Prenatal exposure to nickel and atopic dermatitis at age 3 years: a birth cohort study with cytokine profiles.

BACKGROUND: Nickel, the fifth most common element on Earth, is the leading inducer of contact allergies in humans, with potent immunological effects. Nickel-induced contact allergies predominantly affect females. Maternal exposure to nickel has been associated with several developmental abnormalities. However, how a maternal nickel exposure affects the development of atopic diathesis and immune abnormalities in children has never been addressed. OBJECTIVES: We aimed to determine whether maternal nickel exposure affects the development of atopic dermatitis and immune abnormalities in their children. METHODS: Using a birth cohort study, we analysed 140 mother-child pairs recruited in 2012-2015 from central Taiwan. Maternal exposure to nickel was estimated using urinary nickel levels measured by inductively coupled plasma mass spectrometry (ICP-MS). The serum levels of 65 analytes and IgE in 3-year-old children were profiled with a multiplex ELISA. The correlation between the maternal urinary nickel concentration and serum analyte levels was assessed using Spearmen's correlation. Multivariant regression analysis was performed to evaluate the association between maternal urinary nickel levels and serum analyte concentrations in their children. RESULTS: The geometric means of the maternal urinary nickel and the children's serum IgE levels were 2.27 µg/L and 69.71 IU/mL, respectively. The maternal nickel exposure was associated with increased serum levels of IL-1ß, IL-2, TNF-α, and leukaemia inhibitory factor (LIF) but with decreased serum levels of matrix metalloproteinase-1 (MMP-1), IL-2R, and eotaxin-1 in the children. In addition, the development of childhood atopic dermatitis at 3 years old was significantly associated with the child's serum levels of IgE and IL-2R, but it was negatively associated with the maternal nickel exposure. CONCLUSIONS: This is the first study showing the potential immunological effects of maternal nickel exposure in their children at an early developmental stage.

Morphologies of caustics and dislocation lines: some clues about their interrelation.

According to singular optics, the phase and intensity that characterize structured electromagnetic beams can be understood in terms of concepts that involve subspaces where they or their derivatives exhibit a particular behavior, such as giving rise to extreme values or not being well defined. Caustics are a paradigmatic example of the former, while helical dislocation lines exemplify the latter. In this work the interrelation of the morphology of caustics and the morphology of dislocation lines is theoretically studied. The analysis for highly structured beams requires an efficient methodology that allows the identification of optical vortices, their topological charge, and the helical dislocation lines they belong to. Such a methodology is introduced and applied to paraxial elliptic umbilic beams and nonparaxial Airy symmetric three-dimensional beams. Nonparaxial beams exhibit caustic surfaces that delimit regions with a finite volume and different intensity average. It is shown that in the high intensity region so defined, the dislocation lines play the role of an internal skeleton, i.e., an endoskeleton, of the beam. The exoskeleton created in the low intensity regions shows subtle and interesting features that complement those of the endoskeleton; the caustics that delimit low intensity regions have a strong influence on the morphology of the exoskeleton.

[The relationship between inflammatory factors and depression and its mechanism exploration].

Depression is a common and recurrent mental disease, with complex etiology, which is mainly affected by genetic, metabolic and social factors. The specific pathogenesis is still unclear. In recent years, the hypothesis of inflammatory factors related to depression has attracted wide attention of researchers. A large number of clinical experimental studies have shown that depression is related to the increase of proinflammatory factors in central and peripheral blood. The inflammatory factors in peripheral blood can spread in the brain through the way of specific transporters across the blood-brain barrier, and activate or participate in the brain inflammatory response, and ultimately affect the neuronal activity and neurotransmitter release in the emotional regulation area of the brain, which in turn leads to depressive symptoms. This paper summarizes the relationship between inflammatory factors and depression and its possible mechanism, which provides reference for further prevention and control, clinical treatment and scientific research of depression.

[Well differentiated grade 3 gastroenteropancreatic neuroendocrine tumors:new insights into diagnosis and therapeutic strategy].

Gastroenteropancreatic neuroendocrine tumor G3(GEP-NET G3) is a novel subtype of neuroendocrine neoplasms proposed in 2019,which has unique biological behavior characteristics. However,there are still many challenges and controversies in its diagnosis and treatment. There are obvious differences between GEP-NET G3 and neuroendocrine carcinoma (NEC) in genetic alterations and molecular profiles. The most frequently mutated genes in NET G3 are MEN1,DAXX/ATRX,while in NEC,TP53 and Rb are the most frequently mutated genes. Currently,the mainstream view is that NET G3 and NEC are two distinct diseases with different genetic backgrounds,and NET G3 will not develop into NEC. Several clinical and pathological factors should be considered to distinguish GEP-NET G3 and NEC,which including patients' medical history,histopathological morphology of neoplasms,Ki-67 index,immunohistochemical results of TP53,Rb,DAXX/ATRX and other markers. Multidisciplinary treatment,including radical resection,chemotherapy,targeted therapy,peptide receptor radionuclide therapy,immunotherapy should be applied in patients with GEP-NET G3. Overall,given its relatively indolent biological behavior,the therapeutic strategy should be more actively. Although the cure strategy of NET G3 has many similarities with NET G1/2,it is completely different from NEC.

Impact of the radiation effect on the energy storage density and wake-up behaviors of antiferroelectric-like Al-doped HfO2 thin films.

The effect of the γ-ray total dose radiation on the energy storage density (ESD) and the phase transition of antiferroelectric-like (AFE-like) Al-doped HfO2 (HfAlO) thin films was investigated. The ESD property and wake-up behavior of the phase transition during the field cycling of the AFE-like HfAlO thin films were quantified before and after the radiation. The efficiency of the AFE-like thin films for energy storage slightly decreases as the total dose increases from 200 krad (Si) to 5 Mrad (Si), which is attributed to the radiation-induced trapped defects at the interfaces of HfAlO/TiN. Both the J-E, C-V, and εr-f characteristics of the AFE-like HfAlO thin films were also measured before and after the radiation at the same electrodes. These results further confirm that the ferroelectricity of the thin films can be reduced due to the radiation oxide trapped defects. It is worth noting that an enhanced wake-up behavior of the AFE-like HfAlO thin films can be observed after the radiation, which indicates that the transition from the antiferroelectric phase to the ferroelectric phase could be accelerated by the increased radiation-induced defects.

Fetal heart rate variability responsiveness to maternal stress, non-invasively detected from maternal transabdominal ECG.

PURPOSE: Prenatal stress (PS) during pregnancy affects in utero- and postnatal child brain-development. Key systems affected are the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS). Maternal- and fetal ANS activity can be gauged non-invasively from transabdominal electrocardiogram (taECG). We propose a novel approach to assess couplings between maternal (mHR) and fetal heart rate (fHR) as a new biomarker for PS based on bivariate phase-rectified signal averaging (BPRSA). We hypothesized that PS exerts lasting impact on fHR. METHODS: Prospective case-control study matched for maternal age, parity, and gestational age during the third trimester using the Cohen Perceived Stress Scale (PSS-10) questionnaire with PSS-10 over or equal 19 classified as stress group (SG). Women with PSS-10 < 19 served as control group (CG). Fetal electrocardiograms were recorded by a taECG. Coupling between mHR and fHR was analyzed by BPRSA resulting in fetal stress index (FSI). Maternal hair cortisol, a memory of chronic stress exposure for 2-3 months, was measured at birth. RESULTS: 538/1500 pregnant women returned the questionnaire, 55/538 (10.2%) mother-child pairs formed SG and were matched with 55/449 (12.2%) consecutive patients as CG. Maternal hair cortisol was 86.6 (48.0-169.2) versus 53.0 (34.4-105.9) pg/mg (p = 0.029). At 36 + 5 weeks, FSI was significantly higher in fetuses of stressed mothers when compared to controls [0.43 (0.18-0.85) versus 0.00 (- 0.49-0.18), p < 0.001]. CONCLUSION: Prenatal maternal stress affects the coupling between maternal and fetal heart rate detectable non-invasively a month prior to birth. Lasting effects on neurodevelopment of affected offspring should be studied. TRIAL REGISTRATION: Clinical trial registration: NCT03389178.

An unusual case of pigmented plaques on the sole.

Palmoplantar lichen planus is a rare variant of lichen planus with diverse clinical presentations, making the diagnosis challenging. We present an unusual case of a young patient who presented with asymptomatic non-pruritic flat-topped pigmented plaques on his left sole and no other lesions elsewhere. Histology was consistent with lichen planus. We emphasize a high index of suspicion owing to varied clinical presentation and the necessity of a biopsy for diagnosis.

[Study on the relationships between precollege sexual abuse experiences at different stages and adult attachment in college students].

Objective: To explore the association between precollege sexual abuse experiences at different periods and adult attachment in college students. Methods: In October 2018,a total of 4 034 college students were selected from 4 colleges in Hefei City by using the stratified cluster sampling method. A self-designed questionnaire was used to investigate the demographic characteristics, sexual abuse experience, and attachment style of participants. Multivariate linear regression analysis was performed to analyze the association between different periods, types of precollege sexual abuse experiences and attachment style in college students. Results: The rate of total precollege sexual abuse, noncontact sexual abuse, and contact sexual abuse was 14.1% (569), 12.7% (512) and 5.4% (219), respectively. Multivariate linear regression analysis showed that secure attachment [ß(95%CI)=-0.205 (-0.292, -0.117)] was negatively correlated with total precollege sexual abuse experiences, whereas anxiety attachment [ß(95%CI)=0.211 (0.110, 0.310)], avoidant attachment [ß(95%CI)=0.117 (0.020, 0.216)] were positively correlated with total precollege sexual abuse experiences. The number of periods of precollege noncontact sexual abuse was negatively correlated with secure attachment [ß(95%CI)=-0.106(-0.171, -0.041)]and positively correlated with anxiety attachment [ß(95%CI)=0.158 (0.084, 0.231)]and avoidant attachment [ß(95%CI)=0.080 (0.008, 0.152)]. The noncontact [ß(95%CI)=0.427 (0.018, 0.775)] and contact sexual abuse [ß(95%CI)=0.468 (0.251, 0.687)] in high school were positively correlated with anxiety attachment (P<0.05). Conclusion: Different periods, types of precollege sexual abuse experiences were all associated with adult attachment in college students.

[Predictive effects of pubertal timing and tempo on adolescent depressive symptoms: a 6-year prospective cohort study].

Objective: To examine the prospective association of pubertal timing and tempo with depressive symptoms in adolescents. Methods: Since 2013, 2 084 students in grade 1-3 were selected from two primary schools in Bengbu, Anhui Province were selected by using convenience sampling method to establish the adolescence pubertal development cohort. Followed up for 6 years, physical examination, secondary sexual development evaluation (testicular volume for boys and breast development for girls) and depressive symptoms were evaluated biennially. Non-linear growth model was used to estimate pubertal timing and tempo for boys and girls respectively. Depressive symptoms were interviewed by using the Short Mood & Feeling Questionnaire (SMFQ) at baseline and Mood & Feeling Questionnaire (MFQ) during follow-up for students in grade 1-2. Children Depression Inventory (CDI) was used for students in grade 3 at baseline and during follow-up. Depressive symptom scores were standardized by using the Z-score method. Multivariate linear regression model was used to analyze the predictive effects of modeling pubertal timing and tempo on depressive symptoms of adolescence boys and girls. Results: There were 1 909 students with complete questionnaire and puberty development information, including 1 052 boys (59.19%) and 857 girls (43.81%), with average age about (13.94±0.87) years and 91.60 percent follow-up rate. The average modeling pubertal timing of girls (11.25 years) was earlier than that of boys (12.70 years), and the average pubertal tempo of girls about 1.47 Tanner stage/year was faster than that of boys about 1.28 Tanner stage/year. After controlling for depressive symptoms, maternal education and adverse childhood experiences at baseline and age, body mass index (BMI) classification and sleep time during follow-up, this predictive effect of pubertal timing and tempo on depressive symptoms was only significant among girls. Compared with girls with on time pubertal timing, girls in the delay timing group had a lower level of depressive symptoms (ß=-0.19, 95% CI:-0.34,-0.01). Compared with girls in average pubertal tempo group, the fast tempo group associated with an increasing risk of depressive symptoms (ß=0.23, 95%CI: 0.05, 0.40), while the slow tempo group associated with an decreasing risk of depressive symptoms (ß=-0.21, 95％CI:-0.39,-0.03). Insignificant effects were found in puberty timing and tempo on depressive symptoms of boys (P>0.05). Conclusion: Fast pubertal tempo increases the risk of development of depressive symptoms of adolescent girls. There is no predictive effect of pubertal timing and tempo on depression symptoms of adolescent boys.

[A birth cohort study of the association between prenatal serum bisphenol A concentration and infant neurobehavior development].

Objective: To explore the association between maternal bisphenol A (BPA) exposure during pregnancy and neurobehavioral development in infant. Methods: Participants were from the Ma'anshan Birth Cohort, which was established from October 2008 to October 2010 based on four municipal medical and health institutions in Ma'anshan. High-performance liquid chromatography-tandem mass spectrometry was applied for the determination of serum BPA concentration in 1 783 pregnant women sampled at their first filing, and during 2.97 to 28.1 months age of the infants. Neurobehavioral development were assessed by 0-6-year-old pediatric examination table of neuropsychological development. Generalized linear model was used to analyze the association between serum BPA levels during pregnancy and infants' neurobehavioral development. Results: A total of 931 mother-child pairs had complete data on serum BPA detection during pregnancy and assessment of infants' neurobehavioral development status. The age of pregnant women at their first filing was (26.67±3.45) years old, and the M (P25,P75) of serum BPA concentration (ng/ml) was 0.23 (0.11, 0.52), with a detection rate of 84.1% (783/931). The age of infants was (13.18±5.46) months, and 53.5% (498) were boys. The developmental quotient scores of large motor, fine motor, adaptive ability, language ability and social behaviors of infants were (97.88±16.32), (97.16±15.35), (99.64±15.47), (95.3±16.04) and (98.95±14.76) points, respectively. Generalized linear model showed that after adjusting for factors such as delivery mode, feeding mode, family per capita monthly income, preterm delivery, gender, maternal age, residence, pre-pregnancy body mass index and residence time, serum BPA level in pregnancy was negatively associated with infant's development of social behavior [ß (95%CI):-2.42 (-4.71, -0.12)]. The post-stratification analysis by infant age revealed that the serum BPA level in pregnancy was only negatively associated with the development of language and social behavior developmental quotient scores in infants between the ages of 12 and 18 months, with ß (95%CI) about -6.66 (-13.06, -0.25) and -7.401 (-12.97, -1.83), respectively. Conclusion: BPA exposure during pregnancy affects language and social behavior development in infants, and the detection window is between 12 and 18 months old of the infant.

[Strengthening the quality control of coronary artery bypass grafting].

The quality control of coronary artery bypass grafting (CABG) is an important prerequisite to the graft patency and the long-term outcomes. The evaluation of target vessel is the basis, the choice of surgical types is the means, the high-quality acquisition of graft harvesting is the guarantee, and the anastomotic method and quality is the core. As the most commonly used quality control tool, intraoperative transit time flow measurement can effectively detect the coronary graft failure caused by anastomotic stenosis and guide to repair of the graft. However, some studies showed that the positive predictive value is low, and the evidence is insufficient for the relationship with the long-term patency rate of grafts. Intraoperative instantaneous flow measurement combined with high-resolution epicardial ultrasound can improve the quality, safety and effectiveness of CABG, which should be an important recommendation for CABG quality control. Once the shape of the grafts and anastomotic ports is abnormal and the blood flow is not satisfied, it needs to adjust or re-anastomose immediately. The quality control of CABG requires comprehensive judgment and individualized measures to ensure the safety and long-term outcome of patients.

[The role of hypothalamus polycomb gene methylation in bisphenol A exposure during pregnancy and premature puberty in female offspring].

Objective: To explore the role of hypothalamus Polycomb Group (PcG) gene (Eed, Ezh) methylation in the relationship between bisphenol A (BPA) exposure during pregnancy and premature puberty in female offspring. Methods: A total of 40 pregnant CD-1 mice were randomly and averagely assigned into four groups: control group (corn oil) and low, middle and high BPA-exposed groups (the poisonous doses were 8 mg/kg, 40 mg/kg, and 200 mg/kg, respectively) by random number table method. Each group was administered by gavage from gestational day (GD) 1 to 18. The vaginal opening of female offspring was observed from postnatal day (PND) 21 to 33. All female offsprings were sacrificed, and hypothalamus was remained on the PND 34. The methylation levels of Eed and Ezh in the hypothalamus were measured. The early puberty of CD-1 mice was evaluated by the rate of vaginal opening in advance, initial time of vaginal opening, the first estrus occurrence and vaginal opening days in advance. The path model was used to explore the role of Eed and Ezh gene methylation in the early puberty of female offspring with maternal BPA exposed including the number of days of vaginal opening in advance as a dependent variable and BPA exposure as an independent variable. Results: The rate of vaginal opening on the 28 day in each maternal BPA-exposure group [low, middle and high BPA-exposed groups were 40.00% (29/72), 47.62% (25/53) and 37.84% (20/53), respectively] was higher than that rate in the control group [14.06%(9/64)]. Similarly, the P(50)(P(25), P(75)) values of initial time of vaginal opening in low, middle and high BPA-exposed group were 28 (26, 30), 28 (26, 29), 28 (26, 30) days, respectively and the P(50)(P(25), P(75)) values of the first estrus occurrence in low, middle and high BPA-exposed group were 31 (27, 32), 30 (27, 31), 31 (28, 33) days, respectively, which were earlier than those in the control group [initial time of vaginal opening was 30(28, 31) days, and the first estrus occurrence was 32(30, 33) days] (all P values<0.05). Compared with the control group (the methylation levels of Eed1, Eed2, Ezh2 were 1.47%, 1.26%, 2.56%, respectively), the methylation levels of Eed1 (1.61%-1.82%), Eed2 (1.36%-1.43%) and Ezh2 (2.87%-3.05%) in female offspring were significantly higher in BPA-exposed groups (all P values<0.05). The results of path model analysis showed that BPA had no direct influence on puberty in advance, but had an indirect effect on puberty in advance (indirect effect path coefficient was 0.045 and 0.142, respectively) by mediating methylation of Eed2, and Ezh2. Conclusion: Early puberty in female offspring induced by maternal exposure to BPA during pregnancy through the increased methylation levels of hypothalamus PcG gene (Eed, Ezh) in female offspring.

[Screening of pathogenic genes in a Chinese familial dilated cardiomyopathy pedigree from Inner Mongolia].

Objective: Screen the pathogenic genes of a pedigree with clinical manifestation of familial dilated cardiomyopathy in Inner Mongolia. Methods: A total of 3 patients with dilated cardiomyopathy and 20 family members from the same family were examined in Ordos Central Hospital in Inner Mongolia from October, 2003 to August, 2017. Data on medical history, physical examinations, electrocardiograms, and echocardiography were obtained. 5 ml peripheral blood was sampled for per person. Chip Capture Sequencing technology was used to capture all the exons and splice sites of the genes that associated with hereditary cardiomyopathy and hereditary arrhythmia. The mutations in these genes were detected by high-throughput sequencing. All suspected pathogenic loci identified by high-throughput sequencing were verified by Sanger sequencing used for mutation detection. One hundred and fifty gender, age and race matched healthy people were included as the control group. Results: Pathogenic gene variations were detected in 3 symptomatic family members and 1 carrier from the pedigree. Five pathogenic gene variations were identified in the proband (Ⅱ1), a pSer236Gly and a pArg215Cys variation in the MYBPC3 gene, a pGln90Arg variation in the DSP gene, and pAsn2912Asp and pGlu2910Val variation in the DMD gene. One pathogenic variation was detected in Ⅲ3, which was a pArg215Cys variation in the MYBPC3 gene. Two pathogenic variations were detected in Ⅲ7, a pSer236Gly variation in the MYBPC3 gene and a pGln90Arg variation in the DSP gene. Two pathogenic variations were detected in the Ⅳ7, a pSer236Gly variation in the MYBPC3 gene and a pGln90Arg variation in the DSP gene. No gene variation loci were detected in the other family members and the control group. Conclusion: MYBPC3 gene, DSP gene and DMD gene variations are present in the familial dilated cardiomyopathy pedigree from Inner Mongolia, and these variations may be related with familial dilated cardiomyopathy.

[Association between early pregnancy bisphenol A exposure and sleep problems among preschool children].

Objective: To analyze the association between maternal bisphenol A exposure during early pregnancy and sleep problems among preschool children. Methods: Research subjects were from one of the sub-cohorts(Ma'anshan Cohort) of the China-Anhui Birth Cohort Study (C-ABCS) in Ma'anshan city. The basic situation of pregnant women and sleep information of preschool children were investigated. We selected preschool children whose mother's maternal serum bisphenol A concentrations of the first trimester had been already detected between December 2012 to Januray 2014. 1 259 pairs of mothers and children were included. The concentrations of bisphenol A exposure during early pregnancy were divided into low, medium and high exposure groups according to 25(th) percentile (P(25)) and 75(th) percentile (P(75)) levels. Multivariate multinomial logistic regression model was used to analyze the association between maternal bisphenol A exposure during early pregnancy and sleep-related problems in preschool children. Results: The P(50) (P(25)-P(75)) of serum bisphenol A exposure level during early pregnancy was 0.231 (0.106-0.512) ng/ml. The sleep-related problems scores of 1 259 preschool children were (16.43±3.82) points. The occasional sleep-related problems were detected about 47.8% (602 cases) and frequent sleep-related problems were detected about 18.3% (230 cases). After the adjustment of the confounding factors such as children's gender, age, BMI, sleep position (lying down, sleeping on one's back), the length of time to sleep and the length of sleep at night, in comparison with bisphenol A low exposure group, the OR (95%CI) value of preschool children with occasional sleep-related problems in maternal bisphenol A high exposure group during early pregnancy was 1.44 (1.01-2.06). After the gender stratification, the results showed that in comparison with bisphenol A low exposure group, the OR (95%CI) value of preschool girls with occasional sleep-related problems in maternal bisphenol A medium and high exposure group during early pregnancy were 1.61 (1.05-2.46) and 2.40 (1.42-4.04), respectively. The OR (95%CI) value of preschool girls with frequent sleep-related problems in maternal bisphenol A high exposure group during early pregnancy was 2.64 (1.34-5.17). However, in boys, there was no statistically significant association between maternal bisphenol A exposure during early pregnancy and sleep-related problems (P>0.05). Conclusion: Maternal bisphenol A exposure during early pregnancy might be related to sleep-related problems in preschool children.

[Clinicopathologic and molecular features of cribriform morular variant of papillary thyroid carcinoma].

Objective: To investigate the clinicopathologic and molecular features of the rare cribriform morular variant of papillary thyroid carcinoma (CMV-PTC). Methods: The clinicopathologic data of 10 patients with CMV-PTC were retrospectively reviewed. Immunohistochemical (IHC) staining was done using LSAB method. DNA sequencing for APC were applied using Sanger method. BRAF V600E mutation was examined using ARMS method. The cytological, morphological, IHC and molecular features were analyzed. Results: All patients were female at an average age of 27 years old. The tumors were mostly located in the right lobe of thyroid. Fine needle aspiration cytology was performed in three patients; two were diagnosed as suspicious for PTC and one as PTC. Nine tumors presented as solitary nodule and two as multiple nodules in both lobes. Infiltration was demonstrated in three cases. The average size was 2.6 cm. The neoplastic cells were arranged in papillary, cribriform, solid and glandular patterns, with rare or without colloid inside the lumen. The number of morula varied, ranging from zero to many. The neoplastic cells were variably enlarged, showing round, oval or spindle shape. Nuclear irregularity was identified as irregular membrane, nuclear grooves or pseudoinclusion, but no typical ground glass feature. Peculiar nuclear clearing could be observed in the morular cells. IHC staining showed the neoplastic cells were negative for thyroglobulin and p63, but positive for TTF1, cytokeratin 19 and estrogen receptor. Diffuse staining with cytokeratin was seen in the neoplastic cells and the morula. Specific cytoplasmic and nuclear staining of ß-catenin was seen in the neoplastic cells but not the morula. Ki-67 proliferation index was 1%-30%. No recurrence or metastasis was observed. One patient was demonstrated to harbor both somatic and germline mutations of the APC gene, who was found to have adenomatous polyposis and her mother died of colonic carcinoma. No BRAF V600E mutation was detected. Conclusions: CMV-PTC is rare and shows atypical cytological and clinicopathological features, and it is easily misdiagnosed.TG, TTF1, ER and ß-catenin are specific IHC markers for CMV-PTC. The morula is negative for cytokeratin 19, in contrast to squamous metaplasia. Although CMV-PTC has indolent clinical behavior, a definite diagnosis is necessary to rule out the possibility of APC gene mutation and related extra-thyroidal neoplasm, such as FAP and Gardner syndrome.

Misassembly of full-length Disrupted-in-Schizophrenia 1 protein is linked to altered dopamine homeostasis and behavioral deficits.

Disrupted-in-schizophrenia 1 (DISC1) is a mental illness gene first identified in a Scottish pedigree. So far, DISC1-dependent phenotypes in animal models have been confined to expressing mutant DISC1. Here we investigated how pathology of full-length DISC1 protein could be a major mechanism in sporadic mental illness. We demonstrate that a novel transgenic rat model, modestly overexpressing the full-length DISC1 transgene, showed phenotypes consistent with a significant role of DISC1 misassembly in mental illness. The tgDISC1 rat displayed mainly perinuclear DISC1 aggregates in neurons. Furthermore, the tgDISC1 rat showed a robust signature of behavioral phenotypes that includes amphetamine supersensitivity, hyperexploratory behavior and rotarod deficits, all pointing to changes in dopamine (DA) neurotransmission. To understand the etiology of the behavioral deficits, we undertook a series of molecular studies in the dorsal striatum of tgDISC1 rats. We observed an 80% increase in high-affinity DA D2 receptors, an increased translocation of the dopamine transporter to the plasma membrane and a corresponding increase in DA inflow as observed by cyclic voltammetry. A reciprocal relationship between DISC1 protein assembly and DA homeostasis was corroborated by in vitro studies. Elevated cytosolic dopamine caused an increase in DISC1 multimerization, insolubility and complexing with the dopamine transporter, suggesting a physiological mechanism linking DISC1 assembly and dopamine homeostasis. DISC1 protein pathology and its interaction with dopamine homeostasis is a novel cellular mechanism that is relevant for behavioral control and may have a role in mental illness.

Predictive value of nodal maximum standardized uptake value of pretreatment [18F]fluorodeoxyglucose positron emission tomography imaging in patients with esophageal cancer.

We retrospectively reviewed 102 patients with esophageal cancer (97.1% squamous cell carcinoma, 96.1% stage III) received FDG-PET staging and were treated by chemoradiotherapy with or without resection to assess whether the pretreatment [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) maximum standardized uptake value (SUVmax) of the primary tumor and metastatic lymph nodes can predict the prognosis of patients with esophageal cancer. Receiver operating characteristic analysis was performed to find the cutoff values for primary tumor SUVmax and nodal SUVmax. The influence of clinical factors including primary tumor SUVmax and nodal SUVmax on local progression-free survival, nodal progression-free survival (NPFS), distant metastases-free survival (DMFS), and overall survival (OS) were evaluated using univariate and multivariate analyses. A total of 40 patients received esophagectomy after neoadjuvant chemoradiotherapy (trimodality), while 62 patients received definitive chemoradiotherapy (dCRT). The median follow-up was 26.4 months. The SUVmax of primary tumor had no significant predictive value on all outcomes, while the SUVmax of metastatic lymph nodes had predictive value on several outcomes. High nodal SUVmax (≥7) predicted for worse outcomes than low nodal SUVmax (<7) in the patients who received dCRT (two-year DMFS, 17% vs. 92%, P < 0.001; NPFS, 14% vs. 81%, P = 0.001; OS, 21% vs. 50%, P = 0.003), but not in those received trimodality. On multivariate analysis of patients receiving dCRT, nodal SUVmax was the strongest independent predictor on DMFS (hazard ratio [HR] 13.93, P < 0.001), NPFS (HR 3.99, P = 0.026), PFS (HR 2.90, P = 0.003), and OS (HR 3.80, P = 0.001). High pretreatment nodal SUVmax predicts worse treatment outcomes for the patients treated with dCRT.

[Prospective association between early adiposity rebound and adolescent development in girls].

Objective: To determine possible relations between early adiposity rebound and adolescent development. Methods: Prospective children cohort from 2 kindergartens selected through clustering convenience sampling method in Anhui Province was established since Sep. 2010. Participants were classified as Cohort 1 (2010), Cohort 2 (2011) and Cohort 3 (2012) according to the recruiting year. Till Sep. 2015, a toal of 802 girls were included in this study, and received follow-up till primary school. During kindergarten period, physical examination was carried out every 3 months, 8 times in total. In primary school, physical examination was carried out annually; till Sep.2015, the cohort 1, 2, 3 took physical examination for 12, 11, 10 times, respectively. Information on household economic status and child physical activity was acquired through parents questionnaire survey, and breast development were assessed through visual inspection and palpation. Adiposity rebound was determined according to Rolland-Cachera's method for each girl. Differences between early adiposity rebound and normal adiposity rebound groups were compared by using t test and χ(2) test. Multivariate regression analysis was applied to explore the association between early adiposity rebound and breast development. Results: The average age of participants was (8.90±0.87) years old and the BMI was (17.48±2.70) kg/m(2). The average age at adiposity rebound was (6.16±0.90) years old and the BMI was (15.33±1.82) kg/m(2). Premature breast development was found significantly higher in girls in early adiposity rebound group (27.8%, 54/802) than it in normal adiposity rebound group (13.7%) (P<0.001). After current adiposity, age, household economic status, childhood physical activity adjusted, the OR of premature beast development in early adiposity rebound group was 2.41(95%CI: 1.41-4.12). Conclusion: Early adiposity rebound increases the risk of premature puberty in girls.