Long-term hyperglycemia in patients with diabetes leads to human serum albumin (HSA) glycation, which may impair HSA function as a transport protein and affect the therapeutic efficacy of anticoagulants in patients with diabetes. In this study, a novel mass spectrometry approach was developed to reveal the differences in the profiles of HSA glycation sites between patients with diabetes and healthy subjects. K199 was the glycation site most significantly changed in patients with diabetes, contributing to different interactions of glycated HSA and normal HSA with two types of anticoagulant drugs, heparin and warfarin. An in vitro experiment showed that the binding affinity to warfarin became stronger when HSA was glycated, while HSA binding to heparin was not significantly influenced by glycation. A pharmacokinetic study showed a decreased level of free warfarin in the plasma of diabetic rats. A preliminary retrospective clinical study also revealed that there was a statistically significant difference in the anticoagulant efficacy between patients with diabetes and patients without diabetes who had been treated with warfarin. Our work suggests that larger studies are needed to provide additional specific guidance for patients with diabetes when they are administered anticoagulant drugs or drugs for treating other chronic diseases.

Latoya Rose used the last $3,000 she had to invest in 26 baby chicks and feed with the hope of turning a profit after they matured. Last Friday, as the Spaldings resident went to her coop to feed the chickens, they were all gone. “When I don’t see...

BRIDGETOWN, Barbados, CMC – The Barbados-based the Caribbean Disaster Emergency Management Agency (CDEMA) says its executive director, Ronald Jackson, is leaving the post after seven years “of unwavering and exemplary service to the...

PORT AU PRINCE, Haiti, CMC – The Ministry of Public Health has confirmed that a 20-year-old man has become the seventh person in Haiti to die of the coronavirus (COVID-19). It is urging the population to follow restriction measures, including...

HAMILTON, Bermuda, CMC –  Bermuda recorded its seventh COVID-19 death on Saturday as Finance Minister Curtis Dickinson announced that he would need to rewrite this year’s budget because of the battering from the global...

Jon Miller is having trouble believing that baseball legend Frank Robinson is gone. Robinson, 83, passed away Thursday morning.

THE EDITOR, Madam: COVID-19 can be made to be the blame bearer for every ill, unless careful disaggregation is done to separate what is truly attributable to both its real scope and the understandable ripple effects of the virus. The quality of...

At the outset, author Ivy Slater shares the existential crisis that spurred her to change careers. Slater’s psychosocial experience after the passing of her father and the stagnation she experienced at her printing business proved exhaustively...

Fasting hyperinsulinemia precedes the development of type 2 diabetes. However, it is unclear whether fasting insulin hypersecretion is a primary driver of insulin resistance or a consequence of the progressive increase in fasting glycemia induced by insulin resistance in the prediabetic state. Herein, we have discovered a mechanism that specifically regulates non–glucose-stimulated insulin secretion (NGSIS) in pancreatic islets that is activated by nonesterified free fatty acids, the major fuel used by β-cells during fasting. We show that the mitochondrial permeability transition pore regulator cyclophilin D (CypD) promotes NGSIS, but not glucose-stimulated insulin secretion, by increasing mitochondrial proton leak. Islets from prediabetic obese mice show significantly higher CypD-dependent proton leak and NGSIS compared with lean mice. Proton leak–mediated NGSIS is conserved in human islets and is stimulated by exposure to nonesterified free fatty acids at concentrations observed in obese subjects. Mechanistically, proton leak activates islet NGSIS independently of mitochondrial ATP synthesis but ultimately requires closure of the K_ATP channel. In summary, we have described a novel nonesterified free fatty acid–stimulated pathway that selectively drives pancreatic islet NGSIS, which may be therapeutically exploited as an alternative way to halt fasting hyperinsulinemia and the progression of type 2 diabetes.

Studies on magnetic resonance neurography (MRN) in diabetic polyneuropathy (DPN) have found proximal sciatic nerve lesions. The aim of this study was to evaluate the functional relevance of sciatic nerve lesions in DPN, with the expectation of correlations with the impairment of large-fiber function. Sixty-one patients with type 2 diabetes (48 with and 13 without DPN) and 12 control subjects were enrolled and underwent MRN, quantitative sensory testing, and electrophysiological examinations. There were differences in mechanical detection (Aβ fibers) and mechanical pain (A fibers) but not in thermal pain and thermal detection clusters (C fibers) among the groups. Lesion load correlated with lower Aα-, Aβ-, and A-fiber but not with C-fiber function in all participants. Patients with lower function showed a higher load of nerve lesions than patients with elevated function or no measurable deficit despite apparent DPN. Longer diabetes duration was associated with higher lesion load in patients with DPN, suggesting that nerve lesions in DPN may accumulate over time and become clinically relevant once a critical amount of nerve fascicles is affected. Moreover, MRN is an objective method for determining lower function mainly in medium and large fibers in DPN.

Current therapeutic strategies for diabetic foot ulcer (DFU) have focused on developing topical healing agents, but few agents have controlled prospective data to support their effectiveness in promoting wound healing. We tested a stem cell mobilizing therapy for DFU using a combination of AMD3100 and low-dose FK506 (tacrolimus) (AF) in streptozocin-induced type 1 diabetic (T1DM) rats and type 2 diabetic Goto-Kakizaki (GK) rats that had developed peripheral artery disease and neuropathy. Here, we show that the time for healing back wounds in T1DM rats was reduced from 27 to 19 days, and the foot wound healing time was reduced from 25 to 20 days by treatment with AF (subcutaneously, every other day). Similarly, in GK rats treated with AF, the healing time on back wounds was reduced from 26 to 21 days. Further, this shortened healing time was accompanied by reduced scar and by regeneration of hair follicles. We found that AF therapy mobilized and recruited bone marrow–derived CD133⁺ and CD34⁺ endothelial progenitor cells and Ym1/2⁺ M2 macrophages into the wound sites, associated with enhanced capillary and hair follicle neogenesis. Moreover, AF therapy improved microcirculation in diabetic and neuropathic feet in GK rats. This study provides a novel systemic therapy for healing DFU.

2 July 2014 , Volume 90, Number 4

25 November 2014

This paper accompanies a series of assessments on China, France, Japan, the Netherlands, the UK, the US and Vietnam, providing details on how the estimates of the level of illegality of imports of wood-based products into those countries were derived.

Research Event

Invitation Only Research Event

Event participants

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

Invitation Only Research Event

15 November 2016

Research Event

Event participants

Tom Butler, Chief Executive Officer, International Council for Mining and Metals (ICMM)
Evelyn Dietsche, Associate Fellow, Energy, Environment and Resources, Chatham House
Chair: Bernice Lee, Executive Director, Hoffman Centre, Chatham House 

5 December 2017

Lower-income countries are in many ways more ‘circular’ than their developed-economy counterparts – the question is how to turn this into a development opportunity.

GEORGETOWN, Guyana (AP): Four months after Guyana became one of the world’s newest crude oil exporters, the South American country says it is already reaping the rewards with about $60 million in payments. The money is linked to Guyana’s...

7 May 2020 , Volume 96, Number 3

Research Event

Research Event

Research Event

Knowledge of the molecular events in mitochondrial DNA (mtDNA) replication is crucial to understanding the origins of human disorders arising from mitochondrial dysfunction. Twinkle helicase is an essential component of mtDNA replication. Here, we employed atomic force microscopy imaging in air and liquids to visualize ring assembly, DNA binding, and unwinding activity of individual Twinkle hexamers at the single-molecule level. We observed that the Twinkle subunits self-assemble into hexamers and higher-order complexes that can switch between open and closed-ring configurations in the absence of DNA. Our analyses helped visualize Twinkle loading onto and unloading from DNA in an open-ringed configuration. They also revealed that closed-ring conformers bind and unwind several hundred base pairs of duplex DNA at an average rate of ∼240 bp/min. We found that the addition of mitochondrial single-stranded (ss) DNA–binding protein both influences the ways Twinkle loads onto defined DNA substrates and stabilizes the unwound ssDNA product, resulting in a ∼5-fold stimulation of the apparent DNA-unwinding rate. Mitochondrial ssDNA-binding protein also increased the estimated translocation processivity from 1750 to >9000 bp before helicase disassociation, suggesting that more than half of the mitochondrial genome could be unwound by Twinkle during a single DNA-binding event. The strategies used in this work provide a new platform to examine Twinkle disease variants and the core mtDNA replication machinery. They also offer an enhanced framework to investigate molecular mechanisms underlying deletion and depletion of the mitochondrial genome as observed in mitochondrial diseases.

This discussion on the 1986 Immigration Reform and Control Act (IRCA) showcases MPI Fellow Charles Kamasaki's book, Immigration Reform: The Corpse That Will Not Die. Kamasaki is joined by other veterans of the IRCA debate for a conversation on the lessons, the intended and unintended consequences, and how the law’s legacy has shaped contemporary politics on immigration.

The Armenian diaspora, which significantly exceeds the country's resident population, has played an instrumental role in Armenia's political and economic development since independence in 1991. Yet a picture emerges of divergent currents within the diaspora, often seen from above as a unified entity. Delve into differences in engagement among Armenia's "old" and "new" diasporas with this feature article.

For generations, migrants have emigrated from Senegal, particularly from in and around the Senegal River Valley. With France a key destination, French policy changes have had significant impact on Senegalese migrants and the hometown associations through which they support development in Senegal. This article explores how these policy shifts influence development and quality of life in the Senegal River Valley.

Migration and development are intimately linked, but they have not always shared the international policy stage. As UN Member States kick off negotiations for the Global Compact for Safe, Orderly, and Regular Migration—and with adoption planned for 2018—this brief examines the evolving relationship between these policy areas and considers what a global compact has to offer, if well designed.

Development assistance may be a blunt tool for reshaping migration patterns—and indeed one that could increase flows over the short term. Shifting the focus away from increasing individuals’ skills and assets toward investments in the broader economic or governance structures that are a prerequisite for growth and stability may offer more alternatives to emigration in the long run.

As policymakers look for ways to address the drivers of illegal immigration, many have called for migration aims to be incorporated into development work and development tools into migration partnerships. This policy brief analyzes the benefits and risks of heightened cooperation between actors in these fields, and identifies areas where joint initiatives may prove fruitful.

As the final phase of preparations for the historic adoption of a Global Compact for Safe, Orderly, and Regular Migration approaches, this webinar explores two central objectives of the compact: enhancing the availability and flexibility of pathways for regular migration, and investing in skills development. 

As the final phase of preparations for the historic adoption of a Global Compact for Safe, Orderly, and Regular Migration approaches, this webinar explores two central objectives of the compact: enhancing the availability and flexibility of pathways for regular migration, and investing in skills development.

From ongoing emigration flows and a surge in asylum seekers, to more than 150,000 returnees, this country profile examines contemporary and historical migration trends in Albania. Driven by extreme poverty and unemployment, more than one-third of Albania's population has emigrated in the last 25 years. The government now seeks to capitalize on diaspora resources by linking migration and development policies.

In the Philippines, a pervasive culture of migration has led millions to seek opportunities abroad, particularly since an economic downturn in the 1970s. The government has long embraced exporting labor as official economic policy, but over time, the focus has shifted: first to protecting workers overseas and much more recently to linking migration and development. This article explores the evolution of Filipino migration policy and trends.

With nearly 1.4 million internally displaced persons (IDPs), Ukraine is home to one of the largest IDP populations in the world. Five years after Russia's annexation of Crimea, displaced Ukrainians continue to face challenges related to national identity, social cohesion, and political participation. While the Ukrainian government has had some success integrating IDPs, the conflict’s end remains uncertain, and many are unlikely to return to their communities of origin no matter the outcome.

This report summarizes the economic and social development policy achievements of Central American countries over the past 20 years, as well as the notable obstacles to development that remain. The author identifies long-term challenges and outlines how they can be incorporated into a new development agenda.

This policy brief explores the relationship between environmental change and migration to Europe in light of recent scholarship challenging the notion that environmental change triggers mass migration. It presents an overview of European policy response in this area and summarizes the spectrum of proposed solutions.

This policy brief, which concludes a nine-brief series examining what is known about the linkages between migration and development, suggests that the policy framework on migration and development remains relatively weak, and few development agencies have made it a priority to promote the positive impact of international migration.

While partnerships to facilitate skilled migration have had mixed success in the past, the Global Compact for Migration is advancing a new approach that may change this. This policy brief compares this new partnership model with the traditional one, highlighting the questions policymakers will need to answer if they are to encourage mobility, sustain employer engagement, and see development benefits in countries of origin.

OBJECTIVE

To evaluate and compare the efficacy of long-term use of low-dose aspirin for the prevention of dementia in men and women.