherence to the minimum inter-birth interval, constituted all inter-birth intervals <33 months long. Inter-birth intervals ≥33 months long were considered to be adherent to the recommendation. Chi-Square was used as a test of association between non-adherence and each of the explanatory variables. Factors affecting non-adherence were identified using a multilevel logistic model. Data analysis was conducted using STATA (11) statistical software.A total of 15,373 inter-birth intervals were recorded from 8,980 women aged 15–49 years in Rufiji district over the follow-up period of 11 years. The median inter-birth interval was 33.4 months. Of the 15,373 inter-birth intervals, 48.4% were below the WHO recommended minimum length of 33 months between two live births. Non-adherence was associated with younger maternal age, low maternal education, multiple births from the preceding pregnancy, non-health facility delivery of the preceding birth, being an in-migrant resident, multi-parity and being married.Generally, one in every two inter-birth intervals among 15–49 year-old women in Rufiji district is poorly spaced, with significant variations by socio-demographic and behavioral characteristics of mothers and newborns. Maternal, newborn and child health services should be improved with a special emphasis on community- and health facility-based optimum birth spacing education in order to enhance health outcomes of mothers and their babies, especially in rural settings. Poorly spaced pregnancies have been documented worldwide to result in adverse maternal and child health outcomes . An estiWith regard to maternal health, women who space their pregnancies inappropriately have an elevated risk of preeclampsia, high blood pressure, and premature rupture of membranes . UndesirSibling competition has been reported to occur in the situation of shorter inter-birth intervals. With the birth of a child, a family may invest more of its limited resources in the care of the newborn while other children may receive an inadequate share of resources distributed among siblings. Furthermore, disease transmission is another mechanism through which shorter inter-birth intervals may be pernicious. Presence of numerous young children in a household may facilitate the spread of various communicable diseases such as respiratory infections and measles .Research findings show also that births occurring within 2 years are riskier and their intervals are considered to be too short . Recent In Tanzania like in many other African countries, fertility, maternal and child mortality are still high. Maternal mortality is estimated at 454 deaths per 100,000 live births, while neonatal mortality approximates 26 deaths per 1,000 live births . While tIn 2005, the World Health Organization (WHO) held a Technical Consultation and Scientific Review of Birth Spacing , and endConsidering slow progress towards achieving the Millennium Development Goals (MDGs) 4  and 5 for Tanzania  and the Ndengereko. Others include Matumbi, Ngindo and Zaramo. In terms of religion, about 90% of the people are Muslim. Most people speak their ethnic languages, even though the national language, Kiswahili, is well understood and widely spoken. Further details about the study area are available [The Rufiji Health and Demographic Surveillance System (HDSS) is located in Rufiji district of the Coast region, 178 kilometres south of Dar es Salaam, Tanzania. A HDSS is a longitudinal, population-based health and vital events registration system that monitors demographic events such as births, deaths, pregnancies, in- and out-migrations and socio-economic status of a geographically well-definedsetting of individuals, households and residential units. The Rufiji HDSS was incepted in September 1998 from the Tanzania Essential Health Interventions Project (TEHIP) and as of 2010, it was made up of 33 villages with over 16,000 households in which more than 80,000 people resided. The area is mainly rural with a scattered population, though clustering around Ikwiriri, Kibiti and Bungu townships is known. The largest and original native ethnic group in the HDSS is vailable .st January 1999 to 31st December 2010. Access to the data was permitted by IHI, an institute that owns, manages and maintains the HDSS. The inception of the HDSS was approved by the Medical Research Coordinating Committee (MRCC) of the National Institute for Medical Research (NIMR) in Tanzania. This ethical approval is detailed elsewhere [This study is a secondary analysis of longitudinal data collected by the Ifakara Health Institute (IHI) in its Rufiji HDSS in Tanzania for a period of eleven years from 1lsewhere . Data coA particular focus of the current study was on analyzing inter-birth intervals in light of the WHO’s recommendation on birth spacing. Therefore, resident women of the Rufiji HDSS aged 15–49 years who were followed-up for vital statistics, particularly birth history, were of interest. As the focus of this study was on closed inter-birth intervals, only women who had given birth at least twice (i.e. multiparous) were retained for this analysis. Those who had experienced adverse outcomes in any of their two consecutive births were very few and excluded in this analysis to be analyzed separately in light of the second recommendation of the WHO on birth spacing after experiencing an adverse outcome.This study examined inter-birth interval as a dependent (outcome) variable against background characteristics of the mother and the child. The inter-birth interval was collapsed into two categories according to the WHO recommendation: (1) <33 months, which was referred to as “non-adherence” or poor birth spacing, and (2) ≥33 months, referred to as “adherence” or appropriate birth spacing.Independent variables investigated (with their categories in brackets) were (1) maternal age , (2) maternal education , (3) maternal occupation , (4) marital status of the mother ), and (5) sex of the index child . Others were (6) place of residence , (7) number of births of the preceding pregnancy (singleton and multiple), (8) parity , (9) place of delivery of the index pregnancy  and (10) HDSS entry type (enumeration and in-migration). During the start of the Rufiji HDSS, entry type of all people present at that time was enumeration. Entry into the HDSS area was also possible through birth or in-migration (migrating into the study area). No one of those who became members by birth was eligible for the current analysis because all were below 15 years of age throughout the follow-up period. Therefore the variable, HDSS entry type, had two categories only as enumeration and in-migration.An inter-birth interval was defined as a period of time (in months) between two consecutive live births . This sun = nth interval length between two consecutive births.Where Ik = highest parity a woman has had at a given point in her reproductive lifetime,Dn = date of birth of an nth pregnancy,n-1 = date of birth of the preceding ((n-1)th) pregnancy andD30.4 = average number of days in a monthDuring data analysis, the inter-birth intervals were first analyzed descriptively in order to assess their distributional features. Then a binary outcome variable was defined by assigning the inter-birth intervals into one of the two categories according to the WHO recommendation such that2). Factors associated with non-adherence were assessed using a multilevel logistic model in order to account for the fact that inter-birth intervals of the same woman are highly correlated. The intervals were considered to be nested or clustered among women. This procedure was conducted using the STATA command, ‘xtlogit’, to obtain random-effects logistic regression results. Odds ratios (OR), their corresponding 95% confidence intervals (CI) and P-values were calculated and presented as well. In interpreting effects such as OR, confidence intervals among other things play the role of P-values. Therefore, presenting OR and their corresponding confidence intervals without the P-values may suffice. However, we also presented the P-values because some readers prefer them for quick inferences about significance. The whole process of data analysis was conducted using STATA (version 11) statistical software . A cut-off point (significance level) at which a factor was identified as a predictor of the outcome, non-adherence, was 5%.Proportions of the inter-birth intervals which were below the WHO recommendation by each of the independent variables were computed and presented, and the degree of association between them was tested using Chi-square . Of these 15,373 intervals, 48.4%  were below the WHO recommended minimum inter-birth interval of 33 months between two consecutive live births for better maternal and child health outcomes  and the difference was statistically significant (P = 0.002). While 43% of the inter-birth intervals beginning with children born in health facilities were non-adherent, 57% of the inter-birth intervals beginning with births that did not occur in health facilities were non-adherent (P<0.001).We also observed a significantly higher proportion of non-adherence among women who became members of the study area through in-migration compared to women who became members through enumeration (55% versus 47%) (P<0.001). Finally, the proportion of non-adherence was similar between inter-birth intervals beginning with male and those beginning with female children (48% versus 49%) (P = 0.215).Results of the multivariate (adjusted) random-effects logistic regression of the factors associated with non-adherence to the WHO recommended minimum inter-birth intervals are presented in Table Furthermore, inter-birth intervals beginning with multiple births were 26% less likely to be non-adherent compared to those beginning with singleton births . Also inter-birth intervals beginning with children born elsewhere other than in health facilities were 85% more likely to be non-adherent compared to those beginning with children born in health facilities . Finally, inter-birth intervals observed among women who became members of the HDSS through in-migration were 32% more likely to be non-adherent compared to those from women who became members of the HDSS through enumeration .Having adjusted for all variables in the multivariate model, the association between non-adherence to the recommended minimum inter-birth interval and place of residence was not significant .Our findings reveal that close to half of the inter-birth intervals in Rufiji district were below the WHO recommended minimum of 33 months between two consecutive live births for better maternal and child health outcomes. This corresponded to more than two in every five women (results not shown) not adhering to the recommendation, implying that a significant proportion of mothers in the study area may be at risk of adverse maternal and newborn health outcomes due to improper birth spacing. The median inter-birth interval of 33.4 months observed in this study is similar to that reported in the recent Tanzania Demographic and Health Survey (TDHS)  and thatThe study further identified a number of factors associated with non-adherence to the minimum recommendation of the WHO on birth spacing. Maternal age and non-adherence were inversely related, such that the younger the maternal age the higher the likelihood of non-adherence to the recommendation and vice versa. We found also that the higher the parity the higher the likelihood of non-adherence. However, there was no statistical interaction between maternal age and parity in the prediction of non-adherence to the recommended minimum inter-birth interval. It is possible that older women may have already achieved their desired family sizes as age advances compared to younger women, hence likely to delay subsequent births . Older wEver married women (divorced or widowed) and those who were still single were less likely to space their births poorly compared to married women. This suggested that women who are currently not married may have less opportunity for childbearing and consequently likely to have longer inter-birth intervals than their married counterparts. Research shows that frequency of sexual intercourse tends to be higher in marriage than in any other category of marital status ,30, thusAbsence of formal education (never been to school) was associated with higher likelihood of non-adherence to the recommended minimum inter-birth interval. Although some studies such as one conducted in Korea in the 1980s showed that better educated women space births poorly , our finInter-birth intervals beginning with multiple births were less likely to be non-adherent than those beginning with a singleton birth. This may be partly due to double or even more logistical difficulties and financial expenses that the family has to incur in the process of upbringing two or more children simultaneously. It may also be due to parents’ satisfaction as far as their desired number of children or family size is concerned, thus likely to delay the next birth. For example, a qualitative study with health service providers in Egypt reports that “… postponing pregnancy for longer periods usually occurs following the second child …” , which mWith respect to place of delivery, inter-birth intervals beginning with births that did not occur in health facilities were more likely than those beginning with births that occurred in health facilities to be non-adherent to the WHO recommendation. Women who seek antenatal care or delivery services from health facilities may have access to education on optimum birth spacing, breastfeeding, family planning and adverse risks of pregnancy and pregnancy outcome. This is thought to have a greater role in influencing pregnancy preparedness and care . TherefoFinally, evidence of in-migrant women being more likely to space their births poorly compared to native residents of the study area indicates the possibility of cultural differences, beliefs and practices of birth spacing . SimilarUnfortunately, there were no data available regarding duration of breastfeeding, contraceptive use, religion, biological and genetic factors, which, if available, would have alighted more on the question posed. There may have been a possibility of misclassifying an inter-birth interval ending in a preterm but with a live birth as inappropriately spaced. Since only one district was studied, our findings may not be generalized to the whole population of Tanzania.Close to a half of all inter-birth intervals in Rufiji district is poorly spaced. Younger maternal age, low maternal education, multiple births from the preceding pregnancy, non-health facility delivery of the preceding birth, being an in-migrant resident, multi-parity and being married are significantly associated with non-adherence to the WHO recommended minimum inter-birth interval of 33 months for better maternal and child health outcomes. Improving maternal, newborn and child health (MNCH) services with a special attention on birth spacing is important in Rufiji district. Community- and health facility-based optimum birth spacing education is urgently required to enhance birth spacing and consequently improve health outcomes of mothers and children in Tanzania.The authors declare that they have no competing interests.AE conceptualized the research question and wrote the manuscript drafts. AE, KB, SM and AS designed the study and analyzed the data. DM, GM and HM participated in designing the study and critically reviewed the manuscript drafts. All authors read and approved the final draft of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2393/12/152/prepub


Radicular cyst is the most common odontogenic cystic lesion of inflammatory origin. It is also known as periapical cyst, apical periodontal cyst, root end cyst, or dental cyst. It arises from epithelial residues in the periodontal ligament as a result of inflammation. The inflammation usually follows the death of dental pulp. This paper presents a case report of a patient with radicular cyst associated with a primary molar. Radicular cyst is an inflammatory jaw cyst originating from epithelial remnants of the periodontal ligament as a result of inflammation that is generally a consequence of pulp necrosis. The resulting cyst commonly involves the apex of the affected tooth . They arVery few cases are seen in the first decade, after which there is a fairly steep rise, with a peak frequency in the third decade. Radicular cysts are rare in the primary dentition, representing only 0.5–3.3% of the total number in both primary and permanent dentitions . The malAn 8-year-old male patient reported to the department of pedodontics and preventive dentistry, PMVIDS, Hyderabad, with a chief complaint of extra oral swelling on the left lower back region of the jaw since 2 months. Past dental history revealed that he had undergone extraction in the same region 7 days ago.On extraoral examination, a well-defined, nontender, hard bony swelling was noticed on the left side of the body of the mandible measuring 2 × 3 cm in size. Intraoral examination revealed grossly decayed left mandibular primary second molar with buccal cortical plate expansion . OrthopaConservative treatment was planned to save premolar tooth bud; treatment plan included extraction of left mandibular first and second molars and followed by marsupialisation under local anaesthesia. A tissue specimen was then sent for the histological examination which confirmed our provisional diagnosis of a radicular cyst. Findings of the histological view showed stratified squamous epithelium with underlying connective tissue. Epithelium showed an arcading pattern . RegularAfter duration of 8 months, it was noted that underlying permanent mandibular premolars 34, 35) erupted into their normal position in the oral cavity, and a new bone formation was found in cystic lesion space (Figures , 35 erupRadicular cysts originating from primary teeth are considered rare. The frequency is low because pulpal and periapical infections in deciduous teeth tend to drain more readily than those of permanent teeth and antigenic stimuli which evoke the changes leading to formation of radicular cyst may be different .According to Mass et al.  the prevAs these cysts are asymptomatic till secondarily infected, they are usually diagnosed during routine radiographs. The sequelae of an untreated or undiagnosed radicular cyst could be harmful to the patient's future dental development. A patient with an untreated radicular cyst may present with the following consequences: swelling, tenderness, tooth mobility, and a bluish tinge caused by buccal expansion of the cortical plates. Furthermore, displacement of the successor tooth or, even more unforgiving, the loss of its vitality may result , 9, 10.In the present case conservative treatment of the cyst that is marsupialization rather than enucleation is considered to save the premolar tooth bud and monitoring the eruption of the tooth.


Dear Editor,Admission to intensive care unit (ICU) is potentially a stressful experience for both the patients and their families. In addition to pain and severity of the critical diseases, sleeplessness, immobility and overwhelming noises from ICU equipments, anxiety from overhearing the stranger and unfamiliar conversations of the staff and visitors about the patients’ conditions, psychologically affect the ICU patient.2]3] Th[3] Th2][ Th[3] ThTo investigate the current status of the visiting hours and policies, we carried out this descriptive cross-sectional study in summer 2009 in all 71 ICUs in Fars Province, south of Iran. A questionnaire based on a previous study, conducted in Italy, was prepThe main finding of the present survey was the uniform practicing restriction on the visiting policy in all ICUs. Gianini et al. similarly conducted a study in Italy and found almost the same results. TendencyRestricted visiting hours dates back to the late 1800s and for a variety of reasons including creating more discipline in the wards and avoiding the transmission of infection. Berti etConsidering the evidence supporting open policies and the present study findings, we can conclude that the revision of current visiting policies in Iran is required in order to create more positive effects and satisfaction on the part of patients and their families. We do not recommend the universal implementation of unrestricted ICU visiting policies but rather a kind of modification in the policies, based on our cultural background so that a balance is established between the patients’ safety, their families’ need and also the nurses and physicians’ management in the ICUs. To do so, further studies need to be carried out to identify the obstacles to the implementation of open visiting policies.


While survival rates of extremely preterm infants have improved over the last decades, the incidence of neurodevelopmental disability (ND) in survivors remains high. Representative current data on the severity of disability and of risk factors associated with poor outcome in this growing population are necessary for clinical guidance and parent counselling.0/7 and 276/7 weeks gestational age during 2000–2008. Mortality, adverse outcome (death or severe ND) at two years, and predictors for poor outcome were analysed using multilevel multivariate logistic regression. Neurodevelopment was assessed using Bayley Scales of Infant Development II. Cerebral palsy was graded after the Gross Motor Function Classification System.Prospective longitudinal multicentre cohort study of preterm infants born in Switzerland between 240/7 weeks postmenstrual age, bronchopulmonary dysplasia, major brain injury and retinopathy of prematurity were the main predictors for adverse outcome (p < 0.05). Survival without moderate or severe ND increased from 27% to 39% during the observation period (p = 0.02).Of 1266 live born infants, 422 (33%) died. Follow-up information was available for 684 (81%) survivors: 440 (64%) showed favourable outcome, 166 (24%) moderate ND, and 78 (11%) severe ND. At birth, lower gestational age, intrauterine growth restriction and absence of antenatal corticosteroids were associated with mortality and adverse outcome (p < 0.001). At 36In this recent Swiss national cohort study of extremely preterm infants, neonatal mortality was determined by gestational age, birth weight, and antenatal corticosteroids while neurodevelopmental outcome was determined by the major neonatal morbidities. We observed an increase of survival without moderate or severe disability. Advances in perinatal care have resulted in improved survival rates of extremely preterm infants over the last three decades. In cont0/7 and 276/7 weeks in Switzerland from January 1st 2000 to December 31st 2008. Routine follow-up of infants below 280/7 weeks gestational age has been recommended and performed by the Swiss Neonatal Follow-up Group since 2000, and follow-up data are prospectively collected in the network database. After the recommendation was issued to base follow-up examinations on the Bayley Scales of Infant Development II (BSID-II)[This was a prospective longitudinal multicentre cohort study including extremely premature infants live born between 24BSID-II), not all0/7 weeks postmenstrual age (PMA)[Gestational age was the best estimate available from the obstetric measurements based on last menstrual period or prenatal ultrasound findings, as recorded in the maternal chart. Birth weight z-scores were calculated based on the growth curves by Voigt et al.. Major bge (PMA). Retinopge (PMA). NEC wasge (PMA). The prege (PMA). Socioecge (PMA).Neurodevelopmental examination was routinely performed by experienced developmental paediatricians or neuropaediatricians at each Swiss Neonatal Follow-up centre at 18–24 months corrected age (i.e. the age the infant would be if he had been born on his due date). The assessment consisted of a clinical examination, a structured neurological assessment and a developmental assessment using the BSID-II. Vision Outcome at two years of age was defined according to the guidelines of the working group of the British Association of Perinatal Medicine and the National Neonatal Audit Project on the Classification of Health Status:Death before two years of age.i) Severe neurodevelopmental disability; defined as CP with GMFCS level 3–5; or a BSID-II score of < −3SD below the mean (i.e. MDI or PDI <55), or absence of useful hearing even with aids (i.e. >90dB hearing level), or blindness or only perception of light or light reflecting objects.ii) Moderate neurodevelopmental disability; defined as CP with GMFCS level 2, or a BSID-II score between −3 and −2 SD below the mean (i.e. MDI or PDI 55–69), or hearing loss corrected with aids (40-90dB hearing level), or moderately reduced vision but better than severe visual disability, or unilateral blindness with good vision in the contralateral eye.iii) Favourable outcome; defined as absence of any of the above.iv) Adverse outcome was defined as the combination of death or severe ND. Unfavourable outcome was defined as the combination of death, or severe or moderate ND.Chi-square test and Mann–Whitney U test were used to compare subgroups in nonadjusted comparisons.Two different time points were chosen for the outcome prediction models:i) at time of birth: this dataset included all live born children, and the covariates known at birth0/7 weeks PMA: this dataset included all infants surviving up to 360/7 weeks PMA, and the covariates known by 360/7 weeks PMA.ii) at 360/7 weeks PMA. Pre-planned sensitivity analyses were performed excluding children who died in the delivery room since many of these children were a priori treated in a palliative way. We used random-effects multi-level regression models with centre-specific intercepts to allow for clustering on the study centre level (9 centres) and for year of birth . We then performed multivariate regression analysis for each of the outcome parameters. For multivariate analyses, all explanatory variables that showed an association  in the univariate analysis with consistent findings in sensitivity analyses or that are known to act as a confounder were included. The following covariates are included in analyses assessing outcome prediction at birth: gestational age (weeks plus days), birth weight z-score , sex, antenatal corticosteroids and multiple birth. The following covariates are included in analyses assessing outcome prediction at 36 weeks PMA: gestational age (weeks plus days), birth weight z-score, sex, antenatal corticosteroids, multiple birth, PDA, NEC, sepsis, ROP stage 3 or higher, BPD, major brain injury and socioeconomic class.We first selected the clinical and demographic variables known to determine mortality and adverse outcome based on evidence from the literature,27. We t0/7 weeks PMA. BPD, major brain injury, ROP stage 3 or higher, and NEC or proven sepsis were selected for the model given their strong association with outcomes. The risk for adverse and for favourable outcome was estimated according to whether one, two, three or four of the risk factors were diagnosed in an infant. Associations are given as Odd’s ratios (OR) with 95%-confidence intervals (95% CI) and the two-sided p-values. All analyses were performed using STATA 12.2  and R for the models with splines.A logistic regression model was calculated to predict adverse and unfavourable outcome after 360/7 and 276/7 weeks. Of those, 60 were excluded due to major congenital malformations. Of the included 1266 extremely preterm infants, 422 (33%) infants died: 130 died in delivery room, 280 died after delivery room but before 360/7 weeks PMA, and 12 died between 360/7 weeks PMA and two years of corrected age. Of the 844 surviving infants, 160 (19%) did not receive BSID-II testing and were excluded from the analysis: 109 (13%) infants were lost to follow-up , and 51 (6%) were evaluated using other tests. Children not tested with the BSID-II had a significantly higher gestational age and birth weight, and were more likely to be outborn, delivered by vaginal delivery, and less likely to have BPD than those tested with the BSID-II , with a p-value of <0.001). Infants with none of the risk factors had an adverse outcome in 6% and had a favourable outcome in 71% (FigureThis study reports on mortality and outcome at two years of age in extremely preterm infants in a Swiss cohort born after 2000, based on a nationwide prospective registry and follow-up program. Thereby it provides representative outcome information on a national level over a nine-year period. To the best of our knowledge, these data represent one of the largest datasets on a recent birth cohort.The incidence of severe ND was 11%, while 24% of infants survived with moderate ND. The overall rate of any ND was moderately higher than reported in a similar cohort born in 2005 in Victoria, Australia. MortaliAt birth, death and severe ND were mainly predicted by low gestational age and low birth weight, while antenatal corticosteroids to induce fetal lung maturation had a strong protective effect. Male sex increased the risk of adverse outcome, but it played a minor role compared to previous reports,13. Surp0/7 weeks PMA was only weakly influenced by the main perinatal factors gestational age, intrauterine growth, sex and lung maturation. Instead, the major neonatal morbidities such as BPD, ROP, major brain injury and NEC or sepsis played a major role. Our results are in agreement with a previous study reporting that the prognosis for very preterm infants changes during the course of early postnatal life depending on the incidence of neonatal morbidities[Long-term outcome in children surviving to 36bidities. Our finbidities,22. Howebidities.Several limitations of this study need to be mentioned. Nineteen percent of surviving infants did not receive BSID-II testing and were excluded from the logistic regression analyses. Even if our follow-up rate of 81% is comparable to published studies, the infThe strengths of this study include the fact that it is based on a large national prospective database. The definition of neurodevelopmental outcomes was based on a recent consensus definition. The definition of severe ND required extremely low cognitive or motor performances, i.e. <−3SD, and/or severe neurosensory disabilities, thus identifying severely disabled children. In comparison, the definition of neurodevelopmental disability used in several previous studies overlaps with our definition of severe and moderate ND,22,42. TThis population-based study of extremely preterm infants shows that, although more than a third of infants still suffer from moderate or severe ND, the rate of survival without major neurologic sequelae has increased significantly over the last decade, while the mortality rate decreased. Neonatal mortality was predominantly dependant on gestational age, birth weight z-score and antenatal corticosteroids, while outcome at two years of age in children surviving the neonatal period was best predicted by BPD, ROP, and major brain lesions as diagnosed using head ultrasound examination. This study provides representative national data, which may assist in decisions on care of extremely preterm infants, and which can contribute to improve both the quality of care as well as the counselling of parents.Giancarlo Natalucci received financial support by the Swiss National Science Foundation; grant 33CM30-124101. The authors declare no actual or potential conflict of interest in relation to this manuscript.LS, MA, and GN had primary responsibility for the study design, data acquisition, data analysis and writing the manuscript. EP was involved in data analysis and data interpretation and writing of the manuscript. MA, MAe, BL, HUB, SG, CBT, and MBG were involved in study design, data acquisition and in revising the manuscript. All authors approved the final version of this manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/12/198/prepub


A primary hydatid cyst of the adrenal gland is still an exceptional localization. The adrenal gland is an uncommon site even in Morocco, where echinococcal disease is endemic.We report the case of a 64-year-old Moroccan man who presented with the unusual symptom of arterial hypertension associated with left flank pain. Computed tomography showed a cystic mass of his left adrenal gland with daughter cysts filing the lesion (Type III). Despite his negative serology tests, the diagnosis of a hydatid cyst was confirmed on surgical examination. Our patient underwent surgical excision of his left adrenal gland with normalization of blood pressure. No recurrence has occurred after 36 months of follow-up.There are two remarkable characteristics of this case report; the first is the unusual location of the cyst, the second is the association of an adrenal hydatid cyst with arterial hypertension, which has rarely been reported in the literature. Echinococcus granulosus larva and is endemic in many countries, including those in the Middle East, Eastern Europe, Africa, Latin America and China. It poses an important public health problem and disease spread is influenced by socioeconomic status and migration [Hydatid disease (HD) is caused by igration . Althougigration . Other sThe adrenal gland is considered as an exceptional localization of a hydatid cyst. Parasitic cysts involving the adrenal glands are usually secondary and part of generalized echinococcosis. The reported incidence of adrenal hydatidosis is 0.5% . We repoA 64-year-old Moroccan man was admitted to our department for left flank pain with no particular irradiation that had started one month previously and nausea and vomiting of one day's duration. He reported no digestive or urinary symptoms and was afebrile. He had no significant medical history apart from new-onset arterial hypertension one year before  requiring combination therapy with bisoprolol and amlodipine. He denied any contact with dogs or sheep.3) and by eosinophilia (7% eosinophils). His blood biochemistry was normal. Other laboratory results were normal, including his renin, aldosterone and 24-hour urinary vanillylmandelic acid and metanephrine levels. A serologic test of the hydatid cyst was negative.His physical examination was unremarkable and a standing abdominal radiography was normal. Abdominal ultrasonography revealed a large hypoechoic mass, containing an internal cystic component adjacent to the superior pole of his left kidney. Initially it was almost impossible to find its contacts and origin Figure . A compuAfter the radiological findings, the mass was diagnosed as a giant primary adrenal hydatid cyst; although our patient denied animal contact, the cyst was presumed to be hydatid, and surgical exploration was planned, based on these data.Our patient underwent an open laparotomy through a midline incision and the cystic lesion of his left adrenal gland was identified. The exploration found a multivesicular hydatid cyst of the upper pole of the left adrenal measuring 18 cm×10 cm×8 cm. The abdominal cavity and especially the region around the cyst was carefully protected and isolated by pads soaked in hypertonic 20% saline solution. The cyst was not drained nor aspirated during the surgical procedure. An appropriate dissection plane between the cyst and the adrenal gland could not be found, so both the cyst and the adrenal gland were removed. It is noteworthy that our patient remained hemodynamically stable without any hypertensive crisis during the operation. A macroscopic examination revealed a germinate membrane and daughter cysts and a microscopic examination revealed scolices in the cyst fluid. A histological examination confirmed the diagnosis. The postoperative course was uneventful. Our patient underwent therapy with albendazole (800 mg/day) for one month. There was a progressive reduction in his arterial pressure after the operation, and three months after the surgery his blood pressure was about 130/80 mmHg, with no medication and no particular diet. At the most recent follow-up, 24 months later, ultrasound monitoring did not detect any hydatid recurrence, and our patient was doing well and symptom free.E. granulosus passes through lung and liver filters to disseminate through the bloodstream. There have been 20 cases of primary hydatid cyst of the adrenal glands reported up to 2007 [Symptomatic hydatid cystic disease of the adrenal glands is rarely observed in clinical practice and accounts for about 7% of the cysts in the adrenal gland . Most hy to 2007 . Most ad to 2007 , or the  to 2007 . Rarely, to 2007 -11. Clin to 2007 .Our reported case presents two important elements. Firstly, primary HD of the adrenal gland is rare and only a few cases have been reported in the literature . SecondlIn laboratory tests, eosinophilia is present in 25% of cases, as in our patient. A Casoni skin test and indirect hemagglutination tests are not completely reliable for diagnosis. New, more sensitive and specific serological tests are available, including complement fixation, enzyme-linked immunosorbent assays, arc-5 precipitation and a specific hydatid immunoglobulin E test , which cThe imaging features of HD depend on the stage of evolution of the disease. Early lesions appear purely cystic; after modification of the germinal layer and a reduction of intraluminal pressure the capsule becomes fibrotic and sometimes calcified, while the daughter cysts discharge from the wall and float in the lumen.et al. [et al.Hydatid cyst identification in the adrenal gland is based mainly on ultrasonography and CT scans , with thet al. , which iFew reports of magnetic resonance imaging (MRI) of adrenal HD have been published. On MRI, the complex cyst contents can be well displayed and the cyst membrane, whether collapsed or not, can be clearly seen as a low-intensity curvilinear structure on both short and long repetition time spin-echo images .The differential diagnosis of an adrenal cyst should include an endothelial cyst, a pseudocyst due to infarction or hemorrhage in the adrenal gland, cystic neoplasm and a post-traumatic cyst ,18,19.Treatment of HD of the adrenal glands is mostly surgical. Pericystectomy and resection of the entire adrenal gland are the two preferred choices. Resection of the cyst with conservation of the gland remains the optimal procedure. It is preferable to follow an appropriate dissection plane between the cyst and the adrenal gland in order for a complete cystectomy to be achieved. However, it is not always feasible and may cause hemorrhage owing to the close adherence of the cystic wall to the adrenal gland's parenchyma. In case of hemorrhage or a failure to perform the cystectomy, ablation of the entire adrenal gland including the cyst should be performed. Partial cystectomy includes a higher risk of dissemination of the parasite due to the dissection's maneuvers . Access Recent minimally invasive surgical techniques like transabdominal laparoscopy and retroperitoneal endoscopic adrenalectomy have been conducted ,21. HowePuncture, aspiration, injection and re-aspiration (PAIR) treatment of hydatidosis is considered minimally invasive, confirms the diagnosis and improves the efficacy of chemotherapy given before and after puncture. PAIR is usually avoided in patients with adrenal hydatidosis, but can become an alternative method in inoperable cases ; howeverAntihelmintic agents have been used in the treatment of systemic echinococcosis in endemic areas . There aIn endemic countries such as Morocco, primary HD should be considered in the differential diagnosis of an adrenal cyst and no attempt to preoperatively puncture or to perform any other manipulation of the lesion should be done. CT associated with hydatid serology can confirm the diagnosis. The treatment of choice is a pericystectomy of the hydatid cyst if it is possible or, otherwise, total excision of the adrenal gland. The association of an adrenal hydatid cyst with hypertension is very rare. In such cases, surgical removal of the hydatid cyst may also treat the hypertension. Laparoscopic resection of an adrenal hydatid cyst is an alternative to conventional surgery; however, it has been described only sporadically. Finally, the prevention of hydatid infection is a necessary step to prevent HD regardless of its location.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.FT and MA were the principal authors and major contributors in writing the manuscript. AK and SM analyzed and interpreted the patient data and reviewed the literature. RE, SW, MJE and MHF read and corrected the manuscript. All authors read and approved the final manuscript.


Bronchogenic cyst is considered as an uncommon congenital anomaly. It can be mostly found in mediastinum or lung. Intracardiac bronchogenic cyst is very rare. We found 2 cases in more than 20000 cardiac surgical cases in our department. The 2 cases bronchogenic cyst arose from interatrial septum (IAS), the preoperative diagnosis were myxoma, but the histological diagnosis were bronchogenic cyst in both cases. Although it is very rare, it should be considered while intracardiac tumor is diagnosed. It is recommended to complete resection of any bronchogenic cyst for primarily diagnostic and potentially therapeutic reasons, and every effort should be made to prevent complications due to injury to nearby tissues. Bronchogenic cyst is considered as an uncommon congenital anomaly. It can be mostly found in mediastinum or lung. Intracardiac bronchogenic cyst is very rare. We found 2 cases in more than 20000 cardiac surgical cases in our department. The 2 cases bronchogenic cyst arose from interatrial septum (IAS), the preoperative diagnosis were myxoma, but the histological diagnosis were bronchogenic cyst in both cases. It is always misdiagnosed as the other intracardiac tumor.th day postoperative. No recurrence of the tumor was noted during the 5 year follow-up. Under microscopy, the cyst lining was ciliated columnar epithelium or so-called respiratory epithelium (Figure A 36-year-old woman with a short history of palpitation and mild dyspnea on exertion was admitted into our clinic, physical examinations and the chest radiograph were within normal ranges, echocardiography showed the ventricular and valve function were normal, a mass of 3.2 × 2.7 cm attached to the IAS was discovered in the right atrium Figure . The preAnother 29-year-old woman with a history of palpitation and dyspnea on exertion in the last 4 months was referred to us. Systolic murmur was found by auscultation, the chest radiograph was also within normal ranges, echocardiography revealed a 2.5 cm ASD together with a 1.8 × 1.9 cm mass attached to the IAS protruding into the left atrium. Computed Tomography showing a 2.5 cm ASD, a cyst of 2.0 × 1.9 cm was found, the average attenuation value inside the left atria tumor was approximately 15 Hu Figure . The opePostoperative course was uneventful, the patient was discharged 10 days post-operation. Echocardiography revealed no recurrence during the 3 years follow-up.th and the 40th day of intrauterine life, during the most active period of airway development. Cardiac primordia exist in a place very near to the foregut or primitive tracheobronchial tree. At this time, abnormal budding of the tracheobronchial tree may migrate to a myocardial location; bronchogenic cysts arise from such budding. Thus, cysts are usually at the pericardium, and it is very rare that tumors are in the interatrial septum [The location of the bronchogenic cyst can be explained by embryogenesis. Bronchogenic cysts are believed to represent a localized portion of the tracheobronchial tree that becomes separated from normal airways during the branching process and does not undergo further development. Most probably develop between the 26l septum ,2.Intracardiac bronchogenic cysts are rare and are located on the epicardial surface or within the myocardium projecting into one of the cardiac cavities . In the A bronchogenic cyst is a benign tumor. Many cases are asymptomatic with the lesions incidentally detected. Symptoms of intracardiac bronchogenic cysts such as chest pain, shortness of breath and arrhythmias can vary according to the location of the cyst, its size and compression of heart and vessels ,5.st case we presented was larger than the ASD, the symptoms may come from the occlusion by the mass. But the ASD was bigger than the cyst in the 2nd case, the symptoms may due to the ASD.The tumor of the 1Most intracardiac bronchogenic cysts were found by transthoracic and transesophageal echocardiography, the diagnosis was made by contrast-enhanced chest helical CT and cardiac MRI and later was approved intraoperatively ,6.While considering an intracardiac tumor, myxoma, papillary fibroelastoma, thrombus, metastasis, etc. is usually considered. For a cystic tumor in the cardiac chamber, bronchogenic cyst should be in the differential diagnosis list ,6. The pBronchogenic cyst is a benign tumor, but definitive diagnosis should be made by pathology study. It is not possible to perform biopsy in the cardiac chamber because pulmonary or cerebral embolism may be resulted from the fluid contained. Bronchogenic cysts may develop into malignancy -9. St-GeAlthough bronchogenic cyst of interatrial septum is very rare, it should be considered while intracardiac tumor is diagnosed. It is recommended to complete resection of any bronchogenic cyst for primarily diagnostic and potentially therapeutic reasons, and every effort should be made to prevent complications due to injury to nearby tissues.Written informed consent was obtained from the patient for the publication of this report and any accompanying images.The authors declare that they have no competing interests.HJ conceived, designed and drafted the manuscript, and performed the surgery. HSW involved in the clinical discussion of the cases. HBW was the consultant in charge of the patient’s care. XML performed the surgery and collected the imaging data. All authors read and approved the final manuscript.


Asthma is a chronic inflammatory disorder of the lung airways that is associated with airway remodeling and hyperresponsiveness. One of the most critical structural changes that affect airway functionality is fibrotic tissue deposition within the airway wall. Eosinophils have been proposed in different studies to contribute to the production of several mediators and cytokines, including the profibrotic cytokines, TGF-β and IL-11. In this study, we hypothesize that cytokines prevailing in asthmatic tissue such as Th1, Th2, and Th17 cytokines, may induce eosinophils to produce pro-fibrotic cytokines..Eosinophils were isolated from peripheral blood of 6 mild asthmatics and 6 normal control subjects. Eosinophils were stimulated with Th1, Th2 and Th17 cytokines and production of pro-fibrotic cytokines, TGF-β and IL-11, were determined using Intra-cellular cytokine detection and FACS analysis, immunohistochemistry, as well as real time PCRThe level of basal expression of eosinophil TGF-β and IL-11 was significantly upregulated in asthmatic patients compared to healthy individuals. Stimulating eosinophils with Th1 and Th2 cytokines did not induce expression of eosinophils derived pro-fibrotic cytokines. However, stimulating eosinophils with IL-17 resulted in the enhancement of the expression TGF-β and IL-11 in asthmatic individuals.The regulation of expression of pro-fibrotic cytokines within eosinophils is Th1/Th2 independent. However, IL-17 seems to regulate eosinophl profibrotic cytokine release in asthmatic patients and hence contributing to the accumulation of fibrotic tissue in asthmatic airways.


In our recent paper , we suggIn Govarts et al.’s reanalysis, adjustment for GWG resulted in a reduction in the association from a 293-g decrease  in birth weight per 1-µg/L increase in cord serum PCB-153 to 153 g , which represents a 48% reduction in the effect estimate. In comparison, our analyses using pharmacokinetic modeling suggested that 79% of the 150-g  reduction in birth weight per 1-µg/L increase in cord serum PCB-153 reported in the original paper by In their letter, Govarts et al. touched on the assumptions of pharmacokinetic models. Both meta-analyses of observational data  and pharWhether some causal (or perhaps any) association exists between environmental PCB-153 exposure and birth weight is probably beyond the resolution of currently available or practicable methods.


Animal models suggest growth restriction in utero leads to lower levels of motor activity. Furthermore, individuals with very low birth weight report lower levels of physical activity as adults. The aim of this study was to examine whether birth weight acts as a biological determinant of physical activity and sedentary time. This study uses combined analysis of three European cohorts and one from South America . Birth weight was measured or parentally reported. Height and weight were measured and used to calculate Body Mass Index (BMI). PA was objectively measured using accelerometry for ≥3 days, ≥10 hours day. Data was standardized to allow comparisons between different monitors. Total physical activity was assessed as counts per minute (cpm), with time spent above moderate activity (MVPA) >2,000 counts and time spent sedentary (<100 counts). There was no evidence for an association between birth weight and total physical activity (p = 0.9) or MVPA (p = 0.7). Overall there was no evidence for an association between birth weight and sedentary time (p = 0.8). However in the Pelotas study we did find an association between higher birth weight (kg) and lower overall physical activity (cpm)  and higher birth weight and greater sedentary time (mins/day) , although this was attenuated and no longer significant with further adjustment for gestational age. Overall this combined analysis suggests that birth weight may not be an important biological determinant of habitual physical activity or sedentary behaviour in children and adolescents. Lower birth weight individuals may be at greater risk of metabolic diseases in later life, such as diabetes There is some evidence from animal models suggesting that growth restriction in utero can lead to reduced motor activity The aim of this study was to examine whether birth weight acts as a biological determinant of physical activity levels across normal birth weight ranges, using a combined analysis of data from four cohort studies with objectively measured physical activity. We investigated the associations between birth weight and physical activity, not only in terms of overall physical activity, but also sub-components (i.e. time spent at moderate and vigorous intensity activity) of physical activity, as well as the association between birth weight and objectively measured sedentary time.All studies were approved by their respective local medical ethics committees and all participants provided informed parental consent and where appropriate informed child assent.The ‘European Youth Heart Study’ (EYHS) is a large population based cohort from four European countries; Denmark, Norway, Portugal and Estonia, aimed at investigating lifestyle, environmental, and socio-cultural factors associated with cardio-metabolic risk. The sampling procedure, methods and measurements have previously been described in detail The ‘Roots Study’ is a cohort of adolescents, aged 13–15 years at the time of physical activity measurement, selected from schools within the Cambridgeshire region of the UK; the cohort profile has been previously described in detail The ‘Speedy Study’ is a cohort of younger children aged 9–10 years from Norfolk in the UK, which has been previously described The ‘Pelotas 1993 Birth Cohort’ is a population based birth cohort in Southern Brazil Physical activity data was collected using accelerometry in all four studies. EYHS used a 7164 Actigraph monitor, whereas Pelotas and Speedy used a later version of this monitor, the GT1M Actigraph . The Actigraph monitors, used in EYHS, Speedy and Pelotas were worn at the hip using an elastic waist band. The Roots study used a combined heart rate and uniaxial accelerometer  mounted on the chest using ECG electrodes to allow collection of heart rate data in addition to a vertical accelerometer. See Output from different physical activity monitors is not directly comparable As the physical activity data collected the Roots study differed, not only in terms of the monitor itself but also the monitor placement, we developed a suitable conversion factor to apply to the acceleration data from the combined movement and heart rate sensor to ensure it was comparable to the two Actigraph monitors used within the other three studies. Comparable cut points for time spent sedentary, and in moderate activity and vigorous intensity activity were estimated using a laboratory protocol where the volunteers simultaneously wore a 7164 accelerometer and a combined movement and heart rate sensor while walking and running on a treadmill http://www.mrc-epid.cam.ac.uk/Research/Programmes/Programme_5/InDepth/Programme%205_Downloads.html). All data was processed in 60 second epochs. Missing data or monitor ‘non worn time' was assumed from continuous runs of zero activity counts. For the EYHS and Speedy studies, we excluded runs of zeros >10 mins using the MAHUffe program. Two studies (EYHS and Speedy) asked volunteers to wear their physical activity monitor during waking hours only, while the other two studies (Roots and Pelotas) had 24 hour wear protocols. To avoid the data being unduly influenced by the increased wear time, accelerometry data was excluded for the overnight period between 23:00 hours and 07:00 hours for the two studies that employed a 24 hour protocol (Roots and Pelotas). For Pelotas and Roots the MAHUffe programme was used to generate hourly data and thereafter manually processed in a statistical programme to exclude all data between 23:00 and 7:00. Therefore, any runs of >60 mins of zeros were excluded as ‘non worn time’ before further analyses.Raw acceleration data files from each individual were processed using a bespoke computer programme . Since cpm is dependant on the wear time a ‘valid day’ was restricted to those recording >10 hours of accelerometry data.Time spent in moderate and vigorous activity (MVPA) was calculated as time spent above 2,000 counts per minute All studies provided a self-reported parental measure of socio-economic status (SES). EYHS combined the mean of parental income and parental education level, categorised from 3–16. For the Roots study 5 categories based on parental wealth and employment were used, while the Speedy study categorised parental education into 6 groups from no qualifications through to degree/post graduate. Finally Pelotas, used years of maternal education, categorised into three groups 0–4, 5–8, ≥9.2).All studies also measured both height and weight according to standard anthropometric protocols, described in detail elsewhere: EYHS Mean and standard deviations are shown for the key descriptive variables, including testing for differences between the four study populations, using one-way ANOVA. To allow comparisons across the differing age ranges of the four study populations, age and sex specific z-scores were created using the WHO Child Growth Standards 2007 The associations between birth weight, modelled as a continuous variable, and components of physical activity  and sedentary time were estimated by multiple linear regression analysis separately within each study. Initial models included adjustment for age, sex and monitor worn time. Models were then repeated additionally adjusting for SES and then with further adjustment for BMI to investigate whether overall adiposity influenced any observed associations. To investigate any gender interactions, an interaction term of ‘birth weight x sex’ was added to the model. No significant interaction was observed for any of the studies (p>0.05). Therefore all analysis was performed in the whole dataset, adjusting for sex.Associations between birth weight (quartiles) and components of objectively measured physical activity within each individual study are displayed graphically. These were presented as figures, with means and 95% CI for each quartile, adjusted for sex, age, SES, monitor wear time and BMI.The beta coefficients were then combined across studies using random effects meta-analysis, and forest plots were used to display the study-specific and combined estimates of association and 95% confidence intervals. Analyses were performed using SPSS v14.0  and Stata version 10 .Descriptive statistics (mean and SD) for each of the four studies are displayed in Results from the combined analysis suggested that there was no significant association between birth weight and objectively measured total physical activity (cpm), with a positive point estimate, but overlapping the null (p = 0.9) , when adAlthough the 95% confidence intervals for three of the studies overlapped the null, the Pelotas study did show a significant association between higher birth weight and lower levels of total physical activity. In this study a 1 kg increase in birth weight was associated with 34 less cpm  adjusted for age, sex and monitor worn time . After aThere were no significant associations between birth weight and time spent in MVPA , with thThere was no overall association between birth weight and sedentary time (p = 0.8) Data from the Roots study suggested a negative association, with higher birth weight being associated with reduced sedentary time when adjusted for age, sex, SES, monitor worn time and BMI . When displayed graphically, using quintiles of birth weight, the association seemed to be driven by the bottom two quintiles of birth weight .However, the data from the Pelotas study showed a positive association, with higher birth weight associated with greater sedentary time when adjusted for age, sex and monitor worn time  . This asWhile lower birth weight has previously been associated with reduced physical performance This is consistent with the results from a previous study in children and adolescents Some of the individual studies within this combined analysis did however detect significant associations between birth weight and physical activity or sedentary time, which warrants further investigation. The data from the Roots study suggested an association between higher birth weight and lower sedentary time, with a 1 kg increase in birth weight equating to 16 mins less sedentary time during waking hours. This association appeared to be largely driven by those in the lower quintiles of birth weight. We are not aware of any other previous studies suggesting an association between lower birth weight and higher sedentary time, although self reported leisure time activity may be reduced in those at the lower end of the birth weight spectrum While in contrast, the results from the Pelotas study suggested that higher birth weight was associated with reduced total physical activity and increased sedentary time with approximately 16 minutes increased sedentary time during waking hours per 1 kg increase in birth weight. These findings in Pelotas are in the opposite direction to the hypothesized association, such as the lower self reported leisure time activity in those born with very low birth weight As the Pelotas study collected data close to the time of birth we were able to further adjust the analysis for gestational age. The associations between birth weight and both sedentary time and total activity, were attenuated and no longer significant with additional adjustment for gestational age. These findings suggest that the associations in Pelotas may be mediated via gestational age or simply that those born at the lower end of the birth weight spectrum are most likely to also be born with a shorter gestation, as birth weight and gestational age were correlated .Since higher birth weight is associated with both increased BMI It was also possible that these findings may be driven by differences in the collection and processing of the physical activity data. The mean and SD for total activity, time spent in MVPA and sedentary time for the Roots and Pelotas studies were very comparable. However both the Pelotas study and the Roots study had 24 hour monitor wear protocols. While we attempted to standardise the studies by excluding overnight data (between the hours of 22:59 hours and 07:00 hours) this may have influenced the findings, particularly if there are country specific differences in waking and sleeping hours. For example there is evidence that teenagers in western societies displace sleep with increased sedentary activities, such as computer use It is possible that the disparate findings from the Pelotas study and the Roots study may represent genuine differences between these populations, as Pelotas is from a developing country, whereas the participants in the Roots study are from a generally affluent region of the UK (Cambridgeshire), so may experience very different in utero environments as well as differences in physical activity patterns. However it should be recognised that, although statistically significant, the magnitude of the associations between birth weight and physical activity and sedentary time are very small and may not be clinically relevant. For example, the data from the Pelotas study suggested that an increase in birth weight of 1 kg was associated with 31 counts per minute less total physical activity. This corresponds to less than one fifth of a SD unit. Similarly, 1 kg higher birth weight was associated with about 16 minutes (2.9%) more sedentary time per day in the ROOTs study, so while the findings are statistically significant they may not be relevant in practical terms.However there are some limitations to this combined analysis, which should be considered when interpreting the findings. For three of the four studies, birth weight was retrospectively reported. Studies suggest that maternally reported birth weight is particularly well recalled and correlates highly with measured birth weight et alet alThis present analysis was limited to those born in the low to normal weight spectrum of birth weights. The recent meta-analysis of self-reported leisure time activity suggests that both low and high birth weight extremes are associated with lower leisure time physical activity Overall this combined analysis suggests that birth weight is not an important biological determinant of habitual physical activity or sedentary behaviour in children and adolescents. This reassuring finding suggests that although lower birth weight may reduce physical capacity in later life, this does not extend to reducing levels of habitual physical activity.