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Purpose: Studies have shown that children with muscular dystrophy are at increased risk for falls, however there is insufficient information about what predicts the first and subsequent events. The purpose of this study was to describe the experience of injury with emphasis on identifying risk factors for fall-related injuries., Methods: We studied 269 boys with muscular dystrophy describing their injury experience and identifying risk and protective factors associated with 281 non-simultaneous injuries and 127 falls that resulted in Emergency Department visits and/or inpatient hospitalization during the period 1998-2014. We used a Cox model to estimate the predictors of an initial fall and a zero-inflated Poisson model to identify the predictors for the number of falls., Results: Falls accounted for the greatest number of injury occurrences; The most frequent injury type was contusion. The factors that were protective for falls were steroid use, wheelchair use, or having a heart condition. Baseline age was negatively associated with the risk of having any fall, but not significantly related to subsequent falls., Conclusion: Wheelchair use and heart conditions associated with reduced risk of falls likely reflects decreased mobility. Clinicians should help families identify factors associated with falls among those who remain ambulatory.

An array of oncogenic histone point mutations have been identified across a number of different cancer studies. It has been suggested that some of these mutant histones can exert their effects by inhibiting epigenetic writers. Here, we report that the H3.3 G34R (glycine to arginine) substitution mutation, found in paediatric gliomas, causes widespread changes in H3K9me3 and H3K36me3 by interfering with the KDM4 family of K9/K36 demethylases. Expression of a targeted single-copy of H3.3 G34R at endogenous levels induced chromatin alterations that were comparable to a KDM4 A/B/C triple-knockout. We find that H3.3 G34R preferentially binds KDM4 while simultaneously inhibiting its enzymatic activity, demonstrating that histone mutations can act through inhibition of epigenetic erasers. These results suggest that histone point mutations can exert their effects through interactions with a range of epigenetic readers, writers and erasers.

The objective of this study was to investigate whether males who were born preterm took longer to receive a Duchenne muscular dystrophy diagnosis than term males. Data for males with Duchenne muscular dystrophy identified through a population-based surveillance system were analyzed using a Kaplan-Meier estimator. The first signs and symptoms were noted at a median age of 2 years in both groups. Median age when first signs and symptoms prompted medical evaluation was 2.59 years among preterm and 4.01 years among term males. Median age at definitive diagnosis was 4.25 years and 4.92 years for preterm and term males, respectively. Neither difference was statistically significant. Preterm males tended to be seen for their initial medical evaluation earlier than term males, though they were not diagnosed significantly earlier. It may take clinicians longer after the initial evaluation of preterm males to arrive at a Duchenne muscular dystrophy diagnosis.

Mutations in PARK2 (parkin) can result in Parkinson's disease (PD). Parkin shares a bidirectional promoter with parkin coregulated gene (PACRG) and the transcriptional start sites are separated by only ~200 bp. Bidirectionally regulated genes have been shown to function in common biological pathways. Mice lacking parkin have largely failed to recapitulate the dopaminergic neuronal loss and movement impairments seen in individuals with parkin-mediated PD. We aimed to investigate the function of PACRG and test the hypothesis that parkin and PACRG function in a common pathway by generating and characterizing two novel knockout mouse lines harbouring loss of both parkin and Pacrg or Pacrg alone. Successful modification of the targeted allele was confirmed at the genomic, transcriptional and steady state protein levels for both genes. At 18-20 months of age, there were no significant differences in the behaviour of parental and mutant lines when assessed by openfield, rotarod and balance beam. Subsequent neuropathological examination suggested there was no gross abnormality of the dopaminergic system in the substantia nigra and no significant difference in the number of dopaminergic neurons in either knockout model compared to wildtype mice.

Objective: Both diet and physical activity have been shown to be associated with reduced risk for mortality. The current study examined the individual and combined effects of the inflammatory quality of diet and physical activity levels on mortality risk., Methods: Data from the 1999-2004 National Health and Nutrition Examination Survey were used (N = 10,610 adults 20-85 years). Participants were followed through 2011, entailing a median follow-up time of 9.6 yrs. Dietary patterns were assessed using the Dietary Inflammatory Index (DII®), with a higher score indicative of greater diet-related inflammation. Habitual physical activity was assessed via a 30-day recall of leisure-time physical activity as well as objectively via up to seven days of accelerometry assessment. Four lifestyle groups were created: 1) unfavorable DII and inactive (referent); 2) unfavorable DII and active; 3) favorable DII and inactive; and 4) favorable DII and active., Results: Those who had a low DII score (favorable) and who self-reported being active had a 39% reduced hazard of all-cause mortality (HR = 0.61; 95% CI: 0.49-0.76) when compared to those with a higher DII and were inactive. Results based on accelerometer-assessed physical activity indicate a 65% reduced hazard (HR = 0.35; 95% CI: 0.17-0.74). DII and physical activity also were individually associated with mortality in the expected direction. Specifically, DII was positively associated (HR = 1.08; 95% CI: 1.04-1.13) and physical activity inversely associated (HR = 0.97; 95% CI: 0.94-0.99) with all-cause mortality risk., Conclusion: The combination of consuming a more anti-inflammatory diet and having adequate levels of physical activity is associated with a reduced risk of mortality. Additional replicative work is warranted.

ATRX (alpha thalassemia/mental retardation X-linked) complexes with DAXX to deposit histone variant H3.3 into repetitive heterochromatin. Recent genome sequencing studies in cancers have revealed mutations in ATRX and their association with ALT (alternative lengthening of telomeres) activation. Here we report depletion of ATRX in mouse ES cells leads to selective loss in ribosomal RNA gene (rDNA) copy number. Supporting this, ATRX-mutated human ALT-positive tumors also show a substantially lower rDNA copy than ALT-negative tumors. Further investigation shows that the rDNA copy loss and repeat instability are caused by a disruption in H3.3 deposition and thus a failure in heterochromatin formation at rDNA repeats in the absence of ATRX. We also find that ATRX-depleted cells are reduced in ribosomal RNA transcription output and show increased sensitivity to RNA polymerase I (Pol I) transcription inhibitor CX5461. In addition, human ALT-positive cancer cell lines are also more sensitive to CX5461 treatment. Our study provides insights into the contribution of ATRX loss of function to tumorigenesis through the loss of rDNA stability and suggests the therapeutic potential of targeting Pol I transcription in ALT cancers., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Effective emotional regulation is critical for overall psychological well-being; as such, it is important to investigate potential methods to optimize emotion regulation abilities. The purpose of this study was to examine the effects of an acute bout of aerobic exercise and meditation on emotional regulation among young adults. Participants (N=63, mean age=21.3yrs) were randomly assigned to stretch (control group, n=21), walk (n=21), or meditate (n=21) for 10-min, after which they were exposed to a film clip (3min) intended to elicit a negative emotional state (e.g., sadness, anger). Participants then viewed 12 International Affective Picture System images validated to elicit a negative valence. Participants' affect (valence and arousal) states were monitored before, during, and after the stretching, walking, and meditation bouts using the Feeling Scale (FS) and Felt Arousal Scale (FAS). Distinct affect was assessed utilizing an affective circumplex measure before and after the stretch/walk/meditation bout, as well as following the film clip and image viewing. A significant group×time interaction effect was present when evaluating circumplex excited: P=0.001 (η 2 =0.21). Additionally, an interaction effect of meditation and emotional regulation was observed (P=0.009) among those with varying degrees of meditation experience. A 10-min bout of brisk walking and meditation, prior to exposure to a negative emotion cue, did not differentially effect the ability to regulate sadness, anger, or anxiousness when compared to an active stretching control group. Future replicative work addressing this paradigm, which is in support of positive psychology theory, is warranted., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Ambulatory care sensitive conditions (ACSCs) can be seen as failure of access or management in primary care settings. Identifying factors associated with ACSCs for individuals with an Intellectual Disability (ID) provide insight into potential interventions., Method: To assess the association between emergency department (ED) ACSC visits and a number of demographic and health characteristics of South Carolina Medicaid members with ID. A retrospective cohort of adults with ID was followed from 2001 to 2011. Using ICD-9-CM codes, four ID subgroups, totalling 14 650 members, were studied., Results: There were 106 919 ED visits, with 21 214 visits (19.8%) classified as ACSC. Of those, 82.9% were treated and released from EDs with costs averaging $578 per visit. People with mild and unspecified ID averaged greater than one ED visit per member year. Those with Down syndrome and other genetic cause ID had the lowest rates of ED visits but the highest percentage of ACSC ED visits that resulted in inpatient hospitalisation (26.6% vs. an average of 16.8% for other subgroups). When compared with other residential types, those residing at home with no health support services had the highest ED visit rate and were most likely to be discharged back to the community following an ED visit (85.2%). Adults residing in a nursing home had lower rates of ED visits but were most likely to be admitted to the hospital (38.9%) following an ED visit. Epilepsy and convulsions were the leading cause (29.6%) of ACSC ED visits across all subgroups and residential settings., Conclusion: Prevention of ACSC ED visits may be possible by targeting adults with ID who live at home without health support services., (© 2017 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

The objective of this study was to examine the association between dietary inflammatory potential and memory and cognitive functioning among a representative sample of the US older adult population. Cross-sectional data from the 2011-2012 and 2013-2014 National Health and Nutrition Examination Survey were utilised to identify an aggregate sample of adults 60-85 years of age (n 1723). Dietary inflammatory index (DII®) scores were calculated using 24-h dietary recall interviews. Three memory-related assessments were employed, including the Consortium to Establish a Registry for Alzheimer's disease (CERAD) Word Learning subset, the Animal Fluency test and the Digit Symbol Substitution Test (DSST). Inverse associations were observed between DII scores and the different memory parameters. Episodic memory (CERAD) (b adjusted=-0·39; 95 % CI -0·79, 0·00), semantic-based memory (Animal Fluency Test) (b adjusted=-1·18; 95 % CI -2·17, -0·20) and executive function and working-memory (DSST) (b adjusted=-2·80; 95 % CI -5·58, -0·02) performances were lowest among those with the highest mean DII score. Though inverse relationships were observed between DII scores and memory and cognitive functioning, future work is needed to further explore the neurobiological mechanisms underlying the complex relationship between inflammation-related dietary behaviour and memory and cognition.

Background: Limited research has evaluated the relationship between dietary behavior and mortality among those with mobility limitations., Objective: To examine the association between dietary behavior and mortality in a national sample of American adults with mobility limitations., Methods: Data from the 2003-2006 National Health and Nutrition Examination Survey were utilized. Participants were followed through 2011. Based on self-report, analyzed participants included those with mobility limitations (N = 1369). Dietary behavior was assessed from the alternate healthy eating index (AHEI)., Results: For the sample, 108,010 person-months occurred with an all-cause mortality rate of 2.07 per 1000 person-months. Dietary behavior was associated with reduced all-cause mortality risk when expressed both as a continuous variable and binary variable (i.e., meeting dietary guidelines). With regard to the latter, and after adjustments, those meeting dietary guidelines (vs. not) had a 40% reduced hazard of all-cause death (HR = 0.60; 95% CI: 0.38-0.97; P = 0.03)., Conclusion: Among adults with mobility limitations, and thus, who unable to engage in sufficient physical activity, dietary behavior may have survival benefits., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background/aims: Duchenne Muscular Dystrophy (DMD) has childhood onset, primarily affects males, and is usually fatal before the age of 40 years. Previous studies have indicated that this X-linked condition is more prevalent in whites than in blacks, but those were based on active surveillance, and limited to smaller populations and younger ages., Methods: US death data were used to calculate mortality rates by race and ethnicity, with MD as either the underlying or multiple cause of death (MCD). Poisson approximation was used for confidence intervals; chi-square was used to compare rates., Results: From 2006 to 2015, there were 3,256 deaths in males <40 years with MD as MCD, and 71% of these were aged 15-29 years. For whites, the average annual death rate was 0.43/100,000, which was significantly higher (p < 0.0001) that that of blacks (0.28), American Indian/Alaska Natives (0.20), and Asian/Pacific Islanders (0.21). The rate for non-Hispanic whites (0.46) was significantly higher (p < 0.0001) than the rates for Hispanic whites (0.31), Hispanic blacks (0.07), and non-Hispanic blacks (0.29)., Conclusion: Since DMD is the primary cause of deaths in young males with MD, mortality rates are a reasonable proxy for the relative difference in racial prevalence. It appears that DMD is significantly more common in white males than in males of other races., (© 2018 S. Karger AG, Basel.)

Background: Following promising results to increase survival and reduce treatment burden in intracranial non-germinomatous germ cell tumors (NGGCTs), we conducted a European study using dose-intense chemotherapy followed by risk-adapted radiotherapy., Methods: All patients received 4 courses of cisplatin/etoposide/ifosfamide. Non-metastatic patients then received focal radiotherapy only (54 Gy); metastatic patients received 30 Gy craniospinal radiotherapy with 24 Gy boost to primary tumor and macroscopic metastatic sites., Results: Patients with localized malignant NGGCT (n = 116) demonstrated 5-year progression-free survival (PFS) and overall survival (OS) of 0.72 ± 0.04 and 0.82 ± 0.04, respectively. Primary tumor sites were: 67 pineal, 35 suprasellar, 5 bifocal, 9 others. One patient died postsurgery in clinical remission; 3 patients progressed during treatment and 27 (23%) relapsed afterward. Fourteen were local, 6 combined, and 7 distant relapses (outside radiation field). Seventeen of the 27 relapsed patients died of disease. Patients with metastatic disease (n = 33) demonstrated 5-year PFS and OS of 0.68 ± 0.09 and 0.75 ± 0.08, respectively; 1 patient died following progression on treatment and 9 (27%) relapsed afterward (5 local, 1 combined, 3 distant). Only one metastatic patient with recurrence was salvaged. Multivariate analysis identified diagnostic alpha-fetoprotein level (serum and/or cerebrospinal fluid level >1000 ng/mL, 19/149 patients, of whom 11 relapsed; P < 0.0003) and residual disease following treatment, including after second-look surgery (n = 52/145 evaluable patients, 26 relapsed; P = 0.0002) as significant prognostic indicators in this cohort., Conclusion: In localized malignant NGGCT, craniospinal radiotherapy could be avoided without increased relapses outside the radiotherapy field. Chemotherapy and craniospinal radiotherapy remain the gold standard for metastatic disease., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Objective: To evaluate the potential independent and combined associations of cognitive and mobility limitations on risk of all-cause mortality in a representative sample of the US older adult population who, at baseline, were free of cardiovascular and cerebrovascular disease., Patients and Methods: Data from the 1999 to 2002 National Health and Nutrition Examination Survey were used to identify 1852 adults (age, 60-85 years) with and without mobility and/or cognitive limitations. Hazard ratios (HRs) for mortality risk were calculated for 4 mutually exclusive groups: no limitation (group 1 as reference), mobility limitation only (group 2), cognitive limitation only (group 3), both cognitive and mobility limitations (group 4)., Results: Compared with group 1, the adjusted HRs (95% CI) for groups 2, 3, and 4 were 1.72 (1.24-2.38), 2.00 (1.37-2.91), and 2.18 (1.57-3.02), respectively. The mortality risk when comparing group 4 (HR, 2.18) with group 3 (HR, 2.00), however, was not statistically significant (P=.65). Similarly, the mortality risk when comparing group 4 (HR, 2.18) with group 2 (HR, 1.72) was not statistically significant (P=.16)., Conclusion: Although the highest mortality risk occurred in those with both limitations (group 4), this point estimate was not statistically significantly different when compared with those with cognitive or mobility limitations alone., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: Limited research has evaluated the individual and combined associations of physical activity (PA), cardiorespiratory fitness (CRF) and muscle strengthening activities (MSA) on generalized anxiety, panic and depressive symptoms. We evaluated this topic in a representative sample of young (20-39 years) adults, with considerations by sex., Methods: Data from the 1999-2004 National Health and Nutrition Examination Survey (N = 2088) were used. Generalized anxiety, panic and depressive symptoms were assessed via self-report as well as using the Generalized Anxiety Disorder, Panic Disorder, and Depressive Disorders modules of the automated version of the World Health Organization Composite International Diagnostic Interview (CIDI-Auto 2.1). PA and MSA were assessed via validated self-report questionnaires and CRF was determined via a submaximal treadmill-based test. An index variable was created summing the number (range = 0-3) of these parameters for each participant. For example, those meeting PA guidelines, MSA guidelines and having moderate-to-high CRF were classified as having an index score of 3., Results: MSA was not independently associated with generalized anxiety, panic and depressive symptoms, but those with higher levels of PA and CRF had a reduced odds of these symptoms (ranging from 40 to 46% reduced odds). Compared to those with an index score of 0, those with an index score of 1, 2, and 3, respectively, had a 39%, 54% and 71% reduced odds of having generalized anxiety, panic and depressive symptoms. Results were consistent across both sexes., Conclusion: PA and CRF, but not MSA, were independently associated with generalized anxiety, panic and depressive symptoms. There was evidence of an additive association between PA, CRF, and MSA on these symptoms.

Each year in the United States, about 4000 deaths are attributed to cervical cancer, and over 40,000 deaths are attributed to breast cancer (U.S. Cancer Statistics Working Group, 2015). The purpose of this study was to identify predictors of full, partial, and no screening for breast and cervical cancer among women with and without intellectual disability (ID) who are within the age group for screening recommended by the U.S. Preventive Service Task Force (USPSTF), while accounting for changes in recommendations over the study period. Women with ID and an age matched comparison group of women without ID were identified using merged South Carolina Medicaid and Medicare files from 2000 to 2010. The sample consisted of 9406 and 16,806 women for mammography screening and Papanicolaou (Pap) testing adherence, respectively. We estimated multinomial logistic regression models and determined that women with ID were significantly less likely than women without ID to be fully adherent compared to no screening with mammography recommendations (adjusted odds ratio [AOR]: 0.63, 95% confidence interval [CI] 0.55-0.72), and Pap testing recommendations (AOR: 0.17, 95% CI 0.16-0.19). For the 70% of women with ID for whom we had residential information, those who lived in a group home, medical facility, or supervised community living setting were more likely to be fully adherent with both preventive services than those living alone or with family members. For both outcomes, women residing in a supervised nonmedical community living setting had the highest odds of full adherence, adjusting for other covariates., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Colorectal cancer (CRC) is the second leading cause of cancer mortality in the U.S.; however, if the population aged 50 years or older received routine screening, approximately 60% of these deaths could be eliminated. This study investigates whether adults, aged 50-75 years, with one of three disabilities (blind/low vision [BLV], intellectual disability [ID], spinal cord injury [SCI]) receive CRC screening at rates equivalent to adults without the three disabilities, by accounting for combinations of recommended CRC screenings during a 10-year period (colonoscopy, sigmoidoscopy, fecal occult blood test)., Methods: South Carolina Medicaid and Medicare, State Health Plan, and hospital discharge data (2000-2009) were analyzed (2013-2015) to estimate the proportion of adherence to and adjusted odds of CRC screening over time among adults with one of the three disabilities, BLV, ID, or SCI, versus adults without these conditions., Results: The estimated proportion of adults who adhere to changing recommendations over time was lower for adults with ID (34.32%) or SCI (44.14%) compared with those without these disabilities (48.48%). All three case groups had significantly lower AORs of adherence versus those without (BLV: AOR=0.88, 95% CI=0.80, 0.96; ID: AOR=0.55, 95% CI=0.52, 0.59; SCI: AOR=0.88, 95% CI=0.82, 0.95)., Conclusions: In this study, adults with BLV, ID, or SCI were less likely to receive and adhere to CRC screening recommendations than those without these disabilities. This method provides a thorough evaluation of adherence to CRC screening by considering levels of adherence during each month of Medicaid or Medicare coverage., (Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Compared to aerobic-based physical activity, less research has evaluated the effects of muscle-strengthening physical activity (MSPA) on mortality. Additionally, limited research has evaluated this among adults with mobility limitations, which was this study's purpose. Data from the 2003-2006 NHANES, with follow-up through 2011, were used (analyzed in 2016). MSPA was assessed via self-report, with all-cause, CVD-specific, and cancer-specific mortality assessed as the outcome variables. Analyses were limited to adults with mobility limitations (N=1411), assessed via a validated questionnaire. After adjustments, those meeting MSPA guidelines (vs. not) had a 38% reduced hazard of all-cause death (HR=0.62; 95% CI: 0.41-0.95). Results were similar for CVD-specific mortality (HR=0.46; 95% CI: 0.23-0.97) and cancer-specific mortality (HR=0.27; 95% CI: 0.06-1.20). Meeting MSPA guidelines is associated with reduced all-cause and cause-specific mortality among adults with mobility limitations. This is an encouraging observation as adults with mobility limitations may be unable to engage in sufficient amounts of aerobic-based physical activity. Thus, promotion of MSPA among this population may be of critical importance., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To develop a set of accurate 2D models of compressed breasts undergoing mammography or breast tomosynthesis, based on objective analysis, to accurately characterize mammograms with few linearly independent parameters, and to generate novel clinically realistic paired cranio-caudal (CC) and medio-lateral oblique (MLO) views of the breast., Methods: We seek to improve on an existing model of compressed breasts by overcoming detector size bias, removing the nipple and non-mammary tissue, pairing the CC and MLO views from a single breast, and incorporating the pectoralis major muscle contour into the model. The outer breast shapes in 931 paired CC and MLO mammograms were automatically detected with an in-house developed segmentation algorithm. From these shapes three generic models (CC-only, MLO-only, and joint CC/MLO) with linearly independent components were constructed via principal component analysis (PCA). The ability of the models to represent mammograms not used for PCA was tested via leave-one-out cross-validation, by measuring the average distance error (ADE)., Results: The individual models based on six components were found to depict breast shapes with accuracy (mean ADE-CC = 0.81 mm, ADE-MLO = 1.64 mm, ADE-Pectoralis = 1.61 mm), outperforming the joint CC/MLO model (P ≤ 0.001). The joint model based on 12 principal components contains 99.5% of the total variance of the data, and can be used to generate new clinically realistic paired CC and MLO breast shapes. This is achieved by generating random sets of 12 principal components, following the Gaussian distributions of the histograms of each component, which were obtained from the component values determined from the images in the mammography database used., Conclusion: Our joint CC/MLO model can successfully generate paired CC and MLO view shapes of the same simulated breast, while the individual models can be used to represent with high accuracy clinical acquired mammograms with a small set of parameters. This is the first step toward objective 3D compressed breast models, useful for dosimetry and scatter correction research, among other applications., (© 2017 American Association of Physicists in Medicine.)

Purpose: To investigate whether women with visual impairment (VI) receive mammography and Pap testing to the same extent as women without VI among the low income population or those aged 65+ years., Methods: We analyzed the 2000-2010 Medicaid and Medicare data for South Carolina women. Women with VI were identified on the basis of a qualifying diagnosis in billing data. We assessed women's adherence (full adherence, partial adherence and no screening) with two United States Preventive Services Task Force (USPSTF) cancer screening recommendations (mammography and Pap testing) throughout the course of the study period. Multinomial models were estimated to describe the association between VI and adherence to the two cancer screening recommendations., Results: A total of 1308 women with VI and 2635 women without VI (mammography) and 1247 women with VI and 2483 women without VI (Pap testing) were included in the study. After adjusting for age, number of eligible enrollment years, insurance type (Medicare, Medicaid, or both), urban or rural residence and having a hysterectomy, women with VI were significantly less likely than those without VI to have full adherence to mammography recommendations (adjusted odds ratio, OR, 0.49, 95% confidence interval, CI, 0.40-0.60) and Pap testing recommendations (adjusted OR 0.32, 95% CI 0.27-0.39)., Conclusion: We used a new approach to investigate adherence to USPSTF recommendations, accounting for both full and partial adherence. This approach identified disparities in mammography and Pap testing for women with VI. The findings of this study should facilitate the development of effective interventions to increase screening among women with VI.

Introduction: Chronic inflammation is associated with increased risk of cancer, cardiovascular disease (CVD), and diabetes. The role of pro-inflammatory diet in the risk of cancer mortality and CVD mortality in prediabetics is unclear. We examined the relationship between diet-associated inflammation, as measured by dietary inflammatory index (DII) score, and mortality, with special focus on prediabetics., Methods: This prospective cohort study used data from the Third National Health and Nutrition Examination Survey (NHANES III). We categorized 13,280 eligible participants, ages 20-90 years, according to glycosylated hemoglobin (HgbA1c) level and identified 2681 with prediabetes, defined as a glycosylated hemoglobin percentage of 5.7-6.4. Computation of DII scores and all statistical analyses were conducted in 2015. The DII was computed based on baseline dietary intake assessed using 24-h dietary recalls (1988-1994). Mortality was determined from the National Death Index records through 2006. Over follow-up ranging between 135 and 168 person-months, a total of 3016 deaths were identified, including 676 cancer, 192 lung cancer, 176 digestive-tract cancer, and 1328 CVD deaths. Cox proportional hazard regression was used to estimate hazard ratios., Results: The prevalence of prediabetes was 20.19 %. After controlling for age, sex, race, HgbA1c, current smoking, physical activity, BMI, and systolic blood pressure, DII scores in tertile III (vs tertile I) was significantly associated with mortality from all causes (HR 1.39, 95 % CI 1.13, 1.72), CVD (HR 1.44, 95 % CI 1.02, 2.04), all cancers (HR 2.02, 95 % CI 1.27, 3.21), and digestive-tract cancer (HR 2.89, 95 % CI 1.08, 7.71). Findings for lung cancer (HR 2.01, 95 % CI 0.93, 4.34) suggested a likely effect. These results were moderately enhanced after additional adjustment for serum low-density lipoprotein and triglyceride and following eliminating deaths during the first year., Conclusions: A pro-inflammatory diet, as indicated by higher DII scores, is associated with an increased risk of all-cause, CVD, all-cancer, and digestive-tract cancer mortality among prediabetic subjects.

Background: Administrative records from insurance and hospital discharge data sources are important public health tools to conduct passive surveillance of disease in populations. Identifying rare but catastrophic conditions is a challenge since approaches for maximizing valid case detection are not firmly established., Objective: The purpose of our study was to explore a number of algorithms in which International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes and other administrative variables could be used to identify cases of muscular dystrophy (MD)., Methods: We used active surveillance to identify possible cases of MD in medical practices in neurology, genetics, and orthopedics in 5 urban South Carolina counties and to identify the cases that had diagnostic support (ie, true cases). We then developed an algorithm to identify cases based on a combination of ICD-9-CM codes and administrative variables from a public (Medicaid) and private insurer claims-based system and a statewide hospital discharge dataset (passive surveillance). Cases of all types of MD and those with Duchenne or Becker MD (DBMD) that were common to both surveillance systems were examined to identify the most specific administrative variables for ascertainment of true cases., Results: Passive statewide surveillance identified 3235 possible cases with MD in the state, and active surveillance identified 2057 possible cases in 5 actively surveilled counties that included 2 large metropolitan areas where many people seek medical care. There were 537 common cases found in both the active and passive systems, and 260 (48.4%) were confirmed by active surveillance to be true cases. Of the 260 confirmed cases, 70 (26.9%) were recorded as DBMD., Conclusions: Accuracy of finding a true case in a passive surveillance system was improved substantially when specific diagnosis codes, number of times a code was used, age of the patient, and specialty provider variables were used., Competing Interests: Conflicts of Interest: None declared., (©Michael G Smith, Julie Royer, Joshua R Mann, Suzanne McDermott. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 12.01.2017.)

Context: Women with spinal cord injury (SCI) may face barriers that result in disparities in receipt of recommended mammography and Papanicolaou testing., Setting: South Carolina., Participants: South Carolina women with SCI were identified using International Classification of Diseases codes in 2000-2010 Medicaid and Medicare billing data., Outcome Measures: Receipt of mammography and Pap testing was determined using procedure billing codes. Partial proportional odds models were estimated to examine the association between SCI and adherence with screening recommendations from the United States Preventive Services Task Force. Each individual's screening experience was classified as full adherence, partial adherence, or no screening., Results: The cohort for mammography consisted of 3,173 women with SCI and 6,433 comparison women without SCI. The cohort for Pap testing consisted 5,025 women with SCI and 9,538 comparison women. Women with SCI were less likely to have full adherence with mammography recommendations (aOR = 0.69, 95% CI 0.64, 0.76) and Pap test recommendations (aOR = 0.53, 95% CI 0.49, 0.57). They were more likely to have no mammography screening (aOR = 1.44, 95% CI 1.33, 1.57) and no Pap testing (aOR = 1.89, 95% CI 1.77, 2.03) than women without SCI., Conclusion: Using longitudinal data with multiple outcome levels, women with SCI were less likely to be fully adherent with receipt of recommended breast and cervical cancer screenings and more likely to have no screenings during the eligible years when compared to women without SCI.

Background: Receiving recommended services for patients with diabetes is associated with improved outcomes and reduced morbidity. People with diabetes who also have a condition associated with disability represent one group that is at risk for health disparities., Objective: To examine service utilization among persons with selected disabling conditions and diabetes, compared to those without., Methods: 2007-2012 Medical Expenditure Panel Survey Full-Year Consolidated files, medical conditions files, and the 1996-2012 pooled linkage files were merged for this analysis. This analysis focused on five selected conditions that are associated with disability: Visual impairment and blindness, spinal cord injury, intellectual disability, multiple sclerosis, and muscular dystrophy. Unadjusted and adjusted rates of receipt estimated using various multivariable regression techniques., Results: The proportion with diabetes was higher among those with a selected condition (12.1%) than without (7.1%). Respondents with a selected condition were more likely to have a foot exam; for all other services, the rate of receipt across the two groups was similar. Controlling for other factors, having a selected condition was only a significant factor for foot exams (AOR 1.49, 1.07-2.07). Different factors, but not having a selected condition, were associated with the receipt of each additional service., Conclusions: In general, individuals received the full complement of recommended diabetes management services at a low rate, whether or not they had one of the selected disabling conditions. The comparison results indicated few disparities in diabetes management services among those with selected conditions compared those without these conditions, excepting foot exams, which were more common in the group with a disabling condition., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: To assess the relationship between any systemic antibiotic prescription within the first year of life and the presence of an ICD-9-CM diagnosis code for food allergy (FA)., Methods: This was a matched case-control study conducted using South Carolina Medicaid administrative data. FA cases born between 2007 and 2009 were matched to controls without FA on birth month/year, sex, race/ethnicity. Conditional logistic regression was used to model the adjusted odds ratio (aOR) of FA diagnosis. All models were adjusted for presence of asthma, wheeze, or atopic dermatitis., Results: A total of 1504 cases and 5995 controls were identified. Receipt of an antibiotic prescription within the initial 12 months of life was associated with FA diagnosis in unadjusted and adjusted models (aOR 1.21; 95 % CI 1.06-1.39). Compared to children with no antibiotic prescriptions, a linear increase in the aOR was seen with increasing antibiotic prescriptions. Children receiving five or more (aOR 1.64; 95 % CI 1.31-2.05) antibiotic prescriptions were significantly associated with FA diagnosis. The strongest association was noted among recipients of cephalosporin and sulfonamide antibiotics in both unadjusted and adjusted models., Conclusions: Receipt of antibiotic prescription in the first year of life is associated with FA diagnosis code in young children after controlling for common covariates. Multiple antibiotic prescriptions are more strongly associated with increases in the odds of FA diagnosis.

Purpose: We have previously demonstrated the protective effect of bone marrow stem cell (BMSC)-conditioned medium in retinal ischemic injury. We hypothesized here that hypoxic preconditioning of stem cells significantly enhances the neuroprotective effect of the conditioned medium and thereby augments the protective effect in ischemic retina., Methods: Rats were subjected to retinal ischemia by increasing intraocular pressure to 130 to 135 mm Hg for 55 minutes. Hypoxic-preconditioned, hypoxic unconditioned, or normoxic medium was injected into the vitreous 24 hours after ischemia ended. Recovery was assessed 7 days after injections by comparing electroretinography measurements, histologic examination, and apoptosis (TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay). To compare proteins secreted into the medium in the groups and the effect of hypoxic exposure, we used rat cytokine arrays., Results: Eyes injected with hypoxic BMSC-conditioned medium 24 hours after ischemia demonstrated significantly enhanced return of retinal function, decreased retinal ganglion cell layer loss, and attenuated apoptosis compared to those administered normoxic or hypoxic unconditioned medium. Hypoxic-preconditioned medium had 21 significantly increased protein levels compared to normoxic medium., Conclusions: The medium from hypoxic-preconditioned BMSCs robustly restored retinal function and prevented cell loss after ischemia when injected 24 hours after ischemia. The protective effect was even more pronounced than in our previous studies of normoxic conditioned medium. Prosurvival signals triggered by the secretome may play a role in this neuroprotective effect.

Objective: To identify risk factors among children with unknown cause intellectual disability (ID) and to estimate the population-attributable risk (PAR) associated with these factors., Methods: This was a retrospective cohort study of maternal and child pairs born between 2004 and 2010 in South Carolina, and information was obtained from Medicaid billing records, birth certificates, and other administrative data. The data included 123,922 children and logistic generalized estimating equations (GEE) regression models were used to estimate the association of maternal risk factors and ID. We estimated models with and without birth weight as a covariate, since low birth weight is known to be a mediator of the association between some risk factors and ID in children., Results: The prevalence of ID in the children was 3.85% and the associations between risk factors and ID were similar for female and male children. We found that the odds of having ID were increased if a child's mother had a diagnosis of major depression; for male children, the odds ratio (OR) was 1.34 (95% confidence interval [CI] 1.14-1.59, PAR 2.17%); and for females, the OR was 1.59 (95% CI 1.30-1.95, PAR 4.70%). The odds of having ID were also increased for children of women with bipolar disorder (males - OR 1.95, 95% CI 1.53-2.48, PAR 2.85%; females - OR 1.63, 95% CI 1.20-2.22, PAR 2.05%)., Conclusions: Major maternal depression and bipolar disorder were each significantly associated with the odds of ID in children, each accounting for approximately 2-5% of the PAR, when controlling for covariates.

The authors investigated 48 deaths (7% death rate) among 690 adolescents and young adults with spina bifida in South Carolina during 2000-2010. The authors used Medicaid and other administrative data and a retrospective cohort design that included people with spina bifida identified using ICD-9 codes. Cox regression models with time-dependent and time-invariant covariates, and Kaplan-Meier survival curves were constructed. The authors found that 21.4% of the study group had a skin ulcer during the study period and individuals with skin ulcers had significantly higher mortality than those without ulcers (P < .0001). People who had their first skin ulcer during adolescence had higher mortality than those who had the first skin ulcer during young adulthood (P = .0002; hazard ratio = 10.70, 95% confidence interval for hazard ratio: 3.01, 38.00) and those without skin ulcers, controlling for other covariates. This study showed that age at which individuals first had a skin ulcer was associated with mortality., (© The Author(s) 2015.)

This article critically examines federal, state and facility-level policies, as well as clinical practice guidelines regarding postnatal depression in Mexico. Thirteen documents including national health plans, national action plans, federal and state laws and regulations, clinical practice guidelines, and public-sector healthcare facility policies were collected and evaluated according to whether they included a statement of intent and/or actions related to the care of women at risk for or experiencing postnatal depression. While postnatal depression is included in several policies in Mexico, it is not addressed in ways that guide actions to manage postnatal depression. Specific direction on postnatal depression in policies would bridge a gap in maternal mental healthcare given that medication, treatment, and timing of interventions is unique in the postpartum context.

Natural antisense transcripts (NATs) are involved in cellular development and regulatory processes. Multiple NATs at the Sox4 gene locus are spatiotemporally regulated throughout murine cerebral corticogenesis. In the study, we evaluated the potential functional role of Sox4 NATs at Sox4 gene locus. We demonstrated Sox4 sense and NATs formed dsRNA aggregates in the cytoplasm of brain cells. Over expression of Sox4 NATs in NIH/3T3 cells generally did not alter the level of Sox4 mRNA expression or protein translation. Upregulation of a Sox4 NAT known as Sox4ot1 led to the production of a novel small RNA, Sox4&#95;sir3. Its biogenesis is Dicer1-dependent and has characteristics resemble piRNA. Expression of Sox4&#95;sir3 was observed in the marginal and germinative zones of the developing and postnatal brains suggesting a potential role in regulating neurogenesis. We proposed that Sox4 sense-NATs serve as Dicer1-dependent templates to produce a novel endo-siRNA- or piRNA-like Sox4&#95;sir3., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

SRY (Sex Determining Region Y)-Box 4 or Sox4 is an important regulator of the pan-neuronal gene expression during post-mitotic cell differentiation within the mammalian brain. Sox4 gene locus has been previously characterized with multiple sense and overlapping natural antisense transcripts [1], [2]. Here we provide accompanying data on various analyses performed and described in Ling et al. [2]. The data include a detail description of various features found at Sox4 gene locus, additional experimental data derived from RNA-Fluorescence in situ Hybridization (RNA-FISH), Western blotting, strand-specific reverse-transcription quantitative polymerase chain reaction (RT-qPCR), gain-of-function and in situ hybridization (ISH) experiments. All the additional data provided here support the existence of an endogenous small interfering- or PIWI interacting-like small RNA known as Sox4&#95;sir3, which origin was found within the overlapping region consisting of a sense and a natural antisense transcript known as Sox4ot1.

Objective: To investigate the hepatitis B virus (HBV) seroconversion rate among health sciences students., Participants: The study included pharmacy, doctor of nursing, and medical students over 18 years of age enrolled at the University of South Carolina between 2007 and 2011., Methods: The primary end point was HBV seroconversion rates among students at the initial reporting period. Seroconversion was defined as hepatitis B surface antibody (anti-HBs) level greater than or equal to 10 mIU/mL. Multivariate regression analysis was used to determine predictive factors of seroconversion., Results: Of 777 records, data were available for 709 students. An 83.9% seroconversion rate was observed after a mean of 10 years between vaccine receipt and anti-HBs evaluation. Students with incomplete HBV vaccine series and longer time between initial series and evaluation were less likely to exhibit antibody response., Conclusions: These data highlight the importance of assessment and documentation of HBV vaccination series among health sciences students prior to direct patient care activities.

In addition to being a hallmark at active genes, histone variant H3.3 is deposited by ATRX at repressive chromatin regions, including the telomeres. It is unclear how H3.3 promotes heterochromatin assembly. We show that H3.3 is targeted for K9 trimethylation to establish a heterochromatic state enriched in trimethylated H3.3K9 at telomeres. In H3f3a(-/-) and H3f3b(-/-) mouse embryonic stem cells (ESCs), H3.3 deficiency results in reduced levels of H3K9me3, H4K20me3 and ATRX at telomeres. The H3f3b(-/-) cells show increased levels of telomeric damage and sister chromatid exchange (t-SCE) activity when telomeres are compromised by treatment with a G-quadruplex (G4) DNA binding ligand or by ASF1 depletion. Overexpression of wild-type H3.3 (but not a H3.3K9 mutant) in H3f3b(-/-) cells increases H3K9 trimethylation level at telomeres and represses t-SCE activity induced by a G4 ligand. This study demonstrates the importance of H3.3K9 trimethylation in heterochromatin formation at telomeres. It provides insights into H3.3 function in maintaining integrity of mammalian constitutive heterochromatin, adding to its role in mediating transcription memory in the genome., (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Introduction: Transitioning from adolescence to adulthood can be problematic for individuals with rare disabilities such as muscular dystrophy (MD)., Methods: We identified a cohort of 220 individuals with MD and 440 matched comparison individuals and measured emergency room (ER) and inpatient (IP) encounters for the years 2000 through 2010, using all-payer hospital discharge uniform billing data. We compared ER and IP use rates for people with and without MD, and for 15-19-year-olds with MD to 20-24-year-olds with MD., Results: ER and IP use rates were significantly higher among individuals with MD than the comparison group. In addition, ER and IP use rates were significantly higher in the 20-24-year age group than in the 15-19-year group., Conclusions: Additional research is needed to determine whether increased ER and IP use in young adults is attributable to difficulties in healthcare transition versus increased disease severity., (© 2015 Wiley Periodicals, Inc.)

Aqueous two-phase systems (ATPS) provide a mild environment for the partition and separation of cells. We report a combined experimental and theoretical study on the effect of interfacial tension of polymeric ATPS on the partitioning of cells between two phases and their interface. Two-phase systems are generated using polyethylene glycol and dextran of specific properties as phase-forming polymers and culture media as the solvent component. Ultralow interfacial tensions of the solutions are precisely measured using an axisymmetric drop shape analysis method. Partition experiments show that two-phase systems with an interfacial tension of 30 μJ/m(2) result in distribution of majority of cells to the bottom dextran phase. An increase in the interfacial tension results in a distribution of cells toward the interface. An independent cancer cell spheroid formation assay confirms these observations: a drop of the dextran phase containing cancer cells is dispensed into the immersion polyethylene glycol phase to form a cell-containing drop. Only at very small interfacial tensions do cells remain within the drop to aggregate into a spheroid. We perform a thermodynamic modeling of cell partition to determine variations of free energy associated with displacement of cells in ATPS with respect to the ultralow interfacial tensions. This modeling corroborates with the experimental results and demonstrates that at the smallest interfacial tension of 30 μJ/m(2), the free energy is a minimum with cells in the bottom phase. Increasing the interfacial tension shifts the minimum energy and partition of cells toward the interfacial region of the two aqueous phases. Examining differences in the partition behavior and minimum free energy modeling of A431.H9 cancer cells and mouse embryonic stem cells shows that the surface properties of cells further modulate partition in ATPS. This combined approach provides a fundamental understanding of interfacial tension role on cell partition in ATPS and a framework for future studies.

Runt domain transcription factor 3 (RUNX3) is widely regarded as a tumour-suppressor gene inactivated by DNA hypermethylation of its canonical CpG (cytidine-phosphate-guanidine) island (CGI) promoter in gastric cancer (GC). Absence of RUNX3 expression from normal gastric epithelial cells (GECs), the progenitors to GC, coupled with frequent RUNX3 overexpression in GC progression, challenge this longstanding paradigm. However, epigenetic models to better describe RUNX3 deregulation in GC have not emerged. Here, we identify lineage-specific DNA methylation at an alternate, non-CGI promoter (P1) as a new mechanism of RUNX3 epigenetic control. In normal GECs, P1 was hypermethylated and repressed, whereas in immune lineages P1 was hypomethylated and widely expressed. In human GC development, we detected aberrant P1 hypomethylation signatures associated with the early inflammatory, preneoplastic and tumour stages. Aberrant P1 hypomethylation was fully recapitulated in mouse models of gastric inflammation and tumorigenesis. Cell sorting showed that P1 hypomethylation reflects altered cell-type composition of the gastric epithelium/tumour microenvironment caused by immune cell recruitment, not methylation loss. Finally, via long-term culture of gastric tumour epithelium, we revealed that de novo methylation of the RUNX3 canonical CGI promoter is a bystander effect of oncogenic immortalization and not likely causal in GC pathogenesis as previously argued. We propose a new model of RUNX3 epigenetic control in cancer, based on immune-specific, non-CGI promoter hypomethylation. This novel epigenetic signature may have utility in early detection of GC and possibly other epithelial cancers with premalignant immune involvement.

Objective: To compare emergency room (ER) and inpatient hospital (IP) use rates for persons with spina bifida (SB) to peers without SB, when transition from pediatric to adult health care is likely to occur; and to analyze those ER and IP rates by age, race, socioeconomic status, gender, and type of residential area., Design: A retrospective cohort study., Setting: Secondary data analysis in South Carolina., Participants: We studied individuals who were between 15 and 24 years old and enrolled in the State Health Plan (SHP) or state Medicaid during the 2000-2010 study period., Methods: Individuals with SB were identified using ICD-9 billing codes (741.0, 741.9) in SHP, Medicaid, and hospital uniform billing (UB) data. ER and IP encounters were identified using UB data. Multivariable Generalized Estimating Equation (GEE) Poisson models were estimated to compare rates of ER and IP use among the SB group to the comparison group., Main Outcome Measures: Total ER rate and IP rate, in addition to cause-specific rates for ambulatory care sensitive conditions (ACSC) and other condition categories., Results: We found higher rates of ER and IP use in persons with SB compared to the control group. Among individuals with SB, young adults (those 20-24 years old) had higher rates of ER use due to all ACSC (P = .023), other ACSC (P = .04), and urinary tract infections (UTI; P = .002) compared to adolescents (those 15-19 years old)., Conclusions: Young adulthood is associated with increased ER use overall, as well as in specific condition categories (most notably UTI) in individuals 15-24 years old with SB. This association may be indicative of changing healthcare access as people with SB move from adolescent to adult health care, and/or physiologic changes during the age range studied., (Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

We compared hospital encounters between adolescents and young adults with fragile X syndrome (FXS) to peers with intellectual disability (ID) from other causes, autism spectrum disorder (ASD), and a comparison group without these conditions matched by gender, age, and insurance coverage. Those with FXS, ASD, or ID were more likely to have had hospital encounters. In terms of age groups, we found mental illness hospitalizations decreased during adulthood as compared to adolescence for those with FXS, and we found that for conditions unrelated to FXS (e.g., respiratory, genitourinary, gastroenteritis, and pneumonia) adolescents had higher rates of hospitalization compared to their peers with FXS, ID, or ASD. We analyzed epilepsy, common among people with FXS and designated as an ambulatory care sensitive condition that can be treated outside the hospital, and found that people with FXS, ID, and ASD had higher odds of hospitalization due to epilepsy in both age groups than did the comparison group.

In this article we describe the knowledge frameworks that 61 physicians, nurses, social workers, and psychologists from five public-sector health care facilities in Mexico used to conceptualize postpartum depression. We also demonstrate how providers applied social and behavioral antecedents in their conceptualizations of postpartum depression. Using grounded theory, we identify two frameworks that providers used to conceptualize postpartum depression: biochemical and adjustment. We highlight an emerging model of the function of social and behavioral antecedents within the frameworks, as well as the representation of postpartum depression by symptoms of distress and the perception among providers that these symptoms affected responsibilities associated with motherhood. The results provide a foundation for future study of how providers' conceptualizations of postpartum depression might affect detection and treatment practices and might be useful in the development of training materials to enhance the quality of care for women who experience any form of distress in the postpartum period., (© The Author(s) 2014.)

Human ALT cancers show high mutation rates in ATRX and DAXX. Although it is well known that the absence of ATRX/DAXX disrupts H3.3 deposition at heterochromatin, its impact on H3.3 deposition and post-translational modification in the global genome remains unclear. Here, we explore the dynamics of phosphorylated H3.3 serine 31 (H3.3S31ph) in human ALT cancer cells. While H3.3S31ph is found only at pericentric satellite DNA repeats during mitosis in most somatic human cells, a high level of H3.3S31ph is detected on the entire chromosome in ALT cells, attributable to an elevated CHK1 activity in these cells. Drug inhibition of CHK1 activity during mitosis and expression of mutant H3.3S31A in these ALT cells result in a decrease in H3.3S31ph levels accompanied with increased levels of phosphorylated H2AX serine 139 on chromosome arms and at the telomeres. Furthermore, the inhibition of CHK1 activity in these cells also reduces cell viability. Our findings suggest a novel role of CHK1 as an H3.3S31 kinase, and that CHK1-mediated H3.3S31ph plays an important role in the maintenance of chromatin integrity and cell survival in ALT cancer cells., (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The condensin complex plays a key role in organizing mitotic chromosomes. In vertebrates, there are two condensin complexes that have independent and cooperative roles in folding mitotic chromosomes. In this study, we dissect the role of a putative Cdk1 site on the condensin II subunit CAP-D3 in chicken DT40 cells. This conserved site has been shown to activate condensin II during prophase in human cells, and facilitate further phosphorylation by polo-like kinase I. We examined the functional significance of this phosphorylation mark by mutating the orthologous site of CAP-D3 (CAP-D3(T1403A)) in chicken DT40 cells. We show that this mutation is a gain of function mutant in chicken cells; it disrupts prophase, results in a dramatic shortening of the mitotic chromosome axis, and leads to abnormal INCENP localization. Our results imply phosphorylation of CAP-D3 acts to limit condensin II binding onto mitotic chromosomes. We present the first in vivo example that alters the ratio of condensin I:II on mitotic chromosomes. Our results demonstrate this ratio is a critical determinant in shaping mitotic chromosomes., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

There is a need for research that focuses on the correlation between self-perceived quality of life (QoL) and the health outcomes of adolescents with disability transitioning to adulthood. To better understand the transition experience of adolescents and young adults with disability, we developed a questionnaire to assess the impact of disability on QoL. We recruited 174 participants who were 15-24 years old and diagnosed with Fragile X syndrome (FXS), spina bifida (SB) or muscular dystrophy (MD) and conducted an exploratory factor analysis to identify factors that characterize QoL. Five factors emerged: emotional health, physical health, independence, activity limitation, and community participation. To validate the tool, we linked medical claims and other administrative data records and examined the association of the factor scores with health care utilization and found the questionnaire can be utilized among diverse groups of young people with disability., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Histones package DNA and regulate epigenetic states. For the latter, probably the most important histone is H3. Mammals have three near-identical H3 isoforms: canonical H3.1 and H3.2, and the replication-independent variant H3.3. This variant can accumulate in slowly dividing somatic cells, replacing canonical H3. Some replication-independent histones, through their ability to incorporate outside S-phase, are functionally important in the very slowly dividing mammalian germ line. Much remains to be learned of H3.3 functions in germ cell development. Histone H3.3 presents a unique genetic paradigm in that two conventional intron-containing genes encode the identical protein. Here, we present a comprehensive analysis of the developmental effects of null mutations in each of these genes. H3f3a mutants were viable to adulthood. Females were fertile, while males were subfertile with dysmorphic spermatozoa. H3f3b mutants were growth-deficient, dying at birth. H3f3b heterozygotes were also growth-deficient, with males being sterile because of arrest of round spermatids. This sterility was not accompanied by abnormalities in sex chromosome inactivation in meiosis I. Conditional ablation of H3f3b at the beginning of folliculogenesis resulted in zygote cleavage failure, establishing H3f3b as a maternal-effect gene, and revealing a requirement for H3.3 in the first mitosis. Simultaneous ablation of H3f3a and H3f3b in folliculogenesis resulted in early primary oocyte death, demonstrating a crucial role for H3.3 in oogenesis. These findings reveal a heavy reliance on H3.3 for growth, gametogenesis, and fertilization, identifying developmental processes that are particularly susceptible to H3.3 deficiency. They also reveal partial redundancy in function of H3f3a and H3f3b, with the latter gene being generally the most important.

Histone variants can incorporate into the nucleosome outside of S-phase. Some are known to play important roles in mammalian germ cell development, this cell lineage being characterized by long phases of quiescence, a protracted meiotic phase, and genome-wide epigenetic reformatting events. The best known example of such an event is the global-scale erasure of DNA methylation in sexually indifferent primordial germ cells, then its re-establishment in fetal prospermatogonia and growing oocytes. Histone H3 and its post-translationally modified forms provide important waypoints in the establishment of epigenetic states. Using mass spectrometry and immunoblotting, we show that the H3.3 replacement variant is present at an unusually high amount in mouse prospermatogonia at the peak stage of global DNA methylation re-establishment. We speculate that H3.3 facilitates this process through achieving a greater level of accessibility of chromatin modifiers to DNA.

We conducted a retrospective cohort study to investigate the association between prepregnancy obesity in women and risk of cerebral palsy and epilepsy in their children using data from the South Carolina Medicaid program. The cohort included 83,901 maternal-child pairs; 100 cases of cerebral palsy were initially identified, followed by 53 cases that had at least 2 cerebral palsy diagnoses. For confirmed epilepsy, diagnosed on at least 5 occasions or by more than 1 provider, 83,472 observations were included with 338 cases. There was no association between maternal body mass index and risk of childhood epilepsy. A significant association between increasing maternal body mass index and any diagnosis of cerebral palsy was found, and morbid obesity was associated with increased risk of any and confirmed cerebral palsy. In conclusion, there appears to be an association of maternal body mass index with cerebral palsy, but there is no evidence to support an association with epilepsy., (© The Author(s) 2013.)

Background: For people with muscular dystrophy (MD) health care access is crucial and utilization is expected to be high. A multidisciplinary approach is needed for optimal management of symptoms of this rare condition. Regular primary care, specialty care, therapy, and medicine use can improve quality of care and reduce need for emergency treatment and hospitalization. We analyzed health insurance and administrative data to test for racial disparities in regular care use among teenagers and young adults with MD., Methods: We used South Carolina Medicaid and other administrative data for individuals aged 15-24 years to determine annual health care utilization patterns for individuals with MD by race. We studied adolescents and young adults with MD because this age group represents a time when the condition is typically intensifying and the transition from pediatric to adult care is expected. We used Generalized Estimating Equation models to analyze longitudinal utilization data conditional on other factors that may lead to utilization differences., Results: Race is correlated with health care utilization among adolescents and young adults with MD. Blacks have lower overall utilization, and less primary care, therapy, and specialist care use but higher incidence of hospitalization and emergency treatment use compared with whites and also to other races. The most striking disparity was the use of outpatient services. Blacks utilized these services 50% less compared with whites and 70% less compared with others. Even in regression analysis, where we take into account individual unobserved factors and allow clustering at the individual level, these differences remained and were in most cases statistically significant., Conclusions: Our results indicate that there are differences in health care utilization by race even when individuals have access to the same health care benefits. This means simply offering coverage to individuals with MD may not be sufficient in eliminating health disparities. Future studies will be needed to examine other possible sources of these racial disparities, such as resource awareness, health knowledge, or access barriers such as transportation.

Aqueous solutions of different polymers can separate and form aqueous two-phase systems (ATPS). ATPS provide an aqueous, biocompatible, and mild environment for separation and fractionation of biomolecules. The interfacial tension between the two aqueous phases plays a major role in ATPS-mediated partition of biomolecules. Because of the structure of the two aqueous phases, the interfacial tensions between the phases can be 3-4 orders of magnitude smaller than conventional fluid-liquid systems: ∼1-100 μJ/m(2) for ATPS compared to ∼72 mJ/m(2) for the water-vapor interface. This poses a major challenge for the experimental measurements of reproducible interfacial tension data for these systems. We address the need for precise determination of ultralow interfacial tensions by systematically studying a series of polymeric ATPS comprising of polyethylene glycol (PEG) and dextran (DEX) as the phase-forming polymers. Sessile and pendant drops of the denser DEX phase are formed within the immersion PEG phase. An axisymmetric drop shape analysis (ADSA) is used to determine interfacial tensions of eight different ATPS. Specific criteria are used to reproducibly determine ultralow interfacial tensions of the ATPS from pendant and sessile drops. Importantly, for a given ATPS, pendant drop and sessile drop experiments return values within 0.001 mJ/m(2) indicating reliability of our measurements. Then, the pendant drop technique is used to measure interfacial tensions of all eight ATPS. Our measured values range from 0.012 ± 0.001 mJ/m(2) to 0.381 ± 0.006 mJ/m(2) and vary with the concentration of polymers in equilibrated phases of ATPS. Measurements of ultralow interfacial tensions with such reproducibility will broadly benefit studies involving partition of different biomolecules in ATPS and elucidate the critical effect of interfacial tension.

Background: Effective care of young people with rare conditions requires ongoing coordinated medical treatment as well as educational and social support services. However, information on treatment is often lacking due to limited data. South Carolina has a repository of comprehensive health and human service data with which individuals may be tracked across the data systems of multiple state agencies and organizations., Objective: To develop a method for studying health care of young persons with rare conditions using this repository., Methods: We identified individuals aged 15 to 24 years diagnosed during 2000-2010 with Fragile X syndrome (FXS), spina bifida (SB), or muscular dystrophy (MD) using a series of algorithms. ICD-9-CM codes were used to initially identify the cohort from medical billing data. Demographics, medical care, employment, education, and socioeconomic status data were then extracted from linked administrative sources., Results: We identified 1,040 individuals with these rare conditions: 125 with FXS, 695 with SB, and 220 with MD. The vast majority of the cases (95%) were identified in the Medicaid database. Half of the cohort was male, with a higher percentage in the FXS and MD groups. Sixty-two percent of the cohort was enrolled in the last year of high school. Over half of the cohort received support services from the state's disability and special-needs agency; 16% received food assistance. Thirty-eight percent were employed at some point during the study period. Forty-nine individuals with SB and 56 with MD died during the study period., Conclusions: We used a linked statewide data system to study rare conditions. Strengths include the diversity of information, rigorous identification strategies, and access to longitudinal data. Despite limitations inherent to administrative data, we found that linked state data systems are valuable resources for investigating important public health questions on rare conditions.

The field of epigenetics is expanding rapidly, yet there is persistent uncertainty in the definition of the term. The word was coined in the mid-twentieth century as a descriptor of how intrinsic, yet largely unknown, forces act with genes to channel progenitor cells along pathways of differentiation. Near the end of the twentieth century, epigenetics was defined more specifically as the study of changes in gene activity states. In some definitions, only those activity states that are inherited across cell division were considered. Other definitions were broader, also including activity states that are transient, or occurring in non-dividing cells. The greatest point of disagreement in these current definitions, is if the term should concern only inherited activity states. To alleviate this disparity, an alternative term, 'memigenetics', could be used in place of epigenetics to describe inherited chromatin activity states. The advantage of this term is that it is self-defining, and would serve to emphasize the important concept of cell memory. It would also free the term epigenetics to be used in a broader sense in accord with the meaning of the prefix 'epi', that is, as a descriptor of what is 'over' DNA at any point in time.

Purpose: Azithromycin use has been associated with increased risk of death among patients at high baseline risk, but not for younger and middle-aged adults. The Food and Drug Administration issued a public warning on azithromycin, including a statement that the risks were similar for levofloxacin. We conducted a retrospective cohort study among US veterans to test the hypothesis that taking azithromycin or levofloxacin would increase the risk of cardiovascular death and cardiac arrhythmia compared with persons taking amoxicillin., Methods: We studied a cohort of US veterans (mean age, 56.8 years) who received an exclusive outpatient dispensation of either amoxicillin (n = 979,380), azithromycin (n = 594,792), or levofloxacin (n = 201,798) at the Department of Veterans Affairs between September 1999 and April 2012. Azithromycin was dispensed mostly for 5 days, whereas amoxicillin and levofloxacin were dispensed mostly for at least 10 days., Results: During treatment days 1 to 5, patients receiving azithromycin had significantly increased risk of death (hazard ratio [HR] = 1.48; 95% CI, 1.05-2.09) and serious arrhythmia (HR = 1.77; 95% CI, 1.20-2.62) compared with patients receiving amoxicillin. On treatment days 6 to 10, risks were not statistically different. Compared with patients receiving amoxicillin, patients receiving levofloxacin for days 1 to 5 had a greater risk of death (HR = 2.49, 95% CI, 1.7-3.64) and serious cardiac arrhythmia (HR = 2.43, 95% CI, 1.56-3.79); this risk remained significantly different for days 6 to 10 for both death (HR = 1.95, 95% CI, 1.32-2.88) and arrhythmia (HR = 1.75; 95% CI, 1.09-2.82)., Conclusions: Compared with amoxicillin, azithromycin resulted in a statistically significant increase in mortality and arrhythmia risks on days 1 to 5, but not 6 to 10. Levofloxacin, which was predominantly dispensed for a minimum of 10 days, resulted in an increased risk throughout the 10-day period.