To determine if temporal glucose profiles differed between
) women who were randomized to real-time continuous glucose monitoring (RT-CGM) or self-monitored blood glucose (SMBG),
) women who used ...insulin pumps or multiple daily insulin injections (MDIs), and
) women whose infants were born large for gestational age (LGA) or not, by assessing CGM data obtained from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT).
Standard summary metrics and functional data analysis (FDA) were applied to CGM data from the CONCEPTT trial (RT-CGM,
= 100; SMBG,
= 100) taken at baseline and at 24- and 34-weeks' gestation. Multivariable regression analysis determined if temporal differences in 24-h glucose profiles occurred between comparators in each of the three groups.
FDA revealed that women using RT-CGM had significantly lower glucose (0.4-0.8 mmol/L 7-14 mg/dL) for 7 h/day (0800 h to 1200 h and 1600 h to 1900 h) compared with those with SMBG. Women using pumps had significantly higher glucose (0.4-0.9 mmol/L 7-16 mg/dL) for 12 h/day (0300 h to 0600 h, 1300 h to 1800 h, and 2030 h to 0030 h) at 24 weeks with no difference at 34 weeks compared with MDI. Women who had an LGA infant ran a significantly higher glucose by 0.4-0.7 mmol/L (7-13 mg/dL) for 4.5 h/day at baseline, by 0.4-0.9 mmol/L (7-16 mg/dL) for 16 h/day at 24 weeks, and by 0.4-0.7 mmol/L (7-13 mg/dL) for 14 h/day at 34 weeks.
FDA of temporal glucose profiles gives important information about differences in glucose control and its timing, which are undetectable by standard summary metrics. Women using RT-CGM were able to achieve better daytime glucose control, reducing fetal exposure to maternal glucose.
The CONCEPTT trial compared real-time Continuous Glucose Monitoring (RT-CGM) to capillary glucose monitoring in pregnant women with type 1 diabetes. We analyzed CGM and glycated hemoglobin (HbA
) ...measures in first (
= 221), second (
= 197), and third (
= 172) trimesters, aiming to examine target glucose attainment and associations with pregnancy outcomes. CGM targets were Time-in-range (TIR) > 70%, Time-above-range (TAR) <25%, and Time-below-range (TBR) < 4%, and HbA
targets < 6.5% (National Institute for Health and Care Excellence NICE) and HbA
< 6.0% in second and third trimesters (American Diabetes Association ADA). TIR/TAR/TBR targets were achieved by 7.7/14.5/30.3% participants in first, 10.2/14.2/52.8% in second, and 35.5/37.2/52.9% in third trimesters. CGM target attainment was low but increased during pregnancy and with RT-CGM use. In the adjusted analyses, achieving TBR target was associated with a higher risk of pre-eclampsia and neonatal hypoglycemia. ADA HbA
target attainment was low and unchanged during pregnancy (23.5/27.9/23.8%) but increased with RT-CGM use. In the adjusted analyses, HbA
target attainment was associated with a lower risk of preterm birth, large-for-gestational age and neonatal hypoglycemia. We conclude that CONCEPTT trial participants had a low rate of CGM and of HbA
target attainment. Attainment of CGM and NICE HbA
targets increased throughout gestation and all targets (both NICE/ADA HbA
and CGM) were more likely to be achieved by RT-CGM users, at 34 weeks' gestation. ADA HbA
target achievement was independently associated with better perinatal outcomes, while the independent association of TBR target achievement with increased risk warrants further study. ClinicalTrials.gov Registration Identifier NCT01788527.
BRAZIL ROAD-KILL Grilo, Clara; Coimbra, Michely R.; Cerqueira, Rafaela C. ...
Ecology (Durham),
11/2018, Volume:
99, Issue:
11
Journal Article
Peer reviewed
Open access
Mortality from collision with vehicles is the most visible impact of road traffic on wildlife. Mortality due to roads (hereafter road-kill) can affect the dynamic of populations of many species and ...can, therefore, increase the risk of local decline or extinction. This is especially true in Brazil, where plans for road network upgrading and expansion overlaps biodiversity hotspot areas, which are of high importance for global conservation. Researchers, conservationists and road planners face the challenge to define a national strategy for road mitigation and wildlife conservation. The main goal of this dataset is a compilation of geo-referenced road-kill data from published and unpublished road surveys. This is the first Data Paper in the BRAZIL series (see ATLANTIC, NEOTROPICAL, and BRAZIL collections of Data Papers published in Ecology), which aims make public road-kill data for species in the Brazilian Regions. The dataset encompasses road-kill records from 45 personal communications and 26 studies published in peer-reviewed journals, theses and reports. The road-kill dataset comprises 21,512 records, 83% of which are identified to the species level (n = 450 species). The dataset includes records of 31 amphibian species, 90 reptile species, 229 bird species, and 99 mammal species. One species is classified as Endangered, eight as Vulnerable and twelve as Near Threatened. The species with the highest number of records are: Didelphis albiventris (n = 1,549), Volatinia jacarina (n = 1,238), Cerdocyon thous (n = 1,135), Helicops infrataeniatus (n = 802), and Rhinella icterica (n = 692). Most of the records came from southern Brazil. However, observations of the road-kill incidence for non-Least Concern species are more spread across the country. This dataset can be used to identify which taxa seems to be vulnerable to traffic, analyze temporal and spatial patterns of road-kill at local, regional and national scales and also used to understand the effects of road-kill on population persistence. It may also contribute to studies that aims to understand the influence of landscape and environmental influences on road-kills, improve our knowledge on road-related strategies on biodiversity conservation and be used as complementary information on large-scale and macroecological studies. No copyright or proprietary restrictions are associated with the use of this data set other than citation of this Data Paper.
After intravascular delivery of genetically marked adult mouse bone marrow into lethally irradiated normal adult hosts, donor-derived cells expressing neuronal proteins (neuronal phenotypes) ...developed in the central nervous system. Flow cytometry revealed a population of donor-derived cells in the brain with characteristics distinct from bone marrow. Confocal microscopy of individual cells showed that hundreds of marrow-derived cells in brain sections expressed gene products typical of neurons (NeuN, 200-kilodalton neurofilament, and class III β-tubulin) and were able to activate the transcription factor cAMP response element-binding protein (CREB). The generation of neuronal phenotypes in the adult brain 1 to 6 months after an adult bone marrow transplant demonstrates a remarkable plasticity of adult tissues with potential clinical applications.
Transplanted bone marrow-derived cells (BMDCs) have been reported to fuse with cells of diverse tissues, but the extremely low frequency of fusion has led to the view that such events are ...biologically insignificant. Nonetheless, in mice with a lethal recessive liver disease (tyrosinaemia), transplantation of wild-type BMDCs restored liver function by cell fusion and prevented death, indicating that cell fusion can have beneficial effects. Here we report that chronic inflammation resulting from severe dermatitis or autoimmune encephalitis leads to robust fusion of BMDCs with Purkinje neurons and formation of hundreds of binucleate heterokaryons per cerebellum, a 10-100-fold higher frequency than previously reported. Single haematopoietic stem-cell transplants showed that the fusogenic cell is from the haematopoietic lineage and parabiosis experiments revealed that fusion can occur without irradiation. Transplantation of rat bone marrow into mice led to activation of dormant rat Purkinje neuron-specific genes in BMDC nuclei after fusion with mouse Purkinje neurons, consistent with nuclear reprogramming. The precise neurological role of these heterokaryons awaits elucidation, but their frequency in brain after inflammation is clearly much higher than previously appreciated.
The pathogenesis of cystic nephroma of the kidney has interested pathologists for over 50 years. Emerging from its initial designation as a type of unilateral multilocular cyst, cystic nephroma has ...been considered as either a developmental abnormality or a neoplasm or both. Many have viewed cystic nephroma as the benign end of the pathologic spectrum with cystic partially differentiated nephroblastoma and Wilms tumor, whereas others have considered it a mixed epithelial and stromal tumor. We hypothesize that cystic nephroma, like the pleuropulmonary blastoma in the lung, represents a spectrum of abnormal renal organogenesis with risk for malignant transformation. Here we studied DICER1 mutations in a cohort of 20 cystic nephromas and 6 cystic partially differentiated nephroblastomas, selected independently of a familial association with pleuropulmonary blastoma and describe four cases of sarcoma arising in cystic nephroma, which have a similarity to the solid areas of type II or III pleuropulmonary blastoma. The genetic analyses presented here confirm that DICER1 mutations are the major genetic event in the development of cystic nephroma. Further, cystic nephroma and pleuropulmonary blastoma have similar DICER1 loss of function and ‘hotspot' missense mutation rates, which involve specific amino acids in the RNase IIIb domain. We propose an alternative pathway with the genetic pathogenesis of cystic nephroma and DICER1-renal sarcoma paralleling that of type I to type II/III malignant progression of pleuropulmonary blastoma.
Hepatocellular carcinoma (HCC), the fourth leading cause of cancer mortality worldwide, develops almost exclusively in patients with chronic liver disease and advanced fibrosis
. Here we interrogated ...functions of hepatic stellate cells (HSCs), the main source of liver fibroblasts
, during hepatocarcinogenesis. Genetic depletion, activation or inhibition of HSCs in mouse models of HCC revealed their overall tumour-promoting role. HSCs were enriched in the preneoplastic environment, where they closely interacted with hepatocytes and modulated hepatocarcinogenesis by regulating hepatocyte proliferation and death. Analyses of mouse and human HSC subpopulations by single-cell RNA sequencing together with genetic ablation of subpopulation-enriched mediators revealed dual functions of HSCs in hepatocarcinogenesis. Hepatocyte growth factor, enriched in quiescent and cytokine-producing HSCs, protected against hepatocyte death and HCC development. By contrast, type I collagen, enriched in activated myofibroblastic HSCs, promoted proliferation and tumour development through increased stiffness and TAZ activation in pretumoural hepatocytes and through activation of discoidin domain receptor 1 in established tumours. An increased HSC imbalance between cytokine-producing HSCs and myofibroblastic HSCs during liver disease progression was associated with increased HCC risk in patients. In summary, the dynamic shift in HSC subpopulations and their mediators during chronic liver disease is associated with a switch from HCC protection to HCC promotion.
This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by ...participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field.
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