Gestational Age at Birth and Risk of Developmental Delay: The Upstate KIDS Study.

OBJECTIVE: The aim of this study is to model the association between gestational age at birth and early child development through 3 years of age. STUDY DESIGN: Development of 5,868 children in Upstate KIDS (New York State; 2008-2014) was assessed at 7 time points using the Ages and Stages Questionnaire (ASQ). The ASQ was implemented using gestational age corrected dates of birth at 4, 8, 12, 18, 24, 30, and 36 months. Whether children were eligible for developmental services from the Early Intervention Program was determined through linkage. Gestational age was based on vital records. Statistical models adjusted for covariates including sociodemographic factors, maternal smoking, and plurality. RESULTS: Compared with gestational age of 39 weeks, adjusted odds ratios (aOR) and 95% confidence intervals of failing the ASQ for children delivered at <32, 32-34, 35-36, 37, 38, and 40 weeks of gestational age were 5.32 (3.42-8.28), 2.43 (1.60-3.69), 1.38 (1.00-1.90), 1.37 (0.98-1.90), 1.29 (0.99-1.67), 0.73 (0.55-0.96), and 0.51 (0.32-0.82). Similar risks of being eligible for Early Intervention Program services were observed (aOR: 4.19, 2.10, 1.29, 1.20, 1.01, 1.00 [ref], 0.92, and 0.78 respectively for <32, 32-34, 37, 38, 39 [ref], 40, and 41 weeks). CONCLUSION: Gestational age was inversely associated with developmental delays for all gestational ages. Evidence from our study is potentially informative for low-risk deliveries at 39 weeks, but it is notable that deliveries at 40 weeks exhibited further lower risk.

Combination therapy with c-met inhibitor and TRAIL enhances apoptosis in dedifferentiated liposarcoma patient-derived cells.

BACKGROUND: Liposarcoma (LPS) is a tumor derived from adipose tissue, and has the highest incidence among soft tissue sarcomas. Dedifferentiated liposarcoma (DDLPS) is a malignant tumor with poor prognosis. Recurrence and metastasis rates in LPS remain high even after chemotherapy and radiotherapy following complete resection. Therefore, the development of advanced treatment strategies for LPS is required. In the present study, we investigated the effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) treatment, and of combination treatment using TRAIL and a c-Met inhibitor on cell viability and apoptosis in LPS and DDLPS cell lines of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) treatment, and of combination treatment using TRAIL and a c-Met inhibitor. METHODS: We analyzed cell viability after treatment with TRAIL and a c-Met inhibitor by measuring CCK8 and death receptor 5 (DR5) expression levels via fluorescence activated cell sorting (FACS) in both sarcoma cell lines and DDLPS patient-derived cells (PDCs). Moreover, we validated the effects of TRAIL alone and in combination with c-Met inhibitor on apoptosis in LPS cell lines and DDLPS PDCs via FACS. RESULTS: Our results revealed that combination treatment with a c-Met inhibitor and human recombinant TRAIL (rhTRAIL) suppressed cell viability and induced cell death in both sarcoma cell lines and DDLPS PDCs, which showed varying sensitivities to rhTRAIL alone. Also, we confirmed that treatment with a c-Met inhibitor upregulated DR5 levels in sarcoma cell lines and DDLPS PDCs. In both TRAIL-susceptible and TRAIL-resistant cells subjected to combination treatment, promotion of apoptosis was dependent on DR5 upregulation. CONCLUSION: From these results, our findings validated that DR5 up-regulation caused by combination therapy with a c-Met inhibitor and rhTRAIL enhanced TRAIL sensitization and promoted apoptosis. We propose the use of this approach to overcome TRAIL resistance and serve as a novel treatment strategy for clinical trials.

Development of a Geant4-based independent patient dose validation system with an elaborate multileaf collimator simulation model.

Despite the improvements in the dose calculation models of the commercial treatment planning systems (TPS), their ability to accurately predict patient dose is still limited. One of the limitations is caused by the simplified model of the multileaf collimator (MLC). The aim of this study was to develop a Monte Carlo (MC) method-based independent patient dose validation system with an elaborate MLC model for more accurate dose evaluation. Varian Clinac 2300 IX was simulated using Geant4 toolkits, after which MC commissioning with measurements was performed to validate the simulation model. A DICOM-RT interface was developed to obtain the beam delivery conditions including the hundreds of MLC motions. Finally, the TPS dose distributions were compared with the MC dose distributions for water phantom cases and a patient case. Our results show that the TPS overestimated the absolute abutting leakage dose in the closed MLC field, with about 20% more of the maximum dose than that of the MC calculation. For water phantom cases, the dose distributions inside the target region were almost identical with the dose difference of less than 2%, while the dose near the edge of the target shows difference about 10% between Geant4 and TPS due to geometrical differences in MLC model. For the patient analysis, the Geant4 and TPS doses of all organs were matched well within 1.4% of the prescribed dose. However, for organs located in areas with high ratio of leaf pairs with distances less than 10 mm leaf pair (LP(<10mm) ), the maximum dose of TPS was overestimated by about 3% of the prescribed dose. These dose comparison results demonstrate that our system for calculating the patient dose is quite accurate. Furthermore, if the MLC sequences in treatment plan have a large ratio of LP(short) , more than 3% dose difference in normal tissue could be seen.

Maternal polycystic ovarian syndrome and early offspring development.

STUDY QUESTION: Is maternal polycystic ovarian syndrome (PCOS) associated with developmental delays in offspring? SUMMARY ANSWER: Offspring of mothers with PCOS were at higher risk of failure on the Ages and Stages Questionnaire (ASQ). WHAT IS KNOWN ALREADY: There is growing evidence that offspring of mothers with PCOS may be at higher risk for developmental disorders due to potential exposure to hyperandrogenism and insulin resistance. Few studies exist regarding maternal PCOS and early childhood development in the USA. STUDY DESIGN, SIZE, DURATION: The Upstate KIDS Study is a population-based prospective cohort study of infants born between 2008 and 2010 in New York State (excluding New York City), originally designed to study-and finding no impact of-infertility treatment exposure on child development. Children were followed up to 36 months of age. In all, 4453 mothers completed one or more developmental screening instruments for 5388 children (35.5% twins) up to 36 months of age. PARTICIPANTS/MATERIALS, SETTING, METHODS: In our study, 458 mothers (10.3%) reported a healthcare provider's diagnosis of PCOS, as well as the related treatment received, on the baseline study questionnaire. Parents completed the ASQ on their child's development at 4, 8, 12, 18, 24, 30 and 36 months of age to assess fine motor, gross motor, communication, personal-social functioning and problem-solving cognitive domains. We used generalized linear mixed models to estimate odds ratios (OR) between PCOS diagnosis and failures in the ASQ adjusted for maternal age, race, BMI, education, marital status, smoking, alcohol consumption, diabetes, insurance and plurality. MAIN RESULTS AND THE ROLE OF CHANCE: Diagnosis of PCOS was associated with increased risk of the offspring failing the fine motor domain (adjusted odds ratio (aOR) = 1.77; 95% CI: 1.09, 2.89), largely driven by higher risk in female singletons (aOR = 2.23; 1.16, 4.29). Twins of mothers with PCOS had higher risk of failing the communication (aOR = 1.94; 1.19, 3.18) and personal-social functioning (aOR = 1.76; 1.12, 2.77) domains compared to twins born to mothers without PCOS. Compared to offspring of women without PCOS, offspring of women who reported receiving no treatment for their PCOS had a stronger association with failing the ASQ (aOR = 1.68; 0.95, 2.75) than the association among offspring of women who reported PCOS treatment (aOR = 1.16; 0.79, 1.73). LIMITATIONS, REASONS FOR CAUTION: Further study is needed to confirm the role of maternal PCOS in early offspring development with provider-validated diagnosis of PCOS. WIDER IMPLICATIONS OF THE FINDINGS: If confirmed, these findings suggest that offspring of women with PCOS may be at increased risk for developmental delay. STUDY FUNDING/COMPETING INTEREST(S): Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; contracts HHSN275201200005C, #HHSN267200700019C). Authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Enhanced effect of human mesenchymal stem cells expressing human TNF-αR-Fc and HO-1 gene on porcine islet xenotransplantation in humanized mice.

BACKGROUND: Porcine islet xenotransplantation is considered an attractive alternative treatment for type 1 diabetes mellitus. However, it is largely limited because of initial rejection due to Instant Blood-Mediated Inflammatory Reaction (IBMIR), oxidative stress, and inflammatory responses. Recently, soluble tumor necrosis factor-ɑ receptor type I (sTNF-αR) and heme oxygenase (HO)-1 genes (HO-1/sTNF-αR) have been shown to improve the viability and functionality of porcine islets after transplantation. METHODS: In this study, genetically modified mesenchymal stem cells (MSCs) expressing the HO-1/sTNF-αR genes (HO-1/sTNF-αR-MSC) were developed using an adenoviral system, and porcine islet viability and function were confirmed by in vitro tests such as GSIS, AO/PI, and the ADP/ATP ratio after coculturing with HO-1/sTNF-αR-MSCs. Subsequently, isolated porcine islets were transplanted underneath the kidney capsule of diabetic humanized mice without MSCs, with MSCs or with HO-1/sTNF-αR-MSCs. RESULTS: According to the results, the HO-1/sTNF-αR-MSC-treated group exhibited improved survival of porcine islets and could reverse hyperglycemia more than porcine islets not treated with MSCs or islets cotransplanted with MSCs. Moreover, the HO-1/sTNF-αR-MSC group maintained its morphological characteristics and the insulin secretion pattern of transplanted porcine islets similar to endogenous islets in immunocompetent humanized mice. CONCLUSIONS: Our results suggest that HO-1/sTNF-αR-MSCs are efficient tools for porcine islet xenotransplantation, and this study may provide basic information for pre-clinical animal models and future clinical trials of porcine islet xenotransplantation.

Radical Nephrectomy for Primary Retroperitoneal Liposarcoma Near the Kidney has a Beneficial Effect on Disease-Free Survival.

BACKGROUND: The purpose of this study is to analyze the clinical impact of radical nephrectomy on retroperitoneal liposarcoma near the kidney. METHODS: Data of patients who underwent surgery for unilateral primary retroperitoneal liposarcoma near the kidney were retrospectively collected. Patients were divided into four groups according to whether they underwent nephrectomy and combined resection of other organs. Kaplan-Meier survival analysis was used to estimate disease-free survival and overall survival. Multivariable Cox analysis was used to analyze factors related to disease-free survival and overall survival. RESULTS: Nephrectomy (HR = 0.260, CI = 0.078-0.873, p = 0.029) had a beneficial effect on disease-free survival, while interaction model of nephrectomy*other organ resection (HR = 4.655, CI = 1.767-12.263, p = 0.002) showed poor disease-free survival. Other organ resection was not related to disease-free survival (HR = 1.543, CI = 0.146-16.251, p = 0.718). Operation method (p = 0.007) and FNCLCC grade (p < 0.001; G2, HR = 1.833, CI = 0.684-4.915, p = 0.228; G3, HR = 9.190, CI = 3.351-25.199, p < 0.001) were significant factors for disease-free survival. While combined organ resection without nephrectomy group (HR = 1.604, CI = 0.167-15.370, p = 0.682) and radical nephrectomy with combined organ resection group (HR = 1.309, CI = 0.448-3.825, p = 0.622) did not show significant difference in disease-free survival from the mass excision only group, radical nephrectomy without combined organ resection group (HR = 0.279, CI = 0.078-0.991, p = 0.048) showed superior disease-free survival. CONCLUSIONS: Radical nephrectomy of unilateral primary retroperitoneal liposarcoma near the kidney has a beneficial effect on disease-free survival.

Case Report of Kidney Paired Donation (KPD) with Desensitization: the Strategy and Experience of 3-Way KPD in Samsung Medical Center.

As the need for the organ donation increases, strategies to increase kidney transplantation (KT) through expanded living donation have become essential. These include kidney paired donation (KPD) programs and desensitization in incompatible transplantations. KPD enables kidney transplant candidates with incompatible living donors to join a registry with other incompatible pairs in order to find potentially compatible living donor. Positive cross match and ABO incompatible transplantation has been successfully accomplished in selective cases with several pre-conditionings. Patients who are both difficult-to-match due to broad sensitization and hard-to-desensitize because of donor conditions can often be successfully transplanted through a combination of KPD and desensitization. According to the existing data, KPD can increase the number of KTs from living donors with excellent clinical results. This is also a cost-effective treatment as compared with dialysis and desensitization protocols. We carried out 3-way KPD transplantation with one highly sensitized, positive cross match pair and with two ABO incompatible pairs. Herein we report our first successful 3-way KPD transplantation in a single center. To maximize donor-recipient matching and minimize immunologic risk, KPD programs should use proper algorithms with desensitization to identify optimal donor with simultaneous two-, three- or more complex multi-way exchanges.

Comparative characterization of mesenchymal stromal cells from multiple abdominal adipose tissues and enrichment of angiogenic ability via CD146 molecule.

BACKGROUND: There are various types of adipose tissue in the human body, and their morphology is known to be closely related to cell function and metabolism. However, the functional differences among the mesenchymal stromal cells (MSCs) of different abdominal adipose tissues have not been clearly elucidated. METHODS: MSCs were isolated from different abdominal adipose tissues according to their regional distribution and included superficial subcutaneous, deep subcutaneous, omentum, mesentery and retroperitoneal MSCs. The immunophenotype, proliferative ability and angiogenic function of these MSCs were compared based on flow cytometry analysis, CCK-8 proliferation, in vitro differentiation, tubule formation and in vivo plug assay. RESULTS: The plastic adherence, cell morphology and general immunophenotype are similar among the MSCs. However, subcutaneous adipose tissue-derived MSCs have a faster growth rate and a higher level of CD146 expression than the other MSCs. Moreover, according to the fluorescence-activated cell sorting (FACS) enrichment procedure, the expression level of CD146 is positively related to the growth rate and angiogenic capability of MSCs. DISCUSSION: MSCs in adipose tissue showed slightly different characteristics depending on their location of origin, and they possessed different angiogenic abilities that were mediated by the expression of CD146. This study provides evidence that subcutaneous adipose tissue is the most appropriate source of MSCs for therapeutic cell transplantation in vascular disease.

Therapeutic strategies for locally recurrent and metastatic de-differentiated liposarcoma with herpes simplex virus-thymidine kinase-expressing mesenchymal stromal cells.

BACKGROUND AIMS: Major challenges in de-differentiated liposarcoma (DDLPS) therapy are the high rate of sequential recurrence (>80%) and metastasis (20-30%) following surgical removal. However, well-defined therapeutic strategies for this rare malignancy are lacking and are critically needed. METHODS: We investigated a new approach to DDLPS therapy with mesenchymal stromal cells expressing herpes simplex virus-thymidine kinase (MSC-TK). In an effort to evaluate this efficacy, in vitro cytotoxicity of MSC-TK against DDLPS cells was analyzed using an apoptosis assay. For pre-clinical study, the MSC-TK-induced reduction in recurrence and metastasis was validated in a recurrent DDLPS model after the macroscopic complete resection and lung metastasis DDLPS model. RESULTS: MSC-TK induced apoptosis in DDLPS cells by bystander effects via gap junction intracellular communication (GJIC) of toxic ganciclovir (GCV). Recurrent DDLPS models following no residual tumor/microscopic tumor resection and lung metastasis DDLPS models were established, which suggested clinical relevance. MSC-TK markedly reduced locoregional recurrence rates and prolonged recurrence-free survival, thus increasing overall survival in the recurrent DDLPS model. MSC-TK followed by GCV treatment yielded a statistically significant reduction in early- and advanced-stage lung metastasis. DISCUSSION: This therapeutic strategy may serve as an alternative or additional strategy by applying MSC-TK to target residual tumors following surgical resection, thus reducing local relapse and metastasis in these patients.

Comparison of retroperitoneal liposarcoma extending into the inguinal canal and inguinoscrotal liposarcoma.

BACKGROUND: This study was designed to analyze differences between retroperitoneal liposarcoma (RLPS) extending into the inguinal canal and inguinoscrotal liposarcoma. METHODS: We retrospectively reviewed the records for patients who were managed for inguinal liposarcoma at Samsung Medical Center, a tertiary hospital, between January 1998 and December 2016. Patient data on demographics, tumour location, surgery, adjuvant therapy, histology, recurrence and death were collected. We used Mann-Whitney, Fisher exact and Kaplan-Meier log-rank tests to analyze differences between groups. RESULTS: Seven of 179 (3.9%) patients with abdominal liposarcoma had inguinoscrotal liposarcoma, and 6 of 168 (3.6%) patients with RLPS had extension to the inguinal canal. No differences were observed between groups in sex (p > 0.99), mean age (49.7 ± 6.4 yr v. 52.1 ± 12.5 yr, p = 0.37), laterality (p > 0.99) or scrotal involvement (40.0% v. 66.7%, p = 0.57). The RLPS group had significantly larger tumours than the inguinoscrotal group (27.9 ± 6.8 cm v. 7.8 ± 4.2 cm, p = 0.001). Postoperative complications were significantly more common in the RLPS group (n = 4, 83.3%); patients in the inguinoscrotal group experienced no postoperative complications (p = 0.021). Log-rank tests showed that the groups had no statistical differences in disease-free survival (p = 0.94) or overall survival (p = 0.10). However, inoperable disease-free survival was significantly poorer in the RLPS group (p = 0.010). CONCLUSION: Although initial signs and symptoms can be similar, RLPS extending into the inguinal canal was associated with significantly higher morbidity and mortality than inguinoscrotal liposarcoma.

CONTEXTE: Cette étude visait à examiner les différences entre le liposarcome rétropéritonéal s'étendant au canal inguinal et le liposarcome inguino-scrotal. MÉTHODES: Nous avons procédé à une analyse rétrospective des dossiers de patients traités pour un liposarcome inguinal au Samsung Medical Center, un hôpital de soins tertiaires, entre janvier 1998 et décembre 2016. Nous avons recueilli les données des patients en ce qui a trait aux caractéristiques démographiques, au siège de la tumeur, à la chirurgie, au traitement adjuvant, à l'histologie, à la récidive et au décès. Nous avons utilisé le test de Mann-Whitney, la méthode exacte de Fisher et les tests logarithmiques par rangs de Kaplan-Meier pour analyser les différences entre les 2 groupes. RÉSULTATS: Sept des 179 (3,9 %) patients atteints de liposarcome abdominal avaient un liposarcome inguino-scrotal, et 6 des 168 (3,6 %) patients atteints de liposarcome rétropéritonéal présentaient une extension au canal inguinal. Aucune différence n'a été observée entre les groupes pour le sexe (p > 0,99), l'âge moyen (49,7 ± 6,4 ans c. 52,1 ± 12,5 ans, p = 0,37), la latéralité (p > 0,99) ou l'atteinte scrotale (40 % c. 66,7 %, p = 0,57). La taille de la tumeur était significativement plus grande dans le groupe du liposarcome rétropéritonéal que dans celui du liposarcome inguino-scrotal (27,9 ± 6,8 cm c. 7,8 ± 4,2 cm, p = 0,001). De même, les complications postopératoires étaient significativement plus courantes dans le groupe du liposarcome rétropéritonéal (n = 4, 83,3 %), les patients du groupe du liposarcome inguino-scrotal n'en ayant pratiquement pas présenté (p = 0,021). Les tests logarithmiques par rangs ont révélé l'absence de différences statistiques entre les groupes pour la survie sans récidive (p = 0,94) et la survie globale (p = 0,10). Cependant, la survie sans récidive du patient inopérable était significativement plus faible dans le groupe du liposarcome rétropéritonéal (p = 0,010). CONCLUSION: Malgré la similarité des premiers signes et symptômes, le liposarcome rétropéritonéal s'étendant au canal inguinal était associé à des taux de morbidité et de mortalité significativement plus élevés que le liposarcome inguino-scrotal.

Outcomes of dialysis and the transplantation options for patients with diabetic end-stage renal disease in Korea.

BACKGROUND: The best therapeutic option for diabetic end-stage renal disease (DMESRD) has not been established among living donor kidney transplantation (LDKT), deceased donor kidney transplantation (DDKT), simultaneous pancreas and kidney transplantation (SPK), and dialysis. METHODS: We retrospectively analyzed the outcomes of DMESRD patients at two Korean centers from February 2000 to December 2011. RESULTS: Among 674 patients, 295 underwent kidney transplantation (LDKT, 175; DDKT, 72; and SPK, 48), while 379 were still on dialysis. The dialysis group had a higher mortality rate than the transplantation group. From the time after dialysis initiation, LDKT group had a better patient survival rate than DDKT registration group and SPK registration group. From the time after transplantation, LDKT had a better patient survival rate than DDKT; however, there was no significant difference between LDKT and SPK. In SPK, patient survival and kidney or pancreas graft survival rates were not different between types 1 and 2 DMESRD. CONCLUSION: LDKT is better than waiting for SPK/DDKT in DMESRD patients, if a living donor is available, and this conclusion may be unique to Korea where waiting time for SPK is long. SPK can be used in non-obese Asians with type 2 as well as type 1 DMESRD.

Mycobacterium tuberculosis infections in cynomolgus monkey transplant recipients and institution of a screening program for the prevention and control of tuberculosis.

BACKGROUND: Tuberculosis is a major health concern in not only humans, but also in non-human primates. In this paper, we report recent cases of Mycobacterium tuberculosis in cynomolgus monkeys from Cambodia used in transplantation research in a Korean facility and describe a program instituted to prevent and control subsequent infections. CASE PRESENTATION: All monkeys were antibody negative for tuberculosis during quarantine; however, suspected tuberculosis gross lesions were observed in two cynomolgus monkeys who underwent allograft kidney transplantation. Lung tissue from one monkey was found to be weakly positive by PCR for detection of M. tuberculosis. After PCR confirmation of tuberculosis, we decided to sacrifice the remaining animals and instituted a program for preventing subsequent infections. During necropsy of the remaining monkeys, two additional suspected tuberculosis cases were observed. A total of four monkeys with nodular lesions in the respiratory tract, suspected to be tuberculosis, demonstrated no clinical signs. Acid-fast bacilli were identified on slides from the lung or liver in all four monkeys. Two of four monkeys tested PCR positive. We decided that new monkeys entering from Cambodia should undergo a single gastric aspiration PCR and tuberculin skin testing (TST) every 2 weeks until four consecutive negatives to detect latent tuberculosis are obtained before starting experiments. Monkeys should then undergo a chest X-ray monthly and TST every 6 months. CONCLUSIONS: Detection of latent tuberculosis by an effective preventive screening program before starting experiments is an essential process to reduce the risk of reactivation of tuberculosis, especially in studies using immunosuppressive drugs. It also serves to protect the health of captive non-human primates, their caretakers and researchers.

Infant birthweight in the US: the role of preconception stressful life events and substance use.

The purpose of this study was to determine the relationships among preconception stressful life events (PSLEs), women's alcohol and tobacco use before and during pregnancy, and infant birthweight. Data were from the Early Childhood Longitudinal Study-Birth Cohort (n = 9,350). Data were collected in 2001. Exposure to PSLEs was defined by indications of death of a parent, spouse, or previous live born child; divorce or marital separation; or fertility problems prior to conception. Survey data determined alcohol and tobacco usage during the 3 months prior to and in the final 3 months of pregnancy. We used staged multivariable logistic regression to estimate the effects of women's substance use and PSLEs on the risk of having a very low (<1,500 g, VLBW) or low (1,500-2,499 g, LBW) birthweight infant, adjusting for confounders. Women who experienced any PSLE were more likely to give birth to VLBW infants (adjusted odds ratio [AOR] = 1.35; 95 % confidence interval [CI] = 1.10-1.66) than women who did not experience any PSLE. Compared to women who never smoked, women who smoked prior to conception (AOR = 1.31; 95 % CI = 1.04-1.66) or during their last trimester (AOR = 1.98; 95 % CI = 1.56-2.52) were more likely to give birth to LBW infants. PSLEs and women's tobacco use before and during pregnancy are independent risk factors for having a lower birthweight baby. Interventions to improve birth outcomes may need to address women's health and health behaviors in the preconception period.

Assessment of Factors Contributing to Health Outcomes in the Eight States of the Mississippi Delta Region.

INTRODUCTION: The objective of this observational study was to examine the key contributors to health outcomes and to better understand the health disparities between Delta and non-Delta counties in 8 states in the Mississippi River Delta Region. We hypothesized that a unique set of contributors to health outcomes in the Delta counties could explain the disparities between Delta and non-Delta counties. METHODS: Data were from the 2014 County Health Rankings for counties in 8 states (Alabama, Arkansas, Illinois, Kentucky, Louisiana, Mississippi, Missouri, and Tennessee). We used the Delta Regional Authority definition to identify the 252 Delta counties and 468 non-Delta counties or county equivalents. Information on health factors (eg, health behaviors, clinical care) and outcomes (eg, mortality) were derived from 38 measures from the 2014 County Health Rankings. The contributions of health factors to health outcomes in Delta and non-Delta counties were examined using path analysis. RESULTS: We found similarities between Delta counties and non-Delta counties in the health factors (eg, tobacco use, diet and exercise) that significantly predicted the health outcomes of self-rated health and low birthweight. The most variation was seen in predictors of mortality; however, Delta counties shared 2 of the 3 significant predictors (ie, community safety and income) of mortality with non-Delta counties. On average across all measures, values in the Delta were 16% worse than in the non-Delta and 22% worse than in the rest of the United States. CONCLUSION: The health status of Delta counties is poorer than that of non-Delta counties because the health factors that contribute to health outcomes in the entire region are worse in the Delta counties, not because of a unique set of health predictors.

Neighborhood disadvantage, preconception stressful life events, and infant birth weight.

OBJECTIVES: We sought to determine whether the effects of preconception stressful life events (PSLEs) on birth weight differed by neighborhood disadvantage. METHODS: We drew our data from the Early Childhood Longitudinal Study, Birth Cohort (2001-2002; n = 9300). We created a neighborhood disadvantage index (NDI) using county-level data from the 2000 US Census. We grouped the NDI into tertiles that represented advantaged, middle advantaged, and disadvantaged neighborhoods. Stratified multinomial logistic regressions estimated the effect of PSLEs on birth weight, controlling for confounders. RESULTS: We found a gradient in the relationship between women's exposure to PSLEs and having a very low birth weight (VLBW) infant by NDI tertile; the association was strongest in disadvantaged neighborhoods (adjusted odd ratio [AOR] = 1.62; 95% confidence interval [CI] = 1.04, 2.53), followed by middle (AOR = 1.39; 95% CI = 1.00, 1.93) and advantaged (AOR = 1.29; 95% CI = 0.91, 1.82) neighborhoods. We observed a similar gradient for women with chronic conditions and among minority mothers. CONCLUSIONS: Women who experienced PSLEs, who had chronic conditions, or were racial/ethnic minorities had the greatest risk of having VLBW infants if they lived in disadvantaged neighborhoods; this suggests exacerbation of risk within disadvantaged environments. Interventions to reduce rates of VLBW should focus on reducing the deleterious effects of stressors and on improving neighborhood conditions.

Predictors of alcohol and tobacco use prior to and during pregnancy in the US: the role of maternal stressors.

The purpose of the study was to understand the association between stressful life events prior to conception (PSLEs) and women's alcohol and tobacco use prior to and during pregnancy, and the continuation of such use through pregnancy. Data were from the Early Childhood Longitudinal Study-Birth Cohort (n = 9,350). Data were collected in 2001. Exposure to PSLEs was defined by indications of death of a parent, spouse, or previous live born child, divorce or marital separation, or fertility problems prior to conception. Survey data determined alcohol and tobacco usage during the 3 months prior to and in the final 3 months of pregnancy. Weighted regressions estimated the effect of PSLEs on alcohol and tobacco use at each time point and on the continuation of use, adjusting for confounders. Experiencing any PSLE increased the odds of tobacco use prior to (adjusted odds ratio [AOR] 1.52, 95 % confidence interval (CI) 1.23-1.87) and during pregnancy (AOR 1.57, 95 % CI 1.19-2.07). Women exposed to PSLEs smoked nearly five additional packs of cigarettes in the 3 months prior to pregnancy (97 cigarettes, p = 0.011) and consumed 0.31 additional alcoholic drinks during the last 3 months of pregnancy than unexposed women. PSLEs are associated with tobacco use before pregnancy and alcohol and tobacco use during pregnancy. Alcohol and tobacco screening and cessation services should be implemented prior to and during pregnancy, especially for women who have experienced PSLEs.

Development of a nationally representative built environment measure of access to exercise opportunities.

We sought to develop a county-level measure to evaluate residents' access to exercise opportunities. Data were acquired from Esri, DeLorme World Vector (MapMart), and OneSource Global Business Browser (Avention). Using ArcGIS (Esri), we considered census blocks to have access to exercise opportunities if the census block fell within a buffer area around at least 1 park or recreational facility. The percentage of county residents with access to exercise opportunities was reported. Measure validity was examined through correlations with other County Health Rankings & Roadmaps' measures. Included were 3,114 of 3,141 US counties. The average population with access to exercise opportunities was 52% (range, 0%-100%) with large regional variation. Access to exercise opportunities was most notably associated with no leisure-time physical activity (r = -0.47), premature death (r = -0.38), and obesity (r = -0.36). The measure uses multiple sources to create a valid county-level measure of exercise access. We highlight geographic disparities in access to exercise opportunities and call for improved data.

Impact of county disadvantage on behavior problems among US children with cognitive delay.

OBJECTIVES: We investigated relationships among cognitive delay, community factors, and behavior problems over 2 years in early childhood with a national sample of US families. METHODS: Data were from 3 waves of the Early Childhood Longitudinal Study, Birth Cohort (2001-2005; n = 7650). We defined cognitive delay as the lowest 10% of mental scores from the Bayley Short Form-Research Edition, administered at 9 and 24 months. At 24 months, we classified children as typically developing or as having resolved, newly developed, or persistent cognitive delays. Behavior was measured at age 4 years with the Preschool and Kindergarten Behavior Scales (range = 0-36). Community factors included perceived neighborhood safety and an index of county disadvantage. RESULTS: Behavior scores at age 4 years (mean = 12.4; SD = 4.9) were higher among children with resolved (Β = 0.70; SE = 0.20), newly developed (Β = 1.92; SE = 0.25), and persistent (Β = 2.96; SE = 0.41) cognitive delays than for typically developing children. The interaction between county disadvantage and cognitive delay status was statistically significant (P < .01), suggesting that county disadvantage was particularly detrimental for children with persistent delays. CONCLUSIONS: The community context may provide an opportunity for public health interventions to improve the behavioral health of children with cognitive delays.

The analysis of mutations and exon deletions at TSC2 gene in angiomyolipomas associated with tuberous sclerosis complex.

Angiomyolipomas (AMLs) are relatively rare hamartomatous or benign tumors that occasionally occur as part of tuberous sclerosis complex (TSC). Mutations in either of the two genes, TSC1 and TSC2, have been attributed to the development of TSC. Between 1994 and January 2009, 83 patients were diagnosed with AML at the Samsung Medical Center. In that group of patients, 5 (6%) had AML with TSC (AML-TSC). Mutational analysis of the TSC2 gene was performed using 7 samples from the 5 AML-TSC patients and 14 samples from 14 patients with sporadic AML without TSC (AML-non-TSC). From this analysis, mutations in TSC genes were identified in 5 samples from the AML-TSC patients (mutation detection rate=71%) and 3 samples from AML-non-TSC patients (mutation detection rate=21%). In the case of AML-TSC, 6 mutations were found including 3 recurrent mutations and 3 novel mutations, while in the case of AML-non-TSC, 4 mutations were identified once, including 1 novel mutation. Also MLPA analysis of the TSC2 gene showed that TSC2 exon deletion is more frequently observed in AML-TSC patients than in AML-non-TSC patients. This is the first mutation and multiplex ligation-dependent probe amplification (MLPA) analyses of TSC2 in Korean AMLs that focus on TSC. This study provides data that are representative of the distribution of mutations and exon deletions at TSC genes in clinically diagnosed AML-TSC cases of the Korean population.

Long-term results of biliary atresia in the era of liver transplantation.

PURPOSE: The purpose of this study was to analyze the survival of patients with biliary atresia (BA) after Kasai operation and liver transplantation (LT) and to analyze the factors affecting survival. METHODS: Seventy-two patients diagnosed with BA were operated on between April 1995 and December 2009 and retrospectively analyzed. RESULTS: Out of the 72 patients, 59 received Kasai operation and 13 received LT without prior Kasai operation. Twenty-seven patients received LT after Kasai operation. Survival with native liver was 39 % at 10 years. With the application of LT, overall 10-year survival for patients with BA was 94.9 %. Among patients alive with native livers after Kasai operation, 14 patients (58.3 %) have at least one complication associated with biliary cirrhosis and portal hypertension. Age at which Kasai operation was performed (60 days) and postoperative normalization of bilirubin were independent risk factors for survival with the native liver, according to multivariate analysis (HR 2.90, p = 0.033 and HR 9.89, p = 0.002). CONCLUSIONS: Survival of BA patients has greatly increased in the era of LT. However, many patients surviving with native livers after Kasai operation continue to have signs of biliary cirrhosis and abnormal liver function.