Seasonal and pandemic influenza causes 650,000 deaths annually in the world. The emergence of drug-resistance to specific anti-influenza drugs such as oseltamivir and baloxavir marboxil highlights the urgency of novel anti-influenza chemical entity discovery. In this study, we report a series of novel thiazolides derived from an FDA-approved drug nitazoxanide with antiviral activity against influenza and a broad range of viruses. The preferred candidates 4a and 4d showed significantly enhanced anti-influenza potentials with 10-fold improvement, compared with nitazoxanide, and were effective against a variety of influenza subtypes including oseltamivir-resistant strains. Notably, the combination using of compounds 4a/4d and oseltamivir carboxylate or zanamivir displayed synergistic antiviral effect against oseltamivir-resistant strain. Mode of action analysis demonstrated that compounds 4a/4d acted at the late phase of viral infection cycle through inhibiting viral RNA transcription and replication. Further experiments showed that treatment with compounds 4a/4d significantly inhibited influenza virus infection in human lung organoids, suggesting the druggability of the novel thiazolides. In-depth transcriptome analysis revealed a series of up-regulated cellular genes that may contribute to the antiviral activities of 4a/4d. Together, our study pointed the optimization direction of nitazoxanide as anti-influenza drug, and discovered two novel-structured candidates 4a/4d with relatively broad-spectrum antiviral potential.

CYP450 enzymes are involved in biotransformation of chloroquine (CQ), but the role of the different metabolism profiles of this drug has not been properly investigated in relation to P. vivax recurrences. To investigate the influence of CYPs genotypes associated with CQ-metabolism on early recurrence rates of P. vivax, a case-control study was carried out. Cases included patients presenting an early recurrence (CQ-recurrent), defined as recurrence during the first 28 days after initial infection, plasma concentrations of CQ plus desethylchloroquine (DCQ, the major CQ metabolite) higher than 100 ng/mL. A control (CQ-responsive) with no parasite recurrence over the follow-up was also included. CQ and DCQ plasma levels were measured on Day 28. CQ CYPs (CYP2C8, CYP3A4 and CYP3A5) genotypes were determined by real-time PCR. An ex vivo study was conducted to verify CQ and DCQ efficacy in P. vivax isolates. The frequency of alleles associated with normal and slow metabolism was similar between the cases and controls for CYP2C8 (OR=1.45, 95% CI=0.51-4.14, p=0.570), CYP3A4 (OR=2.38, 95% CI=0.92-6.19, p=0.105) and CYP3A5 (OR=4.17, 95% CI=0.79-22.04, p=1.038) genes. DCQ levels were higher than CQ, regardless of the genotype. Regarding the DCQ/CQ rate, there was no difference between groups or between those patients who had a normal or mutant genotype. DCQ and CQ showed similar efficacy ex vivo. CYPs genotypes had no influence on early recurrence rates. Similar efficacy of CQ and DCQ ex vivo could explain the absence of therapeutic failure, despite presence of alleles associated with slow metabolism.

The local bourse inched higher on Wednesday as global stocks took a breather following consecutive sessions of weakness.

Richard A. Ehrenkranz
Apr 1, 2006; 117:1253-1261
ARTICLES

John Penders
Aug 1, 2006; 118:511-521
ARTICLES

To mark the 20th anniversary of International Crisis Group, we are publishing a series of 20 essays by foreign policy leaders forecasting the “Future of Conflict”.

As armed conflicts in Afghanistan, Iraq, Nigeria, South Sudan, Syria, Yemen, and elsewhere continued to inflict much suffering and instability around the world, the heads of the UN and International Committee of the Red Cross issued an unprecedented joint warning about the impact of today’s conflicts on civilians and called on states to redouble their efforts to find sustainable solutions to conflicts. Welcoming the call to action, Jean-Marie Guéhenno, President & CEO of the International Crisis Group, said: “It is imperative that the world do much more to respond to early warning signs and prevent wars breaking out in the first place”.

November saw further military escalation and setbacks in Syria, particularly after Turkey shot down a Russian warplane it claimed had violated its airspace. Meanwhile, several countries faced extremist attacks claimed by the Islamic State (IS), including in Lebanon, France and Bangladesh. Violence also rose in Turkey between the state and Kurdish insurgents. In Venezuela, political tensions and violence increased ahead of parliamentary elections scheduled for 6 December and could worsen, while both Nepal and Kosovo faced deepening political crises. In a positive step forward, Burkina Faso and Myanmar experienced peaceful and openly-contested elections last month.

The month saw an intensification of deadly violence in Burundi’s capital, Bujumbura, with over 80 people killed following clashes with security forces. The African Union Peace and Security Council (AU PSC) made a welcome statement of intent to deploy forces to halt the slide toward civil war and mass atrocities. In Afghanistan, fighting raged between government and Taliban forces, particularly in Helmand province, while in Djibouti, Ethiopia and Niger, political tensions heightened. In a positive step forward, a peace deal was signed in Libya but uncertainties remain over the viability of the agreement. As stressed by Jean-Marie Guéhenno, President and CEO of the International Crisis Group, in today’s Ten Conflicts to Watch in 2016, it “should be seen as a beginning, not an end, to the peace process”.

The month saw an intensification of Yemen’s war, amid heightened regional rivalries between Saudi Arabia and Iran complicating prospects for peace. Political tensions increased in Haiti, Guinea-Bissau and Moldova, where protests over endemic corruption and a lack of confidence in the government could escalate. In Africa, Boko Haram’s deadly attacks increased in northern Cameroon, and Burkina Faso was hit by an unprecedented terror attack. On the nuclear front, in East Asia, North Korea’s announcement that it had carried out a successful hydrogen bomb test was roundly condemned, while nuclear-related sanctions on Iran were rolled back in accordance with the July 2015 deal.

The month saw conflict continue to rage in Turkey’s south east between Ankara and the Kurdistan Workers’ Party (PKK), looking likely to further escalate in March. Afghanistan and Somalia both saw armed insurgencies capture new territories. In Africa, political tensions rose in Chad, Mozambique and Zimbabwe, while in Venezuela, deadlock between the opposition-held parliament and government has brought the country closer to political and economic implosion. In Asia, North Korea’s announcement of a satellite launch in violation of UN Security Council resolutions prompted international condemnation and calls for tough new sanctions. On a positive note, the coming month brings the possibility of a final agreement to end Colombia’s decades-old insurgency.

The month saw violent extremist movements, including the Islamic State (IS) and al-Qaeda-linked groups, carry out major deadly attacks in Turkey, Pakistan, Côte d’Ivoire, Tunisia and Belgium. In Libya, the arrival of Prime Minister Serraj in Tripoli despite warnings from multiple factions could lead to further destabilisation. Meanwhile in Central Africa, political violence rose in Burundi and could break out in Chad around the 10 April presidential election. Yemen, South Sudan and even Syria saw progress, of varying degrees, toward peace talks or implementation of agreements, and in Colombia the start of talks between the state and the National Liberation Army (ELN) could lead to the end of the 52-year-old conflict.

The month saw fighting escalate again in Syria and Afghanistan, and erupt in Nagorno-Karabakh between Armenian-backed separatists and Azerbaijani forces. In Bangladesh, election violence and killings by extremist groups showed how new heights of government-opposition rivalry and state repression have benefitted violent political party wings and extremist groups alike. Political tensions intensified in Iraq and Macedonia, and security forces severely supressed opposition protests in the Republic of Congo and Gambia. On a positive note, new governments were formed in the Central African Republic and South Sudan to consolidate peace gains, and talks to end Yemen’s one-year-old civil war got underway, albeit later than planned.

The month saw Venezuela’s political, economic and humanitarian crisis worsen amid heightened tensions between the government and opposition, a situation which could lead to state collapse and regional destabilisation. Another major setback in electing a new president in Haiti prompted fears of further civil unrest. In West Africa, deadly violence in central Mali and south-east Nigeria spiked, while a power struggle in Guinea-Bissau led to a dangerous standoff. In Libya, factions for and against the fledgling Government of National Accord (GNA) advanced on Sirte to expel the Islamic State (IS), risking clashes over oil facilities, while Turkey saw heightened political polarisation and an increase in violence in Kurdish areas. Ongoing peace talks, despite slow progress and ongoing violence, remain the best chance to end major combat in Yemen.

The month saw Venezuela’s political, economic and humanitarian crisis worsen amid heightened tensions between the government and opposition, a situation which could lead to state collapse and regional destabilisation. Another major setback in electing a new president in Haiti prompted fears of further civil unrest. In West Africa, deadly violence in central Mali and south-east Nigeria spiked, while a power struggle in Guinea-Bissau led to a dangerous standoff. In Libya, factions for and against the fledgling Government of National Accord (GNA) advanced on Sirte to expel the Islamic State (IS), risking clashes over oil facilities, while Turkey saw heightened political polarisation and an increase in violence in Kurdish areas. Ongoing peace talks, despite slow progress and ongoing violence, remain the best chance to end major combat in Yemen.

For the 2020 RHSU Public Influence finale, we reveal the top 10 finishers for various academic disciplines, as well as the top junior faculty in the country.

A new research study, released just a few days before the U.S. military killed a top Iranian military commander and escalated international tensions, looked at connections between sudden national security crises and education policymaking in Washington.

After two unprofitable forays into augmented reality hardware, Snap is doubling down on its social camera eyewear with the $380 Spectacles 3 glasses featuring more 3D capabilities.

Brands are tapping regional influencers for higher engagement.

According to a study by Broadcast Audience Research Council India and Nielsen India, there has been a 44% increase in time spent on social media in the week of March 28 - April 3 over a sample pre-covid period in January and February.

The May 5-7 poll median of more than 40 economists predicted India's annual consumer price inflation fell to 5.68% in April from March's 5.91%.

DOVER – Delaware authorities are urging poultry and bird owners to be vigilant in the wake of avian influenza cases reported in Oregon and Washington state. “Though it’s far away at the moment, we know that avian influenza can spread rapidly,” said Delaware State Veterinarian Dr. Heather Hirst, who heads the Delaware Department of Agriculture’s […]

To protect against the spread of avian influenza, the Delaware Department of Agriculture is prohibiting waterfowl entries in the poultry competitions at the Delaware State Fair next month. "This action is being taken out of an abundance of caution to guard against the spread of avian influenza," said Delaware State Veterinarian Dr. Heather Hirst. There have been no East Coast cases of the disease. There are no immediate public health concerns, and poultry and eggs which are properly prepared and cooked are still safe to eat.

The spotted lanternfly - a destructive, invasive plant hopper - has been confirmed in New Castle County. This insect is a potential threat to several important agricultural crops including grapes, apples, peaches, and lumber. State plant health and forestry officials are providing information, fact sheets, photographs, and links to other resources at de.gov/hitchhikerbug. Early detection is vital for the protection of Delaware businesses and agriculture.

The spotted lanternfly found in Kent County last week hitched a ride down to Dover where she was found dead and reported by a local citizen. “When you look at the Dover find, there are a few key points that help classify this specimen as a hitchhiker,” said Hauss.

DOVER, Del. – The steady increase in daily temperatures has spurred spotted lanternfly nymphs to hatch out of their egg masses. While the hatching will continue for the next few weeks, this causes concern for businesses, residents, and the agriculture industry because this notorious hitchhiker will be on the move. “From the time we enacted […]

DOVER, Del. – The Delaware Department of Agriculture (DDA) announced today that they expanded the spotted lanternfly quarantine to include all portions of New Castle County north of the Chesapeake and Delaware Canal. This is due to recent detections of established populations outside of the initial quarantine zone enacted in February 2019 that included eleven […]

The Division of Public Health (DPH) is announcing two laboratory-confirmed cases of influenza, just three weeks before the official start of the 2018-2019 flu season, which begins September 30.

Advanced analytics programs can incorporate geospatial data. Learn how such data can be used to augment local marketing plans

Investment gains (in absolute terms) depend on the principal corpus invested and the returns delivered by the fund. Returns are a function of the performance of the asset class invested in.

  Download PDF When developing games and simulations, you may want your users to be able to influence assets that are active in a physics simulation. In this article, you learn how to develop a Unity...

As for growth, the governor stuck to sharing the International Monetary Fund's (IMF) view on India's growth, offering no forecast from the central bank.

Since 2009-10, the SMP has been replaced with fair and remunerative price (FRP) and some states like Uttar Pradesh continue to announce state-advised prices which are higher than FRPs.

According to the new order, barber shops and dine-in restaurants would not be allowed, though there would be no restrictions on the barber visiting the customer at his home, or take-aways from restaurants.

The panel included Anna Lockwood, Head of Global Sales – Telstra; Sally Hancock, Managing Partner, Y Sport and Former Chair of Women in Sport; Aarti Dabas, former head of Media Rights for the ICC, and iSportconnect Chief Executive Officer Sree Varma.

The airline may make further changes in compliance with regulatory guidelines once they are finalized and notified, Vistara said in a statement.

On TV and in the courtroom, Standard & Poor’s has waged war against a US Justice Department lawsuit...

Inflation in the eurozone has fallen to its lowest level since 2009, according to official data released...

Pascal Comvalius is going to discuss with the participants on how to deal with hostile parties on a negotiation table. How to mould the brick into a shape that you are comfortable in! 

• Date & Timing: 28th April, 2020 @4.30 PM
• Meeting Link: Click Here

Covid19 has hit hard on the public health and economic well-being of not only higher income but also higher-governance-capacity countries indicating the vulnerability of some of the wealthiest and most stable states to the fundamental interruptions instigated by an unexpected pandemic.

Industry experts say that lump-sum investments have stopped and even some investors are stopping their SIPs, due to the unpredictable equity markets.

Michael Gewitz, Physician-in-Chief of Maria Fareri Children's Hospital, where the boy passed away, said the child suffered "serious neurological complications" from the pediatric multi-symptom inflammatory syndrome.

Quarterbacks at the top. Elite wide receiver talent. And a top tier of offensive linemen. The Class of 2021 could be special.

Michigan coach Jim Harbaugh has made an open-letter proposal suggesting more flexibility for players considering the jump from college to the NFL, including returning to college if they go undrafted.

Which prospect will rise the most between now and next year's draft? Who has some work to do? And what about Trevor Lawrence vs. Justin Fields? Our college experts explain it all.

Matthew Berry gives players the Love/Hate treatment coming out of the 2020 NFL draft, identifying those who have gained or lost the most fantasy football value.

Ben Roethlisberger and Chandler Jones got some support in the NFL draft, while Alvin Kamara's importance was cemented even more.

With the NFL offseason going virtual, how will teams adapt and what changes can we expect heading into the summer? We answer all of your questions.

France will not make a decision on holidays until early June - while Germany is warning against a "race to allow tourism first", and some smaller EU states, such as Greece, Denmark and Austria, are considering allowing foreign holidays.