Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition, causing progressive decline in lung function leading to premature death. Acute exacerbations in COPD patients are predominantly associated with respiratory viruses. Ribavirin is a generic broad-spectrum antiviral agent that could be used for treatment of viral respiratory infections in COPD. Using the Particle Replication In Nonwetting Templates (PRINT) technology, which produces dry-powder particles of uniform shape and size, two new inhaled formulations of ribavirin (ribavirin-PRINT-CFI and ribavirin-PRINT-IP) were developed for efficient delivery to the lung and to minimize bystander exposure. Ribavirin-PRINT-CFI was well tolerated in healthy participants after single dosing and ribavirin-PRINT-IP was well tolerated in healthy and COPD participants after single and repeat dosing. Ribavirin-PRINT-CFI was replaced with ribavirin-PRINT-IP since the latter formulation was found to have improved physicochemical properties and it had a higher ratio of active drug to excipient per unit dose. Ribavirin concentrations were measured in lung epithelial lining fluid in both healthy and COPD participants and achieved target concentrations. Both formulations were rapidly absorbed with approximately dose proportional pharmacokinetics in plasma. Exposure to bystanders was negligible based on both the plasma and airborne ribavirin concentrations with the ribavirin-PRINT-IP formulation. Thus, ribavirin-PRINT-IP allowed for an efficient and convenient delivery of ribavirin to the lungs while minimizing systemic exposure. Further clinical investigations would be required to demonstrate ribavirin-PRINT-IP antiviral characteristics and impact on COPD viral-induced exacerbations. (The clinical trials discussed in this study have been registered at ClinicalTrials.gov under identifiers NCT03243760 and NCT03235726.)

Nacubactam is a novel β-lactamase inhibitor with dual mechanisms of action as an inhibitor of serine β-lactamases (classes A and C and some class D) and an inhibitor of penicillin binding protein 2 in Enterobacteriaceae. The safety, tolerability, and pharmacokinetics of intravenous nacubactam were evaluated in single- and multiple-ascending-dose, placebo-controlled studies. Healthy participants received single ascending doses of nacubactam of 50 to 8,000 mg, multiple ascending doses of nacubactam of 1,000 to 4,000 mg every 8 h (q8h) for up to 7 days, or nacubactam of 2,000 mg plus meropenem of 2,000 mg q8h for 6 days after a 3-day lead-in period. Nacubactam was generally well tolerated, with the most frequently reported adverse events (AEs) being mild to moderate complications associated with intravenous access and headache. There was no apparent relationship between drug dose and the pattern, incidence, or severity of AEs. No clinically relevant dose-related trends were observed in laboratory safety test results. No serious AEs, dose-limiting AEs, or deaths were reported. After single or multiple doses, nacubactam pharmacokinetics appeared linear, and exposure increased in an approximately dose-proportional manner across the dose range investigated. Nacubactam was excreted largely unchanged into urine. Coadministration of nacubactam with meropenem did not significantly alter the pharmacokinetics of either drug. These findings support the continued clinical development of nacubactam and demonstrate the suitability of meropenem as a potential β-lactam partner for nacubactam. (The studies described in this paper have been registered at ClinicalTrials.gov under NCT02134834 [single ascending dose study] and NCT02972255 [multiple ascending dose study].)

The effects of multiple-dose administration of tenofovir disoproxil fumarate (TDF) on the pharmacokinetics of morinidazole (MOR) were compared in healthy subjects. MOR exposure was similar, with an area under the curve from 0 h to infinity (AUC_0-) treatment ratio for MOR+TDF/MOR of 1.01 (90% confidence interval, 0.97 to 1.06). No relevant differences were observed regarding plasma exposure of metabolites. Renal clearances of MOR and its metabolites were not affected by TDF. No unexpected safety or tolerability issues were observed.

Unlike replicative senescence, oncogene-induced senescence caused heterochromatin-body formation.

Pemigatinib was effective in patients with cholangiocarcinomas with FGFR2 fusions or rearrangements.

In lung cancer, brain metastasis was associated with somatic amplification of MYC, YAP1, or MMP13.

In the plasmaMATCH trial, researchers performed circulating tumor DNA testing on patients with advanced breast cancer and matched those with ESR1, HER2, or AKT1 alterations to targeted therapies. Patients with HER2 and AKT1 mutations experienced response rates greater than 22% with durable benefit.

While smoking is inextricably linked to oral/head and neck cancer (HNSCC), only a small fraction of smokers develop HNSCC. Thus, we have sought to identify other factors, which may influence the development of HNSCC in smokers including microbiology. To determine microbial associations with HNSCC among tobacco users, we characterized oral microbiome composition in smokers with and without HNSCC. 16S rRNA MiSeq sequencing was used to examine the oral mucosa microbiome of 27 smokers with (cases) and 24 without HNSCC (controls). In addition, we correlated previously reported levels of DNA damage with the microbiome data. Smokers with HNSCC showed lower microbiome richness compared with controls (q = 0.012). Beta-diversity analyses, assessed as UniFrac (weighted and unweighted) and Bray–Curtis distances, showed significant differences in oral mucosal microbiome signatures between cases and controls (r² = 0.03; P = 0.03) and higher interindividual microbiome heterogeneity in the former (q ≤ 0.01). Higher relative abundance of Stenotrophomonas and Comamonadaceae and predicted bacterial pathways mainly involved in xenobiotic and amine degradation were found in cases compared with controls. The latter, in contrast, exhibited higher abundance of common oral commensals and predicted sugar degradation pathways. Finally, levels of DNA damage in the oral cavity were correlated with the microbiome profiles above. Oral microbiome traits differ in smokers with and without HNSCC, potentially informing the risk of eventual HNSCC and shedding light into possible microbially mediated mechanisms of disease. These findings present data that may be useful in screening efforts for HNSCC among smokers who are unable to quit.

Real estate insiders and experts said it is essential to develop strict penalties to combat those operating fraudulent property businesses to protect the legitimate rights of consumers and legitimate enterprises.

Electric cars depend on cobalt as a key ingredient in their batteries, but a new analysis reveals we may run out by 2030, while car firm Tesla is moving to other types of battery in China

We’re used to tweaking our digital selves to look thinner or more attractive. A new generation of Instagram filters could drastically change how we perceive ourselves

Adrian Tchaikovsky's latest novel The Doors of Eden rewrites Earth's evolutionary history, with highlights including fish that upload their minds to supercomputers and cats that rule over primates

Julia Ebner infiltrated the hidden forums that extremists use. Her experiences lay bare how they hijack social media and video games to spread hate – and how to beat them

The covid-19 pandemic has many of us stuck at home. The result could completely reshape how we use the internet, writes Annalee Newitz

When the Soviet Union lands on the moon first people in the US are shocked. But For All Mankind provides an even bigger surprise when one cosmonaut's identity is revealed, says Emily Wilson

Your weekly selection of awesome robot videos

The fastest, safest, and most exciting way to launch a quadrotor may be ballistically

The SnotBot project uses drones, data, and deep learning to tell us about the health of whales and the oceans

ARMED forces veterans are facing a threat from an enemy they cannot see.

From Stay at Home T-shirts to NHS baseball caps, here’s a selection from small labels donating some or all of their profits to charities helping healthcare workers and the Covid-19 response

Researchers have developed a set of recommendations to manage the mental health of frontline medical workers during viral outbreaks, such as COVID-19.

A new study found that organic nitrates do not have clinically relevant effects on bone mineral density or bone turnover in postmenopausal women, and the medications caused significant side effects.

New research finds that sleep problems in a baby's first 12 months may not only precede an autism diagnosis, but also may be associated with altered growth trajectory in a key part of the brain, the hippocampus.

The actor said wearing a fat suit for the 2001 movie taught her what it is like to be humiliated as an obese person. Why are TV and film characters so rarely treated with dignity and respect?

‘Disaster” is how Gwyneth Paltrow has summed up her role in the 2001 film Shallow Hal, which will surprise few people who have actually seen it. Jack Black plays Hal, a man so shallow he has to be hypnotised in order to date a fat woman, who, through his boggled eyes, he sees as a very thin woman.

The nastiness of Shallow Hal, which has long appalled critics and fans alike, was front and centre in the trailer, where Hal’s friend attempts to “rescue” him from speaking to a fat woman, Rosemary, who is, in fact, willowy Paltrow dressed in a fat suit. But because he cannot see what she looks like, he falls for her “inner beauty”. It is an uncomfortable mix – a film that pretends to preach body acceptance while simultaneously inviting laughter at bodies that don’t fit into jeans size six and under. Take the scene where she is called a “rhino”, or the one where she cannonballs into a swimming pool causing a tidal wave. The message built into the script’s DNA is simple: fat is funny; it is OK to laugh at fat people.

They come from some of the most prominent hockey families in Manitoba, a group of young men blessed with athletic gifts that allow them to be better than most at ...

High salt intake seems to impair the immune cells in humans that fight bacteria because of a side effect of the hormones that help get rid of salt

Going out into the natural world is good for your health and mind, and you can still get some of the same benefits even when stuck inside, says Graham Lawton

Building muscle reduces the risk of cancer and stroke, boosts brainpower, burns through calories and more – it might even be better for you than cardio

Parasites are a huge global treat to human life, but some of them could actually help us treat disease. Parasitologist Charlotte Evans explores the secret lives of these frightening organisms.

From social isolation to working on the front line, the mental health challenges of the pandemic are wide reaching. We ask experts how to protect ourselves

Whether you are at home alone or juggling work and family, those working in mental health share their advice on how to cope with the covid-19 pandemic

Lessons learned from natural disasters and the military can help guide our responses to help people's mental health during the covid-19 pandemic

We are already seeing the pandemic's effects on mental health, and we need to act urgently to avoid a full-blown crisis, says Sam Howells  

Decades ago, research in Holland about hours of sunshine in January and old people’s mortality rate found that with lots of sun the rate would drop, and vice versa. So in my 80s I am doubly lucky. Edmonton gets plenty of bright sunshine in January, an average of 101 hours — that’s better than Ottawa’s […]

John Legend joins Zane Lowe on Apple Music to run through his ‘At Home With’ playlist. He talks about how he’s coping at home

Justin Bieber discussed his experiences during the latest episode of his and wife Hailey's Facebook Watch series, The Biebers on Watch.

Fans can check out the event, which kicks off at 8.30am PT each day, on 320 Festival's Facebook Live and YouTube Live pages.

Previously, Nike manufactured face shields, air-purifying respiratory lenses and sportswear...

The post Nike To Donate Footwear, Apparel And Equipment To Frontline Healthcare Workers appeared first on Man's World India.

Mike Bloomberg is agreeing to pay for health care through November for the more than 2,000 campaign staffers he laid off after suspending his presidential bid as he faces public pressure and multiple lawsuits.

Chief Justice John Roberts on Friday put a temporary hold on the release of secret materials from former special counsel Robert Mueller's investigation to a Democrat-led House committee.

The order stops the clock on a lower court's ruling requiring the Justice Department to turn over confidential grand jury materials underlying ...

America can take its next steps toward reopening by placing an emphasis on emerging health data and closely examining how early states are performing, Housing and Urban Development Secretary Dr. Ben Carson asserted Saturday.

Parks have remained open amid the coronavirus and become a haven over the past week, prompting fears for staff and large crowds

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Even as Broadway shows were shuttered and Disneyland was closed due to the Covid-19, most US national parks were open for business on Tuesday, confounding public health officials and worrying park staff who did not want to be exposed to the virus.

National parks have become a haven over the past week as the public seeks places to go during spring break. One park employee reported on Facebook that a visitor center at Big Bend national park was full on Monday with hundreds of people. Another shared a photo of shoulder to shoulder crowds at Zion national park waiting to board shuttle buses. (The park closed its shuttle bus system later in the day.)

Tasked with curbing a 1907 outbreak, Esther Pohl emphasized the importance of clean, vermin-free environments

Repurposing existing medicines focused on known drug targets is likely to offer a more rapid hope of tackling COVID-19 than developing and manufacturing a vaccine, argue an international team of scientists.

A new method for reliably identifying the presence of beer or other malted foodstuffs in archaeological finds is described in a new study.

The Monte Conca cave system in Sicily is showing signs of being altered by pollution from above.

"For people that already have mental health concerns it might be more escalated and others who have not had mental health concerns are now experiencing (them) because of some of the anxiety and stress that's caused by COVID-19."