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The Triumvirate: {beta}-Cell, Muscle, Liver: A Collusion Responsible for NIDDM

Ralph A DeFronzo
Jun 1, 1988; 37:667-687
Lilly Lecture 1987




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Use of antiviral drug in poultry is blamed for drug resistant strains of avian flu




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Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study




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Iran Workshop Series: Domestic, Regional and International Outlook

Invitation Only Research Event

17 December 2019 - 10:00am to 3:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

After a summer of regional tensions and continued uncertainty regarding the future of the JCPOA, the Chatham House MENA Programme held a closed workshop to examine the impact of the Trump administration’s maximum pressure campaign.

Discussions focused on the domestic developments and challenges inside Iran, prospects for new negotiations with Iran, and the regional issues facing the country. Participants also considered the differences between American and European approaches towards Iran.

 

Event attributes

Chatham House Rule

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Iran Crisis: The Impact on Oil Markets

14 January 2020

Professor Paul Stevens

Distinguished Fellow, Energy, Environment and Resources Programme
The assassination of Qassem Soleimani has exacerbated the sensitivity of oil markets to political events and brought geopolitics back into global oil prices.

2020-01-14-Hormuz.jpg

Satellite image of the Strait of Hormuz. Photo: Getty Images.

The assassination of General Qassem Soleimani has created much speculation about the possible impact on oil markets and – although any impact will very much depend upon what happens next in terms of political and military responses – theoretically the potential exists for Iran to seriously destabilize oil markets, raising oil prices.

Arguably, it would be in Iran’s interest to do so. It would certainly hurt Trump’s possibility of a second term if higher prices were to last for some time as the 2020 presidential election gets underway. And it would also help shore up Iran’s failing economy. 

The assassination did initially cause oil prices to rise by a few dollars before quickly falling back, and the missile attacks by Iran produced a similar response. However, direct action by Iran to raise prices – for example by trying to close the Strait of Hormuz – is unlikely.

Around one-fifth of the world's oil supplies passes through the Strait of Hormuz, a narrow choke point between Iran and the Arabian Peninsula. Closing it would invite serious military action by the Americans and many of its allies who, so far, have been rather lukewarm over Trump’s actions. It would also possibly limit Iran’s own oil exports.

Similarly, overt attacks on American allies in the region such as Saudi Arabia and the UAE would probably invite too heavy a reaction, although this is uncertain given the lack of response after the alleged Iranian attacks on Abqaiq and Khurais in mid-September.

Indirect action by Iran to affect oil supplies is much more likely as they have many options by using their proxies to affect others’ oil production. This is especially true for Iraq, which is now an important source of global oil supply as Iraqi exports in 2019 averaged 3.53 million barrels per day (Mb/d), a significant amount.

Iraq’s future production has already been damaged as international oil companies are withdrawing staff for safety reasons, anticipating potential attacks by both Iraqi and Iranian sources. It is now very unlikely that the crucial ‘common seawater supply project’ being run by Exxon – essential for expanding production capacity – will go ahead in the near future.

However, one important consequence of the assassination that has attracted little attention is that it has almost fully restored the role of geopolitics into the determination of oil prices. Up to 2014, geopolitics played a key role in determining oil prices in the paper markets where perceptions and expectations ruled.

Prices determined in these markets – NYMEX in New York, ICE in London and other lesser futures markets throughout the world – then influence wet barrel markets where real barrels of oil are traded. 

In 2014, the world was so oversupplied with real oil barrels that the oil price collapsed – the price of Brent crude fell from $110.72 on 23 May to $46.44 eight months later. Thereafter, little if any attention was given to geopolitical events, and geopolitics became marginalized in the determination of crude oil prices.

This began to change in 2019. The market remained physically over-supplied but events in the Gulf began to attract attention. In June, there were a series of attacks on oil tankers close to the Gulf, followed by attacks on Saudi Arabia’s Abqaiq processing facility and the Khurais oil field in September.

The Americans claimed these attacks were launched by Iran, but no convincing evidence for the claim was provided. Both attacks produced an initial price response but it was surprisingly limited and short-lived. However, it did suggest that geopolitics might be creeping back into influencing oil prices.

This became ever more noticeable in the third and fourth quarters as rumours regarding the trade talks between China and US clearly began to affect price – talks going well meant higher oil demand, and prices rose; talks going badly meant lower oil demand, and prices fell.

Meanwhile, the oil market showed signs of tightening towards the end of 2019. Although there was much cheating on the OPEC+ agreement that was trying to restrain production and protect prices, the OPEC meeting last December saw both Iraq and Nigeria agreeing to restrain production. 

US stock levels also began to fall in December and the futures markets began to price in a tightening market towards the end of 2020. Significantly, the tighter the market appears, the greater attention is paid to the level of spare producing capacity.

Just before the attack on Abqaiq, the International Energy Agency (IEA) estimated there was 3.5 Mb/d spare capacity in OPEC which, historically, is quite comfortable. However, 2.5 of this was estimated to be in Saudi Arabia, so how much of this spare capacity still existed after the Abqaiq attack?

The Saudis claimed the Abqaiq capacity was quickly restored but technical experts greeted this with considerable skepticism, not least because the Abqaiq equipment was highly specialized. If spare capacity is tight, this makes the oil price vulnerable to geopolitical scares and rumours, real or imagined. 

Although the assassination of General Soleimani has exacerbated the sensitivity of oil markets to geopolitical events, this becomes irrelevant if a serious shooting war starts in the region. Saudi Arabia, the UAE and Iraq’s oil infrastructure remains highly vulnerable to attack either directly by Iran or one of its many proxies, suggesting oil prices will become increasingly volatile but, at the same time, benefit from a rising geopolitical premium.




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Same Old Politics Will Not Solve Iraq Water Crisis

15 April 2020

Georgia Cooke

Project Manager, Middle East and North Africa Programme

Dr Renad Mansour

Senior Research Fellow, Middle East and North Africa Programme; Project Director, Iraq Initiative

Glada Lahn

Senior Research Fellow, Energy, Environment and Resources Programme
Addressing Iraq’s water crisis should be a priority for any incoming prime minister as it is damaging the country’s attempts to rebuild. But successive governments have allowed the problem to fester.

2020-04-15-Iraq-Water

Punting in the marshes south of the Iraqi city of Ammarah. Photo by Ghaith Abdul-Ahad/Getty Images.

Historically, Iraq lay claim to one of the most abundant water supplies in the Middle East. But the flow of the Tigris and Euphrates rivers has reduced by up to 40% since the 1970s, due in part to the actions of neighbouring countries, in particular Turkey, upstream.

Rising temperatures and reduced rainfall due to climate change are also negatively impacting Iraq’s water reserves. Evaporation from dams and reservoirs is estimated to lose the country up to 8 billion cubic metres of water every year.

A threat to peace and stability

Shortages have dried up previously fertile land, increasing poverty in agricultural areas. Shortages have also served to fuel conflict: communities faced with successive droughts and government inertia proved to be easy targets for ISIS recruiters, who lured farmers into joining them by offering money and food to feed their families. Economic hardship for those whose livelihoods relied upon river water has also driven rural to urban migration, putting significant strain on already over-populated towns and cities, exacerbating housing, job and electricity shortages, and widening the gap between haves and have-nots.

But scarcity isn’t the most crucial element of Iraq’s water crisis – contamination is. Decades of local government mismanagement, corrupt practices and a lack of regulation of dumping (it is estimated up to 70% of Iraq’s industrial waste is dumped directly into water) has left approximately three in every five citizens without a reliable source of potable water.

In 2018, 118,000 residents of Basra province were hospitalised with symptoms brought on by drinking contaminated water, which not only put a spotlight on the inadequacies of a crumbling healthcare system but sparked mass protests and a subsequent violent crackdown.

The water crisis is also undermining the stability of the country’s federal governance model, by occasionally sparking disputes between Baghdad and the Kurdistan Regional Government, as well as between governorates in the south.

The crisis is both a symptom and a cause of poor governance. Iraq is stuck in a cycle whereby government inaction causes shortages and contamination, which result in economic losses, reduced food supply, increased prices and widespread poor health. This in turn leads to increasing levels of poverty, higher demand on services and civil unrest, increasing the pressure on a weak, dysfunctional system of government.

What can be done?

The first priority should be modernising existing water-management infrastructure - a relic of a time when the problem was an excess rather than a shortage of water (the last time Iraq’s flood defences were required was 1968). Bureaucratic hurdles, widespread corruption and an endless cycle of other crises taking precedent prevent good initiatives from being implemented or scaled up.

Diversifying energy sources to improve provision is crucial. Baghdad has a sewage treatment plant that originally ran on its own electricity source, but this capacity was destroyed in 1991 and was never replaced. The city continues to suffer from dangerous levels of water pollution because the electricity supply from the grid is insufficient to power the plant. Solar energy has great potential in sun-drenched Iraq to bridge the gaping hole in energy provision, but successive governments have chosen to focus on fossil fuels rather than promoting investment to grow the renewables sector.

Heightened tension with upstream Turkey could turn water into another cause of regional conflict. But, if approached differently, collaboration between Iraq and its neighbour could foster regional harmony.

Turkey’s elevated geography and cooler climate mean its water reserves suffer 75% less evaporation than Iraq’s. Given that Turkey’s top energy priority is the diversification of its supply of imported hydrocarbons, a win-win deal could see Turkey exchange access to its water-management infrastructure for delivery of reduced cost energy supplies from Iraq.

German-French cooperation on coal and steel in the 1950s and the evolution of economic integration that followed might provide a model for how bilateral cooperation over one issue could result in cooperation with other regional players (in this case Iran and Syria) on a range of other issues. This kind of model would need to consider the future of energy, whereby oil and gas would be replaced by solar-power exports.

These solutions have been open to policymakers for years and yet they have taken little tangible action. While there are leaders and bureaucrats with the will to act, effective action is invariably blocked by a complex and opaque political system replete with vested interests in maintaining power and wealth via a weak state and limited services from central government.

Breaking the cycle

To break this cycle, Iraq needs a group of professional and able actors outside of government to work with willing elements of the state bureaucracy as a taskforce to pressure for action and accountability. Publishing the recommendations from a hitherto withheld report produced in the aftermath of Basra’s 2018 heath crisis would be a great start.

In time, this taskforce could champion the prioritisation of water on the national agenda, the implementation of infrastructure upgrades, and hold more productive conversations with neighbour states.

With such a high degree of state fragmentation and dysfunction in Iraq, looking to the central government to provide leadership will not yield results. Engagement with a coalition of non-state actors can begin to address the water crisis and also open a dialogue around new models of governance for other critical issues. This might even be a starting point for rewriting the tattered social contract in Iraq.

This piece is based on insights and discussion at a roundtable event, Conflict and the Water Crisis in Iraq, held at Chatham House on March 9 as part of the Iraq Initiative.




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Spiraling Violence and Drought Drive Refugee Crisis in South Sudan

Nearly 4 million South Sudanese have been driven from their homes by violence or food insecurity since late 2013, roughly half seeking refuge in neighboring countries. Drought and conflict have converged in the young country to fuel one of the world's most severe humanitarian emergencies. This article examines refugee flows from South Sudan, underlying drivers, and regional and international responses to the crisis.




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Liraglutide, a Long-Acting Human Glucagon-Like Peptide-1 Analog, Given as Monotherapy Significantly Improves Glycemic Control and Lowers Body Weight Without Risk of Hypoglycemia in Patients With Type 2 Diabetes

Tina Vilsbøll
Jun 1, 2007; 30:1608-1610
BR Emerging Treatments and Technologies




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Former intelligence chief Mustafa al-Kadhini named Iraqi prime minister

Former intelligence chief Mustafa al-Kadhini was named prime minister of Iraq on Thursday, after five months of political instability in the Middle Eastern nation.




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Moderate earthquake in Iran hits near Tehran; 2 dead

At least two people died and more than a dozen were hurt Friday when a moderate earthquake struck in Iran's northern city of Damavand, near Tehran.




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DoD releases name of soldier who died in 'non-combat-related' incident in Iraq

The Pentagon announced Tuesday that Sgt. Christopher Wesley Curry died Monday in Iraq in what officials describe as a non-combat-related incident.




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Efficacy and Safety of Liraglutide 3.0 mg in Individuals With Overweight or Obesity and Type 2 Diabetes Treated With Basal Insulin: The SCALE Insulin Randomized Controlled Trial

W. Timothy Garvey
May 1, 2020; 43:1085-1093
Emerging Therapies: Drugs and Regimens




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ADA streams webinar April 27 on respiratory protection

A recorded webinar will stream April 27 outlining the Association’s interim recommendation for personal protective equipment in dental settings as some states consider loosening social distancing mandates.




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Arthritis drug shows promise against respiratory distress caused by COVID-19

Anakinra, a drug developed to treat rheumatoid arthritis might help patients who have developed acute respiratory distress syndrome caused by COVID-19, a small study published by The Lancet Rheumatology has found.




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Combination Therapy With Canagliflozin Plus Liraglutide Exerts Additive Effect on Weight Loss, but Not on HbA1c, in Patients With Type 2 Diabetes

OBJECTIVE

To examine the effect of combination therapy with canagliflozin plus liraglutide on HbA1c, endogenous glucose production (EGP), and body weight versus each therapy alone.

RESEARCH DESIGN AND METHODS

Forty-five patients with poorly controlled (HbA1c 7–11%) type 2 diabetes mellitus (T2DM) on metformin with or without sulfonylurea received a 9-h measurement of EGP with [3-3H]glucose infusion, after which they were randomized to receive 1) liraglutide 1.2 mg/day (LIRA); 2) canagliflozin 100 mg/day (CANA); or 3) liraglutide 1.2 mg plus canagliflozin 100 mg (CANA/LIRA) for 16 weeks. At 16 weeks, the EGP measurement was repeated.

RESULTS

The mean decrease from baseline to 16 weeks in HbA1c was –1.67 ± 0.29% (P = 0.0001), –0.89 ± 0.24% (P = 0.002), and –1.44 ± 0.39% (P = 0.004) in patients receiving CANA/LIRA, CANA, and LIRA, respectively. The decrease in body weight was –6.0 ± 0.8 kg (P < 0.0001), –3.5 ± 0.5 kg (P < 0.0001), and –1.9 ± 0.8 kg (P = 0.03), respectively. CANA monotherapy caused a 9% increase in basal rate of EGP (P < 0.05), which was accompanied by a 50% increase (P < 0.05) in plasma glucagon-to-insulin ratio. LIRA monotherapy reduced plasma glucagon concentration and inhibited EGP. In CANA/LIRA-treated patients, EGP increased by 15% (P < 0.05), even though the plasma insulin response was maintained at baseline and the CANA-induced rise in plasma glucagon concentration was blocked.

CONCLUSIONS

These results demonstrate that liraglutide failed to block the increase in EGP caused by canagliflozin despite blocking the rise in plasma glucagon and preventing the decrease in plasma insulin concentration caused by canagliflozin. The failure of liraglutide to prevent the increase in EGP caused by canagliflozin explains the lack of additive effect of these two agents on HbA1c.




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Cardiovascular Risk Reduction With Liraglutide: An Exploratory Mediation Analysis of the LEADER Trial

OBJECTIVE

The LEADER trial (ClinicalTrials.gov reg. no. NCT01179048) demonstrated a reduced risk of cardiovascular (CV) events for patients with type 2 diabetes who received the glucagon-like peptide 1 receptor agonist liraglutide versus placebo. The mechanisms behind this CV benefit remain unclear. We aimed to identify potential mediators for the CV benefit observed with liraglutide in the LEADER trial.

RESEARCH DESIGN AND METHODS

We performed exploratory analyses to identify potential mediators of the effect of liraglutide on major adverse CV events (MACE; composite of CV death, nonfatal myocardial infarction, or nonfatal stroke) from the following candidates: glycated hemoglobin (HbA1c), body weight, urinary albumin-to-creatinine ratio (UACR), confirmed hypoglycemia, sulfonylurea use, insulin use, systolic blood pressure, and LDL cholesterol. These candidates were selected as CV risk factors on which liraglutide had an effect in LEADER such that a reduction in CV risk might result. We used two methods based on a Cox proportional hazards model and the new Vansteelandt method designed to use all available information from the mediator and to control for confounding factors.

RESULTS

Analyses using the Cox methods and Vansteelandt method indicated potential mediation by HbA1c (up to 41% and 83% mediation, respectively) and UACR (up to 29% and 33% mediation, respectively) on the effect of liraglutide on MACE. Mediation effects were small for other candidates.

CONCLUSIONS

These analyses identify HbA1c and, to a lesser extent, UACR as potential mediators of the CV effects of liraglutide. Whether either is a marker of an unmeasured factor or a true mediator remains a key question that invites further investigation.




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Iraq War Naysayers May Have Hindsight Bias

Antiwar liberals last week got to savor the four most satisfying words in the English language: "I told you so."




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Disagree About Iraq? You're Not Just Wrong -- You're Evil.

The conviction of I. Lewis "Scooter" Libby last week gave Americans a chance to pick at the scab of what has become a favored obsession -- the debate over the motives of the Bush administration in the run-up to the war in Iraq.




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One Thing We Can't Build Alone in Iraq

When Columbia University sociologist Peter Bearman dived into the world of the white-gloved workers who open the front doors of expensive New York apartment buildings, he found that most people who applied for jobs as doormen never got one. Most doormen, however, had not applied for their jobs.




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9/11, Iraq and the Desensitization of the Victimized

In the days after the attacks of Sept. 11, 2001, with the twin towers vanished from Manhattan's skyline, a poem by W.H. Auden could have been the song of a wounded nation. "September 1, 1939," written on the eve of World War II, seemed eerily prescient:




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Simple, effective tech to connect communities in crisis | Johanna Figueira

The world is more connected than ever, but some communities are still cut off from vital resources like electricity and health care. In this solution-oriented talk, activist Johanna Figueira discusses her work with Code for Venezuela -- a platform that gathers technologists to address Venezuela's needs for information and medical supplies -- and shares ideas for how it could be used as a model to help other communities in need.




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2 questions to uncover your passion -- and turn it into a career | Noeline Kirabo

What's your passion? Social entrepreneur Noeline Kirabo reflects on her work helping out-of-school young people in Uganda turn their passions into profitable businesses -- and shares the two questions you can ask yourself to begin doing the same.




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Talking Across Divides And Quashing Conspiracy Theories: The Week’s Best Psychology Links

Our weekly round-up of the best psychology coverage from elsewhere on the web




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Nebraska Education Department accused of software-pirating




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Teacher's Facebook Post on Students' Social Media Secrets Goes Viral

Utah science teacher Skipper Coates asked her students to complete the following sentence: "What my parents don't know about social media is..."




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Pirates of romance / Asta Idonea..

"Xander joins his local am-dram group in order to make friends. He certainly doesn't expect to fall for the group's playboy star. Graeme is confident and easygoing. He believes in fun without commitment. However, all that changes when Xander gets under his skin" -- Pub;isher info.




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The Virago story : assessing the impact of a feminist publishing phenomenon / Catherine Riley.

Virago Press -- History.




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Pirates : a new history, from Vikings to Somali raiders / Peter Lehr.

Piracy -- History.




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Catch and kill : lies, spies, and a conspiracy to protect predators / Ronan Farrow.

Weinstein, Harvey, 1952-




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Spiral movements of the apex of the exposed mammalian heart.

United Kingdom, c.1939.




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Spiral movements of the apex of the exposed mammalian heart.

United Kingdom, c.1939.




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Die Bedeutung des Herzschlages für die Athmung : eine neue Theorie der Respiration dargestellt für Physiologen und Ärzte / von Ernst Fleischl v. Marxow.

Stuttgart : F. Enke, 1887.




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Die Inhalations-Therapie in Krankheiten der Respirations-Organe : mit besonderer Berücksichtigung der durch das Laryngoscop ermittelten Krankheiten des Kehlkopfs / von Georg Lewin.

Berlin : A. Hirschwald, 1865.




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Die pneumatische Behandlung der Respirations- und Circulationskrankheiten : im Anschluss an die Pneumatometrie, Spirometrie und Brustmessung / bearbeitet von L. Waldenburg.

Berlin : A. Hirschwald, 1875.




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Dr Pereira's elements of materia medica and therapeutics : abridged and adapted for the use of medical and pharmaceutical practitioners and students, and comprising all the medicines of the British pharmacopoeia, with such others as are frequently ord

London : Longmans, Green, 1872.




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Du réflexe cutané respiratoire chez le foetus à terme; faits d'expérimentation et de clinique concernant son existence; application de ces données à la pratique des accouchements / par Joseph Magne.

Paris : Steinheil, 1896.




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An elementary treatise on the function of vision and its anomalies / by Dr. Giraud-Teulon ; translated from the second French edition by Lloyd Owen.

London : Bailliere, Tindall, & Cox, 1880.




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Les oeuures du R. P. Gabriel de Castaigne, tant medicinales que chymiques, : diuisées en quatre principaux traitez. I. Le paradis terrestre. II. Le grand miracle de la nature metallique. III. L'or potable. IV. Le thresor philosophique de la medec

A Paris : Chez Iean Dhourry, au bout du Pont-Neuf, près les Augustins, à l'Image S. Iean, M. DC. LXI. [1661]




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O problema do abuso de drogas prevenção através investigação, pesquisa e educação / Murillo de Macedo Pereira, Vera Kühn de Macedo Pereira.

São Paulo : Governo do Estado de Sao Paulo, Secretaria da Segurança Pública, 1975.




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Coca : cocaína / Murillo de Macedo Pereira.

São Paulo : Serviço Grafíco da Secretaria da Segurança Pública, 1976.




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A pesquisa sobre o problema do abuso de drogas / Murillo de Macedo Pereira.

São Paulo : Serviço Grafíco da Secretaria da Segurança Pública, 1976.




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Hierarchical modelling of power law processes for the analysis of repairable systems with different truncation times: An empirical Bayes approach

Rodrigo Citton P. dos Reis, Enrico A. Colosimo, Gustavo L. Gilardoni.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 2, 374--396.

Abstract:
In the data analysis from multiple repairable systems, it is usual to observe both different truncation times and heterogeneity among the systems. Among other reasons, the latter is caused by different manufacturing lines and maintenance teams of the systems. In this paper, a hierarchical model is proposed for the statistical analysis of multiple repairable systems under different truncation times. A reparameterization of the power law process is proposed in order to obtain a quasi-conjugate bayesian analysis. An empirical Bayes approach is used to estimate model hyperparameters. The uncertainty in the estimate of these quantities are corrected by using a parametric bootstrap approach. The results are illustrated in a real data set of failure times of power transformers from an electric company in Brazil.




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Vertebrate and invertebrate respiratory proteins, lipoproteins and other body fluid proteins

9783030417697 (electronic bk.)




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Hepatitis B virus infection : molecular virology to antiviral drugs

9789811391514 (electronic bk.)




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Dynamics of immune activation in viral diseases

9789811510458 (electronic bk.)




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Nasal Respiration Entrains Human Limbic Oscillations and Modulates Cognitive Function

Christina Zelano
Dec 7, 2016; 36:12448-12467
Systems/Circuits




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all old folks go 2 heaven - :pirate:




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Mama Mirabelle




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Interview: Luiz Awazu Pereira da Silva

Interview with Luiz A Pereira da Silva, Deputy General Manager of the BIS, in Central Banking, conducted by Ms Rachael King and published on 16 February 2020.




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Type I Interferons Act Directly on Nociceptors to Produce Pain Sensitization: Implications for Viral Infection-Induced Pain

One of the first signs of viral infection is body-wide aches and pain. Although this type of pain usually subsides, at the extreme, viral infections can induce painful neuropathies that can last for decades. Neither of these types of pain sensitization is well understood. A key part of the response to viral infection is production of interferons (IFNs), which then activate their specific receptors (IFNRs) resulting in downstream activation of cellular signaling and a variety of physiological responses. We sought to understand how type I IFNs (IFN-α and IFN-β) might act directly on nociceptors in the dorsal root ganglion (DRG) to cause pain sensitization. We demonstrate that type I IFNRs are expressed in small/medium DRG neurons and that their activation produces neuronal hyper-excitability and mechanical pain in mice. Type I IFNs stimulate JAK/STAT signaling in DRG neurons but this does not apparently result in PKR-eIF2α activation that normally induces an anti-viral response by limiting mRNA translation. Rather, type I IFNs stimulate MNK-mediated eIF4E phosphorylation in DRG neurons to promote pain hypersensitivity. Endogenous release of type I IFNs with the double-stranded RNA mimetic poly(I:C) likewise produces pain hypersensitivity that is blunted in mice lacking MNK-eIF4E signaling. Our findings reveal mechanisms through which type I IFNs cause nociceptor sensitization with implications for understanding how viral infections promote pain and can lead to neuropathies.

SIGNIFICANCE STATEMENT It is increasingly understood that pathogens interact with nociceptors to alert organisms to infection as well as to mount early host defenses. Although specific mechanisms have been discovered for diverse bacterial and fungal pathogens, mechanisms engaged by viruses have remained elusive. Here we show that type I interferons, one of the first mediators produced by viral infection, act directly on nociceptors to produce pain sensitization. Type I interferons act via a specific signaling pathway (MNK-eIF4E signaling), which is known to produce nociceptor sensitization in inflammatory and neuropathic pain conditions. Our work reveals a mechanism through which viral infections cause heightened pain sensitivity