Eight variants were independently associated with intrauterine growth throughout the pregnancy, while four variants were associated with fetal growth in the periods 20–25 or 25–32 weeks of gestation, indicating that some variants may act in specific time windows during pregnancy. Four of the intrauterine growth variants were associated with type 2 diabetes, hypertension or BMI in the UK Biobank, which may provide basis for further understanding of the link between intrauterine growth and later risk of metabolic disease.Fetal intrauterine growth is influenced by complex interactions between the maternal genes, environment and fetal genes. The aim of this study was to assess the effect of GWAS-identified genetic variants associated with birth weight on intrauterine fetal growth in 665 children. Fetal growth was estimated by two-dimensional ultrasound scans at 20, 25 and 32 weeks of gestation and growth trajectories were modeled using mixed linear regression. A genetic risk score (GRS) of birth weight-raising variants was associated with intrauterine growth showing an attenuating effect on the unconditional daily reduction in proportional weight gain of 8.92 × 10 Maternal factors, such as obesity and diabetes, can result in abnormal fetal growth patterns leading to large-for-gestational age (LGA) fetuses, whereas acquired complications during pregnancy such as pre-eclampsia can lead to small-for-gestational age (SGA) fetuses3. Abnormal fetal growth can increase the risk of perinatal adverse effects, but also the risk of morbidity and mortality in adult life6.Fetal intrauterine growth is influenced by complex interactions between the maternal genes and environment, and fetal geneset al. in 19937. This lead to a number of observational studies, which demonstrated that adverse environmental factors during fetal development increase the lifelong risk of metabolic and cardiovascular complications12. Subsequently, the maternal factors associated with birth weight have been carefully studied in numerous epidemiological studies12.An association between fetal growth and the occurrence of metabolic syndrome later in life was first noted by Barker 13. Similarly, a number of genetic association studies have identified single gene variants associated with abnormal fetal growth. Many of these variants are additionally known to be associated with type 2 diabetes (T2D), maturity-onset diabetes of the young (MODY) subtypes, or rare congenital diseases leading to metabolic alterations16. Most studies have used birth weight as a surrogate of intrauterine growth and have not assessed fetal genetic effects during specific gestational growth periods. Therefore, little is known on how fetal genetic variants may affect intrauterine growth, and if genetic variants have specific gestational periods, in which they are more important for fetal growth. Thus, we aimed to evaluate the prenatal effect of the recently GWAS identified birth weight variants by testing the impact of variants combined in a genetic risk score (GRS) on overall fetal growth during 2nd and 3rd trimester and independently during specific gestational weeks of fetal development. Subsequently, we hypothesized that the variants with the largest effect on fetal intrauterine growth, in this study, may represent essential growth pathways that could provide insight into the well-established link between intrauterine growth and adult disease. We therefore explored if the variants associated with fetal intrauterine weight were also associated with development of hypertension, T2D and BMI in adulthood using data from the UK Biobank.Knowledge about the fetal genetic contribution to intrauterine growth is limited. A recent genome-wide association study (GWAS) identified 60 loci associated with birth weight and concluded that 15% of the variance in birth weight can be explained by fetal genetic variation2  percentage points per day per birth weight-raising allele  percentage points per day, corresponding to a mean difference at term of 410 g  g between a child with the lowest and highest GRS  percentage point lower reduction in daily proportional increase in abdominal circumference per birth weight-raising allele , and in the period week 25–32 , an additionally a strong association in the period week 32 to birth .We tested if the GRS was associated with abnormal fetal weight measured as either LGA or SGA. We found no association between the GRS and LGA ) and similarly, no association between the GRS and SGA was found ).2 × GRS) and the given traits. There was no interaction between maternal pre-pregnancy BMI and intrauterine growth (p = 0.47) or birth weight (p = 0.45), and similarly no interactions when testing across tertiles of the GRS (p = 0.89).We hypothesized that maternal environmental traits such as smoking, BMI and glucose levels might influence the effect of the GRS, and tested if there were any interactions between the additive per allele effect of the GRS on change in daily proportional weight gain per day  percentage points per day per birth weight-raising allele  percentage points per day per birth weight-raising allele compared to 8.92 × 10−6  without co-conditioning of BMI.We assessed the effect of co-conditioning of maternal BMI on fetal growth (including birth weight) and observed a small effect of BMI on the attenuation of the daily proportional weight gain by 5.01 × 102 × GRS × glucose) in the mixed linear regression model of intrauterine growth. We found no interaction of maternal glucose levels on intrauterine weight (p = 0.76) or birth weight (p = 0.90).We then tested if maternal glucose levels were interacting with the GRS. We had measures of 2 hour glucose levels from oral glucose tolerance tests (OGTTs) in 155 women and included the interaction term (GA2 × GRS × smoking) and found no effect of maternal smoking on intrauterine weight (p = 0.82) or birth weight (p = 0.10).Sixty-two of the mothers were smoking during pregnancy. We tested the interaction , with the same direction of effect in the DIAGRAM GWAS (p = 1.7 × 10−7). We tested for association with BMI and found an inverse association with rs700059 , and a positive associations with rs10830963  and rs72851023 . The GIANT GWAS of 339,224 individuals has previously reported same direction of effect for association between variants and BMI , but none of them reaching the GWAS significance threshold (p < 5 × 10−8)21.The eight variants, which were associated with intrauterine fetal growth, were tested for association with T2D, hypertension and BMI in the UK Biobank Table . This waIn this study, we evaluated the combined effect of GWAS-identified birth weight-raising variants on intrauterine fetal growth from 20 gestational weeks to birth. We demonstrate that the birth weight-raising GRS was associated with overall intrauterine fetal growth, suggesting that the fetal genetic contribution to birth weight is mediated throughout pregnancy. We found a difference in birth weight of 410 g in children with low and high GRS, indicating that the combined effect of genetic variants has a marked effect on intrauterine growth, which is measurable at birth. We found eight independent variants with positive effects on intrauterine fetal growth, and our findings suggest that some variants are associated with overall intrauterine weight, while others seem to act in specific gestational time windows. We used an explorative approach to test if the variants, associated with intrauterine growth in this study, were associated with adult metabolic disease in the UK Biobank. We demonstrate that, in particular, two of the variants, rs700059 and rs10830963, are associated with T2D, hypertension or BMI in the UK Biobank. These findings emphasize the importance of the fetal genetic contribution to intrauterine growth, which may provide the basis for further understanding of the link between intrauterine growth and risk of later metabolic disease.−4) corresponding to an attenuation of the reduction in daily proportional weight gain by 8.92 × 10−6 percentage points per day per birth weight-raising allele. We hypothesized that maternal environmental factors might influence the effect of the GRS and found a marginal independent effect of maternal pre-pregnancy BMI. Previous studies, have assessed the impact of maternal BMI on fetal growth, and it is well-established that maternal obesity increases the risk of a large-for-gestational age fetus22. Similarly, greater fetal biometries can be detected in obese women as early as 21 weeks of gestation and estimated fetal weight is progressively greater from 30 weeks of gestation in compared to normal weight women19. However, despite these previous associations between maternal obesity and fetal growth, our study implies that maternal BMI only has a marginal effect on genetic growth trajectories of the fetus. The effect of maternal BMI on genetic growth trajectories could be mediated through a stronger genetic predisposition to obesity, which in the mother leads to a higher BMI, and cause a similar phenotype in the fetus with increased intrauterine growth and higher birth weight23.Birth weight has previously been used for assessment of fetal intrauterine growth, since it is a simple measure, obtained on most individuals at birth, and easy to compare across cohorts. However, birth weight does not give comprehensive information on growth trajectories during pregnancy. In this study, we used ultrasonic measures of fetal weight, which enabled us to draw a detailed picture of the impact of genetic variants on fetal growth at specific time points during pregnancy. We found a significant effect of the GRS on overall intrauterine growth from 20 weeks of gestation to birth  mutations, which causes altered pancreatic glucose-sensing. A fetal GCK mutation causes a ~530 g decrease in birth weight, whereas a maternal GCK mutation causes a ~600 g increase in birth weight; but if the GCK mutation is present in both mother and fetus, no effect on birth weight is observed15. A similar effect has been observed for TCF7L2, a mutation in which causes an increase in birth weight when carried by the fetus and/or mother14; an effect likely mediated by elevated fasting plasma glucose levels. Our results do not indicate that the combined genetic effect of birth weight variants on intrauterine growth is mediated or modified by stimulated plasma glucose. However, it is possible that maternal obesity-related traits could lead to higher birth weight regardless of fetal genotype as we see in the independent effect of BMI on intrauterine growth27.When assessing the impact of fetal genetics on intrauterine growth, it is important to acknowledge that 50% of genes are shared between mother and fetus. In general, the maternal genotypes contribute relatively little to birth weightWe identified eight variants positively associated with intrauterine growth during pregnancy. All eight variants were exerting their effect on fetal growth throughout pregnancy and not in specific gestational weeks. In contrast, two variants (rs61830764 and rs61862780) showed association with fetal growth in the period week 20–25, suggesting that these may be more important for fetal growth in the second trimester of pregnancy. Similarly, two variants (rs6989280 and rs28510415) were associated with fetal growth in week 25–32, indicating that their effect is most important in late second trimester and early third trimester.IGF1) gene, which encodes the insulin-like growth factor 1 hormone (IGF1). In mice, maternal IGF1 has been shown to stimulate fetal growth by increasing the transfer of nutrients across the placenta in vivo29, while in vitro studies have suggested that fetal IGF1 stimulates fetal growth30. Concurrently, ablation or differential methylation of IGF1 has been shown to cause abnormal fetal growth in mice31. In line with these findings, our results suggest that rs7964361 may play a role in fetal intrauterine growth.The variant, rs7964361 had the largest effect size, attenuating the unconditional reduction in daily proportional weight gain and is located in the insulin-like growth factor 1 . rs10830963 is an intronic variant located in the Melatonin receptor 1B gene (MTNR1B), which encodes one of the two receptors of melatonin, a hormone involved in circadian rhythms. Previous studies have reported a strong effect of rs10830963 on fasting glucose levels, insulin secretion and disposition index35, as well as risk of T2D identified through large GWAS37. Similarly, GWAS significant association of rs10830963 and offspring birth weight in maternal carriers have recently been reported38. The association between maternal rs10830963 and birth weight is likely mediated through elevated maternal fasting glucose levels, causing increased placental transfer of glucose, which leads to higher fetal insulin secretion and thereby increased birth weight. Our study suggests that the effect of the fetal variant also leads to increased fetal intrauterine growth. However, whether the effect is caused by maternal transmission of the variant, is mediated through altered maternal glucose levels38 or if the variant affects fetal glucose regulation per se is unknown. Further studies are needed to investigate this.A number of observational studies have highlighted the importance of the intrauterine environment in relation to disease risk later in life, such as development of T2D. The association between birth weight and T2D is mediated through both non-genetic and genetic factors, among which the genetic effects during fetal life may play a substantial role13, that assumes an additive and equal effect of all variants at each time point during pregnancy, which may not be completely accurate. We chose this method, because we expect the effect sizes to vary substantially from second to third trimester and the reported effect estimates are based on birth weight alone13. However, using this method does not take into account any interactions between variants or genes that may be present. Additionally, we have used a cohort of 665 children, which for genetic studies may be of relatively small size and of limited power to detect associations. However, we used birth weight variants identified by GWAS, so it is thus plausible that these variants should be associated during prenatal growth without a strict statistical threshold. Another limitation to this study is that we used fetal weight calculated by the Hadlock formula as an estimation of fetal growth, and there may be some inaccuracies in the estimations. In particular, we expect to have some uncertainties in weight estimations in the third trimester, where it is difficult to achieve precise measures of the fetal head and abdominal circumferences. However, we used the same sonographers throughout the study period, which may limit the intra-observer and inter-observer variations. We did not have data on maternal genotypes in this study, which would have made it possible to assess how maternal genotypes would affect fetal growth and adjust our analyses accordingly. In line with this, detailed information and adjustment for maternal environmental factors such as diet and gestational weight gain would have strengthened the analyses.There are some limitations to this study. First of all, we used an unweighted GRS comprised of GWAS-identified birth weight variantsIn conclusion, we demonstrate that a GRS of birth weight-raising variants is associated with intrauterine fetal growth suggesting that the fetal genetic contribution to birth weight is mediated throughout pregnancy. We show that some variants influence fetal growth in specific gestational weeks and may be more important for fetal growth in these time windows. Additionally, our study supports that variants associated with fetal intrauterine growth may also have an impact on development of metabolic disease later in life.40.Pregnant women (>18 years of age) attending a nuchal translucency scan at 12 weeks of gestation at Roskilde University Hospital were invited for participation in this study, as previously describedIn addition to the nuchal translucency scan at 12 weeks of gestation, the women were invited for a malformation ultrasound scan at 20 weeks of gestation, and for fetal growths scans at 25 and 32 weeks of gestation. A total of 753 pregnancies were included in the study. Exclusion criteria were missing genotypes, maternal gestational diabetes, pre-eclampsia, and twins gestations, incomplete follow-up, inclusion of pregnancy twice, or presence of an acardiac twin, leaving 665 pregnancies in the study.Ultrasound scans were performed on ultrasound scanners from GE Healthcare  by trained midwifes or medical doctors. Estimation of gestational age was based on ultrasound measurements of the fetal crown–rump length (CRL) at the nuchal translucency scan. Assessment of fetal weight were based on two-dimensional ultrasound and included measurements of abdominal circumference (AC) in mm, bi-parietal diameter (BPD) in mm, occipital-frontal diameter (OFD) in mm and length of the femur bone (FL) in mm. BPD was measured using an ultrasound probe in an axial plane, traversing the thalami, and cavum septum pellucidum with the transducer perpendicular to the central axis of the head. The distance from the outer edge of the near calvarial parietal wall to the inner edge of the far parital calvarial wall was termed the BPD, while distance from the near occipital wall to the far frontal calvarial wall was measured as the OFD. FL was measured as the longest length of the femoral bone in a horizontal plane. AC was measured as the transverse abdominal circumference at the level of the fetal ventricle and portal vein.18:Fetal weight in grams was calculated based on the Hadlock formulath percentile) for gestational age at birth. The definition of large-for-gestational-age (LGA) was a child with a birth weight >22% (>90th percentile) for given gestational age at birth42.The definition of small-for-gestational-age (SGA) was a newborn child with a birth weight below −15% , women who had given birth once (parity = 1), twice (parity = 2), three times (parity = 3) or four times (parity = 4) prior to the examined pregnancy.2 (m). Additionally, the mothers reported if they were smoking or not during pregnancy. If they had any medical diseases before or during pregnancy it was reported. Similarly if the women were treated with medication during pregnancy it was recorded.All women reported their age, pre-pregnancy weight and height at the first visit. BMI was calculated as BMI = weight (kg)/height2, family history of diabetes, glucosuria or previous birth of baby weighing ≥ 4500 g were offered an oral glucose tolerance test (OGTT) according to clinical practice in Denmark. The OGTT was performed at 14–20 weeks if the women had two risk factors or previous GDM or at 28–30 weeks of gestation if the woman had only one risk factor. The OGTT was based on intake of 75 g glucose after a minimum 10-hour overnight fast, with plasma glucose concentration measured two hours after ingestion.Women with a pre-pregnancy body mass index (BMI) ≥ 27 kg/mAcid-base testing of the cord blood was performed following delivery in both vaginal and cesarean deliveries. After the sample for acid-base testing was obtained, a sample of cord blood was taken for genotyping. Due to this procedure, it was not possible to obtain blood for genotyping in all children due to either clotting of the cord vessels, not enough blood for sample, or unawareness from the midwife/doctor. In total 753 cord blood samples were retrieved and kept in a −80 °C freezer until DNA extraction.We used DNA from cord blood samples from 753 children for genotyping using the Illumina Infinium HumanCoreExome Beadchip platform . Genotypes were called using the Genotyping module (version 1.9.4) of GenomeStudio software . We excluded, duplicates, ethnic outliers, and samples with extreme inbreeding coefficients, mislabeled or missing sex, or call rate <95%, leaving 701 children who passed all quality control criteria.13. Variants or proxies (r2 ≥ 0.90) for the 60 loci associated with BW were retrieved from the Human ExomeBeadChip. Two loci were not present on the array; rs139975827 was not captured by any proxy and rs11096402 was located on the X-chromosome, which was not imputed. Hence, we included 58 loci in an unweighted GRS, which was constructed by summing the dosages for each birth weight-raising allele. The GRS ranged from 47.5 to 78.8 alleles and was normally distributed. The cut-offs for tertiles were based on the distribution of GRS. The cut-offs for tertiles were GRS < 53.1 (1st tertile), GRS 53.1–56.6 (2nd tertile), GRS > 56.6 (3rd tertile).The genetic variants selected for the GRS were based on 60 GWAS-identified birth weight-raising lociwww.r-project.org). Two-tailed testing was used and statistical significance was defined as a two-sided p-value below 0.05.Data analysis was performed in R version 3.4.1 .Interactions between the GRS and maternal environment traits such as BMI, smoking and glucose levels were tested by including the respective interaction terms in the model (i.e. GA25weeks ~ GRS + Weight20weeks + GA20weeks + GA25weeks).To assess the impact of the GRS during specific gestational growth periods, we used multiple linear regression models. For instance, to assess the impact on growth from the malformation scan at week 20 to the first study-specific scan at 25 weeks of gestation, we specified a model describing weight at 25 weeks as a function of the GRS, including weight at 20 weeks to adjust for growth prior to the period in question and actual gestational age at both measurements to adjust for variation in the actual age at which the ultrasound scans were performed (Weight25weeks ~ GRS + Weight20weeks + GA20weeks + GA25weeks + Sex + BMI).Growth from 25 to 32 weeks and from 32 weeks to birth was modeled in the same way. In order to adjust for effects of fetal sex and maternal pre-pregnancy BMI, main effects of these covariates were added to the model  were involved in development of metabolic disease using data from the UK Biobank of 490,000 individuals. We hypothesized that this would provide insight into the genetic aspects of fetal growth trajectories, and which direction of effect they have on later metabolic disease. The association between intrauterine growth variants and T2D or hypertension (ICD-10) was tested using logistic regression, while association with BMI measured at baseline was tested using simple linear regression. We additionally tested all direction of effects of associations with BMI in the GIANT GWAS summary statistics and for T2D in the DIAGRAM GWAS summary statistics21.We used birth weight-raising variants in the GRS to test for association with intrauterine growth. The variants have previously been tested for association with T2D, hypertension and BMI in a birth weight GWASThe study was approved by the Ethics Committee for Region Zealand (SJ-55 and SJ-347) and the Danish Data Protection Agency and was registered in ClinicalTrials.gov (Identifier: NCT00836524). The study was conducted in accordance with the principles of the Helsinki Declaration. All study participants provided written informed consent.The authors confirm that, for approved reasons, some access restrictions apply to the data underlying the findings. Data are available from the Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics whose authors may be contacted.Supplementary information


The purpose of this retrospective study is to evaluate the role of Spiral Computed Tomography (CT) in the detection of the complications of hepatic hydatid cysts.During a period of 8 years and after establishing the diagnosis of numerous hydatid cysts, 7 patients with complications of hydatid cysts were found. These 7 patients  were studied. Four of them had a known medical history of hydatid disease, while all of them presented to our department as emergency cases.They underwent Spiral CT which revealed the following complications of hydatid cysts: intrabiliary rupture in 2 patients, rupture into the peritoneal cavity resulting to peritonitis in 1 patient, contained rupture and secondary transdiaphragmatic thoracic rupture in 1 patient, rupture into both biliary tract and hepatic subcapsular space in 1 patient, rupture into the subcapsular hepatic space in 1 patient and secondary bacterial infection of the cyst resulting to abscess formation in 1 patient. All of these CT findings were surgically confirmed.CT provided a rapid and accurate diagnosis in all of these cases and proved to be a very useful preoperative imaging method. Hydatid disease is a parasitic infection caused by the tapeworm Echinococcus granulosus and Echinococcus multinocularis and it is endemic usually in raising countries, but also in most developed countries in Mediteranean region, South America, Africa, etc.The liver is the most commonly affected organ with an infestation rate of 60-75%. Specifically, the right hepatic lobe is affected in 80% of cases and the left lobe in 20%. Less common sites are the lungs 15%), spleen, peritoneum, kidneys, brain etc [5%, spleeHydatid disease is mostly asymptomatic and many hydatid cysts represent incidental clinical or radiological findings. Most symptomatic cysts are either complicated with rupture or secondary bacterial infection or due to their large size cause symptoms such as right upper abdominal pain, swelling and discomfort .Complications of hepatic hydatid cysts are uncommon but some, in particular, can be fatal without an early and appropriate intervention and treatment . The mosWithin the last eight years, several cases of echinococcal hydatid cysts have been diagnosed in our department, including seven patients with complicated hydatid cyst . All of them presented to our department as emergency cases, while only four of them had a known history of echinococcal disease. They underwent Spiral CT with 4 - 5 mm sections, before and after intravenous administration of contrast agent. The CT findings of these patients, which were also surgically confirmed, are presented and analyzed, as well as being correlated with clinical and laboratory findings .All the patients underwent Spiral CT, which revealed the following complications of hydatid cysts: Two patients had intrabiliary rupture, rupture into the peritoneal cavity resulting to peritonitis had been diagnosed in 1 patient, contained rupture and secondary thoracic rupture in 1 patient , ruptureThe complications of hepatic hydatid cysts are generally rare and they include two main categories: rupture and secondary bacterial infection . RuptureModern imaging methods, such as ultrasound, computed tomography and magnetic tomography, have now given the option of safe diagnosis of hydatid disease and its complications. Despite the fact that it is supported that ultrasound and ERCP are enough for the preoperative diagnosis of intrabiliary rupture of hepatic echinococcal cyst , the ERCThree types of rupture have been described: contained, communicating and direct. Contained rupture occurs when the endocyst ruptures and hydatid fluid escapes into the space between the pericyst and the endocyst resulting to the collapse of the endocyst . This coCommunicating rupture is the most common type of rupture, appearing in 44-64% of cases and its occurs when the content of hydatid cyst evacuates into the biliary radicles that have been incorporated by the pericyst . The comIntrabiliary rupture of a hepatic hydatid cyst, although a rare entity, is the most common complication of hepatic hydatid cyst with a reported incidence of 3-17% , 12. RupThe last type of rupture of a hepatic hydatid cyst, is the direct rupture which occurs when both the endocyst and pericyst are torn so that the content of the cyst escapes into the peritoneal cavity, the thoracic cavity through the diaphragm, the mediastinum or occasionally a hollow organ such as the colon , 11.Direct rupture of the hepatic hydatid cyst into the peritoneal cavity can be detected on CT by findings such as detached membranes, reduction of the cyst size, cyst wall discontinuity and change in the architecture of the hydatid cyst which are the general imaging findings of rupture , 17. TheDirect rupture of hepatic hydatid cyst can also be limited in the hepatic subcapsular space in a way that the hydatid material will not escape into the peritoneal cavity due to the protective effect of Glisson’s capsule. This does not allow the free spillage of the cyst’s content into the peritoneal cavity and therefore limits the rupture, as observed in 2 of our cases.The transdiaphragmatic intrathoracic rupture of a hepatic hydatid cyst is another complication which occurs in 0.6-16% of patients with hepatic hydatid disease , 19. TheSecondary bacterial infection of the hepatic hydatid cyst is a very rare complication due to the avascularity of the pericyst and the lack of connection between the endocyst and the host vascular system .Essential prerequisite for the bacterial infection of the cyst is the rupture of both pericyst and endocyst, so bacteria can enter the cyst . The preIn conclusion, although a rarity, complications of hepatic hydatid disease can prove to be life-threatening and therefore should be early and accurately recognized. Specific imaging findings on Spiral CT allow definite diagnosis and prompts operative intervention.


Pulmonary disorders and respiratory failure represent one of the most common morbidities of preterm newborns admitted to neonatal intensive care units (NICUs). The use of nasal high-flow therapy (nHFT) has been more recently introduced into the NICUs as a non-invasive respiratory (NIV) support.We performed a retrospective study to evaluate safety and effectiveness of nHFT as primary support for infants born < 29 weeks of gestation and/or VLBW presenting with mild Respiratory Distress Syndrome (RDS).The main outcome was the percentage of patients that did not need mechanical ventilation. Secondary outcomes were rate of bronchopulmonary dysplasia (BDP), air leaks, nasal injury, late onset sepsis (LOS), intraventricular hemorrhage (IVH), retinopathy (ROP), necrotizing enterocolitis (NEC), hemodynamically-significant patent ductus arteriosus (PDA) and death.Sixty-four preterm newborns were enrolled. Overall, 93% of enrolled patients did not need mechanical ventilation. In a subgroup analysis, 88.5% of infants < 29 weeks and 86.7% of infants ELBW (< 1000 g BW) did not need mechanical ventilation.BPD was diagnosed in 26.6% of preterms enrolled . In subgroup analysis, BPD was diagnosed in 53.9% of newborns with GA < 29 weeks, in 53.3% of ELBW newborns and in 11.1% of small for gestational age (SGA) newborns.Neither air leaks nor nasal injury were recorded as well as no exitus occurred. LOS, IVH, ROP, NEC and PDA occurred respectively in 16.1%, 0%, 7.8%, and 1.6% of newborns.According to our results, n-HFT seems to be effective as first respiratory support in preterm newborns with mild RDS. Further studies in a larger number of preterm newborns are required to confirm nHFT effectiveness in the acute phase of RDS. Pulmonary disorders and respiratory failure represent one of the most common morbidities of preterm newborns admitted to neonatal intensive care units (NICU) .Over the previous decades, mechanical ventilation (MV) has been a common practice in post-delivery respiratory care and has significantly improved the survival of preterm newborns . HoweverTherefore, the interest in non-invasive respiratory support has surged, with the aim of reducing the risk of lung injury and the incidence of BPD , 5.Continuous positive airway pressure (CPAP) is the current standard of care for non-invasive respiratory support in very preterm newborns over the immediate postnatal period, when endotracheal intubation is not needed .The use of nasal high-flow therapy (nHFT) has been more recently introduced into the NICU setting with several mechanisms of action proposed .Due to a simple interface and small tapered prongs, nHFT is perceived as easier to use by nursing staff , more coA recent meta-analysis on effectiveness and safety of nHFT in preterm newborns concluded that it is not different compared to other conventional modes of non-invasive respiratory support , but poinHFT can be used in different clinical situations, including primary support in post-delivery respiratory care and as a mode of weaning from either mechanical ventilation or CPAP  .A recent Cochrane Review stated that the vast majority of evidence available concerns the use of nHFT as post-extubation support and that very few trials have included extremely preterm newborns so far .The aim of our study was to evaluate the effectiveness and safety of high-flow nasal cannulae therapy as primary respiratory support for infants born < 29 weeks of gestation and/or VLBW presenting with mild Respiratory Distress Syndrome (RDS).Since 2014, in the NICU of Department of Biomedical Science and Human Oncology, University of Bari “Aldo Moro”, Italy, adopted a protocol in which nHFT (Vapotherm® Precision Flow) substituted nCPAP as the primary mode of non-invasive respiratory support for preterm newborns. NHFT failure was considered as the need of intubation and mechanical ventilation.This retrospective study shows the results from January 2014 to December 2016 and data were gathered from medical records.The aim of the study was to evaluate the success rate and the safety of nHFT in our cohort of VLBW and ELBW preterm newborns.The local Ethics Committee  approved the study protocol.InbornGestational age < 29 weeks and/or birth weight ≤ 1500 g;nHFT as first respiratory support for mild Respiratory Distress Syndrome (RDS), defined by the presence of one or more of the following within 1 h of birth:Silverman score ≥ 5;2 > 0.3 to maintain SaO2 in the range 88–93%;FiORadiological signs .Newborns were eligible for the study if they met the following inclusion criteria:Patients were excluded because of the presence of severe comorbidities, namely: major congenital anomalies, major surgical diseases, genetic-metabolic congenital syndromes.2), FiO2 requirements, Silverman score, resuscitation in delivery room, caffeine prophylaxis and need for surfactant administration.The following baseline data were collected: antenatal maternal steroids administration, sex, birth weight, gestational age, radiological findings, oxygen saturation  during transportation.When intubation at birth was not needed, neonates were transferred to the Neonatal Intensive Unit on n-CPAP  and classified according to the literature .A prophylactic caffeine citrate therapy  was routinely started early (within 2 h of age) in our cohort of preterm infants < 34 weeks GA and given until 34 to 36 weeks corrected gestational age, if free of any apnea episodes for at least one week .Curosurf® CHIESI Farmaceutici, Italy), 200 mg/kg, was administered during nHFT, by INSURE technique, with no pre-medication, if required FiO2 was > 35% to achieve SaO2 85–93% [Surfactant , according to Bancalari et Jobe classification ○ Air leaks (pneumothorax/pneumomediastinum)○ Nasal trauma Rate of adverse events○ Late onset sepsis (LOS)○ Intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL)○ Retinopathy of prematurity (ROP)○ Necrotizing enterocolitis (NEC)○ Hemodynamically-significant patent ductus arteriosus (PDA) requiring a pharmacologic treatmentRate of neonates presenting the following diagnosesDeathsTherefore, to assess the success rate and the safety of nHFT in our population, the following outcomes were evaluated:Data of total parenteral nutrition duration, time to reach full enteral feeding (defined as a daily intake of ≥140 mL/kg/day), time to full suckling feeds and total length of admissions, were also collected to evaluate indirect advantages.Data were gathered from medical records of patients admitted to the Neonatal Intensive Care Unit (NICU) of the University of Bari from January 2014 to December 2016.The database was uploaded as an Ms. Excel spreadsheet and data were analyzed by Stata MP11 software.Data were presented using standard descriptive statistics: categorical variables were reported as percentages, whereas quantitative variables were described as means ± standard deviations. Chi-squared test was used to perform comparisons between percentages. Test t-student was used to perform comparisons between means in independent variables normally distributed, whereas Wilcoxon rank sum test was used to perform comparisons between means in independent variables non-normally distributed and not normalizable.For quantitative variables the analysis of normality was carried out; variables non-normally distributed have been normalized using logarithms.Statistical analysis determined significant factors  related to outcomes .For qualitative variables, in logistic regression we calculated the adjusted Odds Ratio (aOR) value with a 95% confidence interval using the z-score test.p-value of < 0.05 was considered to be statistically significant.For quantitative variables, in linear regression we calculated the correlation coefficient with a 95% confidence interval using the student’s t-test. In all analyses, a Between January 2014 and December 2016, 838 preterm newborns were admitted to the Neonatal Intensive Care Unit of the University of Bari. Of these, according to inclusion/exclusion criteria, 64 preterms were eventually included .Twenty-nine preterm neonates met GA and birth weight inclusion criteria, but were excluded because intubated in the delivery room. Those neonates featured a lower mean GA (26.1 ± 2.5), a lower mean BW (872.2 ± 348.9) and a worse mean Apgar score at 5 min (7.4 ± 1.4) than the enrolled neonates (+2 and 35+3 weeks with a median of 29 weeks (DS = ±2.1). Birth weight ranged between 650 and 1495 g with a mean value of 1166 ± 241 g. Males and females were equally represented.Gestational age of neonates started on HFNC ranged between 262 requirement of 26.4 ± 4.8%.The mean Silverman Anderson Score at the start of nHFT was 5.7 ± 1.0 with a mean FiOAccording to our protocol 25 (39.1%) newborns required surfactant administration during treatment. These subgroup median gestational age was 28.5 with a mean birth weight of 1110 ± 232 g.2 was 28.1 ± 6.5%. Overall, removing patients who needed mechanical ventilation due to NHFT failure, the median duration of treatment was 72.5 h.During NHFT, the mean value of the maximum flow rates reached 7.3 ± 0.9 l/min, whereas the mean value of the maximum FiOThe overall success rate, i.e. no mechanical ventilation within 72 h after nHFT, was 93.7% (IC 95%: 85% – 100%). nHFT failed in 4 newborns  at a mean postnatal age of 13.5 ± 9.9 h: three of these required surfactant administration during nHFT.Χ2 = 2.1; p = 0.295; IC 95%: 70% – 98%) and in ELBW newborns, the success rate was 86.7% .In subgroup analysis, for newborns with GA < 29 weeks, the success rate was 88.5% , three of whom  also needed mechanical ventilation.Χ2 = 3.1; p = 0.117; IC 95%: 0.01–0.36) of SGA. BPD occurred more frequently in newborns with a GA < 29 weeks compared to those of GA ≥ 29 weeks , and in newborns with a birth weight < 1000 g compared to those weighing ≥ 1000 g . Neither air leaks nor nasal injury were recorded and no exitus occurred.In subgroup analysis, BPD was diagnosed in 53.9% (IC 95%: 33% – 73%) of newborns with GA < 29 weeks, in 53.3% (IC 95%: 27% – 79%) of ELBW newborns and in 11.1% , in 40% of ELBW  and in 11.1% of SGA . ROP, hemodynamically-significant PDA and NEC each occurred in 7.8% (IC 95%: 3% – 17%), 9.4% (IC 95%: 4% – 19%), 1.6% (IC 95%: 0% – 8%) of newborns. No cases of IVH or PVL were reported.Regarding morbidities LOS overall incidence was 16.1%. It occurred respectively in 28% of newborns with GA < 29 weeks .t = 4.4; p = 0.000; IC 95%: -0.43 – -0.16), birth weight , antenatal glucocorticoids  were positively related to nHFT duration.In simple linear regression, gestational age  was positively related to nHFT duration.In multiple linear regression, only gestational age .Short and long time NHFT failure as well as nHFT duration are not related to FiOt = 2.7; p = 0.010; IC 95%: -3.38 – -0.47) and a higher FiO2 requirement .Lower gestational age neonates are likely to have a higher flow rate max .Adjusted logistic regression showed that long term failure was positively related to lower gestational age , showing a subgroup success rate of 88.5% and 86.7% respectively. In addition, our data showed that lower gestational ages predict NHFT duration and its long-term failure.Several studies, although conducted for different purposes and enrolling cohorts of either VLBW or very/extremely preterm neonates, reported intubation rates in newborns treated with nCPAP after birth, varying from 12.2% to 52.3% –30.Our intubation rate (6.3%) was much lower so that NHFT seems comparable to nCPAP to avoid the need for mechanical ventilation.Our mean flow rates (7.3 ± 0.9) was higher than other reports , 20, sugAlthough the data from our retrospective study seem to support the use of NHFT as primary treatment for preterm newborns with mild respiratory distress, the recent multicentre, randomized HIPSTER trial showed significantly higher rates of treatment failure in newborns primarily treated with NHFT than nCPAP, so that nCPAP should be recommended as first-line treatment, even though intubation rates did not differ between NHFT and nCPAP .In preterm newborns treated with nCPAP, the injuries of nasal mucosa or external nares have been reported . In our These data are consistent with those published in a recent meta-analysis, which found a lower incidence of nasal trauma in preterm newborns treated with NHFT compared with other forms of NIV .Furthermore, time to reach both full enteral (14.6 ± 9.4 days) and full suckling feeds (32.1 ± 15.0 days) were lower in our cohort compared to those reported in VLBW newborns less than 30 weeks gestational age .These two outcomes are strictly related to the lower duration of parenteral nutrition (13.0 ± 9.3), the lower rate of late onset sepsis (16.1%), and the shorter hospital stay (52.4 ± 20 days), compared to others , 35. We We acknowledge several limitations of this study: the retrospective design and the lack of a control group preclude the possibility to make strong assumptions from the presented data on a relatively small sample size.Our outcome data could be influenced by a large number of SGA newborns (% of the whole sample), but the calculated short term failure rate, with exclusion of SGA newborns, is 8,7% (compared to 6.3%) while the long term failure rate is 32.6%, compared to 26.6% of the entire group (< 29 wks and/or < 1500 g).This retrospective study shows that use of High Flow Nasal Cannula Therapy might be feasible and safe as first respiratory support for mild Respiratory Distress Syndrome (RDS) in preterm newborns with a mean gestational age of 29 weeks.Further well-designed, prospective and randomized trials are needed before to confirm and recommend the use of HFNC in the treatment of respiratory distress of preterm infants.


E. granulosus is a zoonotic disease that may involve many body tissues and organs, mainly liver. Adrenal glands are rarely involved even in regions where hydatid cyst disease is endemic. A limited number of studies have been reported on adrenal gland involvement by hydatid cyst disease. Herein, we aimed to report a recurrent case of adrenal hydatid cyst that was misdiagnosed as a hepatic hydatid cyst. A 16-year-old boy with a history of partial cyst excision and evacuation for perforated adrenal hydatid cyst disease three years ago presented to our outpatient clinic with nonspecific abdominal pain. Ultrasonography and computed tomography showed a lesion with an approximate size of 70 × 70 mm compatible with a hydatid cyst, which originated from the segment 5-6 of the liver and extended to the posterior-inferior direction. A surgical intervention was scheduled after a 2-week prophylactic albendazole treatment. During laparotomy using the old incision, it was noted that the cystic lesion that reportedly located in liver was actually a recurrent right adrenal cyst. As dense adhesions existed, the cystic lesion was excised en bloc with the right adrenal gland. As the lesion was totally removed without getting ruptured, albendazole was not administered at the postoperative period. No recurrence was observed at one-year follow-up.Hydatid cyst disease caused by  E. granulosus is responsible for approximately 95% of all echinococcal cases. Also known as cystic echinococcus, hydatid cyst disease most commonly involves the liver, lungs, spleen, and kidneys [Despite four different parasites belonging to the echinococcal species having been discovered to cause echinococcal disease in humans,  kidneys , 2. Adre kidneys . Most pa kidneys . A smallA 16-year-old boy presented to our outpatient clinic with upper right quadrant pain. He explained that he had presented to our hospital's pediatric surgery clinic with skin redness, impaired general status, and cyanosis three years earlier, when a perforated AHC was diagnosed in radiological studies and treated surgically. Upon review of his previous medical reports, it was noted that the contents of the cyst in the right adrenal gland were removed, followed by the resection part of the cyst's anterior wall and the irrigation of the abdominal space with 10% polyvinylpyrrolidone iodine solution. He stated that he had always resided at a city center and had no animal contact ever before. On physical examination, no abnormality was noted apart from a right-sided subcostal incision. His hemogram and liver and kidney function tests were within normal limits. His serological tests revealed an ELISA IgG: 15.66 (positive). A contrast-enhanced computed tomography showed a lesion with lobulated contours and a size of 70 × 70 mm that was compatible with a hydatid cyst. The lesion originated from the hepatic segment V-VI and gave off exophytic extensions in the posterior-inferior direction, and it contained hypodense areas (daughter vesicles) Figures . The patCystic lesions of the adrenal glands are extremely rare, with the majority being incidentally discovered at autopsy series or detected by radiological studies. Therefore, their actual incidence is unknown although some series have provided incidence values of 0.06–0.18% , 6–8. HyAdrenal glands are one of the organs that are most rarely involved by hydatid cyst disease even in regions where the disease is endemic. AHC disease constitutes for less than 1% of all hydatid cyst cases –12. The Both definitive and differential diagnosis of the AHCD can be made by a combination of patient's history, blood tests for functional adrenal lesions, radiological studies, and serological tests , 2, 13. The general principles of AHCD treatment are the same as those for other organ hydatid cyst diseases. To summarize, the most important parameters used for the management of AHCD are the size and the localization of a cyst, and presence of complications. However, several factors such as the adrenal gland being small, destruction of the adrenal gland by the cyst, and the state of the contralateral adrenal gland determine which treatment modality to apply. The most commonly performed modality for AHCD is total or partial excision of cystic lesion and the administration of pre/postoperative medical treatment. Medical treatment is not needed for cases where the cystic lesion is totally excised. Surgical treatment can be applied by open or laparoscopic approach depending on the surgical expertise of a given center , 6. In pThere exist only two reports of the use of the PAIR method for AHCD , 8. AkhaIn cases with an indication for surgical treatment, the treatment modality to be applied should be selected. Whether open or laparoscopic, there are two surgical treatment approaches: radical  and conservative . Some authors advocate that AHCs usually reach a large size, destroying the adrenal gland during their growth. Hence, they recommend en bloc resection of the adrenal gland together with the cyst , 11, 12.


We characterized a triple mutant of phospomannomutase1 that retains mutase and phosphatase activity, but is unable to bind inosine monophosphate.The most frequent disorder of glycosylation, PMM2-CDG, is caused by a deficiency of phosphomannomutase activity. In humans two paralogous enzymes exist, both of them require mannose 1,6-bis-phosphate or glucose 1,6-bis-phosphate as activators, but only phospho-mannomutase1 hydrolyzes bis-phosphate hexoses. Mutations in the gene encoding phosphomannomutase2 are responsible for PMM2-CDG. Although not directly causative of the disease, the role of the paralogous enzyme in the disease should be clarified. Phosphomannomutase1 could have a beneficial effect, contributing to mannose 6-phosphate isomerization, or a detrimental effect, hydrolyzing the bis-phosphate hexose activator. A pivotal role in regulating mannose-1phosphate production and ultimately protein glycosylation might be played by inosine monophosphate that enhances the phosphatase activity of phosphomannomutase1. In this paper we analyzed human phosphomannomutases by conventional enzymatic assays as well as by novel techniques such as  PMM2 encoding phosphomannomutase2 (UniProt: PMM2_HUMAN)[2) or mannose 1,6 bisphosphate  and catalyse the conversion of glucose 1-phosphate (Glc-1-P) into glucose 6-phosphate (Glc-6-P) beside that of Man-1-P into Man-6-P [2 and Man-1,6-P2. This latter activity is enhanced by increased concentrations of Inosine monophosphate (IMP) [PMM2 cause PMM2-CDG. Patients are either homozygous for a hypomorphic mutation or are compound heterozygous with one inactivating and one hypomorphic mutation. The residual activity of several mutants has been measured [PMM2 have never been observed in humans possibly because total absence of this enzyme is not compatible with life[PMM1 have never been associated to human diseases. These findings are confirmed in mice where disruption PMM2 causes early embryonic lethality [PMM1 restores growth at the restrictive temperature in cells harbouring the conditional lethal sec53-6 allele [PMM1 and PMM2 evolved by gene duplication and are located on chromosomes 16p13 [PMM2 is present on chromosome 18 [2 was recently obtained [PMM2-CDG MIM#212065), also known as CDG-1A or Jaeken syndrome, is an autosomic recessive disease without a cure [2065, alsM2_HUMAN), 4. In hte (IMP) . Mutatiomeasured . Homozygwith life. On the ethality  whereas ethality . PMM1 isethality . Unfortues 16p13 , 15 whilosome 18 . Their pobtained .31P-NMR we could demonstrate that PMM1 as well as PMM2 convert Man-6-P into Man-1-P, this activity had never been monitored directly before. In fact the assays which have been used so far, study the reaction in the non-biological relevant direction (i.e. Man-1-P to Man-6-P), dosing the oxidation of Glu-6-P which is obtained from Man-6-P thanks to ancillary enzymes [31P-NMR we measured the equilibrium constant of mannose-phosphates interconversion too. We demonstrated that IMP is a competitive inhibitor of the mutase activity of PMM1, but activates its phosphatase activity. This is peculiar, since we identified another molecule, the FDA approved drug clodronate, that inhibits both activities. Clodronate recognizes specifically PMM1 and has no effect on PMM2. Although only an X-ray structure of the PMM1-IMP complex could permit to elucidate the interactions between the protein and the nucleotide completely, by modelling and site directed mutagenesis we identified the residues that are primarily responsible for IMP binding. We showed that the triple mutant M186Q-N218D-E219K-PMM1 (QDK-PMM1) is a stable protein that retains mutase and phosphatase, but is not sensitive to IMP. The binding of IMP to PMM1 was modelled with PELE [With this paper we wish to contribute to a better understanding of the specific roles of the two enzymes. Using  enzymes –21. Usinith PELE , 23, a nE. coli, glucose 6-phosphate dehydrogenase from baker's yeast (S. cerevisiae), phosphoglucomutase from rabbit muscle, α-D-Glucose 1,6-bisphosphate potassium salt hydrate, α-D-Glucose 1-phosphate disodium salt hydrate, α-D(+)Mannose 1-phosphate sodium salt hydrate, D-Glucose 6-phosphate, D-Mannose 6-phosphate, β-Nicotinamide adenine dinucleotide phosphate sodium salt, were purchased from Sigma-Aldrich. Sypro Orange was from Invitrogen Molecular Probes. Sodium orthovanadate was from Acros Organics. Creatine phosphate disodium salt tetrahydrate was from Alfa Aesar. Clodronate ((Dichloro-phosphono-methyl)phosphonic acid) and neridronate bis(phosphonic acid) were from ABIOGEN-PHARMA.DEAE-Sepharose ff, Superdex-75, Butyl Sepharose ff, were purchased from GE Healthcare Life Sciences. Phosphoglucose isomerase from rabbit muscle, phosphomannose isomerase from 1H- and 31P-NMR spectroscopy. An internal standard (Trimethylsilylpropanoic acid) was used in order to measure the concentration. All the other reagents were of analytical grade. The ORF encoding QDK-PMM1 was obtained by de novo gene synthesis and was purchased by GeneCust, Luxemburg; it is available upon request.Mannose 1,6-bisphosphate was synthesized as described  and puriE. coli BL21(DE3) strain grown at 37°C in LB broth containing ampicillin 0.2 mg/ml. The expression and purification of wild type was performed as described [2, 1 mM 2-mercaptoethanol, 1% glycerol, and loaded onto a DEAE-Sepharose ff column equilibrated with the same buffer. A gradient (0–0.7 M NaCl) was applied. Functional assay has been carried out to isolate specific fractions that were dialyzed. The sample, after the addition of 20% ammonium sulphate, was loaded onto a Butyl-Sepharose ff column equilibrated with Tris 50 mM pH 7.1 containing 5 mM MgCl2, 1 mM 2-mercaptoethanol, 20% ammonium sulphate, 5% glycerol. A gradient (20–0% ammonium sulphate) was applied and the active fractions, judged pure by SDS-PAGE, were pooled, dialyzed (in buffer containing 5% glycerol), concentrated and stored at -20°C.Wild type PMM2 and PMM1, and QDK-PMM1 were expressed in escribed , 24, 25,PMM1 and PMM2 have three enzymatic activities:2 5 mM, NaCl 150 mM, NADP+ 0.25 mM, BSA 0.1 mg/ml in the presence of the appropriate concentrations of substrates/activators (specified time by time) and the required ancillary enzymes.All the enzymatic activities were routinely measured at 32°C in Hepes 20 mM pH 7.5 containing MgCl2 or Glc-1,6-P2 as the activator) was measured in the presence of 2.6 U/ml glucose 6-phosphate dehydrogenase, 3.7 U/ml phosphoglucose isomerase and 0.003 mg/ml phosphomannose isomerase.In particular, phosphomannomutase activity  was measured in the presence of 2.6 U/ml glucose 6-phosphate dehydrogenase.Phosphoglucomutase activity .Samples contained 10% 2 1 mM, NaCl 150 mM, dithiothreitol 1 mM, Sypro Orange 2.4x, then distributed in 0.2 ml PCR-strip (compatible with the instrument). The appropriate ligand solution (in water) was added , and then the strips were sealed and heated from 20 to 90° at 1°C/min with increments of 0.6°C.Melting profiles were recorded under different conditions by thermal shift assay with the StepOne Real-Time PCR System (Applied Biosystems). The pro2 ranging from 0 to 1 mM. PMM1 and QDK-PMM1were analyzed in the presence of: no ligand, Glc-1-P 0.5 mM, Glc-1-P 0.5 mM plus vanadate 0.5 mM, vanadate 0.5 mM, Glc-1,6-P2 0.5 mM, IMP 0.17 mM.The experiment was performed on PMM1 and PMM2 in the presence of Glc-1,6-PThe starting structure for docking was 2FUE. The X-rThe unconstrained ligand search was carried out under default conditions. The seaThe Bradford colorimetric assay was applied for protein quantification , using tActive site residues were identified by similarity with those of human PMM2, which in turn were identified on the model of the enzyme in closed conformation  with Dro31P-NMR spectra. These experiments require the accumulation of several scans for each NMR spectrum in order to have a good S/N ratio. They cannot be used to measure initial velocities, but have the advantage of monitoring all the species containing 31P.The activity of PMM1 and PMM2 was analysed recording The experiments were carried out recording the spectrum of the substrates, adding the enzyme to the substrates, sealing the NMR tube and starting the acquisition of the spectra.2 0.1 mM: panels A and C are the spectra of substrates, panel B and D are the spectra accumulated for 40 min after the addition of PMM1 or PMM2 respectively.2 . As expected, this value does not depend on the enzyme employed and it is stable over time. After 40 min the activator Man-1,6-P2: panels A and C are the spectra of substrates, panel B and D are the spectra accumulated for 40 minutes after the addition of PMM1 or PMM2 respectively.2, Man-6-P  was recorded together with the accumulation of Glc-6-P (peak 1).The same happened with PMM2 , panel DThe equilibrium constant (Man-6-P/Man-1-P = 10.87±1.51) calculated in this direction (M6P->M1P) is comparable to that calculated in the opposite direction as expected.31P NMR in the presence and in the absence of IMP. It is worth mentioning that the chemical shifts measured for inorganic phosphate (Pi) and Glc-1-P are very similar at the pH used for enzymatic assays leading to the coalescence of the two peaks, hence the notation Glc-1-P+Pi will be used.The phosphatase activity of PMM1 was monitored by 2 with or without IMP: panels A and C are the spectra of substrates, panel B and D are the spectra accumulated for 40 min after the addition of PMM1.2 in the presence of IMP the complete consumption of Glc-1,6-P2 : PMM2 67.0 ± 3.1 U/mg, PMM1 17.0 ± 0.9 U/mg, QDK-PMM1 9.6 ± 0.4 U/mg.In 2 or Man-1,6-P2 whereas PMM1 and QDK-PMM1 do. Up to this point QDK-PMM1 behaves like PMM1 although it shows higher affinity for substrates. The most striking difference between the mutant and its wild type counterpart is observed when the phosphatase activity is measured in the presence of IMP. QDK-PMM1 is insensitive to the activator (The phosphommanomutase activity of PMM2 greatly exceeds phosphoglucomutase activity (approximately 20 times) and this preference is less pronounced with PMM1 and QDK-PMM1. PMM2 does not hydrolyze Glc-1,6-Pctivator .IMP acts as a switch because it enhances phosphatase activity and inhibits competitively the mutase activity of PMM1 .2-ase activities. Another bisphonate, neridronate does not inhibit either PMM1 or PMM2  and a core domain  connected by hinge peptides. It was obtained from the structure 2FUE and used as the input for IMP docking. In the first place an unconstrained simulation was run when the ligand is free to explore the protein surface. "PELE’s heuristic approach generates trial moves based on protein and ligand perturbations. The collection of accepted steps forms a stochastic trajectory" . The ligi et al.  describe2+ catalytic center, Asn218 and Asn225 bind the phosphate. Ser54 and either Arg28 or Lys58 form hydrogen bonds with the purine ring. These residues are conserved in PMM1 and PMM2 (A refinement was run using structure 52 from traj1 as the input. The ligand interaction energy was plotted for each step and for 15 trajectories, but in and PMM2 . Arg183 31P-NMR we could monitor phosphomannomutase activity in the physiologically relevant direction for the first time and we demonstrated that PMM1 indeed produces Man-1-P and Man-1,6-P2 from Man-6-P and Glc-1,6-P2 as well as PMM2 does. Despite its ability to generate the metabolite needed for the synthesis of N- and C-glycosylated proteins and despite its expression in tissues that are affected in the disease, such as liver, lung, pancreas, and in particular in the brain [The development of therapeutic interventions for PMM2-CDG is hindered by many basic questions still unanswered. One of these questions concerns PMM1, a paralog of PMM2. Using he brain , 36, PMMhe brain  and by uVan Schaftingen and coworkers firstly demonstrated that PMM1, but not PMM2, has a phosphatase activity that is enhanced by IMP[in silico docking predicts that low energy binding of IMP occurs in the active site of PMM1. How is it possible that IMP inhibits one activity of PMM1 and promotes the other one? We noticed that contrary to what occurs with PMM2, which binds Glc-1,6-P2, closes up and is strongly stabilized against thermal denaturation [2 and it is not stabilized by IMP. Our hypothesis is that PMM1 does not close as efficiently as PMM2 does and for this reason, the phosphorylated enzyme intermediate is more easily hydrolyzed. The binding of a bulky molecule such as IMP to the active site might further hinder the closure of cap and core domains. Inhibition of both activities occur with the small bisphosphonate clodronate.The apparent paradox of two paralog enzymes, partly co-expressed, but not mutually compensatory, could be explained by differences in the affinities for substrates and relative PGM/PMM activities (ed by IMP. We showturation , PMM1 is2. Hence it would be important to test whether reducing phosphatase activity, either inhibiting selectively PMM1 or acting on the IMP steady state concentration, is beneficial in cells with reduced PMM2 activity. In this paper we identified the residues that are responsible for the binding of IMP and demonstrated that it is possible to express a stable PMM1 mutant insensitive to the nucleotide. It could be possible to test the effect of IMP on N- and C- glycosylation, knocking out wt-PMM1 and expressing QKD-PMM1. On the other hand, the treatment with molecules that selectively inhibit PMM1, but not PMM2, such as clodronate, could help elucidate the effect of phosphatase activity on N-glycosylation.If the main physiological function of PMM1 were its phosphatase activity, it could counteract PMM2 hydrolyzing Glc-1,6-P


The pathogenesis of autoimmune Addison's disease (AAD) is thought to be due to interplay of genetic, immune, and environmental factors. A month-of-birth effect, with increased risk for those born in autumn/winter months, has been described in autoimmune conditions such as type 1 diabetes and autoimmune thyroid disease.Month-of-birth effect was investigated in 2 independent cohorts of AAD subjects.The monthly distribution of birth in AAD patients was compared with that of the general population using the cosinor test. A total of 415 AAD subjects from the United Kingdom cohort were compared with 8 180 180 United Kingdom births, and 231 AAD subjects from the Polish cohort were compared with 2 421 384 Polish births.Association between month of birth and the susceptibility to AAD.P = .028). Analysis of the odds ratio distribution based on month of birth in 2 cohorts of patients with AAD versus the general population revealed a December peak and May trough, and January peak and July trough, in the United Kingdom and Polish cohorts, respectively.In the entire cohort of AAD subjects, month-of-birth distribution analysis showed significant periodicity with peak of births in December and trough in May (For the first time, we demonstrate that month of birth exerts an effect on the risk of developing AAD, with excess risk in individuals born in winter months and a protective effect when born in the summer. Exposure to seasonal viral infections in the perinatal period, coupled with vitamin D deficiency, could lead to dysregulation of innate immunity affecting the risk of developing AAD. We show for the first time that month of birth exerts an effect on the risk of developing AAD, with excess risk in individuals born in winter months and a protective effect when born in the summer. Autoimmune Addison's disease (AAD) is a rare disorder with a reported prevalence of 93–140 per million . Althoug3–AAD often occurs with other organ-specific autoimmune disorders; among the most prevalent are autoimmune thyroid disease, type 1 diabetes and vitiligo . Given tA month-of-birth effect has been described in a number of autoimmune disorders, including type 1 diabetes  and auto3 exposure . In most patients, autoimmune etiology was confirmed by the detection of 21-hydroxylase antibodies, or antiadrenal antibodies in cases with more longstanding diagnosis. Patients with primary adrenal failure due to adrenal gland infiltration or infection, bilateral adrenalectomies, congenital adrenal hyperplasia, or with secondary adrenal failure were excluded from this study.The diagnosis of AAD was based on typical symptoms and signs, confirmed by either the subject having a low basal cortisol with a high adrenocorticotrophic hormone concentration or a subnormal response to the short synacthen test . This cohort included patients who were recruited through local endocrinology clinics in the North East region and patients from other regions of United Kingdom who responded to an invitation, via the Addison's Disease Self-Help Group, to participate in research at the Institute of Genetic Medicine in Newcastle. The data were compared with the pattern of total live births for England and Wales during 1963–1972 (n = 8 180 180). Demographic information was obtained from the Office for National Statistics.The data for the Polish cohort were extracted from the patients' records at the Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences. The Polish cohort comprised 231 AAD patients  attending the University Hospital and other endocrine clinics in the Wielkopolska region. The control data regarding total live births in Poland were derived from the Polish Statistical Annals for the years 1980, 1990, 2000, 2010, and 2012 (n = 2 421 384).Data regarding year of birth, year of AAD diagnosis, and the age at diagnosis are presented in This study was carried out with approval of the Leeds East Ethics Committee (reference number 05/Q1206/144) and the ethical committee at Poznan University of Medical Sciences (decision 457/14).2, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated, to compare the birth rates for each month in subjects with AAD and the control population. This analysis was performed separately for the United Kingdom and polish cohorts. Logistic regression fitting a cosinor model was used to estimate the annual seasonal trend in the month-of-birth distribution across all 12 months .Statistical analysis was conducted using SPSS Version 22 and R  using thP = .028). When the cohorts were analyzed separately, this signal retained its significance in the Polish cohort only (P = .042). AAD patients showed a peak of births in December and nadir in June.To assess whether month of birth influences susceptibility to AAD, we compared the distribution of month of birth in all patients with AAD with that of the control population. Using the cosinor test, a significant signal for periodicity was observed after adjustment for gender and country of origin  and reduced birth rate in May  was detected in the United Kingdom AAD cohort .When monthly ORs were calculated, an increased birth rate in December  and decreased birth rate in July  was detected .In the Polish AAD cohort, an increased birth rate in January .In order to assess the possible effect of latitude on the seasonality of birth in AAD, we divided the entire cohort into 2 groups according to latitude. A latitude of 52° North was chosen, because it provided a reasonable bisection of both cohorts. The highest and the lowest monthly ORs were found north of 52° latitude; however, 95% CIs were overlapping, indicating no significant difference  gene and the CYP27B1 gene encoding 1-α-hydroxylase converting 25-hydroxyvitamin D into its active form 1,25-dihydroxyvitamin D  dividing the cohort into 2 groups according to geographical latitude. Although the effect of seasonality seemed to be more pronounced above 52° North, this did not reach statistical significance. Further studies are required to investigate the association of perinatal vitamin D status and the risk for AAD. Verifying vitamin D deficiency and AAD risk by ascertaining 25 (OH)D status in infancy, however, will be difficult given the rarity of the condition and the fact that diagnosis is usually made in individuals in their third to fifth decade.One of the postulated mechanisms explaining a month-of-birth effect in autoimmune disease is the role that vitamin D deficiency might play in the pathophysiology of such diseases . Severalitamin D , 27, 33.We acknowledge there are potential limitations to our study. Firstly, given the inherent rarity of this condition, our sample size is relatively small. This could potentially limit the ability to detect differences, particularly in relation to the subgroup analysis. Nonetheless, ours represents one of the largest cohorts of this condition published to date. Secondly, the subjects in our study were not recruited from a formal national or regional registry, which could potentially lead to bias, although we feel that this is unlikely and that the described trend in seasonality is a true finding, given the similar pattern in 2 independent cohorts of patients recruited in 2 different countries. Further studies in large cohorts of AAD patients looking at an association of month of birth and the risk of development of the disease would be useful.Lastly, our controls obtained from the Office for National Statistics and the Polish Statistical Annals inevitably include subjects with AAD. However, given the rarity of the disease, the expected number of AAD cases in the control population would be very small and would not influence the overall result.In conclusion, our study demonstrates that month of birth exerts an effect on the risk of developing AAD, with excess risk in individuals born in winter months and a protective effect when born in the summer. This is the first such environmental influence documented in the pathogenesis of AAD. Exposure to seasonal viral infections in the perinatal period coupled with vitamin D deficiency leading to dysregulation of innate immunity could be the potential initial triggers for the eventual development of AAD, although this requires further exploration.


Pseudoaneurysm formation is a rare but potentially life-threatening complication after surgical repair of congenital heart disease. We present a boy with truncus arteriosus communis 14 years after homograft placement in pulmonary position. On follow-up, he presented progressive chronic homograft degeneration. Moreover, a large pseudoaneurysm in the right ventricular outflow tract was surprisingly depicted. We opted for a two-stage interventional approach.The online version of this article (doi:10.1186/s40064-016-3273-3) contains supplementary material, which is available to authorized users. Pseudoaneurysm of the right ventricular outflow tract (RVOT) is a rare complication after surgery for congenital heart disease. A substantial number of patients are asymptomatic, however, compared to true aneurysms, pseudoaneurysms are presumed to be high risk regarding life-threatening complications due to rupture or compression of adjacent mediastinal structures. Once diagnosed, pseudoaneurysms should be treated either by surgery, or via an interventional approach  homograft by percutaneous pulmonary valve implantation (PPVI) and exclusion of a large co-existing pseudoaneurysm.2, dilation of the non-calcified homograft up to 18–24 mm, and a large pseudoaneurysm distal to the homograft´s valve  pressure up to roughly ¾ systemic RV 92/0–12 mmHg). The RVOT angiogram revealed the nearly non-calcified homograft with an elastic appearance and its narrowest diameter measuring around 10 mm exactly on the valve’s level. The lumen of the rounded-shaped pseudoaneurysm measured around 20 mm. Its 5 mm neck was closed with an Amplatzer™ Duct Occluder  , and implanted it in the distal conduit overlapping most of the Amplatzer™ Duct Occluder II  proximal notching towards the RVOT, and a little notching while ballooning the distal conduit  pulmonary artery  RVOT stress. We used non-covered stents with open-cell design for pre-stenting to provide sufficient anchorage in the retention zone while avoiding possible migration during or after valved stent implantation. The final valve implantation proceeded uneventfully. To optimize the result by flaring the stent-edges, we redilated 2–3 mm with an oversized balloon, which is usually well tolerated to this extent due to the Melody valve’s coaptation zone (Cheatham et al. Percutaneous-transvenous exclusion of a large RVOT pseudoaneurysm, followed by PPVI in a very compliant RV-PA homograft succeeded, thus reducing both the risk for sudden rupture and the number of cardiac surgeries in this patient´s lifetime after a Rastelli procedure in early infancy.


Teenage motherhood has been associated with a wide variety of negative offspring outcomes including poorer cognitive development. In the context of limitations of previous research, this paper assesses the contemporary relevance of this finding. In this study we investigate the long-term cognitive status (IQ) among 21 year adult offspring born to teenage parents using the Mater University Study of Pregnancy- a prospective birth cohort study, which recruited all pregnant mothers attending a large obstetrical hospital in Brisbane, Australia, from 1981 to 1983. The analyses were restricted to a sub-sample of 2643 mother-offspring pair. Offspring IQ was measured using the Peabody Picture Vocabulary Test at 21 year. Parental age was reported at first clinic visit. Offspring born to teenage mothers (<20 years) have -3.0 : -4.3, -1.8) points lower IQ compared to children born to mothers ≥20 years and were more likely to have a low IQ (Odds Ratio (OR) 1.7; 95% CI: 1.3, 2.3). Adjustment for a range of confounding and mediating factors including parental socioeconomic status, maternal IQ, maternal smoking and binge drinking in pregnancy, birthweight, breastfeeding and parenting style attenuates the association, though the effect remains statistically significant . Similarly the risk of offspring having low IQ remained marginally significantly higher in those born to teenage mothers . In contrast, teenage fatherhood is not associated with adult offspring IQ, when adjusted for maternal age. Although the reduction in IQ is quantitatively small, it is indicative of neurodevelopmental disadvantage experienced by the young adult offspring of teenage mothers. Our results suggest that public policy initiatives should be targeted not only at delaying childbearing in the population but also at supporting early life condition of children born to teenage mothers to minimize the risk for disadvantageous outcomes of the next generation. Globally, adolescent 10–19 years) birth rates have declined significantly over the last few decades though adolescent mothers still account for 11% of all births globally. It has been estimated that a disproportionate 23% of the overall burden of disease (disability-adjusted life years) due to pregnancy and child birth –7 and lo–19 yearsWhile a good deal is known about the impact of teenage parenting on offspring childhood and adolescent cognitive development –14, relaper se[Early life socioeconomic status, particularly educational status, income support and breastfeeding are important factors that may mediate the association between young parental age and cognitive development of offspring. For instance, by age five those offspring with degree-educated parents may be as much as 18 months ahead on vocabulary and 13 months ahead on problem solving ability. Similarper se.Intellectual differences in children born to teenage parents may become more pronounced as children develop. Small differences are seen in studies in the preschool years while larger differences have been found by the elementary school years . By adolThis study investigates the association between teenage parenthood and young adult offspring IQ at 21 years, adjusting for parental psychosocial, economic, and biological confounders. We also test whether parental educational status, duration of breastfeeding, and child rearing practices- known to influence offspring IQ development, mediate the association between teenage parenting and offspring cognitive development.Data for this study were drawn from the Mater-University of Queensland Study of Pregnancy (MUSP) cohort. MUSP is a mother-offspring pair birth cohort study which commenced in 1981–83 at the Mater Misericordiae Mothers’ Hospital in Brisbane, Australia. Some 7223 mothers gave birth to a live singleton baby at the study hospital. Baseline data were collected at the mother’s first obstetric clinic visit (mean 18 weeks gestation) and follow up data were gathered prospectively on mothers and offspring at 3–5 days postpartum, six months, five, 14, and 21 years of age. Of the 7223 offspring who constituted the original sample, a sub-sample of 2643 had their intelligence assessed at the 21 year follow-up. This latter group constitutes the analytical sample for this study. Details of the study design, sampling and response rates are provided elsewhere , 36.Informed consent from the mothers was obtained at all data collection phases of the study and from the offspring at 14 and 21 years. Ethics committees at the Mater Hospital and the University of Queensland approved each phase of the study.Maternal age at first clinic visit (FCV) was calculated based on the maternal date of birth and FCV survey date. Paternal age was reported by the mothers. Parental age was categorised as teenage parents (pregnancy delivered <20 years of age) vs. all other aged parents (pregnancy delivered 20+ years of age). Mothers and fathers were stratified and those older than 20 years were the reference group in all the comparisons. To assess level of education, mothers, at the time of recruitment, were asked the level at which they and their partner had completed their education. The more detailed original responses were stratified into ‘incomplete high school’, ‘high school completed’ and ‘post-high school’. Maternal smoking during pregnancy was classified as nil, 1–9 cigarettes/day and 10 or more cigarettes/day. Family income in the year of pregnancy was categorised as low , middle  or high . At FCV the mother was asked whether her pregnancy was planned with response options ‘yes’, ‘no’ or ‘unsure’. As the number in the “unsure” group is small we combined this with ‘no’. At 14 years, mothers reported if there had been a change in partner since the birth of the child. Maternal depression was measured using the seven-item depression subscale from the delusions-symptoms-states inventory: state of anxiety and depression (DSSI/SAD). The meaBirth weights were converted into z scores representing birth weight standardized to gender and gestational age, calculated as birth weight minus birth weight mean divided by the SD adjusted for gender and gestational age. A gender and gestational age (in weeks) standardised birth weight z-score was computed to give a measure of intrauterine growth . BreastfMaternal response to misbehaviour was assessed by asking the mother how she would respond to five situations involving her child- to which the mother could respond in one of three possible ways: always, sometimes and never. Summed average means of the items were multiplied by 10. Total score was regrouped into two categories: always (10.0 to 15.0) and not always (15.1 to 30.0). The Cronbach alpha for this scale is 0.819.For both mothers and offspring, intelligence was measured at the 21 year follow-up using the Peabody Picture Vocabulary Test (PPVT–R); the PPVThe Peabody Picture Vocabulary test has been found to be a reliable measure of verbal comprehension , 42. In Parental demographic and socio-economic characteristics and off-spring IQ at 21yrs are separately presented by parental age (<20y vs 20+y) at FCV. The chi-square or Fishers exact test and t-test are used for categorical and continuous variables as appropriate. Simple linear regressions are applied to test the trend of systematic increase or decrease of off-spring mean IQ score over the level of parental age groups. The non-zero slope (rate of increment or decrement of mean IQ) of the regression with p-value <0.05 for t-test is used for linear trend in off-spring IQ across parental age groups. A trend test was also applied for the mutually adjusted parental ages using multiple linear regressions. The normality of the outcome variable is tested applying histogram and discerning whether off-spring IQ approximates the bell curve of a normal distribution.Three regression models are constructed to examine the independent association of parental age and offspring IQ at 21 years. Residual diagnostics are used to examine the regression assumptions and to identify influential and outlier cases. The variance inflation factors for the predictors are screened to avoid multicollinearity. The first model is mutually adjusted for maternal and paternal age. The second model is adjusted for the potential confounders including maternal IQ, income, birth weight, child sex, living with same partner at 14 years as at the birth of child, planned pregnancy, depression, smoking and binge drinking. The final model was additionally adjusted for contextual mediators including parental education, breastfeeding and child rearing factor. All the regression analyses are performed using the multiple imputed data for the missing values on covariates  assumingKHB command. The Karlson-Holm-Breen (KHB) method[To evaluate the extent to which maternal education, paternal education, breastfeeding and child rearing factor  mediates the relationship between maternal age and offspring IQ at 21years, the total effect was decomposed into direct and indirect effect using STATA user-written program B) method disaggreB) method. HoweverParticipant’s characteristics are presented in While 13.7% of mothers were teenagers, only 2.9 percent of fathers were less than 20 years of age at the time of the child’s birth. Unadjusted mean IQ shows a clear trend towards increasing offspring IQ score as parental age increases  . For eveIn the additional analysis, we have explored what proportion of the total association between teenage parenthood and adult offspring IQ was due to direct and indirect effect through the pathways of parental education, breastfeeding and child rearing .The results in This study shows that offspring of teenage mothers and fathers have small but significant mean reductions in cognitive ability as young adults. However, this relationship only remained statistically significant for teenage mothers after controlling for a range of potential confounders and mediators prospectively collected around pregnancy and in early childhood period. We also found a significant linear trend of increasing cognitive outcome with maternal age after adjusting for paternal age. Offspring of teenage mothers were at increased risk of low IQ at 21 years after adjusting for confounding and mediating factors.Direct comparisons with other studies of offspring cognitive development born to teenage parents are difficult because researchers have used a wide range of cognitive measures and have different study designs, age groups and adjusted for different confounding factors. However, the finding that young maternal age is associated with a lower mean IQ of young adult offspring is consistent with three large studies , 15, 45.There are a variety of confounding or mediating factors hypothesised to influence the association between teen parental age and offspring intelligence . In thisResults of this and other studies reporting the significant association between teenage mothers and increased risk of offspring cognitive impairment at 21 years and lower mean cognitive development reinforces the importance of interventions which supports young and socially disadvantaged parents during pregnancy and the early years. The Family Nurse Partnership is one such intervention that has demonstrated a positive impact on early learning development, readiness to school and academic performance of offspring of young mothers , 49. In The findings of this study need to be interpreted in the context of some caveats. Firstly, similar to other longitudinal studies, this study has loss to follow up. Initially, the survey recruited 7223 mothers/children pairs however; only 2643 cases are available for this analysis when offspring IQ is measured after 21 years of postpartum . MothersThis study shows teen maternal child birth is associated with lower offspring IQ and increased risk of offspring cognitive impairment which persists into young adulthood. The small but significant decrease in offspring IQ combined with other challenges often faced by children of teenage mothers may contribute to increased risk of poor educational performance and intergenerational transfer of psychosocial and health disadvantage. With this consequence in mind, our results suggest public policy initiatives should be targeted not only at delaying childbearing in the population but also at supporting early life condition of children born to teenage mothers to minimize the risk for disadvantageous outcomes of the next generation.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.S1 Data(PDF)Click here for additional data file.


Taenia multiceps cyst through molecular phylogeny of the 12S rRNA gene.This study was performed to identify the non-cerebral Eight cyst samples were collected from 385 examined slaughtered goats during October 2015-September 2016 from three slaughterhouses in Chittagong City Corporation. Cysts were removed from the thigh muscle, and scolices were collected for light microscopic examination and molecular identification. The DNA was extracted and analyzed by polymerase chain reaction using 12S rRNA gene primers. Cyst samples were also preserved in 10% buffered formalin for histopathological study.T. multiceps non-cerebral cyst is 2.1% prevalent in goat in this area. Under light microscopic examination, scolex was found with four suckers and a rostellum with the double crown of 32 hooks and hooklets. Molecularly, all the samples were amplified with 12S rRNA gene fragments yielded 270 base pair amplicon. Zenker’s necrosis with focal to diffuse infiltration of lymphocytes and eosinophil was also found around the cyst wall in histopathological examination.T. multiceps is genetically identical with the cerebral cyst, previously published data indicated that cerebral T. multiceps cyst is predominant in other parts of the world as well as in Bangladesh. This study showed that non-cerebral cyst is also prevalent in this country which is very important for public health concern. This study depicts an idea of non-cerebral form of zoonotic T. multiceps cyst which will be helpful in taenia cyst control and prevention.Although the non-cerebral form of the cysts produced by  Taenia multiceps is a causative agents for coenurosis in sheep and goat affect the central nervous system (CNS) particularly the brain of sheep and goats but rarely in the spinal cord also called Coenurus cerebralis [The cestode rebralis ,2. Coenurebralis  and is prebralis . The disrebralis ,6. Envirrebralis .T. multiceps in sheep is genetically identical with the non-cerebral cysts of T. multiceps gaigeri [T. multiceps can cause cerebral coenurosis in sheep and non-cerebral forms in goats but rarely in sheep [T. multiceps has not been done yet, but Echinococcus granulosus has been identified molecularly in cattle in Bangladesh [Besides this, a lack or limited use of anticestodal drug, uncontrolled backyard slaughtering, and improper offal disposal are also responsible for transmission of this cestode . The cer gaigeri ,10 in in gaigeri ,12. Recein sheep . Informangladesh .T. multiceps besides phylogenetic analysis of the goat isolates sequence with NCBI reference sequences for characterization of cyst in this area.The aim of the present study was to determine the prevalence, morphological features of parasite scolex, and molecular detection of All samples were collected and complies with relevant legislation. It follows the international guiding principles for biomedical research involving animals.Eight cyst samples were collected from 385 examined slaughtered goats in three slaughterhouses located in Chittagong City Corporation during October 2015-September 2016. After gross examination cysts were removed from the parasitized organs and preserved in 10% buffered formalin for histopathological study and the scoleces or larval tissue material from cysts was preserved in 90% ethanol for molecular study. Scolices were collected through scraping from the sides of germinal layer of the cyst also stained with eosin stain for light microscopic examination.T. multiceps as follows: Tae-F (5’-GATTCTTTTTAGGGGAAG G-3’) and Tae-R (5’-GCGGTGTGTACMTGAGCTAAAC-3’). 50 µl of PCR reaction was performed using 10 mM Tris-HCl, 50 mM KCl, 1.5 mM MgCl2, 0.2 mM of each deoxynucleotide triphosphate, 20 pmol of each primer, 100 ng template gDNA, and 2 U Taq DNA polymerase  in each reaction under the following cycling conditions: After an initial denaturation at 94°C for 5 min, then 94°C for 30 s (denaturation), 55°C for 1 min , and 72°C for 30 s (extension) for 35 cycles, followed by a final extension at 72°C for 10 min. Samples without genomic DNA were included in each amplification run as negative controls. PCR products were separated on a 1% agarose gel and detected by ethidium bromide staining.Genomic DNA was extracted from protoscolices using iNtRoN Patho gene Spin DNA/RNA Extraction Kit according to the manufacturer’s recommendations. Genomic DNA concentrations were determined spectrophotometrically by Qubit 2.0 , and the DNA samples were stored at −20°C until used. 12S rRNA gene primers were designed according to the mitochondrial genome sequence of www.favorgen.com) according to the manufacturer’s instructions, and then, these purified products send to Bioneer, Korea, for sequencing. Sequence chromatograms were analyzed using the Chromas Pro 2  and Mega 6.0 computer software programs [T. multiceps was retrieved from NCBI GenBank, and E. granulosus (as outgroup) also inferred from other publications [T. multiceps by MEGA6 software.Four PCR products were purified by PCR purification kit  were found infected with taeniid cysts with an average diameter of 2.7 cm . The entT. multiceps larvae was seen in all of the cysts containing clear fluid with numerous fertile protoscolices. A large number of scolices as white clusters were attached to the internal cyst wall  in goats was reported in some area, 2.5% at Patuakhali district [C. cerebralis cyst is found in the thigh muscle [T. multiceps [T. gaigeri [Coenurosis is an endemic disease of Bangladesh although very few studies have been conducted in this country and all of them are only epidemiological or case study . The predistrict  and 35 cdistrict . Coenurodistrict . In comph muscle  and subch muscle  of goat h muscle . In sheeulticeps  or T. ga gaigeri . Genetic gaigeri . Histopa gaigeri ,26.T. multiceps was not done yet. Previously reported studies in other countries were based on amplification of several genes such as 12S rRNA gene, cox1 gene, and nad1 gene. We used only 12S rRNA gene marker. The present molecular genetic approach was employed to characterize the DNA sequence of the non-cerebral metacestodal stage of T. multiceps and compared it with other available data from other countries. Goat non-cerebral thigh muscle cyst isolated sequences of this study were aligned with Greece sheep and goat, Iranian sheep, and complete 12S rRNA gene of China.Although coenurosis particularly in cerebral form in goat was reported in different area of Bangladesh, the molecular identification of T. multiceps cyst which will be helpful in taenia cyst control and prevention.This study showed that non-cerebral cyst is prevalent in this country which is very important for public health concern. This study depicts an idea of the non-cerebral form of zoonotic Research work was done by MOF and partly MSI. Research design was carried out by AMAMZS, MAH, and SC. All the authors participated in data analysis, while MM, AR, and MSI revised the manuscript. All authors read and approved the final manuscript.