After canceling booze, Canada is now coming for your coffee

 Now Canada is putting coffee on ice.

After the country’s health officials released new guidance that having over two drinks a week can be a health detriment, new research from the University of Toronto says heavy coffee consumption is cause for concern as well.

“These findings suggest that heavy coffee intake is associated with increases in the risk of kidney dysfunction among slow metabolizers of caffeine, who genetically comprise approximately half of the population,” an excerpt from the data read, adding that illnesses like hypertension could emerge.

“We made a discovery back in 2006 with a case-control study, where we showed that coffee increases the risk of a heart attack, but only in those who have a particular version of a gene that makes them effectively slow metabolizers of caffeine,” Ahmed El-Sohemy, a professor of nutritional sciences at the Temerty Faculty of Medicine at the University of Toronto, told the Toronto Star.

“Slow metabolizers are less able to get rid of caffeine efficiently from the body, so, it’s more likely to have adverse effects in the people who can’t get rid of it,” he added.

New research from the University of Toronto warns against high coffee intake.

Getty Images/Cavan Images RF

Fortunately, the other half have the genetic makeup to break down coffee’s biggest perk without worry.

Even if you feel jittery after a huge cup of joe — or experience, say, anxiety or withdrawal headaches — you may have the gene that quickly breaks down caffeine, according to the professor.

“Often, when I give a talk, someone will say, ‘oh, I’m definitely a slow metabolizer because if I drink a cup of coffee in the afternoon it keeps me up at night,’ ” El-Sohemy said. “But there’s currently no link in terms of those types of physiological responses to caffeine and speed of metabolism.”

Genetic testing — which usually runs about $200 and takes over a month to get results — is the only way to determine what sort of brew you are made of, according to the Star.

Some genetics don’t allow for the fast breakdown of caffeine and new research warns it can damage kidneys.

Getty Images/iStockphoto

El-Sohemy says it’s not worth the hassle and recommends people err on the side of coffee caution.

“I’d advise people just assume they’re a slow metabolizer and limit intake to one cup per day.”

Last month, researchers from a province at the University of Quebec said that lowering coffee intake could combat climate change due to the reduction in pollution from making a pot.

https://nypost.com/2023/02/16/after-canceling-booze-now-canada-is-coming-for-your-coffee/

‘Fake Ebitda’ Masks Risk in Debt-Laden Companies

 During the days of easy money, one of the most widely tracked numbers in credit markets became an unfortunate punchline.

Ebitda, which stands for earnings before interest, taxes, depreciation and amortization — a figure that’s akin to a company’s cash flow and, thus, its ability to pay its debts — was instead mocked as a marketing gimmick. When bankers and private equity firms asked investors to buy a piece of their loans funding buyouts and other transactions, they would layer on so-called add-backs to earnings projections that, to some, defied reason.

“Ebitda: Eventually busted, interesting theory, deeply aspirational,” one Moody’s analyst joked in 2017. Sixth Street Partners co-founder Alan Waxman had a more blunt assessment, warning an audience at a private conference that such “fake Ebitda” threatened to exacerbate the next economic slump.

Now, amid rising interest rates, persistent inflation and warnings of a potential recession on the horizon, research from S&P Global Ratings is underscoring just how far from reality the earnings projections are proving to be.

As Bloomberg’s Diana Li wrote on Friday, 97% of speculative-grade companies that announced acquisitions in 2019 fell short of forecasts in their first year of earnings, according to S&P. For 2018 deals, it was 96% and 93% for 2017 acquisitions. Even after the economy was flooded with fiscal and monetary stimulus after the pandemic, about 77% of buyouts and acquisitions from 2019 were still short of their projected earnings, S&P’s research shows.

The bigger worry is that years of rosy earnings projections is masking the amount of leverage on the balance sheets of the lowest-rated companies. By 2019, before the Covid-19 pandemic sent markets tumbling the following year, add-backs were accounting for about 28% of total adjusted Ebitda figures used to market acquisition loans, Covenant Review data at the time showed. That was up from 17% in 2017.

The S&P analysts this week said the latest data reinforces their view that those Ebitda figures are “not a realistic indication of future Ebitda and that companies consistently overestimate debt repayment.”

“Together, these effects meaningfully underestimate actual future leverage and credit risk,” they wrote.

https://news.yahoo.com/fake-ebitda-masks-risk-debt-221749057.html

Officials: Arizona spill 'likely not due to speed or alcohol'

 The deadly truck accident this week that caused a hazardous materials spill southeast of downtown Tucson this week did not appear to be caused by high speed, drugs or alcohol, Arizona Department of Public Safety officials said Thursday.

The authorities said at a news conference that truck driver Ricky Immel, 54, was traveling from his home state of Nevada to Alabama with a load of packages of liquid nitric acid Tuesday afternoon when his vehicle left the roadway and flipped onto the left side, then into the median. Immel was later declared dead at the scene.

The cause of the accident and Immel’s death are under investigation.

Immel was traveling with his service dog, which will be reunited with his wife, said officials, who did not say what type of assistance the animal was trained for.

The main freeway in southern Arizona reopened in both directions Wednesday evening, and officials said people living in the area could safely return to their homes or go outside a day after the crash sent acrid red and yellow plumes into the desert sky and evacuation and shelter-in-place orders were issued.

Less than 2 miles (3.2 kilometers) of Interstate 10 had been closed in both directions for over 24 hours after the truck tractor pulling a box trailer crashed, spilling about 40,000 pounds (18,200 kilograms) of packages of nitric acid onto the asphalt roadway that runs through dry land scattered with scrub brush.

The Arizona crash came as Ohio residents continue raising concerns about the release of toxic chemicals on board a freight train that derailed Feb. 3 and left 50 cars in a fiery, mangled mess. There were no injuries, and officials later ordered the evacuation of the immediate area. Residents in that state worried about the potential health impacts from the wreckage.

In Arizona, Pima County’s health department and poison control center recommended that anyone who may have been in contact with the nitric acid for more than 15 minutes get a medical evaluation if they develop respiratory difficulties. They said symptoms could be delayed up to 24 hours after exposure.

Health officials said people who simply drove through or past the accident and chemical plume should not have been affected.

Nitric acid is a highly corrosive colorless liquid used to make ammonium nitrate for fertilizers and the manufacture of plastics and dyes.

The Centers for Disease Control and Prevention’s website says exposure to nitric acid can irritate the eyes, skin and mucous membranes. Depending on how long someone is exposed to the material, and how much, it also can cause delayed pulmonary edema, pneumonitis, bronchitis and dental erosion.

https://apnews.com/article/alabama-arizona-nevada-tucson-health-c779a6d73042395ba5a8a4f908bb5e85

Scynexis Tackling the Rise of Concerning Fungal Infections

 A mutated version of the cordyceps fungus, able to withstand higher temperatures, is capable of jumping from the insect world to humans. Seeking to propagate itself, the parasitic fungus takes over the minds of people and rapidly spreads, causing a global zombie apocalypse.

That’s the premise of the new HBO series “The Last of Us,” based on the 2013 video game of the same name. The show uses the known capabilities of the fungus, commonly known as “zombie ant fungus“, and follows the “what if” scenario to drive the story. While the concept is rooted in science, mycologists and infectious disease experts note the premise is out of the realm of probability.

“There are millions of different species of fungi. They don’t like high temperature growth. The mammalian body temperature isn’t conducive to fungi. That gives us a big, big advantage over fungal infections,” explained Dr. John Perfect, a Duke University mycologist.

Perfect noted the majority of fungal infections most people will have to deal with are those that cause athlete’s foot or yeast infections. These types of infections are readily treated with various antifungal therapeutics. Still, there are some fungal infections that pose a serious health concern, particularly to those who have a compromised immune system, he said.

“A lot of the organisms won’t infect a normal host if their immune system is normal. But, we do have a lot of immune-compromised people. And in them, the mortality rate of some of these infections can be around 40%,” Perfect said.

In October 2022, the World Health Organization released its first-ever list of fungal pathogens that pose a major threat to public health. Among those are Candida auris, Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, which is the type of fungus Perfect primarily works with. Not only are these fungi a global health concern, the WHO noted they are resistant to treatment with only four classes of antifungal medicines currently available, and few candidates in the clinical pipeline.

This is largely due to the complex nature of developing effective antifungal treatments. David Angulo, President and Chief Executive Officer of Jersey City-based SCYNEXIS, said the complexity is related to the cellular nature of fungi, which are more closely related to human cells than other infectious agents such as bacteria. Because fungi share many of the same features as human cells, researchers have to figure out a target that will kill the fungi without damaging us.

“Developing an antifungal is much more tricky than an antibacterial,” he noted.

The difficulty in developing effective therapies is concerning to global health officials, especially as these pathogens develop resistance to our current arsenal of treatments. The SCYNEXIS team is developing its antifungal therapeutic Ibrexafungerp, the first new class of antifungal medication in 20 years, against many of these concerning fungi and has already won approval for the treatment of recurrent vulvovaginal candidiasis, a common fungal infection in women. The antifungal drug is sold under the brand name Brexafemme.

Most fungal infections in people are superficial in nature – an infection on the skin, nails or mucosal areas. However, there are systemic fungal infections that go into deep tissues and can have the capacity to destroy those tissues, Angulo said.

Fungi that can cause systemic infections are frightening enough on their own without the fictionalized version of cordyceps. Angulo, who remarked that he enjoyed the first two episodes of “The Last of Us” pointed to the growing concern of fungal infections such as aspergillosis, which are showing signs of resistance to currently-available antifungals. Another deadly fungal disease is mucormycosis, which has also shown significant antifungal resistance.

“Resistance to antifungal medications is on the rise,” he said.

The SCYNEXIS team believes Ibrexafungerp has a role to play in treating systemic fungal infections. Ibrexafungerp, a triterpenoid antifungal, is being evaluated in multiple Phase III programs for severe fungal infections such as C. auris, which can cause serious and, sometimes fatal, blood infections in people. The fungus, which causes infections with high mortality, is frequently resistant to many antifungal medications, Angulo said. He also noted that it belongs to the most common group of fungi that causes systemic infections.

“It’s a very common cause of infection. It affects very vulnerable populations and has been shown to be passed from people to people very easily. That’s uncommon for most candida infections,” Angulo said.

Many patients ultimately infected with C. auris have undergone blood transfusions or various transplant procedures. The vast majority of systemic infections are hospital-acquired, Angulo said.

In 2019, Mount Sinai Hospital in New York was at the center of a C. auris infection. Following the death of a patient infected by the fungus, hospital officials discovered the room where the patient was housed was covered in the fungus spores that had spread from him. According to the New York Times report highlighting concerns about C. auris, hospital officials said specialized cleaning equipment had to be brought in to clear the spores from where they attached. Additionally, many floor and ceiling tiles had to be removed before the room could be used again.

SCYNEXIS anticipates Phase III data later this year from trials assessing Ibrexafungerp against C. auris. Interim data showed patients infected with C. auris saw a significant response from Ibrexafungerp treatment, Angulo said. If the data continues to show efficacy, SCYNEXIS intends to seek regulatory approval.

And that will be welcome news for treating physicians who are looking for new treatment modalities.

“Fungal infections aren’t going to go away,” Perfect said. “Broad-spectrum antibiotics don’t impact the fungi and we’re still frequently seeing outbreaks of fungal infections. We need more effective agents… more potent drugs.”

https://biobuzz.io/this-new-jersey-biotech-is-tackling-the-rise-of-concerning-fungal-infections/

Most common vector-borne diseases among European travellers arriving from Africa

 So-called arthropod-borne diseases are human illnesses, commonly transmitted by the bite of infected arthropod vectors like ticks, mosquitoes, sandflies, or fleas. Efforts to strengthen disease surveillance in this area across Africa are on-going and supported by the Africa Centres for Disease Control and Prevention (Africa CDC), established in 2017. However, information on circulating pathogens in some African countries is still limited. Using travellers as sentinels for infectious disease surveillance, Gossner et al. [1] assessed travellers’ health data collected in Europe in the attempt to provide actionable information for the Africa CDC.

Malaria most common vector-borne disease among travellers 
In their descriptive analysis, Gossner et al. examined travellers’ volume data and arthropod-borne disease cases reported in Europe between 2015 and 2019. For diseases with at least one hundred cases per year, the authors determined the disease-specific travellers’ infection rate (TIR), which they considered as a proxy for the likelihood of infection.

In the study’s timeframe, around 125 million people arrived by commercial airplane from Africa to Europe according to data from the International Air Transport Association (IATA). Most travellers arrived from Northern Africa (79.3 million), mainly from Morocco (31.1 million).

With 34,235 imported cases (TIR = 28.8/100,000 travellers) between 2015 and 2019, malaria was the most common arthropod-borne disease among travellers from Africa to Europe. Most of the cases were confirmed ones (> 99%). As for the blood parasites causing malaria, for 92% (n=31,404) of the reported cases the respective Plasmodium species were identified. Plasmodium falciparum accounted for the majority of them (89%) with the proportion of P. falciparum ranging from 75% for Eastern Africa to 92% for Western Africa.

In comparison, other mosquito-borne infections among travellers from Europe were reported only sporadically during the period studied: dengue (n=956), chikungunya (n=161), Zika virus disease (n=16), West Nile fever infection (n=9), Rift Valley fever (n=4) and yellow fever (n=1). There were no reports on imported cases of Crimean-Congo haemorrhagic fever, plague, or tick-borne encephalitis from Africa.

Complementing local surveillance
Comparing the results across the assessed infections, the malaria TIR was 36 and 144 times higher than the TIR for dengue and chikungunya, respectively. According to Gossner et al., “this reflects the high level of endemicity of the disease and transmissibility of the parasites in a large part of the African continent, the long durations of detectable (untreated) infections (as compared with the arboviral diseases) and the high proportion of cases presenting clinical manifestation making diagnosis likely.”

The authors also observed that the number of imported cases and TIRs were higher for dengue than for chikungunya, which could imply that particularly in touristic areas dengue virus is circulating more widely than chikungunya virus.

While Gossner et al. acknowledge certain limitations of their study, e.g. potential underestimation of the TIR given that not all cases are diagnosed and reported in returning traveller to Europe or the fact that health data from travellers cannot serve as a substitute for local disease surveillance, they also consider that “travellers health data can efficiently complement local surveillance data, particularly when the country or region has a sub-optimal surveillance system. Similarly, travellers might be index cases of yet unrecognised outbreaks.”

 

References/notes to editors:
[1] Gossner Céline M, Hallmaier-Wacker Luisa, Briet Olivier, Haussig Joana M, de Valk Henriette, Wijermans Ariana, Bakonyi Tamas, Madubuko Theresa, Frank Christina, Noel Harold, Abdulaziz Mohammed. Arthropod-borne diseases among travellers arriving in Europe from Africa, 2015 to 2019. Euro Surveill. 2023;28(7):pii=2200270. Available from: https://doi.org/10.2807/1560-7917.ES.2023.28.7.2200270

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JOURNAL

Eurosurveillance

DOI

10.2807/1560-7917.ES.2023.28.7.2200270

https://www.eurekalert.org/news-releases/980023

How COVID-19 can impact the heart

 COVID-19 infections can cause potentially life-threatening heart issues. Studies suggest that people with COVID-19 are 55% more likely to suffer a major adverse cardiovascular event, including heart attack, stroke and death, than those without COVID-19. They’re also more likely to have other heart issues, like arrhythmias (abnormal heart rhythms) and myocarditis (inflammation of the heart muscle). Andrew Marks, a cardiologist and biophysics professor at Columbia University, Steven Reiken, a research scientist in Marks’ lab, and colleagues, have studied some of the changes that occur in the heart that could lead to these problems. Reiken will present their work on Monday February 20 at the 67th Annual Biophysical Society Meeting in San Diego, California.

In heart tissue from patients who had COVID-19, the team observed increases in oxidative stress (harmful production of unstable molecules) and signals of inflammation, as well as changes in calcium. They also detected adverse changes to a protein called RyR2, which is responsible for regulating the heart’s calcium ion levels. The heart muscle, like all muscle cells, needs calcium ions to contract. The heart’s system for managing calcium ions is essential for the coordinated contractions of the atria and ventricles that pump blood throughout the body. When calcium in the heart becomes dysregulated, it can cause arrhythmias or heart failure.

To study changes to the heart further, they used a mouse model infected with COVID-19. They observed changes to the heart tissue including immune cell infiltration, collagen deposition (indicative of injury), death of heart cells, and blood clots. They also measured changes to the heart proteome—the proteins that are expressed by the heart cells—and found patterns consistent with changes observed to human hearts that were infected with COVID-19, as well as markers of cardiomyopathy, which can make it harder for the heart to pump blood to the body and can lead to heart failure.

“The more awareness you build around particular aspects of a disease, the more likely you are to improve the care of patients. And doctors should be aware of heart changes related to COVID-19 infections and should be looking for them,” Marks said.

Ultimately, “we want to really figure out what's causing the heart disease and how to fix it,” Marks said. Understanding changes at the molecular level may reveal drug targets that could improve cardiac symptoms related to COVID-19 and help healthcare professionals diagnose and treat these issues more effectively. Additionally, understanding the cardiac complications of COVID-19 can also help public health officials make more informed decisions about how to respond to the COVID-19 pandemic, especially in advising those at higher risk for heart problems.

https://www.eurekalert.org/news-releases/979643

Weaponizing part of the SARS-CoV-2 spike protein against itself

 The virus that causes COVID-19, called SARS-CoV-2, uses its spike protein in order to stick to and infect our cells. The final step for the virus to enter our cells is for part of its spike protein to act like a twist tie, forcing the host cell’s outer membrane to fuse with the virus. Kailu Yang, in the lab of Axel Brunger, colleagues at Stanford University, and collaborators at University of California Berkely, Harvard Medical School, and University of Finland have generated a molecule based on the twisted part of the spike protein (called HR2), which sticks itself onto the virus and prevents the spike protein from twisting. Their research shows that it prevents cells from infection even with new SARS-COV-2 variants. Yang’s work was published in the Proceedings of the National Academy of Sciences in October and will be presented on Tuesday, February 21 at the 67th Annual Biophysical Society Meeting in San Diego, California.

Other treatments for COVID-19 have worked by sticking to the outside of the spike protein to block it from infecting cells, but they’ve had drawbacks. For example, bebtelovimab was an antibody treatment that targeted the spike protein, however, it didn’t work well against new COVID-19 variants because that part of the spike protein has mutated over time. Yang and Brunger are hopeful that their molecule, which they call the longHR2_42 inhibitor, is lead compound to develop a new type of antiviral therapeutic to prevent infections even with new variants.

The reason the longHR2_42 inhibitor may work against an evolving virus is that it is based on part of the spike protein that hasn’t changed even as other parts have. “In the virus, there's two parts of the spike protein that come together forming this bundle. So we simply took a short piece of one part of this bundle, and by synthesizing that small piece chemically, it can insert itself into the spike protein and prevent the virus from infecting cells,” Brunger explained. Past research from before this COVID-19 pandemic aimed to create a similar molecule that would work to block infection of the SARS coronavirus, but those past attempts weren’t as effective as the longHR2_42 inhibitor.

Brunger believes their molecule is more effective than past attempts due to Yang’s work determining a detailed structure of the twisted together parts of the SARS-CoV-2 virus, called the postfusion so-called HR1HR2 complex, so they knew longer molecules would help block the spike protein from twisting into the HR1HR2 complex in the first place. “We made the molecule a little longer than previously published work based on the structure, and indeed, we confirmed in our fusion and infection assays that this longer piece inhibits much better,” Brunger said.

The team is currently testing the longHR2_42 inhibitor in mice infected with SARS-CoV-2 (collaboration with Giuseppe Ballisteri and co-workers, University of Finland). They are hopeful that they will be able to deliver it to people via an inhaler so that it gets to the airway, which is exactly where you want to treat an early infection to prevent infection from becoming severe. “The moment people start developing sniffles will be the time to take it,” Brunger explained.

https://www.eurekalert.org/news-releases/979629