Childhood physical abnormalities following paternal exposure to sulfur mustard gas in Iran: a case-control study

Background

Mustard gas, a known chemical weapon, was used during the Iran-Iraq war of 1980-1988. We aimed to determine if exposure to mustard gas among men was significantly associated with abnormalities and disorders among progenies.

Methods

Using a case-control design, we identified all progenies of Sardasht men (exposed group, n = 498), who were born at least nine months after the exposure, compared to age-matched controls in Rabat, a nearby city (non-exposed group, n = 689). We conducted a thorough medical history, physical examination, and appropriate paraclinical studies to detect any physical abnormality and/or disorder. Given the presence of correlated data, we applied Generalized Estimating Equation (GEE) multivariable models to determine associations.

Results

The overall frequency of detected physical abnormalities and disorders was significantly higher in the exposed group (19% vs. 11%, Odds Ratio [OR] 1.93, 95% Confidence Interval [CI], 1.37-2.72, P = 0.0002). This was consistent across sexes. Congenital anomalies (OR 3.54, 95% CI, 1.58-7.93, P = 0.002) and asthma (OR, 3.12, 95% CI, 1.43-6.80, P = 0.004) were most commonly associated with exposure. No single abnormality was associated with paternal exposure to mustard gas.

Conclusion

Our study demonstrates a generational effect of exposure to mustard gas. The lasting effects of mustard gas exposure in parents effects fertility and may impact child health and development in the long-term.     

Dissociation of angiogenesis and tumorigenesis in follistatin- and activin-expressing tumors

The transforming growth factor-beta superfamily member activin and its antagonist, follistatin, act as a pleiotropic growth factor system that controls cell proliferation, differentiation, and apoptosis. Activin inhibits fibroblast growth factor 2-induced sprouting angiogenesis in vitro (spheroidal angiogenesis assay) and in vivo (Matrigel assay). To further study the role of the activin/follistatin system during angiogenesis and tumor progression, activin- and follistatin-expressing R30C mammary carcinoma cells were studied in mouse tumor experiments. Surprisingly, activin-expressing tumors grew much faster than follistatin-expressing tumors although they failed to induce increased angiogenesis (as evidenced by low microvessel density counts). Conversely, follistatin-expressing tumors were much smaller but had a dense network of small-diameter capillaries. Qualitative angioarchitectural analyses (mural cell recruitment, perfusion) revealed no major functional differences of the tumor neovasculature. Analysis of activin- and follistatin-expressing R30C cells identified a cell autonomous role of this system in controlling tumor cell growth. Whereas proliferation of R30C cells was not altered, follistatin-expressing R30C cells had an enhanced susceptibility to undergo apoptosis. These findings in experimental tumors are complemented by an intriguing case report of a human renal cell carcinoma that similarly shows a dissociation of angiogenesis and tumorigenesis during tumor progression. Collectively, the data shed further light into the dichotomous stimulating and inhibiting roles that the activin/follistatin system can exert during angiogenesis and tumor progression. Furthermore, the experiments provide a critical proof-of-principle example for the dissociation of angiogenesis and tumorigenesis, supporting the concept that tumor growth may not be dependent on increased angiogenesis as long as a minimal intratumoral microvessel density is maintained.     

Novel lavendamycin analogues as antitumor agents: synthesis, in vitro cytotoxicity, structure-metabolism, and computational molecular modeling studies with NAD(P)H:quinone oxidoreductase 1

Novel lavendamycin analogues with various substituents were synthesized and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. Pictet-Spengler condensation of quinoline- or quninoline-5,8-dione aldehydes with tryptamine or tryptophans yielded the lavendamycins. Metabolism studies with recombinant human NQO1 revealed that addition of NH2 and CH2OH groups at the quinolinedione-7-position and indolopyridine-2'-position had the greatest positive impact on substrate specificity. The best and poorest substrates were 37 (2'-CH2OH-7-NH2 derivative) and 31 (2'-CONH2-7-NHCOC3H7-n derivative) with reduction rates of 263 +/- 30 and 0.1 +/- 0.1 micromol/min/mg NQO1, respectively. Cytotoxicity toward human colon adenocarcinoma cells was determined for the lavendamycins. The best substrates for NQO1 were also the most selectively toxic to the NQO1-rich BE-NQ cells compared to NQO1-deficient BE-WT cells with 37 as the most selective. Molecular docking supported a model in which the best substrates were capable of efficient hydrogen-bonding interactions with key residues of the active site along with hydride ion reception.     

Impact of Gestational Weight Gain on Cesarean Delivery Risk,Perinatal Birth Weight and Gestational Age in Women with Normal Pre-pregnancy BMI

Background

Gestational weight gain (GWG) proportional to body mass index before pregnancy is one of the factors on maternal and neonatal outcomes. The aim of the current study was to assess association between GWG, and cesarean section, birth weight and gestational age at birth in women with normal BMI prior to pregnancy.

Methods

This was a cross-sectional study carried out in 103 hospitals in Tehran, the capital of Iran, from July 6 to 21, 2015. The data were extracted by 103 trained midwives. Finally, 2394 pregnant women with normal BMI before pregnancy and singleton birth were examined. GWG was categorized based on Institute of Medicine (IOM) recommendations.

Results

Prevalence of low birth weight (LBW) was 5.41% and prevalence of macrosomia was 2.18%. The prevalence of LBW in women with GWG less than the weight gain recommended by IOM was 2.13 times [95% confidence interval (CI) 1.13–4.02, P = 0.019] more than in women with GWG equal to the weight gain recommended by IOM. There was no statistically significant difference in the prevalence of LBW between women with GWG more than recommended weight gain by IOM and women with GWG equal to the weight gain recommended by IOM (OR = 1.21, 95% CI 0.61–2.38, P = 0.580).

Conclusion

After controlling for confounding variables, the prevalence of cesarean section and preterm birth had no significant difference at various levels of GWG. Accordingly, the prevalence of LBW among women with GWG less than the recommended weight gain by IOM was significantly 2.13 more than that among women with GWG equal to the recommended weight gain by IOM.

     

Expression patterns of ERα66 and its novel variant isoform ERα36 in lactotroph pituitary adenomas and associations with clinicopathological characteristics

Pituitary - The regulatory effects of estradiol on pituitary homeostasis have been well documented. However, the expression patterns of ERα66 and ERα36 and their correlations with the...     

Assessment of occurrence of preeclampsia and some clinical and demographic risk factors in Zahedan city in 2017

Background: Blood pressure dysfunctions are one of the biggest complications and causes of maternal mortality during pregnancy. The aim of the present study is to evaluate some of the clinical and demographic risk factors in various aspects, both of which can help to better understand the causes and reduce the incidence of preeclampsia.

Method: This nested case–control study was carried out on 270 pregnant women with preeclampsia as the case group and 270 pregnant women who did not have symptoms of preeclampsia at the time of referral were interviewed according to inclusion criteria as the control group. The factors studied included age, body mass index, history of hypertension in mother, history of diabetes in mother, history of lupus in mother, number of pregnancies, history of preeclampsia in previous pregnancies, twin or more pregnancies, season of occurrence, maternal educational level, maternal blood group, maternal occupation status, infant’s sex and smoking status which were compared etween the two groups. t test and Chi-square tests were used to compare the variables in both groups. Fisher's exact test or Mann–Whitney U test was used if necessary.

Findings: Of the 6929 pregnant women who participated in our study, 541 (7.8%) had preeclampsia. The means of body mass index (BMI) (24.86% versus 23.52%) (P = 0.032), the history of hypertension (19.3% versus 10.7%) (P = 0.006), history of preeclampsia in previous pregnancies (60.2% versus 13.3%) (P < 0.001), low level of education and illiteracy (51.1% versus 39.6%) (P = 0.028), and twin or more pregnancies (5.6% versus 2.2%) (P = 0.045) were significantly higher in the case group when compared to the control group. There was no statistically significant difference between the mean and standard deviation of age and number of pregnancies and the frequency of diabetes and lupus, the frequency of maternal occupation, maternal smoking, maternal blood group, and season of occurrence in the two groups (P > 0.05).

Conclusion: Maternal BMI, maternal hypertension, history of preeclampsia in previous pregnancies, low maternal educational status, and twin or multiple pregnancies might be the risk factors for preeclampsia during pregnancy.