Loss of functional β-cell mass is an essential feature of type 2 diabetes, and maintaining mature β-cell identity is important for preserving a functional β-cell mass. However, it is unclear how β-cells achieve and maintain their mature identity. Here we demonstrate a novel function of protein arginine methyltransferase 1 (PRMT1) in maintaining mature β-cell identity. Prmt1 knockout in fetal and adult β-cells induced diabetes, which was aggravated by high-fat diet–induced metabolic stress. Deletion of Prmt1 in adult β-cells resulted in the immediate loss of histone H4 arginine 3 asymmetric dimethylation (H4R3me2a) and the subsequent loss of β-cell identity. The expression levels of genes involved in mature β-cell function and identity were robustly downregulated as soon as Prmt1 deletion was induced in adult β-cells. Chromatin immunoprecipitation sequencing and assay for transposase-accessible chromatin sequencing analyses revealed that PRMT1-dependent H4R3me2a increases chromatin accessibility at the binding sites for CCCTC-binding factor (CTCF) and β-cell transcription factors. In addition, PRMT1-dependent open chromatin regions may show an association with the risk of diabetes in humans. Together, our results indicate that PRMT1 plays an essential role in maintaining β-cell identity by regulating chromatin accessibility.

State regulation is necessary for safety, says Simon Capewell, professor of public health and policy at the University of Liverpool. Richard Lilford, professor of public health at the University of Warwick, argues that restricting adults’ choice can undermine such aims. Read the debate: http://www.bmj.com/content/355/bmj.i6341

Viral exanthema can cause rash in a pregnant woman and should be considered even in countries that have comprehensive vaccination programmes. Measles and rubella can cause intrauterine death. Intrauterine infection with rubella can lead to congenital rubella syndrome in the liveborn baby. In this podcast, Jack Carruthers, honorary clinical...

The world bank was set up in 1944. In the aftermath of the second world war, the institution was there to give loans to countries rebuilding after the conflict. Their first loan went to France - but with stipulations about repayment that set a tone for future funds. A new series, authored by Devi Sridhar, and her team from the University of...

A new Rapid Recommendation from The BMJ suggests that for pregnant women, they may wish to avoid certain antiviral treatments for HIV. This recommendation differs from the WHO's, and to discuss why that is, and what makes that difference important, we're joined by Reed Siemieniuk, a physician and methodologist from McMaster University, and Alice...

We talk about financial conflicts of interest a lot atThe BMJ - and have take taken the decision that our educational content should be without them. We also talk a lot about non-financial conflicts of interest, but the choppy waters of those are much more difficult to navigate. In this podcast, we discuss whether we should, or if we could even...

Fertility awareness based methods of contraception are increasingly being used for pregnancy prevention. In the US, the proportion of contraceptive users who choose such methods has grown from 1% in 2008 to approximately 3% in 2014.  Relative to other methods of pregnancy prevention, however, substantial misinformation exists around fertility...

G Perseghin
Aug 1, 1999; 48:1600-1606
Articles

The placenta participates in maternal insulin sensitivity changes during pregnancy; however, mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort. All women underwent 75-g oral glucose tolerance tests at ~26 weeks of gestation; we used glucose and insulin measures to estimate insulin sensitivity (Matsuda index). At delivery, we collected samples from placenta (fetal side) and measured DNA methylation using Illumina EPIC arrays. Using linear regression models to quantify associations at 720,077 cytosine-guanine dinucleotides (CpGs), with adjustment for maternal age, gravidity, smoking, BMI, child sex, and gestational age at delivery, we identified 188 CpG sites where placental DNA methylation was associated with Matsuda index (P < 6.94 x 10^–8). Among genes annotated to these 188 CpGs, we found enrichment in targets for miRNAs, in histone modifications, and in parent-of-origin DNA methylation including the H19/MIR675 locus (paternally imprinted). We identified 12 known placenta imprinted genes, including KCNQ1. Mendelian randomization analyses revealed five loci where placenta DNA methylation may causally influence maternal insulin sensitivity, including the maternally imprinted gene DLGAP2. Our results suggest that placental DNA methylation is fundamentally linked to the regulation of maternal insulin sensitivity in pregnancy.

Clinical studies have suggested that changes in peripheral nerve microcirculation may contribute to nerve damage in diabetic polyneuropathy (DN). High-sensitivity troponin T (hsTNT) assays have been recently shown to provide predictive values for both cardiac and peripheral microangiopathy in type 2 diabetes (T2D). This study investigated the association of sciatic nerve structural damage in 3 Tesla (3T) magnetic resonance neurography (MRN) with hsTNT and N-terminal pro-brain natriuretic peptide serum levels in patients with T2D. MRN at 3T was performed in 51 patients with T2D (23 without DN, 28 with DN) and 10 control subjects without diabetes. The sciatic nerve’s fractional anisotropy (FA), a marker of structural nerve integrity, was correlated with clinical, electrophysiological, and serological data. In patients with T2D, hsTNT showed a negative correlation with the sciatic nerve’s FA (r = –0.52, P < 0.001), with a closer correlation in DN patients (r = –0.66, P < 0.001). hsTNT further correlated positively with the neuropathy disability score (r = 0.39, P = 0.005). Negative correlations were found with sural nerve conduction velocities (NCVs) (r = –0.65, P < 0.001) and tibial NCVs (r = –0.44, P = 0.002) and amplitudes (r = –0.53, P < 0.001). This study is the first to show that hsTNT is a potential indicator for structural nerve damage in T2D. Our results indirectly support the hypothesis that microangiopathy contributes to structural nerve damage in T2D.

Research Event

Event participants

Charles Wanguhu, Coordinator, Kenya CSO Platform on Oil and Gas
Ndanga Kamau, Oil and Gas Policy Adviser, Oxfam Kenya
John Ochola, Chairman, Kenya CSO Platform on Oil and Gas / EcoNews Africa
Simon Thompson, Chairman, Tullow Oil
Chair: Alex Vines, Research Director, Area Studies and International Law; Head, Africa Programme, Chatham House 

19 December 2014

This research paper sets out recommendations for enhanced dialogue and intensified international cooperation that could significantly improve the functioning of global mineral markets.

Invitation Only Research Event

Event participants

Moïse Katumbi Chapwe, Governor, Katanga Province, Democratic Republic of the Congo

28 January 2016

How China responds to the challenges of resource security and sustainability, working with others, will help define its reputation as a responsible actor on the world stage in the next decade, according to a new paper.

• It is time to upgrade global resource governance
• Meaningful progress cannot be achieved without China
• China will need to be both innovative and pragmatic in its approach
• New modes of cooperation are needed
• Changes in China’s economy present opportunities and risks

13 July 2016

The updated Guidelines focus on eight key objectives for the petroleum sector in emerging producing countries and include policy-oriented recommendations for each objective.

Immunotherapy is becoming the mainstay for treatment of a variety of malignancies, but only a subset of patients responds to treatment. Tumor-infiltrating CD8-positive (CD8+) T lymphocytes play a central role in antitumor immune responses. Noninvasive imaging of CD8+ T cells may provide new insights into the mechanisms of immunotherapy and potentially predict treatment response. We are studying the safety and utility of ⁸⁹Zr-IAB22M2C, a radiolabeled minibody against CD8+ T cells, for targeted imaging of CD8+ T cells in patients with cancer. Methods: The initial dose escalation phase of this first-in-humans prospective study included 6 patients (melanoma, 1; lung, 4; hepatocellular carcinoma, 1). Patients received approximately 111 MBq (3 mCi) of ⁸⁹Zr-IAB22M2C (at minibody mass doses of 0.2, 0.5, 1.0, 1.5, 5, or 10 mg) as a single dose, followed by PET/CT scans at approximately 1–2, 6–8, 24, 48, and 96–144 h after injection. Biodistribution in normal organs, lymph nodes, and lesions was evaluated. In addition, serum samples were obtained at approximately 5, 30, and 60 min and later at the times of imaging. Patients were monitored for safety during infusion and up to the last imaging time point. Results: ⁸⁹Zr-IAB22M2C infusion was well tolerated, with no immediate or delayed side effects observed after injection. Serum clearance was typically biexponential and dependent on the mass of minibody administered. Areas under the serum time–activity curve, normalized to administered activity, ranged from 1.3 h/L for 0.2 mg to 8.9 h/L for 10 mg. Biodistribution was dependent on the minibody mass administered. The highest uptake was always in spleen, followed by bone marrow. Liver uptake was more pronounced with higher minibody masses. Kidney uptake was typically low. Prominent uptake was seen in multiple normal lymph nodes as early as 2 h after injection, peaking by 24–48 h after injection. Uptake in tumor lesions was seen on imaging as early as 2 h after injection, with most ⁸⁹Zr-IAB22M2C–positive lesions detectable by 24 h. Lesions were visualized early in patients receiving treatment, with SUV ranging from 5.85 to 22.8 in 6 target lesions. Conclusion: ⁸⁹Zr-IAB22M2C imaging is safe and has favorable kinetics for early imaging. Biodistribution suggests successful targeting of CD8+ T-cell–rich tissues. The observed targeting of tumor lesions suggests this may be informative for CD8+ T-cell accumulation within tumors. Further evaluation is under way.

Continuous glucose monitor (CGM) readings are delayed relative to blood glucose, and this delay is usually attributed to the latency of interstitial glucose levels. However, CGM-independent data suggest rapid equilibration of interstitial glucose. This study sought to determine the loci of CGM delays. Electrical current was measured directly from CGM electrodes to define sensor kinetics in the absence of smoothing algorithms. CGMs were implanted in mice, and sensor versus blood glucose responses were measured after an intravenous glucose challenge. Dispersion of a fluorescent glucose analog (2-NBDG) into the CGM microenvironment was observed in vivo using intravital microscopy. Tissue deposited on the sensor and nonimplanted subcutaneous adipose tissue was then collected for histological analysis. The time to half-maximum CGM response in vitro was 35 ± 2 s. In vivo, CGMs took 24 ± 7 min to reach maximum current versus 2 ± 1 min to maximum blood glucose (P = 0.0017). 2-NBDG took 21 ± 7 min to reach maximum fluorescence at the sensor versus 6 ± 6 min in adipose tissue (P = 0.0011). Collagen content was closely correlated with 2-NBDG latency (R = 0.96, P = 0.0004). Diffusion of glucose into the tissue deposited on a CGM is substantially delayed relative to interstitial fluid. A CGM that resists fibrous encapsulation would better approximate real-time deviations in blood glucose.

14 November 2019

As internet governance issues emerge in the wake of innovations such as the Internet of Things and advanced artificial intelligence, there is an urgent need for the EU and US to establish a common, positive multi-stakeholder vision for regulating and governing the internet.

Invitation Only Research Event

Research Event

Research Event

Event participants

In the face of an uptick in unauthorized arrivals in Italy from Tunisia in 2017, the European Union dusted off earlier policy proposals such as funding to increase Tunisia’s border-control capabilities and the creation of disembarkation platforms. This article explores why contemporary developments, including a fragile Tunisian political system, suggest the need for a different approach.

While the Global Compact for Safe, Orderly, and Regular Migration was formally adopted by 164 of the UN's 193 Member States, it's worth asking how it became a point of contention and ultimately was rejected by more than a dozen countries. The answer? A long lag time between negotiation and adoption, during which overheated claims against it went largely unanswered, as this commentary explores.

The vast majority of UN Member States in December 2018 adopted the first-ever international agreement to cooperate on migration. This policy brief traces the trajectory of the Global Compact for Safe, Orderly, and Regular Migration's negotiation and endorsement. It also explores the factors that will determine whether the compact lives up to its aim of improving how states cooperate on international migration.   

This volume from MPI's Transatlantic Council on Migration aims to fill the analytical gap regarding the question of what greater global cooperation on governing the flow of international migrants could achieve. The book focuses on a set of fundamental questions: What are the key steps to building a better, more cooperative system of governance? What are the goals that can be achieved through greater international cooperation? And, most fundamentally, who (or what) is to be governed?

OBJECTIVE

This study aimed to understand the longitudinal relationship between financial, psychosocial, and neighborhood social determinants and glycemic control (HbA_1c) in older adults with diabetes.

Migration and development policy discussions have edged closer to each other on the international stage. The adoption of the Global Compact for Migration in December 2018 marks an important milestone. As all eyes turn toward the compact’s implementation, this brief examines some of the key topics states have pledged to work more closely on—from labor migration and migrants’ rights, to returns and reintegration.

David J Pettitt
Jan 1, 1993; 16:310-314
Supplement 1: Diabetes in Native Americans

Lene R. Nielsen
May 1, 2004; 27:1200-1201
Brief Reports

Johanna M Mooy
Sep 1, 1995; 18:1270-1273
Short Report

As the COVID-19 pandemic begins to take root in Africa, experts say that digitizing financial services could help keep the continent safe

Denice S. Feig
Oct 1, 2011; 34:2329-2330
Editorial (See Rowan et al., p. 2279)

Lene R. Nielsen
May 1, 2004; 27:1200-1201
Brief Reports

The ADA is presenting two free webinars March 27, aiming to help dentists financially weather the economic downturn during the COVID-19 outbreak and illustrate how ADA advocacy has helped turn the tide.

The ADA is calling on third-party payers to support dental practices in the midst of the COVID-19 pandemic.

On the heels of the ADA’s December interim policy on vaping comes a new CDT code that references counseling services about high-risk substance use including vaping.

As part of its ongoing efforts to support dentists during the COVID-19 pandemic, the ADA is offering members two free e-books the week of April 8-14: “Managing Finances: Best Practices” and “The ADA Practical Guide to HIPAA Training.”

Two additional Delta Dental member companies announced details April 27-28 of programs that will provide economic assistance and post-COVID-19 pandemic relief for members of its independent provider networks across 16 states and the District of Columbia.

A team of researchers at the University of California, Los Angeles School of Dentistry has developed a nanoparticle that could improve treatment for bone defects.

OBJECTIVE

To determine if temporal glucose profiles differed between 1) women who were randomized to real-time continuous glucose monitoring (RT-CGM) or self-monitored blood glucose (SMBG), 2) women who used insulin pumps or multiple daily insulin injections (MDIs), and 3) 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).

While migration once was a lower-priority topic for African governments, the last decade has seen a deepening in governance. Policymakers have integrated migration into their national development strategies and mainstreamed it across policy domains such as health and education. The actions are promising on paper, yet questions remain about the extent to which they will translate to more effective migration management.

Presidential press secretary Kayleigh McEnany said Friday the Trump administration is confident in a major economic recovery after several weeks of closures due to the coronavirus pandemic.

The Navy has been particularly hard hit by the coronavirus pandemic and is working to adapt its strategies for maintenance as well as containing outbreaks on ships.

If so, can you do it online? I don't want to catch COVID-19 waiting in some packed line, as I live with an 80 year old.

Amid a significant reshaping of immigration policy by the Trump administration, a range of immigration topics that have not been at the forefront of debate merit further information sharing with the public and policymakers. This report examines eight issues areas that are deserving of additional review and could form the basis for future action by Congress, including H-1B reform and treatment of unaccompanied minors.

The United States is awash in gloom. Overwhelming majorities of Americans say they are dissatisfied with the country's economic direction, and the intensity of unhappiness is greater than it has been in 15 years, according to a recent Washington Post-ABC News poll. The answer, pundits, politicians...

This recipe was featured on Foodie Tuesday, a weekly segment with Raf Epstein on Drive, 774 ABC Melbourne, 3:30 PM, courtesy of Neil Perry. Neil's new book is "Spice Temple."

Our Indian chef whips these delicious naan breads up for us every day to go with her chicken tikka and vegetarian curries Brushed with garlic butter as they come out of the stone oven, they are quite a treat (thats why she has to make so many everyday.....)Thanks Nancylt;i>f