Median raphe cyst is a rare lesion located on the median raphe. The cyst wall is lined by cuboidal to columnar cells, transitional  cells, stratified squamous cells or a mixture of these. The normal urethral mucosa and the median raphe cyst usually lack melanocytes and/or melanin pigment. However, albeit extremely rare, the presence of melanin pigment and/or melanocytes in median raphe cyst, namely pigmented median raphe cyst, has been previously reported. The current case report presents the sixth case of pigmented median raphe cyst and discusses the possible mechanism of melanocytic colonization in this tumor. A 48-year-old male presented with a nodule on the ventral surface of the penis. Histopathological study revealed that the cyst wall was covered by uniform bland cuboidal to urothelial cells. The peculiar observation was the presence of dendritic melanocytes among the epithelial cells. Therefore, a diagnosis of pigmented median raphe cyst was determined. Immunohistochemically, stem cell factor and endothelin-1 were not expressed in the epithelial cells of the cyst wall. It is well-known that melanocytes are rarely found in various non-melanocytic tumors, a phenomenon termed ‘colonization’. The mechanism by which melanocytes appear in median raphe cyst remains unclear. The present report is the first to demonstrate that melanocytic proliferation and differentiation factors, such as stem cell factor and endothelin-1, are not involved in the pigmentation of median raphe cyst. In addition, aberrant melanocytic migration may contribute to the development of this type of lesion. Median raphe cyst is a rare benign lesion located in the median raphe and is thought to be derived from the urethral mucosa or urethral gland (Littre’s gland). It appears commonly in children or adolescents. The normal urethral mucosa and the epithelial cells of the median raphe cyst usually lack melanocytes and/or melanin pigment. However, albeit extremely rare, the presence of melanin pigment and/or melanocytes in median raphe cyst, namely pigmented median raphe cyst, has been reported, although the pathogenesis of melanocytic colonization in this tumor has not been clarified –5. Herei2, on the median raphe of the penis. Surgical resection of the nodule was performed under the clinical diagnosis of median raphe cyst.A 48-year-old male presented with a nodule on the ventral aspect of the penis, which had been recognized since childhood. Physical examination revealed that the nodule was slightly elevated with a smooth surface, skin-colored, elastic, soft and measured 10×3.5 mmThe formalin-fixed, paraffin-embedded tissue blocks of the resected specimen were sectioned (3 μm thick), deparaffinized and rehydrated. Each section was stained with hematoxylin and eosin and then used for immunostaining. Immunohistochemical analyses were performed using an autostainer  according to the manufacturer’s instructions. The following primary antibodies were used: Mouse monoclonal antibodies against α-smooth muscle actin , endothelin-1 , gross cystic disease fluid protein-15 , HMB-45 , Melan-A  and stem cell factor ; and a rabbit polyclonal antibody against S-100 protein .Histopathological analysis revealed that a unilocular cyst was present under the squamous epithelium. The cyst wall was covered by two to several layers of uniform cuboidal to urothelial cells without nuclear atypia. Decapitation secretion and mucinous and ciliated cells were not observed. In addition, no mitotic figures were present. The unusual observation was the presence of dendritic melanocytes among the epithelial cells .Immunohistochemical analyses showed that these dendritic melanocytes were positive for Melan-A and S-100 protein , but negAccording to these histopathological and immunohistochemical results, an ultimate diagnosis of pigmented median raphe cyst was determined.et al summarized the clinicopathological features of pigmented median raphe cyst  cells, stratified squamous cells or a mixture of these . The prephe cyst . Accordiphe cyst .et al reported a case of pigmented squamous cell carcinoma of the hard palate. The authors clearly demonstrated stem cell factor and endothelin-1 expression in the neoplastic squamous cells, which may have led to the development of melanocytic colonization in squamous cell carcinoma (It is well-known that non-neoplastic melanocytes are rarely found in various benign and malignant non-melanocytic tumors of the various sites, a phenomenon known as ‘colonization’ –10. The arcinoma .The current case report is the first to analyze the immunohistochemical expression of stem cell factor and endothelin-1 in median raphe cyst. It was revealed that the epithelial cells of the median raphe cyst showed negative immunoreactivity for these markers. Therefore, colonization of melanocytes in median raphe cyst is not associated with the production of stem cell factor and endothelin-1 by the epithelial cells of the cyst. In addition, aberrant migration of melanocytes may contribute to the development of this rare lesion. In conclusion, this report is the first to analyze the immunohistochemical expression of melanocytic proliferation and differentiation factors, and demonstrate that they are not involved in the pigmentation of median raphe cyst. Therefore, aberrant migration of melanocytes may contribute to the development of this rare lesion. Further analysis is required to clarify the pathogenesis of pigmented median raphe cyst.


Previous Analysis of polymorphism of genes associated with the development of coronary heart disease (CHD) reveals that the frequency distribution of genotypes and alleles depends on the ethnic characteristics of the populations under study. Further impetus is derived from the well -established links between alcoholism  and cardiovascular disorders.The purpose of this study was to examine a number of apolipoprotein gene polymorphisms and correlate these alleles with changes of lipid profile in CHD patients of Kazakh and Uyghur nationalities.Four-Hundred Forty Eight (448) males of Kazakh and Uyghur nationalities residing in Kazakhstan were evaluated and genotyped. The age range of these subjects was 30–55 years which included both afflicted and controls. Specifically, 161- Kazakhs suffered from myocardial infarction compared to 112 health controls; 80- Uyghurs suffered from CHD compared to 95 health controls. Blood lipid profiles were examined in the total cohort. Genotyping was performed by polymerase chain reaction (PCR) using oligonucleotide primers identifying; ApoB; ApoC111; and APOE gene polymorphisms.Initial screening revealed a significant inter-ethnic difference on the frequency of alleles associated with both the ApoB and APOE genes. We found that the X1 ApoB gene polymorphism is overrepresented in healthy Kazakhs relative to Uyghurs [86.4% in Kazakhs vs. 69.4% in Uyghurs]. Moreover, we found that the E4APOE allele was also overrepresented in healthy Kazakhs relative to Uyghurs [16.8% in Kazakhs vs. 9.5% in Uyghurs]. There was a significant relationship of polymorphisms of APOE such as ApoB and ApoC 111 with the value of lipid indices in Kazakhs. Additionally, we found that the E4 allele of the APOE gene also correlated with the value of lipid indices in Kazakhs. Further evaluation showed that the X2 allele of the ApoB and the S2 allele of the ApoCIII gene significantly associated with the lipid indices of Uyghurs.This systematic investigation confirms the association of various alleles of Apolipoprotein gene polymorphisms and contribution to aberrant lipid metabolism. Putatively at least in our population we are proposing that certain gene polymorphisms of Apolipoprotein genes such as ApoB; ApoC111; APOE ; X2 of ApoB; and S2 of ApoCIII differentially represented in either Kazakhs or Uyghurs are genetic markers of hypertriglyceridemia. There is ample evidence linking high alcohol intake and cardiovascular disease throughout the world. Importantly, the prevalence rate of alcoholism in the Kazakhstan region and subsequent suicide is rather high and provides a rationale to evaluate genetic antecedents for coronary heart disease (CHD) . It is kBased on many reviews and controversy related to the importance of genetic testing to determine predisposition of CHD risk , we hypoFour-Hundred Forty Eight (448) males of Kazakh and Uyghur nationalities residing in Kazakhstan were evaluated and genotyped. The age range of these subjects was 30–55 years which included both afflicted and controls. These participants were all living in Kazakhstan, and unrelated by ties of kinship. Each subjects was selected by a by random sampling technique and subsequently interviewed. The University ethics committee approved this study as well as approving a consent form which was signed by each subject selected for the study.Specifically, 161- Kazakhs suffered from myocardial infarction compared to 112 health controls; 80-Uyghurs suffered from CHD compared to 95 health controls. The average age of the Kazakhs with CHD was 46.4 ± 1.9 years, of the apparently healthy Kazakhs – 40.7 ± 2.1 years, of the Uighurs with CHD – 47.3 ± 0.92 years, of the apparently healthy Uighurs – 41.2 ± 1.02 years.Standard blood lipid profiles were examined in the total cohort. The blood lipid profiles analyzed is as follows: total cholesterol (TC) and high-density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), triglycerides (TG). It is noteworthy, that analysis of all blood lipid profiles, were determined by a biochemical analyzer utilizing well-known procedures . In addiGenotyping was performed by polymerase chain reaction (PCR) using oligonucleotide primers identifying; ApoB; ApoC111; and APOE gene polymorphisms. DNA was isolated from blood lymphocytes by a standard technique  to invesFor the genotyping of the Apo C111, the products of polymerase chain reaction (PCR) were digested with SStI, and then analyzed in 10% polyacrylamide gel. Alleles not having the SStI restriction site, were designated as S1, and the site carrying SStI – as S2. The combination of these alleles, form three genotypes: S1S1; S1S2; S2S2.For the genotyping of the Apo B, the resultant material derived from amplification was digested with Xba I. The restriction products were analyzed utilizing electrophoresis in 12% polyacrylamide gel. As a result, two alleles were identified: XI – without a restriction site, X2 – with the restriction site for Xba I.For the genotyping of the Apo E, the amplification product was digested with Hhal utilizing an improved method  and analFollowing plasma measurements (mg/dl) we found that dyslipidemia atherogenicity (DA) is due not only to the buildup of lipid content, but is a function of the apolipoprotein components.We observed a decrease of level of the Apo A1 and increase of level of the Apo B in the Kazakhs as well as Uighurs with CHD, and the indices of the Apo A1 are more prevalent and the indices of the Apo B of blood serum are lower in healthy individuals. While the indices noted for the Kazakhs were found to be significant for Apo A1 (<0.001) and Apo B (<0.05) for the Uighurs we found less significance for Apo A1 (<0.05) than in the Kazakhs but the significance for Apo B (<0.05) was the same for both populations  and 2.As displayed in There is a plethora of population genetics throughout many countries regarding apolipoprotein genetic polymorphisms and structural relationships –14.Following genotyping and analysis of the allelic frequency distribution of the Apo B gene we have found that the X1 allele of the Apo B gene is the most common allele in the Kazakhs and Uighurs . HoweverSince there is a large amount of research devoted to the study of associations of the Xba I polymorphism of the Apo B gene with atherogenic changes in lipid spectrum ,16, we dOur analysis  revealedOn the contrary, in the Uighurs with CHD our analysis (depending on the availability of the restriction site) showed  that in The Apo C111 gene produces a protein product that plays an important role in the metabolism of lipoprotein atherogenic fractions. Seven polymorphisms of the Apo CIII gene are described . The mosBased on our genotyping data most of the surveyed individuals of Kazakh and Uighur ethnic groups are the carriers of the S1 allele of the Apo CIII gene. Among healthy Kazakhs the frequency of this allele is 76.6%, and among healthy Uighurs is 74.5% .When comparing the frequency distribution of the alleles of the Apo CIII gene between the groups of patients with CHD and healthy individuals we have not found any differences among the Kazakhs and the Uighurs.To determine the effect of the Apo CIII gene polymorphism on the levels of the lipid and apolipoprotein blood spectrum in the Kazakhs and Uighurs, we analyzed the average values of these parameters with different genotypes  of the Apo CIII gene  and 8. WWe also found for VLDLC (Very Low Density Lipoprotein Cholesterol): its highest value was determined by the SISI genotype, the smallest – by the S2S2 genotype, the average – by the S1S2 genotype. Significant differences were not found in the Kazakhs compared by genotype with respect to levels of the TC, LDLC, HDLC, AI and levels of the A1, B and E apolipoproteins.In contrast, the increased level of triglycerides was associated with subjects processing the S2 allele in the Uighurs with CHD . SignifiHowever, as depicted in Effect of genetic polymorphism of the Apo E gene on the risk of development of CHD has been extensively studied. However, in terms of our population the prevalence of this gene and associated polymorphisms remains unknown.Thus in our study carriers of the E2/E2 genotype were not found among the Kazakhs and the E4/E4 and E2/E4 genotypes were not found in the group of healthy individuals. However, the E3/E3 genotype was the most common genotype in the Uighurs, the E4/E4 genotype was not found, and the E2/E2 genotype was found in only one patient and as such is a rare variant. Thus a high frequency of the E3 allele was observed in the examined groups of Kazakhs and Uighurs, and the frequency of the E4 allele is greater than or close to the frequency of the E2 allele.It is known that among many of the common polymorphisms the Apo E is an allele polymorphism shown to consistently affect lipids in all populations studied, especially on total cholesterol and triglycerides. The E4 allele is more often found in patients with hypercholesterolemia, whereas the E2 allele – in patients with hypertriglyceridemia. Taking into consideration these data, we conducted a study of the relationship of polymorphisms of this gene with the lipid and apolipoprotein spectrum.We thus observed in Kazakhs with CHD that the increase of TC, LDLC, AI is a function of the E2/E3, E3/E3, E2/E4, E3/E4, E4/E4 genotypes .The average level of total cholesterol  in the Kazakhs having the E4/E4 and E3/E4 genotypes is significantly increased in comparison with this parameter in patients with CHD having the E3/E3 and E2/E3 genotypes  (p < 0.05). The lowest concentrations of LDLC are observed in patients having the E2/E3 genotype  and the highest concentrations – in patients having the E4/E4 genotype , [p < 0.05].Finally, in the Uighurs with CHD the E2/E3 genotype is significantly associated only with hypertriglyceridemia . In the case of other genotypes  of the Apo E gene such an association has not been found .The present work is based on the search of genetic markers of coronary atherosclerosis with the help of analysis of associations of polymorphisms of DNA – with three candidate genes of atherosclerosis.One of the most common polymorphisms of the Apo B gene is the Xba1 restriction endonuclease polymorphism. The appearance of the site for this endonuclease gene in the 26-th exon of the gene is due to nucleotide substitution (T-C) in the third codon position 2488. Due to the results obtained we can conclude that the E2 allele of the Apo E gene is the risk factor for development of hypertriglyceridemia in the Uighurs with CHD. Moreover, the presence of the E4 allele of the Apo E gene is a genetic marker of predisposition to hypercholesterolemia in the Kazakhs with CHD.As described in the literature, the XI allele frequencies are very close in the Caucasian populations and ranged from a minimum - 43.0 % in the Danes to the maximum - 56.0% in the Italians. The XI allele frequency in the Indians is much higher - 75.0 %. This parameter reaches a maximum in the Mongoloids - 90.0 %: in the Chinese - 92.0 %, in the Japanese - 95.0 %, to the total mono-morphism in the Koreans - 100 % [Furthermore, the X1 allele frequency in the Kazakhs is close to the X1 allele frequency in other Mongoloids, while the X1 allele frequency in the Uighurs is close to this parameter in the population of the Hindus (75.0 %). The Uighurs polymorphisms are found in between the Hindus and Kazakhs as for the X1 allele frequency. Probably, such a variety of the distribution of alleles of the Apo B gene reflects not only the region of residence, but to a large extent ethnicity as well.This genetic marker studied globally, has a different degree of association with cardiovascular diseases – based on presence or absence of the X1 and X2 alleles. Specifically, association of the Xba I polymorphism with the risk of CHD  was founFurther confirmation of our present results will establish the fact that the Apo B gene polymorphism is not associated with the development of CHD among the Kazakhs and Uighurs. However, in the Uighurs with CHD the X2 allele of the Apo B gene marks the atherogenic shift of the lipid and apoprotein spectrum, which indicates a significant contribution of the Apo B gene in the determination of abrarrant lipid metabolism.In the literature there are reports on the relationship of allelic frequency of the Apo CIII gene not only with the levels of parameters of blood lipid spectrum, but also with coronary atherosclerosis –22.For eIt is known that the distribution of the S1 and S2 alleles among the Caucasoid ethnic groups is varied. Frequency of the S1 allele varies from 87.0 in the Russians to 94.0% in the British, and frequency of the S2 allele – from 13.0 to 6.0% respectively ,27,29. TSince we have found no differences between any of the analyzed alleles of the Apo CIII gene in the Kazakhs and Uighurs, we are proposing that polymorphisms of this particular gene, is not associated with the development of CHD in this population. Our results are consistent with the results of studies conducted in the world. It is established that the S1 allele identified in the Apo C111 gene can be regarded as a risk genetic marker of predisposition to hypertriglyceridemia which is often linked to both atherosclerosis and CHD .Our finding of an association of the Sst I polymorphism of the Apo CIII gene  with an increased level of triglycerides with the frequency of CHD in Uighurs is consistent with the literature. In fact similar associations have been found in other populations such as England, Canada and Finland, whereas Scottish descendants and some other ethnic groups showed negative associations ,33,41.Thus it is shown that the certain restriction polymorphisms of the Apo CIII gene in patients with CHD living in Kazakhstan are not associated with CHD. However, in particular based on these results, we are proposing that the S1 and S2 alleles of the Apo CIII gene may be considered as genetic markers of predisposition to hypertriglyceridemia in both the Kazakhs and Uighurs with CHD.The largest study of MRFIT demonstrated the association of the Apo E4 allele not only with the increased risk of coronary atherosclerosis, but also with mortality ,42.The fIn general, the E4 allele is associated with high level of the TC, LDLC and the Apo B. The E4 allele correlates more likely than other isoforms with vascular lesions in early atherosclerosis, and is considered to be atherogenic. In contrast, the E2 allele in different populations is associated with the decrease of the Apo B, LDLC, and is considered to be anti-atherogenic .Taking into consideration the universality of the Apo E protein, we must mention the role of the Apo E polymorphism in the development of Alzheimer’s disease. From 34 to 65% of these patients are carriers of the Apo E4 allele, while for the general population it is 24–31%. In all likelihood, this is due to the fact that the Apo E is the major apolipoprotein of human cerebrospinal fluid ,45.The EThus in our study, the Apo E gene polymorphism affects the development of CHD among the Kazakhs through interaction with the lipid metabolism system. It is appears that only the E4 allele is a reliable risk factor for development of hypercholesterolemia, increase of LDLC and AI in Kazakhs with CHD. Additionally, due to the results obtained we can conclude that the E2 allele of the Apo E gene is the risk factor for development of hypertriglyceridemia in the Uighurs with CHD.Thus the presence of the E4 allele of the Apo E gene is a genetic marker of predisposition to hypercholesterolemia in the Kazakhs with CHD. However, the presence of the E2 allele is a genetic marker of predisposition to hypertriglyceridemia in the Uighurs with CHD.The polymorphisms of the Apo B, Apo C111, Apo E genes in the Kazakhs and Uighurs are informative for molecular genetic population and clinical studies. A significant inter-ethnic difference of the frequency distribution of alleles and genotypes of the Apo B, Apo E genes studied in ethnic groups has been found. The X1 allele of the Apo B gene and the E4 allele of the Apo E gene are determined more often in the Kazakhs than in the Uighurs.There are significant association of alleles of the Apo E and Apo C111 genes with the value of lipid parameters in the Kazakhs, which confirms their substantial contribution to the determination of the abarrant lipid metabolism; the E4 allele of the Apo E gene is a leading molecular genetic factor in the development of hypercholesterolemia; the S1 allele of the Apo C111gene predisposes to the development of hypertriglyceridemia.Significant association of alleles of the Apo B, Apo C111 and Apo E genes with the value of lipid parameters have been evaluated in the Uighurs, whereby we confirm the contribution of these genes as risk factors in the development of abarrant lipid metabolism. Carriage of the X2 allele of the Apo B gene significantly predisposes an individual to hypercholesterolemia and increased levels of LDLP and the Apo B.The S2 allele of the Apo C111 gene and the E2 allele of the Apo E gene are also genetic markers of hypertriglyceridemia.Understanding these genetic antecedents in this population as risk factors for CHD may provide the physician with important and relevant facts to persuade both Kazakhs and Uighurs hard drinkers to significantly reduce their alcohol intake . These d


Preterm birth, the birth of an infant prior to 37 completed weeks of gestation, is the leading cause of perinatal morbidity and mortality. Preterm infants are at greater risk of respiratory, gastrointestinal and neurological diseases. Despite significant research in developed countries, little is known about the causes of preterm birth in many developing countries, especially China. This study investigates the association between sciodemographic data, obstetric risk factor, and preterm birth in five Maternal and Child Health hospitals in Beijing, China.A case-control study was conducted on 1391 women with preterm birth (case group) and 1391 women with term delivery (control group), who were interviewed within 48 hours of delivery. Sixteen potential factors were investigated and statistical analysis was performed by univariate analysis and logistic regression analysis. Univariate analysis showed that 14 of the 16 factors were associated with preterm birth. Inter-pregnancy interval and inherited diseases were not risk factors. Logistic regression analysis showed that obesity (odds ratio (OR) = 3.030, 95% confidence interval (CI) 1.166–7.869), stressful life events , sexual activity , placenta previa , gestational diabetes mellitus , hypertensive disorder complicating pregnancy , history of preterm birth  and reproductive abnormalities  were independent risk factors. Women who lived in towns and cities , had a balanced diet  and had a record of prenatal care  were less likely to have preterm birth.Obesity, stressful life events, sexual activity, placenta previa, gestational diabetes mellitus, hypertensive disorder complicating pregnancy, history of preterm birth and reproductive abnormalities are independent risk factors to preterm birth. Identification of remedial factors may inform local health and education policy. Preterm birth, the birth of an infant prior to 37 completed weeks of gestation, continues to be the leading cause of perinatal morbidity and mortality The underlying causes of preterm delivery are multiple and poorly understood.. It may include individual-level behavioral and psychosocial factors, neighborhood characteristics, environmental exposures, medical conditions, infertility treatments, biological factors, and genetics Despite significant research in developed countries, there is little known about the causes of preterm birth in many developing countries. There are significant, persistent, and very disturbing racial, ethnic, and socioeconomic disparities in the rates of preterm birth. The study of the risk factors for preterm birth in China, especially in Beijing is rarely reported. As the capital of China, Beijing has special characteristics. The study on the effect mechanism of the public hygiene, demography, and social circumstance on the preterm birth in Beijing is of theoretical and practical significance for suppressing the preterm birth and thus for increasing the population quality of the capital. Therefore, a nationwide retrospective epidemiological study of preterm birth rates was performed in 2008 by Haidian Maternal and Child Health Hospital and the Medical Genetics Center of Peking University. A total of 55 hospitals in 15 cities were included in the study. There were nearly 300,000 live births, and over 15,000 preterm infants were identified, with a national preterm delivery rate of 5.63%. The rates varied markedly among different provinces as well as different levels of hospital. Although this was a nationwide study, risk factors for preterm birth could not be analyzed because of incomplete information. We thus decided to conduct a case-control, retrospective study in Beijing, China, that would compare pregnant women who had preterm birth with an appropriate control group to determine factors that might be associated with preterm birth.This work was conducted according to the principles expressed in the Declaration of Helsinki, and approved by the Ethics Board, Haidian Maternal and Child Health Hospital, Beijing. Written informed consent was obtained from the participants at the time of their usual hospital care during the birth.This study was designed as a matched case-control study, at a ratio of 1∶1.There are two kinds of hospitals capable to deliver a child in Beijing. They could be classified as Maternal and Child Health (MCH) hospitals and comprehensive hospitals. There are eighteen MCH hospitals in Beijing, with one MCH hospital in one District.This study was conducted between August 1, 2009 and August 31, 2010 at five MCH hospitals in Beijing, China, which are located in five districts: Haidian District, Tongzhou District, Shunyi District, Changping District and Daxing District. The skills of midwifery was almost same in the above five MCH hospitals. The delivery number in these five MCH hospitals was 32712 during the study period, accounted for 18.8% of the total delivery number in Beijing, and they located in different orientation of Beijing.Cases were women who delivered before 37 completed weeks' gestation (20–36 weeks' gestation). Preterm delivery cases were identified by daily monitoring of all new deliveries at postpartum wards of participating hospitals. Controls were women who delivered at term (≥37 weeks' gestation). 1429 deliveries were preterm birth. The total preterm rate was 4.37%. The preterm rate of Haidian MCH, Tongzhou MCH, Shunyi MCH, Changping MCH and Daxing MCH were 5.32%(656/12333), 4.15%(326/7864), 3.93%(175/4458), 4.16%(147/3535) and 2.76%(125/4522) respectively. An eligible control, delivering immediately after a case, with similar age (±3 years), was approached and recruited for the study. Except incomplete data (people who could not be contacted with or would not participate in), there were 1391 preterm births and 1391 full-term deliveries analyzed, accounting for 97.34% (1391/1429) of all the preterm cases.Standard operating procedures were elicited to all research personnel in the launching meeting before the formal study. The usage of standardized data collection instruments were explained in detail.After obtaining informed consent, we asked the women to participate in a 20-minute personal interview in which trained research personnel used a standardized structured questionnaire to elicit information regarding maternal sociodemography, sex activity during pregnancy and medical history. Prenatal and delivery medical records were reviewed by trained research nurses who used a standardized abstraction form. Information abstracted from medical records included prepregnancy weight, height, pregnancy complications and condition of the newborn.Gestational age was based on the last menstrual period (LMP) confirmed by sonographic examination prior to 20 weeks gestation. As for women who had a poor recall of LMP or the LMP and ultrasound date differed by more than 14 days, sonographic examination was used for measurement of gestational age. The total proportion of GW determined by ultrasound date was 20.6% (573/2782). Although the specific proportion of women who had a poor recall of LMP was not documented in this study, it was extremely low according to the daily clinical work.Educational attainment was categorized as elementary school or less (≤6 years), middle school (6–12 years), university (13–18 years) or graduate and beyond (≥19 years of completed education).2. BMI was classified into four categories BMI is defined as body weight divided by the square of height in kg/mAccording to Chinese Nutrition Society, reasonable nutrition requires the heating percentage of three major nutrients were protein  10%–15%, fat  20%–30% and carbohydrates  55%–65%. Self-evaluation of pregnant women was acquired by personal interview.Inter-pregnancy interval was defined as that interval between the termination of one pregnancy and the conception of another and was categorized as four groups: 6 months or less, 7–12 months, 13–24 months and >24 months.All pregnancies were screened for gestational diabetes mellitus (GDM) between 24 and 28 weeks of gestation. The screening test is a 50 g glucose load, given orally at any time of the day, with plasma glucose measured 1 h later. If plasma glucose is 7.8 mmol/L or greater, an oral glucose tolerance test (OGTT) is requested. The OGTT comprises plasma glucose determinations, the first while fasting and subsequently at 1, 2 and 3 h after ingesting a 75 g glucose load. GDM is diagnosed when any two of these plasma glucose values are equal or greater to the following values: fasting ≥5.6 mmol/L, 1 h ≥10.3 mmol/L, 2 h ≥8.6 mmol/L, 3 h ≥6.7 mmol/L).Hypertensive disorder complicating pregnancy was defined according to the textbook of Obstetrics and Gynecology t-test was used for comparison of continuous variables. Comparison of proportions was performed by the McNemar-Bowker test as appropriate. Statistical significance was achieved when at P<0.05. Conditional logistic regression analysis was used to determine independent risk factors for preterm delivery. Cox regression analysis P values are 2 tailed, and confidence intervals(CIs) were calculated at the 95% level.The data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 11.5. Variables with more than 10% missing data were excluded from analyses. A paired-sample Student t = −1.898, P = 0.058). The gestation weeks of the preterm group were in The mean maternal age of the participants was (28.57±4.55) years for the preterm group and (28.68±4.14) years for the full-term group, and the difference was not significant (As shown in 2) was associated with an increased risk of preterm birth. In this study, stressful life events for the participants included hospitalization, surgery or death of family members, and family conflict. Exposure to life events , house or office decorating , as well as having sex during pregnancy  were all risk factors for preterm birth. Fewer women in the preterm group (59.2%) had a balanced diet compared with the control group (69.5%). A balanced diet was associated with a decreased risk of preterm birth . Women with a record of prenatal care were less likely to have preterm birth .The associations between obstetric history, family history and preterm birth are shown in After adjusting for confounding factors, the results of multiple logistic regression analysis are presented in A major strength of this study was its large sample size with matched case-control design and identification of risk factors was based on 1391 women with their pregnancies complicated by preterm birth. The strength of our study also lies in the use of patient interviews and medical record data rather than birth certificate data. Thus, the association between more potential risk factor and the presence of preterm delivery was investigated. It should be noted that estimates generated by logistic regression analysis of data in this retrospective study should be interpreted with caution, especially as the numbers for some risk factors were small and the confidence intervals were wide.We concur with prior studies that GDM There is certain genetic basis for preterm birth After adjustment for potential confounders, multivariate logistic regression analysis indicated that women with prenatal care were less likely to have preterm birth , which is compatible with a previous study The present study showed that living in a town or city was associated with a lower risk of preterm birth, even after adjusting for other factors. Although many efforts have been made in Beijing, there are a wide medical and health care gap and a wide income gap between urban and rural areas. This concurs with studies that showed that living conditions may directly increase the occurrence of preterm birth through neuroendocrine and immune pathways that affect susceptibility to infection and hypertension Life events are major events that individuals experience, such as divorce, a death in the family, illness, or injury. It makes people suffered from stress, threaten the homeostasis. In this study, stressful life events for the participants included hospitalization, surgery or death of family members, and family conflict. Nedra Whitehead and colleagues The potential for adverse effects of sexual activity, particularly intercourse, during pregnancy has been of concern for some time due to the potential for direct effects of semen on initiating preterm labor, alteration of vaginal microflora, or other hypothesized pathways leading to preterm birth. Engaging in sexual activity was associated with an increased risk of preterm birth in our study, but other studies reported an absence of increased risk and even a notably diminished risk of preterm birth Although the definition of balanced diet is rough and the information maybe rough, a balanced diet was associated with a decreased risk of preterm birth in this study, which provided further support for obesity as a risk factor for preterm birth. A previous study showed that obesity was an independent risk factor for late preterm birth Inter-pregnancy interval was not associated with preterm birth in our study, which is not consistent with results from a previous study Given the complexity of the influencing factors of preterm birth, there are some limitations in this study. Firstly, our study may be limited by recall bias since mothers were interviewed after delivery, for example, sexual activity during pregnancy. Secondly, our study did not classify preterm birth by sub-categories. Preterm birth is typically defined as a delivery or birth at a gestational age less than 37 weeks. Other commonly used subcategories of preterm birth have been established. They are extremely preterm (birth at ≤28 weeks of gestation), very preterm (birth at <33 weeks of gestation) and moderately preterm (birth at 33 to 36 weeks of gestation). It could also be classified into three separate subgroups according to clinical presentation: births occurring after spontaneous premature labor; births related to premature contractions; and spontaneous rupture of the membranes and indicated delivery of a premature infant for the benefit of either the infant or the mother. The influencing factors of the different sub-categories of preterm birth needs to be further studied. Lastly, because the five hospitals were not the terminal comprehensive health center, so the pregnancy women with critical disease were referred to the tertiary comprehensive health center, thus the pregnancy complications mainly included hypertensive disorder complicating pregnancy and gestational diabetes mellitus. The representative of the result is subject to certain restriction.In conclusion, this study indicated that obesity, stressful life events, sexual activity, placenta previa, GDM, hypertensive disorder complicating pregnancy, history of preterm birth and reproductive abnormalities are independent risk factors for preterm birth. Although advances in high-risk obstetric and neonatal care have resulted in improved survival of infants born preterm, many studies have documented the prevalence of a broad range of neurodevelopmental impairments in preterm survivors. The spectrum of neurodevelopmental disabilities includes cerebral palsy, mental retardation, visual and hearing impairments, and more subtle disorders of central nervous system function. So, develop new premature predictors to identify high-risk groups and take effective intervention to improve birth outcomes is still an important direction of the future.


The literature shows a variable and inconsistent relationship between socioeconomic position and preterm birth. We examined risk factors for spontaneous and iatrogenic preterm birth, with a focus on socioeconomic position and clinical risk factors, in order to explain the observed inconsistency.We carried out a retrospective population-based cohort study of all singleton deliveries in Nova Scotia from 1988 to 2003. Data were obtained from the Nova Scotia Atlee Perinatal Database and the federal income tax T1 Family Files. Separate logistic models were used to quantify the association between socioeconomic position, clinical risk factors and spontaneous preterm birth and iatrogenic preterm birth.The study population included 132,714 singleton deliveries and the rate of preterm birth was 5.5%. Preterm birth rates were significantly higher among the women in the lowest (versus the highest) family income group for spontaneous  1.03, 1.25) but not iatrogenic preterm birth . Adjustment for maternal characteristics attenuated the family income-spontaneous preterm birth relationship but strengthened the relationship with iatrogenic preterm birth. Clinical risk factors such as hypertension were differentially associated with spontaneous  and iatrogenic preterm  but factors such as diabetes mellitus were not .Socioeconomic position and clinical risk factors have different effects on spontaneous and iatrogenic preterm. Recent temporal increases in iatrogenic preterm birth appear to be responsible for the inconsistent relationship between socioeconomic position and preterm birth. Factors such as multi-fetal pregnancy, congenital malformations, older maternal age and race/ethnicity are strongly associated with preterm birth -4. HowevAnother interesting aspect of the relationship between socioeconomic position and preterm birth is the documented temporal change in the association. For instance, in 1989, preterm birth rates among less educated women in the United States  were 73%We hypothesized that the heterogeneity of preterm birth may constitute one potential explanation for the inconsistent and variable relation between socioeconomic position and preterm birth. It is possible that spatial and temporal variations in the frequency of the preterm birth subtypes, namely, spontaneous preterm birth (following preterm labour) and iatrogenic preterm birth (following labour induction or cesarean delivery before labour onset), or temporal changes in clinical risk factors  for these subtypes of preterm birth underlie the vagaries of the socioeconomic position–preterm birth relationship.The Canadian setting is likely ideal for examining potential changes in the relationship between socioeconomic position, obstetric intervention and preterm birth subtypes, given universal health insurance coverage for obstetric and related medical services. We therefore carried out a study to examine the determinants of spontaneous and iatrogenic preterm birth, with a focus on the effect of socioeconomic position and clinical risk factors.The study cohort included all live births and stillbirths to residents of Nova Scotia, Canada between 1988 and 2003. Detailed information for the study was obtained from the Nova Scotia Atlee Perinatal Database, a population-based database which contains information on maternal characteristics, labor and delivery events, and neonatal diagnoses and procedures. The database is collated from information abstracted from antenatal and medical charts by trained personnel using standardized forms. An ongoing data-quality assurance program, which conducts periodic abstraction studies, and validation studies  have shoBirths with a birth weight <500 g or a gestational age <20 weeks were excluded to avoid potential bias due to changes in the registration of births at the borderline of viability ,12. A coAnnual after-tax family income for each woman (in the year of delivery) was based on the T1 Family Files and adjusted for family size. The latter calculation was carried out by dividing the total family income by the weighted number of family members. Weights were based on a standard formula  . Family Rates of preterm birth <37 completed weeks gestation and preterm birth <32 completed weeks among singletons  were examined within categories of family income and contribution to a retirement savings plan. Gestational age was based on the duration between the last menstrual period and the delivery if it was consistent with the neonatal physical examination of the infant and based on the neonatal physical examination in cases where the discrepancy between the 2 methods of gestational age ascertainment was 3 weeks or greater. Preterm births were categorised as iatrogenic if labor was induced or if a cesarean delivery was carried out in the absence of labor, and as spontaneous otherwise.The crude and adjusted effects of socioeconomic position and other factors on spontaneous/iatrogenic preterm birth were examined in the study population using 3 different logistic models. All models accounted for the non-independence of observations among births to the same women using generalized estimating equations. The first of the three models provided the crude effects of socioeconomic position and included family income and contribution to a retirement savings plan as the independent variates and spontaneous (or iatrogenic) preterm birth as the dependent variate. The second set of logistic models were used to assess the effect of family income and contribution to a retirement savings plan after adjustment for extraneous maternal characteristics that could have confounded the socioeconomic position-spontaneous/iatrogenic preterm birth relation . The last of the 3 models also included medical complications of pregnancy . Other chronic medical disease included cardiovascular disorders, renal disease, gastrointestinal disorders, respiratory disease, endocrine disorders, neurologic disease, blood dyscrasias and miscellaneous illnesses. This most proximal set of potential confounders was added last because some potentially lie in the causal pathway between maternal characteristics and spontaneous/iatrogenic preterm birth. Since rates of preterm birth and its subtypes  were rare, the odds ratios from the logistic models were considered to approximate proportion type rate ratios. The statistical significance of differences in the odds ratios expressing the effect of a risk factor on spontaneous preterm birth vs iatrogenic preterm birth was assessed using a Chi-square test for the heterogeneity . Analysi> = 35 years of age compared with only 4.8% of mothers in the lowest family income category. Such differences were also evident in contrasts by RSP contribution in the year of delivery  was 5.5%; the rate of spontaneous preterm birth was 4.7% and the rate of iatrogenic preterm birth was 0.8%. Crude rates of preterm birth <37 weeks were significantly higher among women with the lowest family income (6.1%) compared with women with the highest family income . Also, women in the middle family income category  had a significantly lower rate of spontaneous preterm birth compared with women in highest family income group. Finally, women who did not contribute to an RSP also had a 14%  higher rate of spontaneous preterm birth compared with women who contributed to an RSP. On the other hand, the crude relationships between family income and iatrogenic preterm birth, and the crude relationship between contribution to an RSP and iatrogenic preterm birth were not statistically significant  times greater risk of spontaneous preterm birth compared with women 20–24 years, while women > = 40 years had a 4.47  times greater risk of iatrogenic preterm birth. These two rate ratios were significantly different from each other (P < 0.05 for heterogeneity). Nulliparous women were at higher risk of both spontaneous and iatrogenic preterm birth compared with women of parity 1, though again the excess risk was higher with iatrogenic preterm birth. However, parity > = 3 was protective against spontaneous preterm birth but not significantly related to iatrogenic preterm birth  had an increased risk of spontaneous preterm birth compared with women with a pre-pregnancy weight of 60–69 kg. However, pre-pregnancy weight was not associated with iatrogenic preterm birth. Maternal smoking was associated with both spontaneous and iatrogenic preterm birth to a similar degree, while a previous cesarean delivery was a protective factor for spontaneous preterm birth  and a strong risk factor for iatrogenic preterm birth . Previous low birth weight and previous perinatal death were similarly associated with spontaneous and iatrogenic preterm birth. Spontaneous preterm birth rates showed an increasing trend over calendar time but the rate in 2000–2003 was not significantly higher than the rate in 1988–1990 . On the other hand, rates of iatrogenic preterm birth increased steadily and the adjusted rate in 2000–2003 was 60%  higher than the rate in 1988–1990.Other differences in risk factors for spontaneous and iatrogenic preterm birth included marital status. Single women and women in a common law relationship had higher rates of spontaneous preterm birth compared with married women, while marital status did not influence rates of iatrogenic preterm birth Table . Women wAssociations between maternal complications and the two subtypes of preterm birth showed distinct differences Table . Gestati> = 35 years compared with 8.7% whose records did not link. Similarly, of the women whose records linked to socioeconomic information 43.8% were nulliparous, 7.5% had a pre-pregnancy weight > = 90 kg, 63.3% were married and 39.4% lived in a rural area compared with 46.6%, 6.8%, 63.3% and 39.2%, respectively, of women whose records did not link. The rate of preterm birth among women with unlinked records was 6.0% (compared with 5.5% among women with linked records).Supplementary analyses showed that women whose perinatal records linked to socioeconomic information in the T1 Family Files (81.3%) were generally similar to women whose records did not link (18.7%); 10.4% of women whose records linked were Our study shows that spontaneous and iatrogenic preterm birth have several common and distinct risk factors. Family income and contribution to a retirement savings plan were associated with crude rates of spontaneous preterm birth but not with crude rates of iatrogenic preterm birth. Similarly, factors such as older maternal age, parity and previous cesarean delivery had significantly different effects on spontaneous and iatrogenic preterm birth. Adjustment for determinants of preterm birth attenuated the socioeconomic associations with spontaneous preterm birth and strengthened associations with iatrogenic preterm birth. Finally, adjusted temporal trends in spontaneous and iatrogenic preterm birth were distinct, with a small, non-significant increase in spontaneous preterm birth and a substantial, significant increase in iatrogenic preterm birth.These data provide some insight into the observed temporal attenuation in the relationship between socioeconomic position and preterm birth seen in several countries ,7. SinceThe overlap between the etiology of spontaneous and iatrogenic preterm birth has been previously described -24. IndiOur study shows that crude rates of spontaneous preterm birth are associated with indices of socioeconomic position including family income and contribution to a retirement savings plan. Adjustment for maternal characteristics such as age, parity, marital status, pre-pregnancy weight and smoking abolished or substantially attenuated these associations strongly suggesting that such lifestyle factors mediate the excess risk of spontaneous preterm birth by socioeconomic position. On the other hand, family income and contribution to a retirement savings plan were not associated with iatrogenic preterm birth. However, this is not unexpected in the Canadian setting where universal coverage for obstetric and related medical services is available under the Canadian health care system ,26.The overall rate of preterm birth in our study was low (5.5%) and the proportion due to iatrogenic preterm birth was also low . This is because the study was restricted to singleton births for the period 1988 to 2003. For instance in 1997, the overall rate of preterm birth in Canada was 7.1% and among singletons, the preterm birth rate was 5.9% . A previThe strengths of our study include the use of information from two high quality databases. The Nova Scotia Atlee Perinatal Database had detailed information that permitted the classification of preterm birth subtypes based on labor characteristics (presence/absence of labor and whether labor was induced or spontaneous). Similarly, information from the federal T1 Family Files and calculation of family income (adjusted for family size and inflation) permitted an accurate estimate of socioeconomic position. The use of contribution to a retirement savings plan as an index of socioeconomic behavior that was distinct from family income was another strength of the study.The limitations of our study included those that are typically associated with information in large databases. Some accuracy may have been compromised due to transcription and related errors. Also, height was not available for calculation of body mass index, and gestational age was assessed based on menstrual dating confirmed by neonatal physical examination. Although we did not have ultrasound confirmed gestational age, the same uniform algorithm for gestational age assessment was used over the entire duration of the study from 1988 to 2003. Finally, our population-based data source, which included all singleton births in Nova Scotia (≥20 weeks gestation or ≥500 g), was affected by our inability to link all perinatal records with T1 Family File socioeconomic information. However, the linkage rate was high (81.3%) and there were only modest differences in maternal characteristics between women whose records did and did not link. Finally, we only examined one dimension of the heterogeneity of preterm birth (spontaneous vs iatrogenic), although several other classification schemes have been previously described in the literature -32. ThisOur study showed that socioeconomic position was associated with crude rates of spontaneous preterm birth but not with crude rates of iatrogenic preterm birth. Older maternal age, parity, previous cesarean delivery and pregnancy complications had significantly different effects on spontaneous and iatrogenic preterm birth. Adjusted temporal trends in spontaneous and iatrogenic preterm birth were distinct, with a small non-significant increase in spontaneous preterm birth and a substantial and significant increase in iatrogenic preterm birth. These findings explain inconsistencies in the literature with regard to the relationship between socioeconomic position and preterm birth and the observed changes in this relationship.The authors declare they have no competing interests.The study was based on a grant proposal submitted by the authors and funded by the Canadian Institutes of Health Research. Analyses were carried out by KSJ who submitted SAS programs to the office of the Small Area and Administrative Data Division of Statistics Canada in Ottawa. All authors reviewed the preliminary and final analyses, and the draft and final manuscripts. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2393/14/117/prepub


Echinococcus granulosus commonly seen in temperate regions. Primary omental hydatid cyst is rare entity. Diagnosis can be achieved with contrast-enhanced computed tomography of abdomen and pelvis along with serology. Eosinophilia is a strong pointer to hydatid cyst as a differential diagnosis. Open or laparoscopic excision of the cyst along with medical therapy remains the treatment of choice.Hydatid cyst is caused by the parasite  Echinococcus granulosus. It is a severe public health problem in the developing parts of the world. HD is commonly seen in liver and lungs but primary omental hydatid is rare.Hydatid disease is a parasitic disease that is caused by E. granulosus was raised above the normal limits . Patient's complete blood counts were normal except eosinophilia. Liver function and renal function tests were within normal limits. A 52-year-old male presented with complaints of upper abdominal pain since one year on and off, which was dull aching nonradiating in the right hypochondrium. He also had occasional dyspepsia. However he had no history of jaundice, fever, or weight loss. Clinical examination did not reveal additional findings. Ultrasonography of abdomen and pelvis revealed cholelithiasis and a 10 × 9 cm solitary cystic lesion in the pelvis which had a well-defined wall with clear liquid. In view of this finding contrast-enhanced computed tomography of abdomen and pelvis was done which revealed a well-defined cyst in the pelvis arising from omentum and measuring approximately 10 × 9.5 cm with clear fluid inside and cholelithiasis . Liver, After preoperative course of Albendazole therapy, patient was planned for exploratory laparotomy. At laparotomy a 10 × 9 cm omental cyst was found without any infiltration into the surrounding structures. The cyst was excised in toto along with the rim of omentum all around . Open chEchinococcus granulosus commonly seen in temperate regions. The adult worm resides in Dog or Wolf's intestine (definitive host). Definite host shed eggs in their stool which contaminate vegetables and fruits. These eggs are then ingested by the cattle or sheep during grazing in the fields. Humans are intermediate and accidental host. Humans are infected by eating contaminated vegetables or fruits. These parasite oncospheres after entering the stomach or intestine start penetrating their wall and reach liver parenchyma through portal circulation. After reaching the liver which acts as a filter for the parasite (dead end), larval stage development begins (cyst formation). Some of the oncospheres may bypass liver and reach lungs through systemic circulation and form larval stage there. Hydatid cyst commonly affects liver and lungs. Primary omental hydatid cyst without liver and lung involvement is rare. Intraperitoneal hydatid disease is seen in about 3.9–12.5% of patients [Hydatid cyst is caused by the parasite A role of lymphatic system in seeding of oncospheres directly from the bowel to the site of development of intra-abdominal cyst has also been shown . PrimaryThe ideal treatment for omental hydatid is controlled open surgical excision as there is a very high possibility of uncontrolled spillage and peritoneal dissemination of the disease leading to recurrence , 10. Lap In conclusion, primary omental hydatid cyst can occur without affecting other viscera. Hydatid cyst should be kept as one of the differential diagnosis for any patient presenting with a cystic lump in the abdomen especially from endemic areas. Eosinophilia on peripheral smear may also help in supporting the diagnosis of parasitic infestation especially in the setting of the diagnostic dilemma. Abdominal tuberculosis should always be ruled out before planning a surgical therapy. Open or laparoscopic excision of the cyst should be performed in a suspected hydatid cyst in the omentum to prevent recurrence.


Electrotherapy is a relatively well established and efficient method of tumor treatment. In this paper we focus on analytical and numerical calculations of the potential and electric field distributions inside a tumor tissue in a two-dimensional model (2D-model) generated by means of electrode arrays with shapes of different conic sections .Analytical calculations of the potential and electric field distributions based on 2D-models for different electrode arrays are performed by solving the Laplace equation, meanwhile the numerical solution is solved by means of finite element method in two dimensions.Both analytical and numerical solutions reveal significant differences between the electric field distributions generated by electrode arrays with shapes of circle and different conic sections . Electrode arrays with circular, elliptical and hyperbolic shapes have the advantage of concentrating the electric field lines in the tumor.The mathematical approach presented in this study provides a useful tool for the design of electrode arrays with different shapes of conic sections by means of the use of the unifying principle. At the same time, we verify the good correspondence between the analytical and numerical solutions for the potential and electric field distributions generated by the electrode array with different conic sections. Electrotherapy is the use of electrical energy as a medical treatment and it was introduced to destroy solid tumors at the end of nineteenth century. Many physicians have successfully used this therapy, also known as electrochemical tumor therapy, Galvanotherapy and electro-cancer treatment, as a standalone treatment in thousands of cases, with some truly spectacular results -4. ElectThe voltage mode produces less pain in the patient than the one induced for the current mode. The voltage range usually used is 6 to 12 V, the electric quantity often is 80 to 100 coulombs and the time needed to deliver this quantity is 20 to 120 minutes, in dependence of consistency, size and type of solid tumor. Permanent tissue damages are observed for voltage values equal and higher than 6 V and convenient distributions of electrodes in the tumor, as shown in our current clinical trial (results not shown) and . As a reThe clinical results carried out up to now reveal that, in both modes, electrotherapy is safe, effective, inexpensive, and induces minimal adverse effects in the organism. Also, it can be applied when the conventional methods  fail. This anti-tumor therapy has not yet been universally accepted because two main reasons: 1) its antitumor mechanism is not fully understood and 2) it is not standardized . The firElectric field strength and its form of distribution, through electrodes play a decisive role in the electrotherapy effectiveness. The proposal for electrode arrays that efficiently distribute the electric field (electric current density) in a tumor and its surrounding healthy tissue is one of the most stimulating problems in the electrotherapy-cancer theme because the tumor may significantly be destroyed with the minimum damage in the organism. Different studies reveal that the electric field (electric current density) spatial distribution in tumor and its surrounding healthy tissue strongly depends on the tumor size, electrodes array parameters  and the electric field orientation -16. AlsoIn previous studies have been showed the two-dimensional (2D) analytical and numerical expressions for the potential and electric field generated by electrode arrays with circular ,13 and eAt present, several researchers have attempted to construct three-dimensional anatomical models for tissues by means of the finite-element method; however, an exact realistic tissue model is very difficult to establish from a computational point of view because it requires a precise knowledge of the electric and physiologic properties of both tissues. These electrical properties are the electrical conductivity, electrical permittivity, among others, whereas, the physiological properties are the type, heterogeneity, size, shape, composition, structure, consistency and water content of the tissue.An aspect not widely discussed in the specialized literature is the knowledge of how the shape of electrode array affects the potential, electric field and electric current density distributions in order to improve the electrotherapy effectiveness. A significant effort is required to comprehend this problem because the exact shapes of different electrode arrays are usually not given, in spite of the existence of mathematical approaches -16 and iDev et al. , Čorovićthen its real part function, denoted by Re (Φ(z)), is also solution at the same region.0(z)) to calculate the electric field strength in lead order approximation, named E0(z) by means of ▽Φ0(z). The details for the calculations of Φ0(z) and E0(z) are reported in [In Equation 1, Φ(z) is the potential that can be written as a sum of multi-poles of all electrodes . The higorted in ,13-15 ann in (3) are calculated from the boundary conditions of the electrodes and given in [where N represents the total number of electrodes placed on the array and z is the position of the point where the calculations are made. a is the electrode radius and d the smallest distance between two consecutive electrodes with alternate polarities. given in ,13-15. In. In this way, rn can easily be shown to have a general expression in polar coordinates (common in form of the three curves) if the origin of coordinates is located in the conic focus, given byThe equations in polar coordinates for the conic sections  may be obtained by using the unifying principle for the electrode position zn y θn are the polar coordinates of the n-th electrode (with the origin on the point F). The parameter e is the conic eccentricity that distinguishes the type of conic section: e < 1 (the locus is an ellipse); e = 1 (the locus is a parabola) and e > 1 (the locus is a hyperbola). Although the unifying principle for the conic sections allows the possibility to obtain the polar equations of all three curves (4), it should be remarked that in the case of hyperbola this equation represents only one of its branches (that whose focus is at the origin), rather than the entire curve. The plus sign corresponds to the left branch of the hyperbola.where m is the distance between the focus (F) and the directrix line (D), as shown in Figure n = b: b is the circle radius) and [n = b1 = b2 = b: b1 and b2 are the major and minor radius of the ellipse, respectively). It is important to point out that the expressions reported in [Figure ius) and ,15  is ± V0 = U/2. Table 0 for each one of these configurations. We fix the electrode radius (a = 0.215 mm) and the number of the electrodes . The angular positions of these six electrodes (θ), with respect to the center of the conic, are fixed in θ = 0, 60, 120, 180, 240 and 300° (for the circle and the ellipse), and θ = 0, 45, 135, 180, 225 and 315° (for the hyperbola). In the case of the parabola, the angular positions are referred to vertex in θ = 60, 65, 75, 285, 295 and 300°. In order to calculate the equation (4), these positions are transformed to those with respect to the focus F.Following the ideas of Čorović et al. , we assuNumerical calculations are performed by using a finite element method for each electrode array in 2D. The electrodes are placed inside a rectangle representing a homogeneous tissue having a constant conductivity. For the analytical and numerical calculations, the electrodes are completely inserted in the tumor because the higher electric field strength (electric current density) is induced in it with the minimum damage in the surrounding healthy tissue ,16.A constant voltage is assigned to the boundary representing the electrodes surface. Isolating boundary conditions are assigned to the outer boundaries of the rectangle. The dimension of the outer square is 20 mm > 2d in all models, since 2d is the error due to the finite size of the model is negligible. The values of the parameters e, m, a, electrode potential and angular position of each electrode are the same as those used for the analytical calculations. Model geometries are meshed by triangular finite elements. The final mesh is obtained by an adaptive method using a relative tolerance criterion of 0.001.max, in V/mm), minimum  and norm  values are used to quantify the differences between the electric field distributions generated for each electrodes array. Emax and Emin represent the local characterization of the electric field and EE is the global characterization of it. Indeed, EE is the sum of the local electric field intensity over all points in the target tissue, given byThe maximum  and p is the total number of points in the target tissue (p = 32 248).where EFinite element method and the expressions (2-5) are implemented in the MATLAB software, version R2011a . The analytical and numerical calculations are performed on a personal computer Intel Pentium 4, dual-core processor 2.16 GHz CPU and 4 GB RAM. Each calculation takes approximately one minute.Figure max, Emin and EE values for each one of the configurations above mentioned. These three quantities are calculated over all nodes within the work region. This table and Figure max. This configuration concentrates the electric field lines mainly around the electrodes.Table The comparison between the electrode elliptical arrays (Configurations II and II-1) and electrode hyperbolic arrays (Configurations IV and IV-1) evidences that there exist differences in the electric field distributions when parameter e varies, keeping constant parameter m, the type of electrode configuration, the angular position and the polarity of the electrodes. It is easy to check that electric field distribution generated for each conic section changes when the electrode polarity and values of the parameter m are varied (results not shown).The analytical results are validated by the numerical calculations for each electrodes configuration. Comparison of the numerical and analytical results are carried out by plotting the potential Figure  and elecin vivo (ex vivo) tissue model.In this paper we do not pretend to discuss whether the analytical solution is better than numerical one or vice versa. The results demonstrate that the analytical calculations shown in ,13-15 caWe use 2D numerical and analytical models in order to compare the potential and electric field strength, for different electrode configurations, in the central plane of a more general 3D model. The 2D results are a good approximation of local electric field distribution in 3D models for needle electrodes since these are usually long and deeply inserted in tissue, as is reported in . Also, tmax, Emin and EE values may be useful to propose electrode configurations more feasible for tumor treatment. Configurations I, II and IV concentrate more the electric field lines in the target tissue between the electrodes. As a consequence, these may be suggested for the solid tumors treatment with electrotherapy and other electric field based therapies, as electrochemotherapy and irreversible tissue ablation. For this, we should keep in mind that electric field strength should be above a certain irreversible threshold value of the electric field in order to cause permanent damages on the target tissue leading to its partial or complete destruction. However, it should not be exposed to excessively high electric field to avoid damages to the surrounding healthy tissue.Emax (10 times lower than that obtained by Configurations II and IV). We have observed that the tumor complete remission and the conversion of an inoperable tumor in operable (patients with breast cancer) are reached, independently of the tumor histological variety for voltage strengths below 6 V. In this case, we make a convenient distribution of the electrodes in the tumor combined with the intra-tumor injected saline solution.At first sight, Configuration III is un-useful for the solid tumors treatment if we keep in mind that it concentrates less the electric field lines in the tumor and shows low values of EE and EA potential clinical application of Configuration III may be in the selective treatment of the tumor-healthy tissue interface (or tumor border), which is a complex region due to the simultaneous presence of both cancerous and healthy cells and other cellular components.This interface is rich in blood and lymphatic vessels, in dependence of the tumor type, in addition to the existence of high sialic and lactic acid concentrations, fact that may indicate that this tumor region has high conductivity. In this case, it is not required high electric field strength. The knowledge of this interface may be interest for the therapist and an indicator of the difference between the tumor and its surrounding healthy tissue, aspects which should be considered in the therapeutic planning before treatment. This allows an adequate insertion and distribution of the electrodes inside and/or at the tumor border, in dependence of the electrodes of the electrodes configuration type in agreement with other studies ,13-16. HAlso, Configuration III may be used for cancer treatment if we use symmetric parabolic configurations (similarly as for Configuration IV) and/or combining it with other pieces of different conic sections and the electrode arrays actually used. From the electrode configurations above mentioned, it is possible to propose other more complex electrode arrays: i) two elliptical pieces with different eccentricities; ii) one elliptical piecewise of eccentricity e with the parabola; iii) one elliptical piecewise of eccentricity given with one branch of the hyperbola; iv) the parabola with one branch of the hyperbola of eccentricity e; and vi) two branches of hyperbola with different eccentricities). For this, we fix the origin (vertex) in the focus of one piecewise the ellipse and hyperbola (parabola) and thus express the equation of the other piecewise of another conic section with respect to this frame of reference (origin) by means of a translation to the focus of the first conic. This allows the use of Configurations I, II, III and IV, though these have not been used in the preclinical and clinical studies.in vivo model may be implemented in order to evaluate the influence of the parameters of these electrode arrays in the tumor growth kinetic, aspect that may be theoretically corroborated, as previously reported by Cabrales et al. [The above mentioned is important in the therapeutic planning previous to the electrotherapy application because we may choose the polarity and positioning of the electrodes, as well as the shape of the electrodes array, which have a marked influence in the potential and electric field distributions. These electric field distributions generated for these electrode arrays may be experimentally verified by means of diverse imaging techniques as the Electric Current Density Imaging ,27, Elecs et al. .We are not aware of the use of the conic sections in electrotherapy (electrochemotherapy and ablation therapy) for the cancer, but the use of these is feasible in the preclinical and clinical studies. In patients with cancer, these electrode configurations should be used in order to evaluate the safety , adverse effects and toxicity , and effectiveness . In clinical studies, the electrodes insertion methodology for Configurations I, II, III and IV is similar to that used at present (electrodes inserted into the base perpendicular to the tumor long axis) -6,17,19.1. The tumor size is determined by clinic and/or any imaging techniques . Plastic cannulae with style are inserted, through holes (printed in a plastic board and distributed in a family of conic sections that completely cover the tumor size), as shown in Figure 2. The styles are withdrawn and the electrodes are inserted in the tumor mass through the cannulae to ensure that the electric field will cover all the tumor mass when the voltage is applied to the electrodes Figure . After iThe results of this study suggest that different physical and chemical quantities, such as heat, temperature, pH fronts and electrochemical reactions around electrodes may be calculated from the electric field generated by electrode arrays with shapes of conical sections, which may contribute to the understanding of the electrotherapy antitumor mechanisms, as previously report other authors ,18,20,32In conclusion, the mathematical approach presented in this study is an extension of the works of Dev et al. , ČorovićThe authors declare that they have no competing interests.JBR developed the mathematical idea on which this manuscript is based. All the computer simulations and results analysis were making by AEBP. LEBC and JMBC supervised this research and helped in the results analysis. Also, all authors read and approved the final version of the manuscript.


The human brain development is a complicated yet well-organized process. Metrics derived from diffusion tensor imaging (DTI), including fractional anisotropy (FA), radial (RD), axial (AxD), and mean diffusivity (MD), have been used to noninvasively access the microstructural development of human brain white matter (WM). At birth, most of the major WM tracts are apparent but in a relatively disorganized pattern. Brain maturation is a process of establishing an organized pattern of these major WM tracts. However, how the linkage pattern of major WM tracts changes during development remains unclear. In this study, DTI data of 26 neonates and 28 children around puberty were acquired. 10 major WM tracts, representing four major tract groups involved in distinctive brain functions, were traced with DTI tractography for all 54 subjects. With the 10 by 10 correlation matrices constructed with Spearman's pairwise inter-tract correlations and based on tract-level measurements of FA, RD, AxD, and MD of both age groups, we assessed if the inter-tract correlations become stronger from birth to puberty. In addition, hierarchical clustering was performed based on the pairwise correlations of WM tracts to reveal the clustering pattern for each age group and pattern shift from birth to puberty. Stronger and enhanced microstructural inter-tract correlations were found during development from birth to puberty. The linkage patterns of two age groups differ due to brain development. These changes of microstructural correlations from birth to puberty suggest inhomogeneous but organized myelination processes which cause the reshuffled inter-tract correlation pattern and make homologous tracts tightly clustered. It opens a new window to study WM tract development and can be potentially used to investigate atypical brain development due to neurological or psychiatric disorders. The human brain is complicated yet well organized. The major cerebral white matter (WM) tracts connecting different brain regions are involved in different brain functions. These major cerebral WM tracts are often categorized into different tract groups based on their distinct functions. There are roughly four tract groups, namely limbic, projection, callosal, and association tract groups , a modality of MRI. The widely used diffusion tensor imaging (DTI) , recent tract analyses , left and right inferior fronto-occipital fasciculus (IFO_L and IFO_R), left and right cingulate part of cingulum tract (CGC_L and CGC_R), left and right hippocampal part of cingulum tract (CGH_L and CGH_R), forceps major (FMajor) and forceps minor (FMinor). The tract level comparisons of all four DTI-derived metrics were conducted between the two age groups. Spearman's pairwise inter-tract correlations were performed. We tested if significant correlations of homologous WM tracts exist in neonates and children around puberty. After obtaining four 10 by 10 inter-tract correlation matrices corresponding to four DTI-derived metrics, FA, RD, AxD, and MD, for each age group, we tested these correlation matrices against the identity matrix or a matrix with equal non-diagonal entries. We then assessed if the inter-tract correlations become statistically stronger from birth to puberty. In addition, hierarchical clustering was performed with the pairwise correlations based on FA, RD, AxD, and MD measurements for each age group to reveal the pattern of clustering in either age group and reveal the pattern shift from birth to puberty.Twenty six normal neonates  and 28 normal children around puberty , free of current and past neurological or psychiatric disorders, were recruited at Children's Medical Center (CMC) at Dallas and Advanced Imaging Research Center (AIRC) of the University of Texas Southwestern Medical Center (UTSW), respectively. The parents of all the subjects gave written informed consents approved by Institutional Review Board of UTSW.FOV = 200/200/100 mm, in-plane imaging matrix = 100 × 100, axial slice thickness = 2 mm. dMRI parameters for children around puberty were: FOV = 224/224/143 mm, in-plane imaging matrix = 112 × 112, axial slice thickness = 2.2 mm. The common parameters for dMRI acquisition of both neonate and child group were: b-value = 1000 s/mm2, TE = 97 ms, TR = 7.6 s, 30 independent diffusion-weighted directions  with SENSE parallel imaging scheme . dMRI parameters for neonates were: 1 − 3) and eigenvectors (ν1 − 3). FA, MD, AxD and RD, derived from DTI, were obtained for all the subjects with the following equations of eigenvalues:dMRI acquired from all the subjects was processed offline using DTIStudio , left and right inferior fronto-occipital fasciculus (IFO_L and IFO_R), left and right cingulate part of cingulum tract (CGC_L and CGC_R), left and right hippocampal part of cingulum tract (CGH_L and CGH_R), forceps major (FMajor) and forceps minor (FMinor). These tracts could be reproducibly traced with DTI of all neonates and children and cover all four major tract groups, namely projection, limbic, commissural and association tract group. Other major WM tracts such as SLF could not be traced reproducibly with our cohort of neonate DTI dataset. Following the literature  using the mid-sagittal plane and the region containing the entire cingulum in the desired hemisphere is selected. All the fibers in this coronal plane passing through the cingulum were selected using the “OR” operation. The second ROI was drawn by selecting a coronal plane in the middle of the genu of the CC and all the CGC fibers were selected using the “AND” operation.For the first ROI, a coronal plane in the middle of the splenium of the CC was selected using the mid-sagittal plane and the cingulum below the CC of the desired hemisphere was delineated. All the fibers in this coronal plane passing through the cingulum were selected using the “OR” operation. The second ROI was drawn at a coronal slice anterior to the pons using the mid-sagittal plane and the fibers passing through the cingulum in this hemisphere were selected using the “AND” operation.For the first ROI, a coronal slice at the middle point between the posterior edge of the cingulum and the posterior edge of the parieto-occipital sulcus was selected and the entire occipital lobe of the desired hemisphere was delineated. All the fibers in this hemisphere were selected using the “OR” operation. The second ROI was drawn at the anterior edge of the CC using a coronal slice and all the fibers in this hemisphere were selected using the “AND” operation. The fibers running through to the thalamus were removed by using the “NOT” operation.For the first ROI, a coronal plane including only the left occipital lobe was selected at the most posterior edge of the parieto-occipital sulcus. The “OR” operation in this coronal plane delineated all the fibers of FMajor. The second ROI was drawn in the same coronal plane on the right hemisphere using the “AND” operation such that all the fibers in the right occipital lobe was selected.For the first ROI, a coronal plane at the middle point between the anterior tip of the frontal lobe and the anterior edge of the genu of the CC was selected using the mid-sagittal plane. The “OR” operation was used to select all the fibers in the entire left hemisphere. The second ROI was drawn in the same coronal plane on the right hemisphere and all the fibers in the right hemisphere were selected using the “AND” operation.p > 0.05) from normality. However, distributions of DTI-derived metrics of most of the tracts in the child group differed significantly (p < 0.05) from normality. Hence, following the method in the literature /2 = 45 nontrivial independent correlation values in each correlation matrix.Shapiro-Wilk normality test was performed with DTI-derived metrics of all the 10 WM tracts of 26 neonate brains and 28 child brains. Distributions of DTI-derived metrics for most of the tracts in the neonate group did not show significant difference  can be observed for these 4 pairs of tracts in both age groups.Figure p < 0.05, Bonferroni-corrected) were observed for tests of all inter-tract correlation matrices of both groups against identity matrix or matrix with equal non-diagonal entries. The inter-tract correlation matrices of neonate and child group and the differences of these correlation matrices for FA, RD, AxD and MD are shown in Figures z-scores  inter-tract correlations become stronger with RD measurements, compared to those with any other DTI metric measurements. In addition, the dendrograms based on RD Figure  demonstr3 for neonates and 2 × 2 × 2.2 mm3 for children around puberty, the partial volume effects are inevitable. However, it seems the effects of imperfect WM fiber tracing offsets the partial volume effects for obtaining accurate tract-level DTI metrics, in that the tracing algorithm adopted in this study cannot trace the small branches of the fibers where the problem of partial volume effects is most prominent. Ranks of the DTI measurements, instead of measured metrics themselves, were used for correlation pattern analysis. Despite possibly different levels of biases of the DTI metric measurements caused by partial volume effects due to different head sizes between neonates and children, the similar shifts of measurements in the same age group could have minimum effects on the rank of metric measurements and therefore minimum effects on the Spearman's rank correlation patterns. Although same types of scanners were used in this study, systematic differences of the scanners may affect the DTI analysis results. To make sure that the effects of systematic differences caused by two different scanners are minimal, a healthy young subject (“in vivo human phantom”) was scanned in both scanners used in this study and with the same DTI sequence. The quantitative comparisons were also conducted. Quantitative DTI measurement differences caused by scanner difference were tested to be within the range of variability of scanning the same subject twice with one scanner  (Smith et al., In the future, several improvements can be made to address the issues affecting accuracy of measuring tract-level DTI metrics. The tracking methods (e.g., Tournier et al., In conclusion, inter-tract correlation changes during development from birth to onset of adolescence were investigated with tract-level FA, RD, AxD, and MD measurements. Stronger and enhanced microstructural inter-tract correlations were found during development. The linkage patterns of the major tracts also differ with the dendrograms of two age groups due to brain development. These changes of microstructural correlations from birth to puberty suggest inhomogeneous but organized myelination processes which cause the reshuffled inter-tract correlation pattern and make homologous tracts tightly clustered. Especially RD-based dendrograms reveal that all 4 pairs of homologous tracts and FMajor/FMinor investigated in this study are tightly clustered for children around puberty while only 2 out of these 5 pairs of tracts are clustered at birth, indicating important role of myelination to reshape the WM configuration. It opens a new window to study WM tract development and can be potentially used to investigate atypical brain development due to neurological or psychiatric disorders.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Adult height is a useful biological measure of long term population health and well being. We examined the cohort differences and socioeconomic patterning in adult height in low- to middle-income countries.We analyzed cross-sectional, representative samples of 364538 women aged 25-49 years drawn from 54 Demographic and Health Surveys (DHS) conducted between 1994 and 2008. Linear multilevel regression models included year of birth, household wealth, education, and area of residence, and accounted for clustering by primary sampling units and countries. Attained height was measured using an adjustable measuring board. A yearly change in birth cohorts starting with those born in 1945 was associated with a 0.0138 cm  increase in height. Increases in heights in more recent birth year cohorts were largely concentrated in women from the richer wealth quintiles. 35 of the 54 countries experienced a decline (14) or stagnation (21) in height. The decline in heights was largely concentrated among the poorest wealth quintiles. There was a strong positive association between height and household wealth; those in two richest quintiles of household wealth were 1.988 cm  and 1.018 cm  taller, compared to those in the poorest wealth quintile. The strength of the association between wealth and height was positive (0.05 to 1.16) in 96% (52/54) countries.Socioeconomic inequalities in height remain persistent. Height has stagnated or declined over the last decades in low- to middle-income countries, particularly in Africa, suggesting worsening nutritional and environmental circumstances during childhood. Although height is highly heritable, improvements in attained height over time underscore the importance of environmental factors including nutrition, exposure to infections, and socioeconomic status, especially during childhood www.measuredhs.com/pubs/search/search_results.cfm?Type=5&srchTp=type&newSrch=1). The DHS is modular in structure, comprising a core questionnaire, a set of country-relevant sections, and country-specific variables. The DHS provides data with standardized variables across surveys and imputed dates of key events (see www.measuredhs.com/pubs/pdf/DHSG4/Recode4DHS.pdf). A multistage stratified cluster design with probabilistic sampling, with each unit of selection having a defined, and non-zero, probability of selection is employed for the DHS www.measuredhs.com/pubs/search/search_results.cfm?Type=5&srchTp=type&newSrch=1. Information from Demographic and Health Surveys (DHS) conducted in 54 countries between 1994 and 2008 provided the data for this study Table 1 n = 454272) aged 25–49 years. There were 89577 women (19.72% of the sample) for whom height was intentionally not measured. Among those for whom height should have been measured, 4050 (<1%) did not have a height measure in the data, and a further 136 women (<1%) had implausible or extreme values (less than 100 cm or greater than 200 cm). One hundred and fifty seven observations (<1%) were missing data on covariates. The final analytical sample was 364538 women surveyed and measured between 1994 and 2008 in 54 countries.The study population comprises women (Attained height (expressed in centimeters) was specified as a continuous outcome. Trained investigators measured each woman using an adjustable board calibrated in millimeters, and theoretically accurate to 1 millimeter Year of birth, household wealth, education, and place of residence  were the key independent variables Table 2.i.e., rural women born in 1945 with no schooling and in poorest wealth quintile) across all countries; and Individual country files were created ensuring consistency of variable definitions across countries. We used three types of analytical strategies. First, we conducted a pooled analysis of all the individual data from all countries with height modeled as a function of birth cohort (specified as year of birth), household wealth quintiles, highest educational attainment, urban/rural residence, and country fixed effects in a linear regression model, adjusted for clustering of the individual data by primary sampling units within countries with robust standard errors. The results from these models were used to draw global inference about the association between year of birth, household wealth, and height across all countries. We also specified and tested for interactions between household wealth quintiles and year of birth to assess whether the cohort differences in heights varied by household wealth. Second, we repeated the above strategy separately for every country to estimate the country-specific cohort differences, socioeconomic patterning in addition to assessing the interaction between wealth and year of birth in each country. Finally, since the pooled individual data yields a multilevel data structure of women at level-1 nested within primary sampling units (PSU) at level-2 nested within countries at level-3, we additionally estimated a multilevel linear regression to model the variation in height  Institutional Review Board as well as by the relevant body in each country which approves research studies on human subjects. Oral informed consent for the interview/survey was obtained from respondents by interviewers. The study was reviewed by Harvard School of Public Health Institutional Review Board and was considered exempt from full review because the study was based on an anonymous public use data set with no identifiable information on the survey participants.The pooled mean height in sample was 155.8 cm (SD 7.2), and mean height varied between 147.3 cm (SD 6.3) in Guatemala and 163.0 cm (SD 6.7) in Senegal Table 1.In mutually adjusted pooled models, on average, height increased by 0.0138 cm  with one increase in year of birth Table 3.There was a substantial interaction effect between year of birth and wealth quintile (p = 0.0015), with the annual increase in height being largely restricted to the wealthiest quintile with stagnation in height for the poorest two wealth quintiles Figure 2Of the total variation in height, 14.07% was attributable to environments  Figure 3Country-specific variability around the average was considerable; of the 54 countries, 26 countries were significantly taller than the global (pooled sample) average, and 14 were significantly (α = 0.05) shorter Table 5.There was considerable variation in the association between year of birth and height across countries Table 6.In 51 of 54 countries, there was a statistically significant (p<0.05) difference between the poorest two and richest two wealth quintiles in the association between year of birth and height Table 8.The strength of the positive association between height and wealth also varied across countries; in 41 out of 54 countries there was a positive and statistically significant (á = 0.05) association for the effect of a change in wealth quartile on height, varying between 0.121 cm in Malawi to 1.132 cm in Honduras. The association between wealth and adult height, while positive, was not statistically significant in 9 countries. In Ethiopia and Uganda there was a statistically significant negative association between height and wealth such that women in wealthier households were shorter Table 6.The study has three salient findings. First, the birth cohort differences in attained heights among women living in low- to middle-income countries suggest a decline or stagnation in height in a majority of the countries. While decline in height was particularly concentrated in Africa, about half of the countries surveyed in South America showed stagnation. Second, cohort differences in height varied substantially by individuals' socioeconomic status both in pooled analysis as well as country-specific analysis, such that decline and stagnation are largely observed for socioeconomically disadvantaged groups, while the increases are concentrated among the socioeconomically advantaged groups. Finally, the positive association between socioeconomic status and attained height appears to be a consistent and universal pattern in low- to middle-income countries, with some heterogeneity in the strength of such an association.Figure S1, and Table S1). At the other extreme it is known that humans also shrink with age Before we interpret these findings, we outline the limitations of our data. First, our assessment of increases or decreases in attained height in birth cohort differences is based upon self-reports of current age. Age reporting in low- to middle-income countries has been raised as an important concern because reporting of ages in multiples of five or ten is relatively common and leads to age clustering. However, an analysis of the quality of age reporting in the DHS for all surveys between 1985–2003 found that the overall quality of age-reporting was found to be high with most surveys exhibiting few problems Our findings related specifically to estimating overall birth cohort differences in height for countries are in agreement with an ecological study that examined changes in heights over time in low- to middle-income countries using the same data within the US, it suggests a pattern similar to what we observe for lower socioeconomic groups within and among low- to middle-income countries. Other country-specific studies on height trends from developing countries from Turkey Twenty six percent (14/53) of the low- and middle-income countries included in this study experienced a significant (p = 0. 05) decline in attained height since 1945 while another 43% experienced no change in height over birth cohorts. This is driven entirely by declining heights in Africa; with half of countries in South America showing stagnation in height since 1945 and heights modestly increasing in the rest of the world. Importantly, in most cases, the increases within countries were restricted to the socioeconomically advantaged groups. This differs from evidence on changes in height in developed countries. For instance, the evidence from European countries showed a mostly positive increase in height over the last century, including during the same time period as this study The association between socioeconomic status and height has consistently been shown across developed countries In summary, a salient finding of our study is the decline or stagnation in attained heights over the last 40 years, particularly in Africa and for the poorer populations across the world. Increases in height are largely restricted to non-African better off populations. Thus, even though infant mortality and other acute childhood morbidities have decreased substantially over time in these countries, the stagnation and decline across cohorts in attained height suggest little improvements, and perhaps deterioration, in early childhood living conditions including nutritional and environmental circumstances. While our study focuses on attained height for women from birth years that preceded the concerted global efforts on improved childhood health and nutrition spurred by the Millennium Development Goals, it will be important to monitor the height patterns for subsequent birth cohorts in these populations. The persistent country differences in adult height even among recent birth cohorts indicate the intergenerational continuity in differences in childhood living conditions. The marked socioeconomic differentials observed consistently within every country suggest that health inequalities in these countries will be persistent in future. Further research is needed to understand the environmental determinants that enable realization of the potential height of a child, and especially a girl child, which in turn have substantial consequences for their own health and social well being as well as the health of their offspring.Figure S1Mean Height (cm) By Age Pooled Across Countries.(DOCX)Click here for additional data file.Table S1Mean Height (cm) By Age Groups, By Country.(DOCX)Click here for additional data file.