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Comment by Dr. Krishna Kumari Challa on August 11, 2021 at 12:21pm

In the complementary bladder-on-chip model, the researchers looked at the growth dynamics of bacteria within intracellular bacterial communities over time. They grew human umbrella and endothelial cells together under a simulated urine-flow system, and applied mechanical stresses to mimic the natural expansion and contraction of the bladder. This study focused on the role of neutrophil recruitment in response to infection, revealing that neutrophils cannot eliminate intracellular bacterial communities. By tracking intracellular bacterial communities over successive cycles of antibiotic treatment, the researchers found them to be highly dynamic and resistant to antibiotics. “These studies are part of the NCCR-funded “AntiResist” consortium aimed at developing more realistic in vitro models for infectious diseases, and using this knowledge to develop optimal treatment strategies, which could potentially have an enormous impact on human health,” says McKinney. “Microphysiological models bridge the gap between simple cell culture systems and animal models,” says Vivek V. Thacker, a senior author on both studies. “The two models complement each other well and are tailored to study specific aspects of the disease. We hope they will serve as a resource for the wider microbiology community and advance the synergies between the tissue engineering and infectious diseases communities.” https://researchnews.cc/news/8264/Organoid-bladders-reveal-secrets-... part3

Comment by Dr. Krishna Kumari Challa on August 11, 2021 at 12:20pm

To address this, the group of Professor John McKinney at EPFL’s School of Life Sciences developed two complementary bladder models to study UTIs in a more controlled way. The first model consists of bladder organoids that recreate the 3D stratified architecture of the bladder epithelium. Organoids are tiny lab-grown tissues and organs that are anatomically correct and physiologically functional.

The second model is a bladder-on-a-chip that incorporates physiological stimuli, e.g. the mechanical effect of bladder filling and voiding, as well as an interface with the vasculature to study immune cell migration to sites of infection. The advances were published in the journals Cell Reports and eLife.

“By generating organoids from a mouse with a fluorescent label incorporated within cell membranes, we could use live-cell confocal imaging at EPFL’s BioImaging & Optics Core Facility to identify specific bacterial niches within the organoid with a high spatial resolution,” says Sharma. “By imaging multiple organoids, we managed to identify heterogeneity and diverse outcomes of host-pathogen interactions. This proof-of-concept system has shown promising potential for follow up studies on bacterial persistence to antibiotics and the dynamics of immune cell responses to infection.”

In combination with volumetric electron microscopy performed by EPFL’s Biological Electron Microscopy Facility, the researchers found that solitary bacteria rapidly invade into deeper layers of the bladder, independently of the formation of intracellular bacterial communities, where they are protected from antibiotics and host immune cells. These findings could be leveraged to improve UTI treatment strategies.

part 2

Comment by Dr. Krishna Kumari Challa on August 11, 2021 at 12:20pm

Organoid bladders reveal secrets of UTIs

Urinary tract infections (UTIs) are among the most common bacterial infections. They usually require treatment with antibiotics, and almost a quarter of treated cases lead to recurrent infection. The vast majority of UTIs are caused by a subspecies of the bacterium Escherichia coli, which infect cells that line the bladder wall and form what are known as “intracellular bacterial communities”.

The “communities” repeatedly rupture and bacteria re-enter neighboring cells, eventually killing off the so-called “umbrella cells” that line the outermost layer of the bladder’s epithelium. The loss of umbrella cells then allows the bacteria to invade the deeper layers of the bladder, where they can form “quiescent intracellular reservoirs” that are resistant to antibiotics and cause UTI recurrences. The dynamics of these events are hard to capture in vivo in animal models.

“Infection dynamics are difficult to capture from static imaging of tissue explants at serial time points,” says Kunal Sharma, the lead author on the two studies. “Thus far, in vitro models have not recapitulated bladder architecture with sufficient fidelity to study the time course of these events.”

Part 1

Comment by Dr. Krishna Kumari Challa on August 11, 2021 at 10:29am

Middle-age height loss linked to heightened death risk in northern European women

Height loss in middle age is linked to a heightened risk of early death, primarily from heart disease or stroke—at least in Northern European women—suggests research published in the online journal BMJ Open.

But regular physical activity may help to stave off mid-life shrinkage, as well as lowering cardiovascular disease risk, the findings indicate.

People tend to start losing height once they reach their 50s, a process that speeds up during their 70s. Height loss is usually caused by vertebral disc shrinkage, spinal compression fractures, and changes in posture.

While some degree of height loss is associated with natural aging, previous research suggests that it may also be associated with an increased risk of death from heart disease.

In the study, each cm of height loss was associated with 14% and 21% greater odds of death from any cause among the Swedish and Danish women, respectively, after adjusting for potentially influential factors.

Short stature and high leisure time physical activity (including participation in competitive sports) at study entry were associated with less height loss, independent of age.

Major height loss, defined as more than 2 cm, was associated with 74% and 80% greater odds of death, respectively, among two groups of women.

Other unmeasured factors may also have influenced the findings, they add. These include early life physical activity and exposure to tobacco (either through second-hand smoke or smoking themselves], peak bone mass, underlying health conditions and medical treatments.

Nevertheless, the findings prompt the researchers to conclude that mid-life height loss "is a risk marker for earlier mortality in northern European women."

Specifically, the risk of cardiovascular disease is increased in women who lose height, with death from stroke a major contributor to this association, they add.

 Loss of height predicts total and cardiovascular mortality: a cohort study of northern European women, BMJ Open (2021). DOI: 10.1136/bmjopen-2021-049122

https://medicalxpress.com/news/2021-08-middle-age-height-loss-linke...

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Comment by Dr. Krishna Kumari Challa on August 10, 2021 at 11:16am

Comment by Dr. Krishna Kumari Challa on August 10, 2021 at 9:13am

'It's not climate change, it's climate chaos', wars UN | UN Climate report 2021

Comment by Dr. Krishna Kumari Challa on August 10, 2021 at 9:11am

The new report also makes clear that the warming we've experienced to date has made changes to many of our planetary support systems that are irreversible on timescales of centuries to millennia.

The oceans will continue to warm and become more acidic. Mountain and polar glaciers will continue melting for decades or centuries.

"The consequences will continue to get worse for every bit of warming," said Prof Hawkins.

"And for many of these consequences, there's no going back."

One key aspect of the report is the expected rate of temperature rise and what it means for the safety of humanity.

This new report says that under all the emissions scenarios considered by the scientists, both targets will be broken this century unless huge cuts in carbon take place.

While this report is more clear and confident about the downsides to warming, the scientists are more hopeful that if we can cut global emissions in half by 2030 and reach net zero by the middle of this century, we can halt and possibly reverse the rise in temperatures.

https://www.ipcc.ch/report/ar6/wg1/

Part 3

Comment by Dr. Krishna Kumari Challa on August 10, 2021 at 9:07am

IPCC report key points

• Global surface temperature was 1.09C higher in the decade between 2011-2020 than between 1850-1900.
• The past five years have been the hottest on record since 1850
• The recent rate of sea level rise has nearly tripled compared with 1901-1971
• Human influence is "very likely" (90%) the main driver of the global retreat of glaciers since the 1990s and the decrease in Arctic sea-ice
• It is "virtually certain" that hot extremes including heatwaves have become more frequent and more intense since the 1950s, while cold events have become less frequent and less severe

part 2

Comment by Dr. Krishna Kumari Challa on August 10, 2021 at 9:07am

Climate change: IPCC report is 'code red for humanity'

Human activity is changing the climate in unprecedented and sometimes irreversible ways, a major UN scientific report has said.

The landmark study warns of increasingly extreme heatwaves, droughts and flooding, and a key temperature limit being broken in just over a decade.

The report "is a code red for humanity", says the UN chief.

But scientists say a catastrophe can be avoided if the world acts fast.

There is hope that deep cuts in emissions of greenhouse gases could stabilise rising temperatures.

The sober assessment of our planet's future has been delivered by the UN's Intergovernmental Panel on Climate Change (IPCC), a group of scientists whose findings are endorsed by the world's governments.

Their report is the first major review of the science of climate change since 2013. Its release comes less than three months before a key climate summit in Glasgow known as COP26.

According to Prof Ed Hawkins, from the University of Reading, UK, and one of the report's authors, the scientists cannot be any clearer on this point.

"It is a statement of fact, we cannot be any more certain; it is unequivocal and indisputable that humans are warming the planet."

The authors say that since 1970, global surface temperatures have risen faster than in any other 50-year period over the past 2,000 years.

This warming is "already affecting many weather and climate extremes in every region across the globe".

Part 1

Comment by Dr. Krishna Kumari Challa on August 9, 2021 at 1:00pm

Researchers find possible culprit of inflammation that causes death...

As clinical evidence mounts that the leading cause of death in COVID-19 patients is the dangerous condition known as a cytokine storm, researchers have identified a protein in the blood that could be responsible. The team found that COVID-19 patients have significantly elevated levels of a protein called galectin-9 in their blood plasma. Perhaps more importantly, they also found a positive correlation between the levels of galectin-9 and pro-inflammatory cytokines released in the blood, which can lead to a cytokine storm. 

The findings suggest that galectin-9 levels in the body could be used as a biomarker to diagnose COVID-19 using a patient’s blood, potentially providing another non-invasive tool for COVID-19 testing. The levels could also be used to indicate the severity of the disease, though further study on that aspect is required.

The discovery of elevated galectin-9 levels in COVID-19 patients is important because of the positive correlation between the protein and a wide range of pro-inflammatory cytokines.

Cytokines as small cell-signalling proteins are involved in checks and balances in the immune system; they can turn on or turn off some cells to regulate the immune system. In the context of COVID, the problem is that there is a dysregulation of cytokine production—they are released very quickly in elevated levels. That’s what we call a ‘cytokine storm.

 galectin-9 is responsible for instructing immune cells to release the pro-inflammatory cytokines quickly in response to COVID-19 infection by binding to immune cells and forcing them to produce the cytokines. Further, as tissues are damaged as a result of inflammation, more galectin-9 is released from the cells—which activates more immune cells and releases more cytokines in a vicious cycle. The resulting cytokine storm damages tissue and organs, causes severe inflammation and can lead to death.

The next step is to develop treatments that block or inhibit the protein

https://journals.asm.org/doi/full/10.1128/mBio.00384-21

https://www.ualberta.ca/folio/2021/08/researchers-find-possible-cul...

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