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Comment by Dr. Krishna Kumari Challa on December 12, 2024 at 9:53am

Drug-free pain relief: Solvent molecules offer non-addictive alternative

Researchers have made a discovery regarding the TRPV1 (transient receptor potential vanilloid 1) ion channel and its role in pain perception. The study reveals how solvent molecules can modulate pain signals, offering a potential pathway for a safer, non-addictive pain management approach.

Pain management is a critical aspect of health care, directly impacting quality of life and overall well-being. The TRPV1 ion channel, essential for pain sensing, undergoes pore expansion when activated, allowing ions and larger molecules to pass through. However, the ability of water molecules to permeate the TRPV1 channel has remained uncertain.

To address this, the research team developed an upconversion nanoprobe capable of distinguishing between ordinary water (H₂O) and deuterated water (D₂O). This advanced technology enabled real-time tracking of water dynamics at both the single-cell and single-molecule levels. 

The study showed that when D₂O passed through the TRPV1 channel, it suppressed pain signal transmission and achieved effective analgesia.

The findings were published in the journal Nature Biomedical Engineering on 21 November 2024.

Administering D₂O to pre-clinical models, the team successfully reduced both acute and chronic inflammatory pain transmission without affecting other neurological responses. This solvent-mediated analgesia mechanism provides an effective, biocompatible, and non-addictive alternative to traditional pain medications, circumventing issues related to drug dependency and tolerance.

The solvent-mediated analgesia mechanism represents an innovative breakthrough in pain relief, potentially driving the development of safer, non-addictive pain therapies for clinical use.

Yuxia Liu et al, Solvent-mediated analgesia via the suppression of water permeation through TRPV1 ion channels, Nature Biomedical Engineering (2024). DOI: 10.1038/s41551-024-01288-2

Comment by Dr. Krishna Kumari Challa on December 12, 2024 at 9:26am

Personalized blood count could lead to early intervention for common diseases

A complete blood count (CBC) screening is a routine exam requested by most physicians for healthy adults. This clinical test is a valuable tool for assessing a patient's overall health from one blood sample.

Currently, the results of CBC tests are analyzed using a one-size-fits-all reference interval, but a new study led by researchers from Mass General Brigham suggests that this approach can lead to overlooked deviations in health. In a retrospective analysis, researchers show that these reference intervals, or setpoints, are unique to each patient.

The study revealed that one healthy patient's CBC setpoints can be distinguishable from 98% of other healthy adults. Results are published in Nature.

Complete blood counts are common tests, and this study suggests CBCs vary a lot from person to person even when completely healthy, and a more personalized and precision medicine approach could give more insight into a person's health or disease.

The long-term stability and patient-specificity of setpoints may provide new opportunities for the personalized management of healthy adults envisioned by precision medicine.

CBC indices are known to shift due to genetics, disease history, and age. But the new study suggests that individual patients have a "setpoint"—a stable value around which measures fluctuate.

By considering CBC setpoints tailored to an individual, clinicians may be able to diagnose diseases in their early stages in adults that appear otherwise healthy, including disorders such as diabetes, heart disease, and kidney failure, all of which can benefit from early intervention.

The study found that for multiple diseases, setpoints produce a two- to four-fold relative risk stratification which is comparable to that provided by common disease screening factors.

The researchers note that these setpoints create new opportunities to investigate the mechanisms of varying CBC thresholds and that the information from CBC setpoints could be used to create more specific treatment plans, including determining if additional screening is needed for an accurate diagnosis.

Foy BH et al, Haematological setpoints are a stable and patient-specific deep phenotype, Nature (2024). DOI: 10.1038/s41586-024-08264-5. www.nature.com/articles/s41586-024-08264-5

Comment by Dr. Krishna Kumari Challa on December 12, 2024 at 7:15am

Sepsis trial finds better biomarker guidance reduces antibiotic use

The ADAPT-Sepsis research group has demonstrated that using procalcitonin (PCT) as a biomarker to guide antibiotic duration in critically ill adults with suspected sepsis can significantly reduce treatment length without increasing mortality risks.

Following similar protocols using C-reactive protein (CRP) failed to show reductions in antibiotic duration and yielded inconclusive safety outcomes.

Pressure to improve our collective antibiotic stewardship is reflected in global initiatives to address antimicrobial resistance. Overusing antibiotics in the past has accelerated resistance in their targets, causing treatments we rely on to become increasingly less effective.

For patients who need prolonged antibiotic treatment, antimicrobial resistance can dangerously affect treatment outcomes, creating an urgent need for markers that can inform clinicians when it is safe to stop treatment.

Critically ill patients with sepsis often receive lengthy antibiotic courses. With substantial and unpredictable variations in antibiotic treatment responses between individuals, clinicians simply do not know what the optimal duration of treatment should be.

Efforts to refine treatment have relied on biomarkers, the expression of certain proteins during an illness typically retrieved through a blood test. For biomarkers involved in the trial, levels of PCT and CRP are known to be associated with infection and inflammation. Used as a form of status update, biomarker levels can guide when to stop antibiotics.

Clinical trials examining biomarker-guided protocols have yielded inconsistent recommendations. Conflicting evidence, coupled with a high mortality risk in sepsis, has compelled the search for better validated, more evidence-based strategies.

In the randomized clinical trial study, "Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis: The ADAPT-Sepsis Randomized Clinical Trial," published in JAMA, researchers at 41 National Health Service intensive care units in the United Kingdom, evaluated daily biomarker (PCT or CRP) guided protocols compared with standard care among 2,760 adults.

Patients received either daily PCT-guided advice, daily CRP-guided advice, or standard care guidance without biomarker input. Each  protocol was initiated within 24 hours of starting intravenous antibiotics for suspected sepsis and continuing for up to 28 days.

Results indicated a significant reduction in total antibiotic days for the PCT-guided group compared with standard care, with a mean difference of approximately 0.9 days. Noninferiority was achieved for 28-day all-cause mortality in the PCT-guided group, establishing a safe reduction in antibiotic exposure.

CRP guidance did not reduce overall antibiotic duration, and mortality outcomes were inconclusive when compared to standard care.

These findings support the incorporation of PCT-guided protocols into standard sepsis care for critically ill adults.

Paul Dark et al, Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis, JAMA (2024). DOI: 10.1001/jama.2024.26458

Comment by Dr. Krishna Kumari Challa on December 11, 2024 at 12:35pm

Early life exposure to toxic chemicals may cause behavioral, psychological problems

Early life exposure to a class of endocrine-disrupting chemicals (EDCs) called polychlorinated biphenyls (PCBs) may lead to behavioral problems in rats, according to a new animal study published in the Journal of the Endocrine Society.

Endocrine-disrupting chemicals (EDCs) are chemicals that mimic, block or interfere with hormones in the body's endocrine system and contribute to endocrine diseases such as cancer, reproductive disorders, obesity and neuroendocrine disorders.

PCBs have been banned for decades but are still persistent in the environment. PCBs are found in contaminated soil, sediment and certain types of fish due to environmental contamination. They have been linked to reproductive and anxiety disorders.

People may be more vulnerable to the endocrine-disrupting effects of PCB exposure during the perinatal period, the time from conception until about one year after giving birth.

Researchers found rats exposed to PCBs during the perinatal period may have developmental and hormonal changes. This study emphasizes and supports previous research on how PCB exposure can affect neurobehavioral outcomes.

The researchers fed a human-relevant PCB mixture or the placebo to about 40 pregnant rats and found the EDCs can reprogram their pups' developing neuroendocrine system and lead to neurobehavioral problems in early life.

Andrea C Gore et al, Neuroendocrine and Developmental Impacts of Early Life Exposure to EDCs, Journal of the Endocrine Society (2024). DOI: 10.1210/jendso/bvae195

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Comment by Dr. Krishna Kumari Challa on December 11, 2024 at 12:27pm

Brain mechanisms underpinning loss of consciousness identified

The shift from an awake state to unconsciousness is a phenomenon that has long captured the interest of scientists and philosophers alike, but how it happens has remained a mystery—until now. Through studies on rats, a team of researchers at Penn State has pinpointed the exact moment of loss of consciousness due to anesthesia, mapping what happens in different brain regions during that moment.

The study has implications for humans as well as for other types of loss of consciousness, such as sleep, the researchers said. They published their results in Advanced Science.

In this study the researchers combined two different methods: electrophysiology studies and functional magnetic resonance imaging (fMRI). By measuring electrophysiological signals—or electrical activity—in the brain very quickly over time, the researchers determined the precise moment that the rat transitioned from an awake state to an unconscious one.  

They next overlaid this time-stamped data with the fMRI map of activity in the whole brain to investigate different regions of the brain during that transition.

They  found that there were three regions in the brain that showed transient changes in their activities during the moment of lost consciousness: the medial prefrontal cortex, the hippocampus and the thalamus.

While these regions have been implicated in unconscious states in the existing scientific literature, this new research was the first to indicate how these regions might interact with each other and what kind of role they might play during the moment of loss of consciousness.

The researchers said previous work also did not indicate whether the activity in those three regions was a cause or an effect of loss of consciousness.

The results suggest that loss of consciousness may be triggered by sequential events in these three regions, while activity increases in other cortical regions may be a consequence, rather than a cause, of loss of consciousness.

The results do provide new insights into the roles of these brain regions in loss of consciousness.

Xiaoai Chen et al, Sequential Deactivation Across the Hippocampus‐Thalamus‐mPFC Pathway During Loss of Consciousness, Advanced Science (2024). DOI: 10.1002/advs.202406320

Comment by Dr. Krishna Kumari Challa on December 11, 2024 at 12:08pm

Toxoplasma gondii parasite uses unconventional method to make proteins for evasion of drug treatment, research reveals

A study by  Medicine researchers sheds new light on how Toxoplasma gondii parasites make the proteins they need to enter a dormant stage that allows them to escape drug treatment. The research is published in the Journal of Biological Chemistry.

Toxoplasma gondii is a single-celled parasite that people catch from cat feces, unwashed produce or undercooked meat. The parasite has infected up to one-third of the world's population, and after causing mild illness, it persists by entering a dormant phase housed in cysts throughout the body, including the brain.

Toxoplasma cysts have been linked to behavior changes and neurological disorders like schizophrenia. They can also reactivate when the immune system is weakened, causing life-threatening organ damage.

While drugs are available to put toxoplasmosis into remission, there is no way to clear the infection. A better understanding of how the parasite develops into cysts would help scientists find a cure.

 Researchers have shown that Toxoplasma forms cysts by altering which proteins are made. Proteins govern the fate of cells and are encoded by mRNAs.

But mRNAs can be present in cells without being made into protein. Researchers have  shown that Toxoplasma switches which mRNAs are made into protein when converting into cysts.

Researchers examined the so-called leader sequences of genes named BFD1 and BFD2, both of which are necessary for Toxoplasma to form cysts.

mRNAs not only encode for protein, but they begin with a leader sequence that contains information on when that mRNA should be made into protein.

All mRNAs have a structure called a cap at the beginning of their leader sequence. Ribosomes, which convert mRNA into protein, bind to the cap and scan the leader until it finds the right code to begin making the protein.

What the researchers now found is during cyst formation, BFD2 is made into protein after ribosomes bind the cap and scan the leader, as expected. 

But BFD1 does not follow that convention. Its production does not rely on the mRNA cap like most other mRNAs."

The team further showed that BFD1 is made into protein only after BFD2 binds specific sites in the BFD1 mRNA leader sequence. This is a phenomenon called cap-independent translation, which is more commonly seen in viruses.

Finding it in a microbe that has cellular anatomy like our own was surprising.

Vishakha Dey et al, Cap-independent translation directs stress-induced differentiation of the protozoan parasite Toxoplasma gondii, Journal of Biological Chemistry (2024). DOI: 10.1016/j.jbc.2024.107979

Comment by Dr. Krishna Kumari Challa on December 11, 2024 at 11:09am

Human disruption is driving 'winner' and 'loser' tree species shifts across Brazilian forests, study shows

An international team of researchers examined a unique dataset of more than 1,200 tropical tree species over more than 270 forest plots across six regions of Brazilian Amazon and Atlantic forests that have been altered by people through activities such as deforestation and local disturbances like logging, hunting and burning.

Fast-growing and small-seeded tree species are dominating Brazilian forests in regions with high levels of deforestation and degradation, a study shows. This has potential implications for the ecosystem services these forests provide, including the ability of these "disturbed" forests to absorb and store carbon. This is because these "winning" species grow fast but die young, as their stems and branches are far less dense than the slow growing tree species they replace.

Wildlife species adapted to consuming and dispersing the large seeds of tree species that are being lost in human-modified landscapes may also be affected by these shifts.

Authors of the study, "Winner-loser plant trait replacements in human-modified tropical forests" published in Nature Ecology & Evolution, say their findings highlight the urgent need to conserve and restore tropical forests, prevent degradation, and implement measures to protect and boost populations of the large-bodied birds like toucans and mammals such as spider monkeys that disperse the seeds of "losing" slow-growing large-seeded tree species.

The researchers looked at the overall structure of the landscapes surrounding each forest plot and, using multiple statistical models, they were able to identify the causal effects of habitat loss, fragmentation and local degradation on the composition of forests, as well as identifying the attributes of so-called "winners" and "losers" species.

They found that the tree species dominating landscapes with high forest cover tend to have dense wood and large seeds, which are primarily dispersed by medium to large-bodied animals typical of Brazil's rainforests. 

In contrast, in highly deforested landscapes, where remaining forests face additional human disturbances, these tree species are losing out to so-called 'opportunistic' species, which have softer wood and smaller seeds consumed by small, mobile, disturbance-adapted birds and bats. These species typically grow faster and have greater dispersal capacity.

The researchers found this was happening despite differing geography, climate and land-use contexts.

This study highlights the urgent need to strengthen the conservation and restoration of tropical forests to preserve these vital ecosystems.

Tropical forests constitute the most important reservoir of terrestrial biodiversity. They play a major role in absorbing greenhouse gases and provide essential ecosystem services. Yet they are victims of rapid deforestation and fragmentation, with the loss of 3 to 6 million hectares per year over the last two decades.

Winner-loser plant trait replacements in human-modified tropical forests, Nature Ecology & Evolution (2024). DOI: 10.1038/s41559-024-02592-5

Comment by Dr. Krishna Kumari Challa on December 11, 2024 at 10:57am

To test this antidote, they injected hydrogen sulfide-treated mice with met-hemoCD-I. The results were very promising—mice injected with met-hemoCD-I showed improved survival rates compared to mice that were not given the antidote. Additionally, CcO activity in the brain and heart tissues (which had decreased because of poisoning) recovered and returned to normal.
Another aspect of met-hemoCD-I that makes it a very promising antidote is its demonstrated safety—it was found that injected met-hemoCD-I was excreted in the urine of the rats without undergoing any chemical decomposition in their body.

The results of this study show that hemoCD-Twins could be used as a powerful antidote to treat carbon monoxide, hydrogen cyanide, and now hydrogen sulfide poisoning without the risk of any side effects.
Using hemoCD-Twins, we can provide one powerful solution for multiple gas poisoning, even if the cause of poisoning is unknown.
Clinical trials are about to be started with this antidote.

 Nakagami, A., et al. Detoxification of hydrogen sulfide by synthetic heme model compounds, Scientific Reports (2024). DOI: 10.1038/s41598-024-80511-1

Part 2

Comment by Dr. Krishna Kumari Challa on December 11, 2024 at 10:48am

New antidote could save lives from deadly hydrogen sulfide gas

Hydrogen sulfide, a colorless gas that smells like rotten eggs, is produced naturally from decaying matter. This gas is lethal to breathe in, and hydrogen sulfide present in high concentrations can cause death very rapidly.

Its relative density is also greater than air, causing it to accumulate at lower altitudes and posing an enormous threat to workers at sites, such as manholes, sewage systems and mining operations.

Why is hydrogen sulfide so dangerous? It binds strongly to the heme-containing cytochrome c oxidase (CcO) enzyme and blocks the cellular process of aerobic (oxygen-dependent) respiration.
What is even more concerning is that, as of now, there is no identified antidote that can treat hydrogen sulfide poisoning. Hence, there is an urgent need to develop therapeutic agents that can be stored for long durations and are effective against hydrogen sulfide poisoning immediately.

A study  published online on December 10, 2024, in Scientific Reports has proposed a novel antidote for hydrogen sulfide poisoning.

Researchers decided to tackle this problem by using artificial heme-model compounds that would have a higher affinity towards hydrogen sulfide than the native hemes present in our bodies.

They  have developed and studied synthetic heme-model compounds (hemoCDs) over the last two decades.

In this study, they decided to test if  two of those complexes had the potential to "scavenge" hydrogen sulfide in an aqueous medium. Interestingly, they found that met-hemoCD-I in particular had a very high affinity for hydrogen sulfide under normal physiological conditions—almost 10 times higher than that of human met-hemoglobin.

Met-hemoCD-I was able to convert toxic hydrogen sulfide into nontoxic sulfite and sulfate ions, indicating that it could be used to treat hydrogen sulfide poisoning.

Part 1

Comment by Dr. Krishna Kumari Challa on December 11, 2024 at 10:32am

The analysis showed that sea-surface temperatures dropped by 3°C as an after-effect of the merging of the cyclones, and deep, cold water masses were churned upwards towards the surface from a depth of 200 meters in a process known as "upwelling." The cooling effect was "exceptionally high" in relation to the cyclones' intensity, the researchers observed.

The highest wind speeds of around 130 kilometers per hour were reached on 11 April, after the merging of the cyclones, and corresponded to Category 1 on the Hurricane Scale. The observed cooling and the depth of the upwelling, on the other hand, were of a scale observed in Category 4 or 5 hurricanes.
The researchers were particularly surprised by the strength of the upwelling: there were periods when the deep-water masses rose to the sea surface at a speed of up to 30 meters per day. By comparison, the typical upward velocity of the ocean is only between 1 and 5 meters per day.

In this specific case, a downward velocity of the ocean was observed shortly before the cyclones merged. Thanks to satellite technology and autonomous deep-sea ARGO floats, they were able to demonstrate how the rotation of the cyclones transports cold water from the depths of the ocean to the surface.
Although encounters between tropical cyclones during their one to two-week lifespan have been rare to date, according to climate models, the number and intensity of tropical cyclones is likely to increase as a result of global warming—and by extension also the likelihood of full-blown hurricane-force cyclones colliding.
This could result in "the most extreme interactions between the ocean and the atmosphere," the authors of the paper write. The fact that the merging of two cyclones can lead to an abrupt change of course also makes it more difficult to predict how they will behave afterwards.
They also point to another important consequence: "As a result of the interactions of a cyclone with the ocean and the upwelling of cold, deep water, the ocean absorbs additional heat from the air and then transports it to higher latitudes—a crucial process that influences the climate worldwide."
In addition, cyclones also convert thermal energy into mechanical energy which they then transport to higher latitudes as they progress.

Oliver Wurl et al, Intense Cooling of the Upper Ocean with the Merging of Tropical Cyclones: A Case Study in the Southeastern Indian Ocean, Tellus A: Dynamic Meteorology and Oceanography (2024). DOI: 10.16993/tellusa.4083

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