Background and objectives

Uromodulin is exclusively produced by tubular epithelial cells and released into urine and serum. Higher serum uromodulin has been associated with lower risk for kidney failure in Chinese patients with CKD and with lower risk for mortality in the elderly and in patients undergoing coronary angiography. We hypothesized that lower serum uromodulin is associated with mortality, cardiovascular events, and kidney failure in white patients with CKD.

Combined pre-and post-capillary hypertension (CpcPH) is a relatively common complication of heart failure (HF) associated with a poor prognosis. Currently, there is no specific therapy approved for this entity. Recently, treatment with beta-3 adrenergic receptor (β3AR) agonists was able to improve pulmonary hemodynamics and right ventricular (RV) performance in a translational, large animal model of chronic PH. The authors present the design of a phase II randomized clinical trial that tests the benefits of mirabegron (a clinically available β3AR agonist) in patients with CpcPH due to HF. The effect of β3AR treatment will be evaluated on pulmonary hemodynamics, as well as clinical, biochemical, and advanced cardiac imaging parameters. (Beta3 Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure [SPHERE-HF]; NCT02775539)

A 40-year-old, male non-smoker was diagnosed with asthma 6 years ago. He now presents with a 1-week history of worsening breathlessness with fever, cough, and purulent expectoration. He has had >10 emergency department visits and two admissions to hospital in the last 3 months. At each admission, he received bronchodilators and systemic steroids resulting in rapid improvement within 24 h. However, in the current presentation, the patient has no relief with corticosteroids and bronchodilators. His pulse is 140 per min, respiratory rate is 40 per min, blood pressure is 90/60 mmHg and room air oxygen saturation is 80%. Arterial blood gas (ABG) analysis shows hypercapnic respiratory failure. In view this respiratory failure, the patient is intubated and mechanical ventilation initiated. A chest radiograph is shown in figure 1. The therapy initiated includes bronchodilators, a systemic steroid, antibiotics and supportive care.

Etravirine (ETR) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) used in treatment-experienced individuals. Genotypic resistance test-interpretation systems can predict ETR resistance; however, genotype-based algorithms are derived primarily from HIV-1 subtype B and may not accurately predict resistance in non-B subtypes. The frequency of ETR resistance among recombinant subtype C HIV-1 and the accuracy of genotypic interpretation systems were investigated. HIV-1_LAI containing full-length RT from HIV-1 subtype C-positive individuals experiencing virologic failure (>10,000 copies/ml and >1 NNRTI resistance-associated mutation) were phenotyped for ETR susceptibility. Fold change (FC) was calculated against a composite 50% effective concentration (EC₅₀) from treatment-naive individuals and three classifications were assigned: (i) <2.9-FC, susceptible; (ii) ≥2.9- to 10-FC, partially resistant; and (iii) >10-FC, fully resistant. The Stanford HIVdb-v8.4 was used for genotype predictions merging the susceptible/potential low-level and low-level/intermediate groups for 3 x 3 comparison. Fifty-four of a hundred samples had reduced ETR susceptibility (≥2.9-FC). The FC correlated with HIVdb-v8.4 (Spearman’s rho = 0.62; P < 0.0001); however, 44% of samples were partially (1 resistance classification difference) and 4% completely discordant (2 resistance classification differences). Of the 34 samples with an FC of >10, 26 were HIVdb-v8.4 classified as low-intermediate resistant. Mutations L100I, Y181C, or M230L were present in 27/34 (79%) of samples with an FC of >10 but only in 2/46 (4%) of samples with an FC of <2.9. No other mutations were associated with ETR resistance. Viruses containing the mutation K65R were associated with reduced ETR susceptibility, but 65R reversions did not increase ETR susceptibility. Therefore, genotypic interpretation systems were found to misclassify ETR susceptibility in HIV-1 subtype C samples. Modifications to genotypic algorithms are needed to improve the prediction of ETR resistance for the HIV-1 subtype C.

Plasmodium vivax relapse is one of the major causes of sustained global malaria transmission. Primaquine (PQ) is the only commercial drug available to prevent relapses, and its efficacy is dependent on metabolic activation by cytochrome P450 2D6 (CYP2D6). Impaired CYP2D6 function, caused by allelic polymorphisms, leads to the therapeutic failure of PQ as a radical cure for P. vivax malaria. Here, we hypothesized that the host immune response to malaria parasites modulates susceptibility to P. vivax recurrences in association with CYP2D6 activity. We performed a 10-year retrospective study by genotyping CYP2D6 polymorphisms in 261 malaria-exposed individuals from the Brazilian Amazon. The immune responses against a panel of P. vivax blood-stage antigens were evaluated by serological assays. We confirmed our previous findings, which indicated an association between impaired CYP2D6 activity and a higher risk of multiple episodes of P. vivax recurrence (risk ratio, 1.75; 95% confidence interval [CI], 1.2 to 2.6; P = 0.0035). An important finding was a reduction of 3% in the risk of recurrence (risk ratio, 0.97; 95% CI, 0.96 to 0.98; P < 0.0001) per year of malaria exposure, which was observed for individuals with both reduced and normal CYP2D6 activity. Accordingly, subjects with long-term malaria exposure and persistent antibody responses to various antigens showed fewer episodes of malaria recurrence. Our findings have direct implications for malaria control, since it was shown that nonimmune individuals who do not respond adequately to treatment due to reduced CYP2D6 activity may present a significant challenge for sustainable progress toward P. vivax malaria elimination.

Flying car hopefuls were meant to take off at a competition on a NASA airbase, but no team claimed the prize after a string of crashes and no-shows

Whether it was driverless cars, lab-grown meat or faster-than-light neutrinos, some things just didn't live up to the hype in the 2010s

The creators of Kiki believe they can build an emotionally engaging social home robot that is also "completely useless"

Failed to get friends list and several more Pokemon GO friends list errors are once again impacting players on iOS and Android.

Systemic flaws within Glynn county’s district attorney offices led to a lack of action against the men involved in this ‘modern lynching’In the days and weeks after Ahmaud Arbery was shot and killed, multiple Glynn county law enforcement officials failed to thoroughly investigate his death and, in one case, refused to allow police officers to make arrests, the Guardian has learned.Arbery, 25, was jogging through the neighborhood just outside Brunswick, Georgia, on 23 February when he was shot dead by two white men. Gregory McMichael, 64, and his son Travis, 34, were charged with murder and aggravated assault on Thursday evening, after graphic video footage of the killing was released publicly and sparked national outrage.Lawyers for Arbery’s family have called the killing a “modern lynching” and decried the lack of action in the case prior to the release of the video, pointing to racial inequalities in the criminal justice system.In the police report, Gregory McMichael claimed Arbery “violently attacked” his son, who shot Arbery in self defense.Jackie Johnson, the Glynn county district attorney, refused to allow police officers who responded to arrest the two men, Glynn county commissioner Peter Murphy told the Guardian in a phone call on Friday.The police department was put in touch with one of Johnson’s assistant district attorneys after the shooting, but Johnson made the decision not to charge the father and son, the former having worked in her office for more than 20 years, Murphy said.“The police at the scene went to her, saying they were ready to arrest both of them,” Allen Booker, the Glynn county district 5 commissioner, told the Atlanta Journal-Constitution on Friday. “These were the police at the scene who had done the investigation. She shut them down to protect her friend McMichael.”Days later, Johnson recused herself. Johnson did not immediately respond to a request for comment. By 27 February, George Barnhill, the Waycross judicial district attorney, and the second of three DAs on the case, took over. Less than 24 hours after seeing the video and evidence compiled by the police, Murphy said, Barnhill decided to not charge the McMichaels.“And so within 24 hours the Glynn county police had been told by two separate DA offices not to make any arrests,” Murphy said. “And obviously, they want to assume no responsibility for their actions.”On 2 April, Barnhill sent an email to law enforcement authorities saying the 25-year-old Arbery had an “apparent aggressive nature” and that his family were “not strangers to the local criminal justice system”.“Arbery’s mental health records & prior convictions help explain his apparent aggressive nature and his possible thought pattern to attack an armed man,” Barnhill said in the email, which was first reported by the New York Times.“What it appears is he was purposely trying to assault the character of the victim and there’s just no reason why,” said Chris Stewart, one of the lawyers representing Arbery’s family.The family have pointed to the McMichaels’ connection to local law enforcement both at the district attorney’s office and police department as evidence of systemic flaws and roadblocks in their search for justice. It was only after the video of Arbery’s death was released this week that the third DA’s office requested the Georgia Bureau of Investigations (GBI) get involved.On Friday, GBI director Vic Reynolds told reporters he could not “answer what another agency did or didn’t see” in the first two months of the investigation.“But I can tell you that based on our involvement in this case and considering the fact we hit the ground running Wednesday morning and within 36 hours we had secured warrants for two individuals for felony murder, I think that speaks volumes for itself.”In a 7 April email sent to the office of Georgia attorney general Chris Carr, Barnhill recused himself because his son worked on a case involving Arbery while working in Johnson’s office.Lee Merritt, one of the lawyers who represents Arbery’s family, said Wanda Cooper-Jones, Arbery’s mother, found the connection between Barnhill’s son and her own on Facebook and brought it to the attention of his office.“She followed the links. That’s exactly how it happened,” he said to the Guardian on Friday by phone.According to a police report filed 23 February, Gregory and Travis McMichael grabbed their weapons, a .357 Magnum revolver and a shotgun, jumped into a truck and followed Arbery as he ran.In the email to Carr from early April, Barnhill references a “decent cell phone video of the entire shooting incident”, an apparent reference to the one leaked this week.Reynolds said on Friday that the investigation into the shooting, the video and the person who filmed it, would continue.“Every stone will be uncovered,” Reynolds said.

Wildlife conservation efforts are essential to preventing outbreaks, scientists and advocates say

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For more than five years, wildlife conservationists in the US have been clamoring for the government to provide Endangered Species Act protections to pangolins, a group of imperiled ant-eating mammals that are widely, and often illicitly, trafficked for their scales and meat. The Trump administration, however, has refused to act and that refusal has suddenly taken on grave new implications.

Earlier this year, scientists in China identified pangolins, along with bats, as one of the possible animal hosts involved in the transmission of the deadly coronavirus from wildlife to humans.

Australian Olympic and world champion Steve Hooker turned his first indoor pole vault of the year into an easy qualifier at the IAAF world championships on Friday.

(This May 7 story changes monthly to weekly in paragraph 35)

Coronavirus: the symptoms Read our LIVE updates on the coronavirus here

Coronavirus: the symptoms Read our LIVE updates on the coronavirus here

Hospital leaders have criticised the Government after a shipment which contained vital equipment for NHS staff was delayed.

Shielding of care and nursing homes has "completely failed", a GP and academic said today amid fears that the number of elderly people who have died is far higher than official statistics show.

John Lewis sales have plunged, despite a surge in online orders, after it was forced to shut stores in face of coronavirus.

Police in New York broke up a "4/20" marijuana party in Manhattan after receiving a tip that nearly 40 people were not practising social distancing during the coronavirus outbreak.

Piers Morgan today hit out at the Government's "spectacular failure" for doing fewer coronavirus tests than 12 days ago.

More than 1,800 people are set to lose their jobs at Oasis, Warehouse and two other brands, after administrators were unable to find a buyer for the business.

Posts from high-profile accounts tout questionable virus therapies and cures.

The Senate failed to override President Trump's veto of legislation that would have prevented him from taking military action in Iran without congressional approval. On Thursday, the Senate voted 49-44 in favor of the override, falling short of the two-thirds majority needed for it to be approved. Both chambers of Congress passed the bipartisan resolution earlier this year.

The Senate failed to override President Trump's veto of legislation that would have prevented him from taking military action in Iran without congressional approval. On Thursday, the Senate voted 49-44 in favor of the override, falling short of the two-thirds majority needed for it to be approved. Both chambers of Congress passed the bipartisan resolution earlier this year.

'We propose that Sars-Cov-2 may have the potential to be transmitted via aerosols,' researchers say

Max Kalnitz

The post No Student Deserves to Fail During a Pandemic appeared first on The Nation.

The Government has failed to meet its 100,000 coronavirus daily testing target for the fifth day running as criticism mounts on ministers to bolster supplies.

Handing out contracts out to firms like Serco and G4S is now second nature to those in power. We need to rebuild state capacity

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The coronavirus pandemic has revealed a lot about British society – the fragility of the economy, the insecure situation so many workers find themselves in – but it has also shone a light on the state itself. Many comparisons have been made between the current mobilisation of state resources and the second world war. But while that crisis involved a ramping up of public sector capacity, this one is being managed by a state that believes itself to be utterly dependent on the private sector.

First, there are the outsourcing giants, shadowy corporations who have been handed numerous contracts over the past 20 years. Matt Hancock has put Serco in charge of the phonelines for contact tracing, a vital part of the government’s public health strategy. This is a company that mismanaged data at a GP surgery, and failed to train staff properly for a breast cancer hotline service. Along with G4S, it claimed money from the government for tracking prisoners who were later found to be dead.

The cardinal maintains he didn’t know about the Victorian town’s notorious paedophile priests, a claim the royal commission found ‘implausible’

“Why isn’t all of Australia talking about what happened here in Ballarat?”

That’s the question Clare Linane remembers asking her husband, Peter Blenkiron, 12 years ago as they were sitting in the kitchen talking about his abuse. Linane’s husband, brother and cousin had all been abused when they were children between 1973 and 1974 by Christian Brother and now convicted paedophile Edward “Ted” Dowlan. They knew they were among thousands of people living in and around Ballarat – Victoria’s largest inland city – who had been affected by child sexual abuse perpetrated by clergy.

Of $75 million in loans, state gets $2.5 million from "tapped out" baseball star.

Former Manchester United defender Rafael da Silva has warned the club against making the same old mistakes in the transfer window.

Sir Alex Ferguson retired at Manchester United after failing to sign Cristiano Ronaldo and Gareth Bale, according to Patrice Evra.

Ryan Giggs has revealed how an attempt to emulate Liverpool's attacking tactics 'didn't quite work' for Wales during a recent meeting with Croatia.

Macclesfield Town have been hit with an immediate seven-point deduction for failing to fulfil a fixture along with non-payment of their players.

Lionel Messi is largely to blame for Philippe Coutinho's failure to succeed at Barcelona, according to club legend Rivaldo.

A team of scientists studied more than 1,300 patients admitted to a hospital for COVID-19

The San Francisco brokerage is bringing its financial firepower and sizeable client base to one of the hottest investment trends.

The UK government made key failings in their strategic preparations and emergency response to coronavirus and this, in turn, undermined the NHS's ability to cope with the crisis.These are the findings recently published in a research paper for the Journal of Risk Research by academics from Cass Business School, Glasgow Caledonian University, Vlerick Business School, and Nottingham University Business School.

JASON Day recorded yet another top-10 finish at a major but was left to rue what might have been after his unlikely final round US Open charge was snuffed out in a sand trap.

Human activities have destroyed more than 7.7 million hectares of threatened species habitat.

Regional centres are concerned they could be badly hit by the potential collapse of Virgin Australia, with higher airfares and less competition.