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Correction: Comparative structure-function analysis of bromodomain and extraterminal motif (BET) proteins in a gene-complementation system. [Additions and Corrections]

VOLUME 295 (2020) PAGES 1898–1914Yichen Zhong's name was misspelled. The correct spelling is shown above.




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Correction: Rational design, synthesis, and evaluation of uncharged, “smart” bis-oxime antidotes of organophosphate-inhibited human acetylcholinesterase. [Additions and Corrections]

VOLUME 295 (2020) PAGES 4079–4092There was an error in the abstract. “The pyridinium cation hampers uptake of OPs into the central nervous system (CNS)” should read as “The pyridinium cation hampers uptake into the central nervous system (CNS).”




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Maritime security: the uncharted politics of the global sea

4 September 2019 , Volume 95, Number 5

A special section in the latest issue explores recent developments in maritime security and ocean governance.

Christian Bueger, Timothy Edmunds and Barry J. Ryan

In this introduction to a special section of the September 2019 issue of International Affairs, we revisit the main themes and arguments of our article ‘Beyond seablindness: a new agenda for maritime security studies’, published in this journal in November 2017. We reiterate our call for more scholarly attention to be paid to the maritime environment in international relations and security studies. We argue that the contemporary maritime security agenda should be understood as an interlinked set of challenges of growing global, regional and national significance, and comprising issues of national, environmental, economic and human security. We suggest that maritime security is characterized by four main characteristics, including its interconnected nature, its transnationality, its liminality—in the sense of implicating both land and sea—and its national and institutional cross-jurisdictionality. Each of the five articles in the special section explores aspects of the contemporary maritime security agenda, including themes of geopolitics, international law, interconnectivity, maritime security governance and the changing spatial order at sea.




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Marking failure, making space: feminist intervention in Security Council policy

6 November 2019 , Volume 95, Number 6

Sam Cook

Feminist interventions in international politics are, more often than not, understood (and visible) as interventions in relation to policy documents. These policies—in this case the United Nations Security Council's resolutions on Women, Peace and Security—often feature as the end point of feminist advocacy efforts or as the starting point for feminist analysis and critique. In this article the author responds to the provocations throughout Marysia Zalewski's work to think (and tell) the spaces of international politics differently, in this case by working with the concept of feminist failure as it is produced in feminist policy critique. Inspired by Zalewski's Feminist International Relations: exquisite corpse, the article explores the material and imaginary spaces in which both policies and critique are produced. It picks up and reflects upon a narrative refrain recognizable in feminist critiques on Women, Peace and Security policy—that we must not make war safe for women—as a way to reflect on the inevitability of failure and the ostensible boundaries between theory and practice. The author takes permission from Zalewski's creative interventions and her recognition of the value of the ‘detritus of the everyday’—here a walk from New York's Grand Central Station to the UN Headquarters, musings on the flash of a particular shade of blue, and the contents of a footnoted acknowledgement, begin to trace an international political space that is produced through embodied and quotidian practice.




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Brexit and the UN Security Council: declining British influence?

6 November 2019 , Volume 95, Number 6

Jess Gifkins, Samuel Jarvis and Jason Ralph

The United Kingdom's decision to leave the European Union has ramifications beyond the UK and the EU. This article analyses the impact of the Brexit referendum on the UK's political capital in the United Nations Security Council; a dimension of Brexit that has received little attention thus far. Drawing on extensive elite interviews we show that the UK has considerable political capital in the Council, where it is seen as one of the most effective actors, but the reputational costs of Brexit are tarnishing this image. With case-studies on the UK's role in Somalia and Yemen we show how the UK has been able to further its interests with dual roles in the EU and Security Council, and the risks posed by tensions between trade and human rights after Brexit. We also analyse what it takes to be influential within the Security Council and argue that more attention should be paid to the practices of diplomacy. Influence is gained via penholding, strong diplomatic skill and a well-regarded UN permanent representative. The UK accrues political capital as a leader on the humanitarian and human rights side of the Council's agenda, but this reputation is at risk as it exits the EU.




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The Security Council's peacekeeping trilemma

4 March 2020 , Volume 96, Number 2

Paul D. Williams

The United Nations (UN) Security Council is stuck in a peacekeeping trilemma. This is a situation where the Council's three strategic goals for peacekeeping operations—implementing broad mandates, minimizing peacekeeper casualties and maximizing cost-effectiveness—cannot be achieved simultaneously. This trilemma stems from longstanding competing pressures on how the Council designs UN peacekeeping operations as well as political divisions between peacekeeping's three key groups of stakeholders: the states that authorize peacekeeping mandates, those that provide most of the personnel and field capabilities, and those that pay the majority of the bill. Fortunately, the most negative consequences of the trilemma can be mitigated and perhaps even transcended altogether. Mitigation would require the Council to champion and implement four main reforms: improving peacekeeper performance, holding peacekeepers accountable for misdeeds, adopting prioritized and sequenced mandates, and strengthening the financial basis for UN peacekeeping. Transcending the trilemma would require a more fundamental reconfiguration of the key stakeholder groups in order to create much greater unity of effort behind a re-envisaged peacekeeping enterprise. This is highly unlikely in the current international political context.




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China and Russia in R2P debates at the UN Security Council

7 May 2020 , Volume 96, Number 3

Zheng Chen and Hang Yin

While China and Russia's general policies towards the Responsibility to Protect (R2P) are similar, the two reveal nuanced differences in addressing specific emergencies. Both express support for the first two pillars of R2P while resisting coercive intervention under its aegis, as they share anxieties of domestic political security and concerns about their international image. Nonetheless, addressing cases like the Syrian crisis, Russian statements are more assertive and even aggressive while Chinese ones are usually vague and reactive. This article highlights the two states’ different tones through computer-assisted text analyses. It argues that diplomatic styles reflect Russian and Chinese perceptions of their own place in the evolving international order. Experiences in past decades create divergent reference points and status prospects for them, which leads to their different strategies in signalling Great Power status. As Beijing is optimistic about its status-rising prospects, it exercises more self-restraint in order to avoid external containments and is reluctant to act as an independent ‘spoiler’. Meanwhile, Moscow interprets its Great Power status more from a frame of ‘loss’ and therefore is inclined to adopt a sterner approach to signal its status. Although their policies complement each other on many occasions, there is nothing akin to a Sino–Russian ‘bloc’.




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US$10,000 gofundme launched to support animals at Hope Zoo

A gofundme account has been launched with the hope of keeping animals feed and to preserve endangered wildlife at the Hope Zoo in St Andrew. Curator, Joey Brown, organiser of the fundraiser, indicated that as a non-profit organisation,...




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More changes announced to court operations

Additional changes have been made to the operations of the island's courts in light of COVID-19. Changes below: Criminal Cases All hearings in the Home Circuit Court Division of the Gun Court, the High Court Division of the Gun Court, the...




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Russia’s Uncertain Regime Transformation

11 March 2020

Professor Nikolai Petrov

Senior Research Fellow, Russia and Eurasia Programme, Chatham House

Dr Ben Noble

Lecturer in Russian Politics, University College London; Senior Research Fellow, HSE, Moscow
Despite the drama, Vladimir Putin’s announcement endorsing a constitutional change allowing him to remain president from 2024 does surprisingly little to change the status quo.

2020-03-11-Putin-Constitution.jpg

Russian President Vladimir Putin addresses lawmakers debating on the second reading of the constitutional reform bill during a session of the State Duma, Russia's lower house of parliament March 10, 2020. Photo by ALEXANDER NEMENOV/AFP via Getty Images.

With Putin’s current term as head of state due to run out in 2024, the question everybody has been asking is what he will do to remain in power. The Russian president’s recent speech, made in person in the State Duma during the second reading of his own constitutional reform bill, has been interpreted by many as a clear answer. Summaries such as “Putin forever” and “perpetual Putin” abound. But the reality is not so clear.

Putin has not committed to standing for re-election in 2024, never mind staying in power until 2036, when two additional six-year terms from 2024 would run out. What he has done is provide the constitutional grounds to retain power as president. It creates a highly credible option without committing him to it.

And the uncertainty matters. Because as long as members of the elite are unsure whether Putin will take up the option to remain president, they are kept in check.

Broader constitutional reform

With the flurry of interest around Putin’s announcement, we should not lose sight of his moves to further strengthen the presidency. As part of the broader constitutional reform package, Russia’s existing “super-presidency” will gain additional powers, such as the authority to fire top-tier judges and to block legislation when the legislature has overridden a presidential veto (in other words, a “super-veto”).

The proposals also put the autonomy of local self-government at risk, with Moscow and regional executives gaining the constitutional power to hire and fire officials who are not even technically part of the state. And the president now has a formalised role as “general leader” of the government. Putin is creating the “Great Presidency”.

However, the majority of constitutional changes do not relate to the presidency – they have different purposes. Firstly, to revitalise support for the regime which took a hit following unpopular pension reforms in 2018. Secondly, to distract or appease those worried by Putin remaining in a strengthened presidency. And perhaps most significantly, to boost turnout in the nationwide vote on reforms.

This desire to re-energise popular support becomes apparent as the changes – some of which will have to be inserted rather awkwardly into the constitution’s structure – focus on three elements aimed squarely at improving the regime’s appeal: increased material support from the state for citizens, including indexing state pensions; an emphasis on “traditional values”, including a declaration that marriage can only be a union between a man and a woman; and increased Russian sovereignty, including a “nationalisation” of the elite, with a constitutional ban on top-level officials having bank accounts abroad. 

Constitutional reform is, moreover, the most visible part of a broader political transformation already underway, including a major propaganda drive. Putin has promised a significant increase in resources for its “maternity capital” programme, putting more money in the pockets of young Russian families.

And he has instructed Prime Minister Mikhail Mishustin’s government to focus on delivering his “national projects” – goals aimed at improving Russians’ lives across a range of areas, from infrastructure to education and healthcare.

Taking advantage of several imminent historical milestones is also on the cards. It has been reported Putin will sign the constitutional reform bill on March 18 – the anniversary of Russia’s annexation of Crimea. And May 9 is the 75th anniversary of the end of the Great Patriotic War (the Russian term for the Second World War), with foreign dignitaries invited to attend events in Moscow.

Putin has also been filling the airwaves with a high-production-values series called “20 Questions for Vladimir Putin”, as well as holding public meetings with citizens in provinces such as Cherepovets and Ivanovo. There is a clear aim to demonstrate the president is not only still in control, but also concerned with the well-being of everyday Russians.

With parliamentary elections scheduled for September 2021 the Kremlin knows that, to maintain its control of a super-majority of seats in the State Duma, its ratings-raising drive has to work – even if it does always have the option of using manifestly authoritarian methods for realising desired election results. A proposal to call early State Duma elections was made during the second reading of Putin’s reform bill, but was quickly withdrawn after Putin spoke out against the idea.

Russia’s complex architecture of “power”

Throughout this transformation, maintaining control of the elite – particularly of the siloviki – is key for Putin. A reshuffling and removal of senior officials in the Procuracy has seen Yury Chaika replaced as general prosecutor by Ivan Krasnov, previously a deputy chair of the Investigative Committee, which is widely seen as a rival structure in Russia’s complex architecture of “power” bodies.

When considered alongside the constitutional changes giving the president broader powers in appointing regional prosecutors, this is textbook “divide and rule”. Power balancing is also on display with the Security Council, as the job description for Dmitry Medvedev’s new role as its deputy chair could provide fertile ground for clashes with the body’s secretary, Nikolai Patrushev.

Pitting rival patronal networks against each other means Putin can keep rivals in check within the broader structure of the “Great Presidency”, while staying firmly in control himself.

The prospect of Putin remaining president is unlikely to be popular. According to data from independent Russian polling agency the Levada Centre, only 27 per cent of Russians want Putin to stay in the post after 2024. This figure could, of course, change in either direction as the prospect becomes more real for Russians. But if Putin’s announcement galvanises mass opposition, the authorities may well use responses to the COVID-19 outbreak to keep protesters at bay – something already on display in Moscow.

What this all means for Russia is that, despite the drama, considerable uncertainty remains following Putin’s announcement. What we can say for certain, however, is that it dashes hopes of serious political change any time soon.




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Implications of climate change for the UN Security Council: mapping the range of potential policy responses

6 November 2015 , Volume 91, Number 6

 

 

Shirley V. Scott




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Mark Wignall | Dunces, COVID-19 and the long haul

Chupski dons her mask once she ventures out in public. To the bank, the supermarket, the ­pharmacy, the ATM. So far I have never even tried on the one I have. Maybe I should have worn it last Thursday mid-­morning as I stood at the entrance to the...




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Online lunch service

Alatiffy provide Tiffin service like Healthy Food, Lunch & Dinner online home delivery in Delhi area like New Delhi, Connaught Place, Narela, Kanjhawala, Rajouri Garden, Dwarka, Saket, Defence Colony, Daryaganj, Seelampur, Shahdara, Preet Vihar, Chanakyapuri, Rohini, Patel Nagar, Kotwali, Gandhi Nagar, Delhi Cantonment, Narela, Kanjhawala, Punjabi Bagh, Najafgarh, Hauz Khas, Kalkaji, Civil Lines, Yamuna Vihar, Vasant Vihar, Alipur, Saraswati Vihar, Rajouri Garden, Kapashera, Mehrauli, Sarita Vihar, Karol Bagh, Karawal Nagar, Vivek Vihar, Mayur Vihar, laxmi nagar.




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Spring Training launches new era for Orioles

As pitchers and catchers reported Tuesday to Ed Smith Stadium, it marked the end to an offseason of overhaul in Baltimore, and the dawn of a new era. The focus will shift even further, from the front office to the field, when the club's first full squad workouts commence on Monday.




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Unexpected findings, with uncertain implications, in research imaging

When healthy volunteers are scanned as part of a research project, unexpected findings, with uncertain implications, can be thrown up. Joanna Wardlaw, professor of applied neuroimaging and honorary consultant neuroradiologist at the University of Edinburgh, joins us to discuss how her group deals with these incidental findings, and what...




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Should doctors prescribe acupuncture for pain?

Our latest debate asks, should doctors recommend acupuncture for pain? Asbjørn Hróbjartsson from the Center for Evidence-based Medicine at University of Southern Denmark argues no - evidence show's it's no worse than placebo. Mike Cummings, medical director of the British Medical Acupuncture Society argues yes - that there is evidence of efficacy,...




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Born equal - the launch of The BMJ special issue on race in medicine

Last week the BMJ published it’s first special edition into Racism in Medicine. The issues tacked ranged from differential attainment in medical school, to the physiological effects that experiencing everyday discrimination has. The issue was guest edited by Victor Adebowale, the Chief Executive of the social care enterprise Turning Point, and...




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Talk Evidence Covid-19 update - Confused symptoms, fatality rate uncertainty, Iceland's testing

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give...




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Endothelial Progenitor Cell Dysfunction: A Novel Concept in the Pathogenesis of Vascular Complications of Type 1 Diabetes

Cindy J.M. Loomans
Jan 1, 2004; 53:195-199
Complications




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Preservation of Pancreatic {beta}-Cell Function and Prevention of Type 2 Diabetes by Pharmacological Treatment of Insulin Resistance in High-Risk Hispanic Women

Thomas A. Buchanan
Sep 1, 2002; 51:2796-2803
Pathophysiology




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Quantification of the Relationship Between Insulin Sensitivity and {beta}-Cell Function in Human Subjects: Evidence for a Hyperbolic Function

Steven E Kahn
Nov 1, 1993; 42:1663-1672
Original Article




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Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes

David E. Kelley
Oct 1, 2002; 51:2944-2950
Metabolism and Signal Transduction




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De Novo Mutations in EIF2B1 Affecting eIF2 Signaling Cause Neonatal/Early-Onset Diabetes and Transient Hepatic Dysfunction

Permanent neonatal diabetes mellitus (PNDM) is caused by reduced β-cell number or impaired β-cell function. Understanding of the genetic basis of this disorder highlights fundamental β-cell mechanisms. We performed trio genome sequencing for 44 patients with PNDM and their unaffected parents to identify causative de novo variants. Replication studies were performed in 188 patients diagnosed with diabetes before 2 years of age without a genetic diagnosis. EIF2B1 (encoding the eIF2B complex α subunit) was the only gene with novel de novo variants (all missense) in at least three patients. Replication studies identified two further patients with de novo EIF2B1 variants. In addition to having diabetes, four of five patients had hepatitis-like episodes in childhood. The EIF2B1 de novo mutations were found to map to the same protein surface. We propose that these variants render the eIF2B complex insensitive to eIF2 phosphorylation, which occurs under stress conditions and triggers expression of stress response genes. Failure of eIF2B to sense eIF2 phosphorylation likely leads to unregulated unfolded protein response and cell death. Our results establish de novo EIF2B1 mutations as a novel cause of permanent diabetes and liver dysfunction. These findings confirm the importance of cell stress regulation for β-cells and highlight EIF2B1’s fundamental role within this pathway.




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A Novel Model of Diabetic Complications: Adipocyte Mitochondrial Dysfunction Triggers Massive {beta}-Cell Hyperplasia

Obesity-associated type 2 diabetes mellitus (T2DM) entails insulin resistance and loss of β-cell mass. Adipose tissue mitochondrial dysfunction is emerging as a key component in the etiology of T2DM. Identifying approaches to preserve mitochondrial function, adipose tissue integrity, and β-cell mass during obesity is a major challenge. Mitochondrial ferritin (FtMT) is a mitochondrial matrix protein that chelates iron. We sought to determine whether perturbation of adipocyte mitochondria influences energy metabolism during obesity. We used an adipocyte-specific doxycycline-inducible mouse model of FtMT overexpression (FtMT-Adip mice). During a dietary challenge, FtMT-Adip mice are leaner but exhibit glucose intolerance, low adiponectin levels, increased reactive oxygen species damage, and elevated GDF15 and FGF21 levels, indicating metabolically dysfunctional fat. Paradoxically, despite harboring highly dysfunctional fat, transgenic mice display massive β-cell hyperplasia, reflecting a beneficial mitochondria-induced fat-to-pancreas interorgan signaling axis. This identifies the unique and critical impact that adipocyte mitochondrial dysfunction has on increasing β-cell mass during obesity-related insulin resistance.




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Inhibition of NFAT Signaling Restores Microvascular Endothelial Function in Diabetic Mice

Central to the development of diabetic macro- and microvascular disease is endothelial dysfunction, which appears well before any clinical sign but, importantly, is potentially reversible. We previously demonstrated that hyperglycemia activates nuclear factor of activated T cells (NFAT) in conduit and medium-sized resistance arteries and that NFAT blockade abolishes diabetes-driven aggravation of atherosclerosis. In this study, we test whether NFAT plays a role in the development of endothelial dysfunction in diabetes. NFAT-dependent transcriptional activity was elevated in skin microvessels of diabetic Akita (Ins2+/–) mice when compared with nondiabetic littermates. Treatment of diabetic mice with the NFAT blocker A-285222 reduced NFATc3 nuclear accumulation and NFAT-luciferase transcriptional activity in skin microvessels, resulting in improved microvascular function, as assessed by laser Doppler imaging and iontophoresis of acetylcholine and localized heating. This improvement was abolished by pretreatment with the nitric oxide (NO) synthase inhibitor l-NG-nitro-l-arginine methyl ester, while iontophoresis of the NO donor sodium nitroprusside eliminated the observed differences. A-285222 treatment enhanced dermis endothelial NO synthase expression and plasma NO levels of diabetic mice. It also prevented induction of inflammatory cytokines interleukin-6 and osteopontin, lowered plasma endothelin-1 and blood pressure, and improved mouse survival without affecting blood glucose. In vivo inhibition of NFAT may represent a novel therapeutic modality to preserve endothelial function in diabetes.




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n-3 Fatty Acid and Its Metabolite 18-HEPE Ameliorate Retinal Neuronal Cell Dysfunction by Enhancing Müller BDNF in Diabetic Retinopathy

Diabetic retinopathy (DR) is a widespread vision-threatening disease, and neuroretinal abnormality should be considered as an important problem. Brain-derived neurotrophic factor (BDNF) has recently been considered as a possible treatment to prevent DR-induced neuroretinal damage, but how BDNF is upregulated in DR remains unclear. We found an increase in hydrogen peroxide (H2O2) in the vitreous of patients with DR. We confirmed that human retinal endothelial cells secreted H2O2 by high glucose, and H2O2 reduced cell viability of MIO-M1, Müller glia cell line, PC12D, and the neuronal cell line and lowered BDNF expression in MIO-M1, whereas BDNF administration recovered PC12D cell viability. Streptozocin-induced diabetic rats showed reduced BDNF, which is mainly expressed in the Müller glia cell. Oral intake of eicosapentaenoic acid ethyl ester (EPA-E) ameliorated BDNF reduction and oscillatory potentials (OPs) in electroretinography (ERG) in DR. Mass spectrometry revealed an increase in several EPA metabolites in the eyes of EPA-E–fed rats. In particular, an EPA metabolite, 18-hydroxyeicosapentaenoic acid (18-HEPE), induced BDNF upregulation in Müller glia cells and recovery of OPs in ERG. Our results indicated diabetes-induced oxidative stress attenuates neuroretinal function, but oral EPA-E intake prevents retinal neurodegeneration via BDNF in Müller glia cells by increasing 18-HEPE in the early stages of DR.




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D-backs announce record turnout to Fan Fest

As he walked around D-backs Fan Fest on Saturday afternoon at Salt River Fields, general manager Mike Hazen was pleasantly surprised to see the fan reaction as a record crowd of over 40,000 poured into the event.




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18F-Fluorocholine PET/CT in Primary Hyperparathyroidism: Superior Diagnostic Performance to Conventional Scintigraphic Imaging for Localization of Hyperfunctioning Parathyroid Glands

Primary hyperparathyroidism (PHPT) is a common endocrine disorder, definitive treatment usually requiring surgical removal of the offending parathyroid glands. To perform focused surgical approaches, it is necessary to localize all hyperfunctioning glands. The aim of the study was to compare the efficiency of established conventional scintigraphic imaging modalities with emerging 18F-fluorocholine PET/CT imaging in preoperative localization of hyperfunctioning parathyroid glands in a larger series of PHPT patients. Methods: In total, 103 patients with PHPT were imaged preoperatively with 18F-fluorocholine PET/CT and conventional scintigraphic imaging methods, consisting of 99mTc-sestamibi SPECT/CT, 99mTc-sestamibi/pertechnetate subtraction imaging, and 99mTc-sestamibi dual-phase imaging. The results of histologic analysis, as well as intact parathyroid hormone and serum calcium values obtained 1 d after surgery and on follow-up, served as the standard of truth for evaluation of imaging results. Results: Diagnostic performance of 18F-fluorocholine PET/CT surpassed conventional scintigraphic methods (separately or combined), with calculated sensitivity of 92% for PET/CT and 39%–56% for conventional imaging (65% for conventional methods combined) in the entire patient group. Subgroup analysis, differentiating single and multiple hyperfunctioning parathyroid glands, showed PET/CT to be most valuable in the group with multiple hyperfunctioning glands, with sensitivity of 88%, whereas conventional imaging was significantly inferior, with sensitivity of 22%–34% (44% combined). Conclusion: 18F-fluorocholine PET/CT is a diagnostic modality superior to conventional imaging methods in patients with PHPT, allowing for accurate preoperative localization.




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Manual acupuncture versus sham acupuncture and usual care for prophylaxis of episodic migraine without aura: multicentre, randomised clinical trial




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Anti-bullying programme is launched by orthopaedic trainees




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Royal College of Surgeons launches postgraduate surgical certificate




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The Dysfunction of Functions in Abstract Algebra

Kathleen Melhuish & Kristen Lew Texas State University “[Functions] are completely different, which is what makes this course so challenging.” – Abstract Algebra Student Functions are hard for students, even students in abstract algebra courses. Even if students have seen … Continue reading




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Elevated Liver Function Tests in Type 2 Diabetes

Elizabeth H. Harris
Jul 1, 2005; 23:115-119
Feature Articles




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Diabetes and Erectile Dysfunction

Neelima V. Chu
Jan 1, 2001; 19:
Practical Pointers




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Severe Hypoglycemia and Cognitive Function in Older Adults With Type 1 Diabetes: The Study of Longevity in Diabetes (SOLID)

OBJECTIVE

In children with type 1 diabetes (T1D), severe hypoglycemia (SH) is associated with poorer cognition, but the association of SH with cognitive function in late life is unknown. Given the increasing life expectancy in people with T1D, understanding the role of SH in brain health is crucial.

RESEARCH DESIGN AND METHODS

We examined the association between SH and cognitive function in 718 older adults with T1D from the Study of Longevity in Diabetes (SOLID). Subjects self-reported recent SH (previous 12 months) and lifetime history of SH resulting in inpatient/emergency department utilization. Global and domain-specific cognition (language, executive function, episodic memory, and simple attention) were assessed. The associations of SH with cognitive function and impaired cognition were evaluated via linear and logistic regression models, respectively.

RESULTS

Thirty-two percent of participants (mean age 67.2 years) reported recent SH and 50% reported lifetime SH. Compared with those with no SH, subjects with a recent SH history had significantly lower global cognition scores. Domain-specific analyses revealed significantly lower scores on language, executive function, and episodic memory with recent SH exposure and significantly lower executive function with lifetime SH exposure. Recent SH was associated with impaired global cognition (odds ratio [OR] 3.22, 95% CI 1.30, 7.94) and cognitive impairment on the language domain (OR 3.15, 95% CI 1.19, 8.29).

CONCLUSIONS

Among older adults with T1D, recent SH and lifetime SH were associated with worse cognition. Recent SH was associated with impaired global cognition. These findings suggest a deleterious role of SH on the brain health of older patients with T1D and highlight the importance of SH prevention.




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Endothelial Dysfunction in Diabetes: The role of reparatory mechanisms

Angelo Avogaro
May 1, 2011; 34:S285-S290
Hypertension




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Effects of Metformin, Metformin Plus Rosiglitazone, and Metformin Plus Lifestyle on Insulin Sensitivity and {beta}-Cell Function in TODAY

TODAY Study Group
Jun 1, 2013; 36:1749-1757
TODAY Study




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Air Force sets May 16 launch for X-37B spy plane

The Air Force said Wednesday it will launch the sixth mission of the uncrewed X-37B spy plane May 16 from Florida with a record number of experiments on board.




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Raytheon nabs $19M for RAM missiles, GMLS launchers

Raytheon Missile Systems was awarded a $19 million contract modification to exercise options for Navy Rolling Airframe Missile and Guided Missile Launching Systems, according to the Department of Defense.




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Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial

Helena W. Rodbard
Dec 1, 2019; 42:2272-2281
Emerging Therapies: Drugs and Regimens




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Treatment of Type 2 Diabetes: From "Guidelines" to "Position Statements" and Back: Recommendations of the Israel National Diabetes Council

Ofri Mosenzon
Aug 1, 2016; 39:S146-S153
II. Diabetes Treatment Options




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Time Course of Normalization of Functional {beta}-Cell Capacity in the Diabetes Remission Clinical Trial After Weight Loss in Type 2 Diabetes

OBJECTIVE

To assess functional β-cell capacity in type 2 diabetes during 2 years of remission induced by dietary weight loss.

RESEARCH DESIGN AND METHODS

A Stepped Insulin Secretion Test with Arginine was used to quantify functional β-cell capacity by hyperglycemia and arginine stimulation. Thirty-nine of 57 participants initially achieved remission (HbA1c <6.5% [<48 mmol/mol] and fasting plasma glucose <7 mmol/L on no antidiabetic drug therapy) with a 16.4 ± 7.7 kg weight loss and were followed up with supportive advice on avoidance of weight regain. At 2 years, 20 participants remained in remission in the study. A nondiabetic control (NDC) group, matched for age, sex, and weight after weight loss with the intervention group, was studied once.

RESULTS

During remission, median (interquartile range) maximal rate of insulin secretion increased from 581 (480–811) pmol/min/m2 at baseline to 736 (542–998) pmol/min/m2 at 5 months, 942 (565–1,240) pmol/min/m2 at 12 months (P = 0.028 from baseline), and 936 (635–1,435) pmol/min/m2 at 24 months (P = 0.023 from baseline; n = 20 of 39 of those initially in remission). This was comparable to the NDC group (1,016 [857–1,507] pmol/min/m2) by 12 (P = 0.064) and 24 (P = 0.244) months. Median first-phase insulin response increased from baseline to 5 months (42 [4–67] to 107 [59–163] pmol/min/m2; P < 0.0001) and then remained stable at 12 and 24 months (110 [59–201] and 125 [65–166] pmol/min/m2, respectively; P < 0.0001 vs. baseline) but lower than that of the NDC group (250 [226–429] pmol/min/m2; P < 0.0001).

CONCLUSIONS

A gradual increase in assessed functional β-cell capacity occurred after weight loss, becoming similar to that of NDC group participants by 12 months. This result was unchanged at 2 years with continuing remission of type 2 diabetes.




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Association launches new ADA Science & Research Institute

The American Dental Association launched the new ADA Science & Research Institute LLC on Jan. 1, bringing together the Science Institute in Chicago and research group in Gaithersburg, Maryland, that previously reported to the ADA Foundation.




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New clinical dental licensure examination to launch in June

The Dental Licensure Objective Structured Clinical Examination, or DLOSCE, is expected to launch in June, the Joint Commission on National Dental Examinations announced April 2.




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ADA council affirms importance of code of ethics during COVID-19 pandemic

The ADA Council on Ethics, Bylaws and Judicial Affairs’ ethics subcommittee authored an online essay as part of its Ethical Moment series in the May issue of The Journal of the American Dental Association, affirming that the ADA Principles of Ethics and Code of Professional Conduct is just as important as ever when making the difficult decisions they encounter on a daily basis.




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North Carolina interactive map launches to help public find emergency dental treatment during pandemic

A North Carolina oral health coalition, in collaboration with multiple state partners, has developed an interactive map to help guide the public to sites where emergency dental services are available throughout the Tar Heel State both during and after the COVID-19 outbreak.




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SBA announces funding no longer available for Economic Injury Disaster Loans, Paycheck Protection Program

The Small Business Administration said that as of April 16, the agency is unable to accept any new applications for the Paycheck Protection Program or the Economic Injury Disaster Loans due to a lack of funding.




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3M granted injunction against New Jersey company in N95 price-gouging scheme

A federal judge on May 4 granted 3M, the maker of N95 masks, an injunction against a New Jersey-based company accused of using 3M’s trademarks and deliberately inflating the price of the face masks.




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Johns Hopkins to launch trials of blood plasma treatment for COVID-19

Johns Hopkins University will start two clinical trials of convalescent blood plasma for treatment of COVID-19, the disease caused by the new coronavirus.




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Effects of Low-Energy Diet or Exercise on Cardiovascular Function in Working-Age Adults With Type 2 Diabetes: A Prospective, Randomized, Open-Label, Blinded End Point Trial

OBJECTIVE

To confirm the presence of subclinical cardiovascular dysfunction in working-age adults with type 2 diabetes (T2D) and determine whether this is improved by a low-energy meal replacement diet (MRP) or exercise training.

RESEARCH DESIGN AND METHODS

This article reports on a prospective, randomized, open-label, blinded end point trial with nested case-control study. Asymptomatic younger adults with T2D were randomized 1:1:1 to a 12-week intervention of 1) routine care, 2) supervised aerobic exercise training, or 3) a low-energy (~810 kcal/day) MRP. Participants underwent echocardiography, cardiopulmonary exercise testing, and cardiac magnetic resonance (CMR) at baseline and 12 weeks. The primary outcome was change in left ventricular (LV) peak early diastolic strain rate (PEDSR) as measured by CMR. Healthy volunteers were enrolled for baseline case-control comparison.

RESULTS

Eighty-seven participants with T2D (age 51 ± 7 years, HbA1c 7.3 ± 1.1%) and 36 matched control participants were included. At baseline, those with T2D had evidence of diastolic dysfunction (PEDSR 1.01 ± 0.19 vs. 1.10 ± 0.16 s–1, P = 0.02) compared with control participants. Seventy-six participants with T2D completed the trial (30 routine care, 22 exercise, and 24 MRP). The MRP arm lost 13 kg in weight and had improved blood pressure, glycemia, LV mass/volume, and aortic stiffness. The exercise arm had negligible weight loss but increased exercise capacity. PEDSR increased in the exercise arm versus routine care (β = 0.132, P = 0.002) but did not improve with the MRP (β = 0.016, P = 0.731).

CONCLUSIONS

In asymptomatic working-age adults with T2D, exercise training improved diastolic function. Despite beneficial effects of weight loss on glycemic control, concentric LV remodeling, and aortic stiffness, a low-energy MRP did not improve diastolic function.