Effect of Carelink, an Internet-Based Insulin Pump Monitoring System, on Glycemic Control in Children with Type 1 Diabetes Mellitus

Objective : To determine whether use of the internet-based Carelink system improved glycemic control in children on insulin pump therapy. Research Design and Methods - We reviewed records of 146 children treated with insulin pump therapy between the years 2004-2007, and compared glycemic control and diabetes self-care measures associated with Carelink use. Forty percent of the patients resided one hour or more from our clinic. Results: Patients who used the Carelink software and website showed significant improvement in HbA1c levels following use (8.0 ± 0.1 (SE) vs 7.7 ± 0.1 (SE), p=0.002). They uploaded data from their pump and glucometer 2.2 ± 1.8 times per month over 0.8 ± 0.4 (SD) years. Patients who had no access to Carelink software and were followed in a conventional manner showed no change in HbA1c ( 8.0 ± 0.1 (SE) vs 8.1 ± 0.1 (SE), p=0.27) during the study period. These patients did not differ significantly from Carelink users in diabetes self care behaviors. Patients who had Carelink access but did not use it had a higher HbA1c level at the onset and did not change over the study period (HbA1c 8.9 ± 0.2 (SE) vs 8.9 ± 0.3 (SE), p=0.76). These patients differed significantly from Carelink users in self-care behaviors, but not in the frequency of blood glucose monitoring. Patients in a rural location benefited equally as compared to patients who lived within one hour of our clinic. Conclusions: The Carelink software program is a powerful tool that can be used by diabetes care providers and parents to manage insulin pump therapy in children and to improve glycemic control, especially in states with a large rural population

Pregnancy after breast cancer: Are young patients willing to participate in clinical studies?

Young patients with breast cancer (BC) are often concerned about treatment-induced infertility and express maternity desire. Conception after BC does not seem to affect outcome, but information in estrogen-receptor positive (ER+) disease is not definitive. From September 2012-March 2013, 212 evaluable patients with ER+ early BC,37 years at diagnosis, from 5 regions (Europe/US/Canada/Middle-East/Australia) answered a survey about fertility concerns, maternity desire and interest in a study of endocrine therapy (ET) interruption to allow pregnancy. Overall, 37% of respondents were interested in the study; younger patients (≤30 years) reported higher interest (57%). Motivation in younger patients treated30 months was higher (83%) than in older women (14%), interest was independent of age in patients treated for ≤30 months. A prospective study in this patient population seems relevant and feasible. The International-Breast-Cancer-Study-Group (IBCSG), within the Breast-International-Group (BIG) - North-American-Breast-Cancer-Groups (NABCG) collaboration, is launching a study (POSITIVE) addressing ET interruption to allow pregnancy

Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

BACKGROUND The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.This work was partially supported by salaries from the NOAA Coral Reef Conservation Program to the NOAA Coral Reef Conservation Program authors. NOAA provided funding to Caribbean ReefCheck investigators to undertake surveys of bleaching and mortality. Otherwise, no funding from outside authors' institutions was necessary for the undertaking of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Birth weight and the risk of atrial fibrillation in whites and African Americans: The atherosclerosis risk in communities (ARIC) study

Background: Low birth weight (LBW) has been associated with an increased risk of cardiovascular disease (CVD). A previous study, however, found higher risk of atrial fibrillation (AF) in individuals with higher birth weight (BW). To further understand this apparent paradox, we examined the relationship between AF and BW in the Atherosclerosis Risk in Communities (ARIC) cohort. Methods: The analysis included 10,132 individuals free of AF at baseline (1996-1998), who provided BW information, were not born premature, and were not a twin. Self-reported BW was categorized as low (<2.5 kg), medium (2.5-4 kg), and high (>4.0 kg). AF incidence was ascertained from hospital discharge codes and death certificates. We used multivariable Cox proportional hazard models to determine the hazard ratios (HR) and 95% confidence intervals (CI) of AF across BW groups. Results: During an average follow-up of 10.3 years, we identified 882 incident AF cases. LBW was associated with higher risk of AF. Compared to individuals in the medium BW category, the HR (95% CI) of AF was 1.33 (0.99, 1.78) for LBW and 1.00 (0.81, 1.24) for high BW after adjusting for sociodemographic variables (p for trend = 0.29). Additional adjustment for CVD risk factors did not attenuate the associations (HR 1.42, 95% CI 1.06, 1.90 for LBW and HR 0.86, 95% CI 0.69-1.07 for high BW, compared to medium BW, p for trend = 0.01).Conclusion: LBW was associated with a higher risk of AF. This association was independent of known predictors of AF and is consistent with that observed for other cardiovascular diseases. © 2014 Lawani et al.; licensee BioMed Central Ltd

Switching Multiple Sclerosis Patients with Breakthrough Disease to Second-Line Therapy

BACKGROUND: Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to natalizumab or immunosuppressants. The effect of natalizumab monotherapy in patients with breakthrough disease is unknown. METHODS: This is an open-label retrospective cohort study of 993 patients seen at least four times at the University of California San Francisco MS Center, 95 had breakthrough disease on first-line therapy (60 patients switched to natalizumab, 22 to immunosuppressants and 13 declined the switch [non-switchers]). We used Poisson regression adjusted for potential confounders to compare the relapse rate within and across groups before and after the switch. RESULTS: In the within-group analyses, the relapse rate decreased by 70% (95% CI 50,82%; p<0.001) in switchers to natalizumab and by 77% (95% CI 59,87%; p<0.001) in switchers to immunosuppressants; relapse rate in non-switchers did not decrease (6%, p =  0.87). Relative to the reduction among non-switchers, the relapse rate was reduced by 68% among natalizumab switchers (95% CI 19,87%; p = 0.017) and by 76% among the immunosuppressant switchers (95% CI 36,91%; p = 0.004). CONCLUSIONS: Switching to natalizumab or immunosuppressants in patients with breakthrough disease is effective in reducing clinical activity of relapsing MS. The magnitude of the effect and the risk-benefit ratio should be evaluated in randomized clinical trials and prospective cohort studies

Bmp7 Functions via a Polarity Mechanism to Promote Cloacal Septation

During normal development in human and other placental mammals, the embryonic cloacal cavity separates along the axial longitudinal plane to give rise to the urethral system, ventrally, and the rectum, dorsally. Defects in cloacal development are very common and present clinically as a rectourethral fistula in about 1 in 5,000 live human births. Yet, the cellular mechanisms of cloacal septation remain poorly understood.We previously detected Bone morphogenetic protein 7 (Bmp7) expression in the urorectal mesenchyme (URM), and have shown that loss of Bmp7 function results in the arrest of cloacal septation. Here, we present evidence that cloacal partitioning is driven by Bmp7 signaling in the cloacal endoderm. We performed TUNEL and immunofluorescent analysis on cloacal sections from Bmp7 null and control littermate embryos. We found that loss of Bmp7 results in a dramatic decrease in the endoderm survival and a delay in differentiation. We used immunological methods to show that Bmp7 functions by activating the c-Jun N-terminal kinase (JNK) pathway. We carried out confocal and 3D imaging analysis of mitotic chromosome bundles to show that during normal septation cells in the cloacal endoderm divide predominantly in the apical-basal direction. Loss of Bmp7/JNK signaling results in randomization of mitotic angles in the cloacal endoderm. We also conducted immunohistochemical analysis of human fetal sections to show that BMP/phospho-SMAD and JNK pathways function in the human cloacal region similar as in the mouse.Our results strongly indicate that Bmp7/JNK signaling regulates remodeling of the cloacal endoderm resulting in a topological separation of the urinary and digestive systems. Our study points to the importance of Bmp and JNK signaling in cloacal development and rectourethral malformations

Attentional Performance in Children and Adolescents with Tic Disorder and Co-Occurring Attention-Deficit/Hyperactivity Disorder: New Insights from a 2 × 2 Factorial Design Study

The aim of the present study was to investigate the effect of both tic disorder (TD) and attention-deficit/hyperactivity disorder (ADHD) on attentional functions. N = 96 children and adolescents participated in the study, including n = 21 subjects with TD, n = 23 subjects with ADHD, n = 25 subjects with TD+ADHD, and n = 27 controls. Attentional performance was tested based on four computerized attention tasks (sustained attention, divided attention, go/nogo and set shifting). The effect of TD as well as ADHD on attentional performance was tested using a 2 × 2 factorial approach. A diagnosis of TD had no negative impact on attentional functions but was associated with improved performance in the set shifting task. By contrast, regardless of a diagnosis of TD, subjects with ADHD were found to perform worse in the sustained attention, divided attention and go/nogo task. No interaction effect between the factors TD and ADHD was revealed for any of the attention measures. Our results add to findings from other areas of research, showing that in subjects with TD and ADHD, ADHD psychopathology is often the main source of impairment, whereas a diagnosis of TD has little or no impact on neuropsychological performance in most cases and even seems to be associated with adaptive mechanisms

Cigarette smoke induces endoplasmic reticulum stress and the unfolded protein response in normal and malignant human lung cells

<p>Abstract</p> <p>Background</p> <p>Although lung cancer is among the few malignancies for which we know the primary etiological agent (i.e., cigarette smoke), a precise understanding of the temporal sequence of events that drive tumor progression remains elusive. In addition to finding that cigarette smoke (CS) impacts the functioning of key pathways with significant roles in redox homeostasis, xenobiotic detoxification, cell cycle control, and endoplasmic reticulum (ER) functioning, our data highlighted a defensive role for the unfolded protein response (UPR) program. The UPR promotes cell survival by reducing the accumulation of aberrantly folded proteins through translation arrest, production of chaperone proteins, and increased degradation. Importance of the UPR in maintaining tissue health is evidenced by the fact that a chronic increase in defective protein structures plays a pathogenic role in diabetes, cardiovascular disease, Alzheimer's and Parkinson's syndromes, and cancer.</p> <p>Methods</p> <p>Gene and protein expression changes in CS exposed human cell cultures were monitored by high-density microarrays and Western blot analysis. Tissue arrays containing samples from 110 lung cancers were probed with antibodies to proteins of interest using immunohistochemistry.</p> <p>Results</p> <p>We show that: 1) CS induces ER stress and activates components of the UPR; 2) reactive species in CS that promote oxidative stress are primarily responsible for UPR activation; 3) CS exposure results in increased expression of several genes with significant roles in attenuating oxidative stress; and 4) several major UPR regulators are increased either in expression (i.e., BiP and eIF2α) or phosphorylation (i.e., phospho-eIF2α) in a majority of human lung cancers.</p> <p>Conclusion</p> <p>These data indicate that chronic ER stress and recruitment of one or more UPR effector arms upon exposure to CS may play a pivotal role in the etiology or progression of lung cancers, and that phospho-eIF2α and BiP may have diagnostic and/or therapeutic potential. Furthermore, we speculate that upregulation of UPR regulators (in particular BiP) may provide a pro-survival advantage by increasing resistance to cytotoxic stresses such as hypoxia and chemotherapeutic drugs, and that UPR induction is a potential mechanism that could be attenuated or reversed resulting in a more efficacious treatment strategy for lung cancer.</p

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine