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Unlocking New Hope for Sepsis Treatment: A Breakthrough in Drug Discovery

The immune system typically can ramp up the body’s defenses to clear out an invading threat without issue. Glitches can happen, however, with sepsis occurring when the mustered army of cells also attacks the body’s own tissues and organs as if they were enemy combatants. Sepsis is dangerous, particularly when it isn’t treated early, and it can lead to the even more deadly condition of septic shock — a massive drop in blood pressure that can quickly damage organs by starving them of nutrients. Scientists demonstrate the promise of a new approach to uncovering potential treatments for sepsis.

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The fight against sepsis has been a long-standing challenge in the medical community. This life-threatening condition occurs when the body’s defense mechanisms, meant to eliminate invaders, turn against its own tissues and organs. Despite the best efforts of researchers, treatments for sepsis have remained limited, relying primarily on antibiotics and supportive care.

A recent study published in ACS Omega by scientists at Sanford Burnham Prebys and CUNY Advanced Science Research Center has brought new hope to this field. The research team, led by Lutz Tautz, PhD, focused on an enzyme called Vaccinia-H1-related phosphatase (VHR), which plays a crucial role in controlling the immune system’s response to danger.

Previous studies had shown that genetically modifying mice to produce less VHR provided protection against sepsis and septic shock. However, previous attempts to develop drugs that block VHR have been unsuccessful due to the enzyme’s active site, where it binds to specific molecules to carry out its function in the immune system.

Tautz and his team took a different approach by building a fragment-based drug discovery platform for VHR. This strategy involves identifying small molecular fragments that can interact with the enzyme and then using these fragments as building blocks to create effective drug candidates.

The research team tested 1,000 fragments and identified multiple promising starting points for future drugs. Notably, they discovered fragments capable of binding to novel sites beyond the active site, which could potentially be optimized to enable selective degradation of VHR for combating sepsis and septic shock.

This breakthrough has significant implications for the treatment of sepsis, a condition responsible for nearly 20% of global deaths. The discovery platform developed by Tautz and his team can also be applied to other protein tyrosine phosphatases, which have been implicated in various diseases.

In conclusion, this study offers new hope for the development of effective treatments for sepsis. By unlocking the secrets of VHR and identifying promising fragments for drug candidates, researchers are one step closer to finding a cure for this devastating condition.

Agriculture and Food

The Dark Side of Cannabis Use in Pregnancy

A systematic evidence review finds that consuming cannabis while pregnant appears to increase the odds of preterm birth, low birth weight and infant death.

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The Dark Side of Cannabis Use in Pregnancy

A recent systematic review has raised significant concerns about the risks associated with consuming cannabis while pregnant. The study, conducted by researchers at Oregon Health & Science University, analyzed 51 observational studies involving over 21 million people to examine the potential adverse effects of cannabis use during pregnancy.

The findings are alarming: consuming cannabis appears to increase the odds of preterm birth, low birth weight, and infant death. These results are consistent with definitive evidence in nonhuman primate models exposed to THC, the main psychoactive compound in cannabis.

The placenta, a vital organ responsible for supplying oxygen and nutrients to the fetus, is particularly affected by cannabis use during pregnancy. Research has shown that cannabis can lead to decreased blood flow and reduced availability of oxygen in the placenta, ultimately affecting fetal development and growth.

While many pregnant women may view cannabis as a harmless substance due to its increasingly widespread legalization, the reality is far more concerning. Cannabis remains a Schedule 1 substance under federal law, and its use during pregnancy is not recommended by medical professionals.

The lead author of the study, Dr. Jamie Lo, emphasizes the importance of prioritizing fetal health over any perceived benefits of cannabis use during pregnancy. “Abstinence is ideal,” she notes, “but it’s not realistic for many patients.” In such cases, a harm-reduction approach can be recommended, advising pregnant women to reduce their cannabis consumption and frequency to minimize potential risks.

The research, part of the Systematically Testing the Evidence on Marijuana (STEM) project, highlights the need for more comprehensive studies on the effects of cannabis use during pregnancy. By understanding these risks, healthcare providers can better counsel expectant mothers and promote healthier outcomes for both mother and child.

Sources:

* The study was published in JAMA Pediatrics.
* Funding for this research was provided by the Office of Rural Health in the Veterans Health Administration of the U.S. Department of Veterans Affairs and the National Institute on Drug Abuse of the National Institutes of Health.

Key Takeaways:

* Consuming cannabis during pregnancy appears to increase the odds of preterm birth, low birth weight, and infant death.
* The placenta is particularly affected by cannabis use during pregnancy, leading to decreased blood flow and reduced availability of oxygen.
* A harm-reduction approach can be recommended for pregnant women who cannot abstain from cannabis use.
* More comprehensive studies are needed to fully understand the effects of cannabis use during pregnancy.

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Animal Learning and Intelligence

The Link Between Cannabis Use and Psychosis: Uncovering the Brain’s Dopamine System

A new study found that people with cannabis use disorder (CUD) had elevated dopamine levels in a brain region associated with psychosis.

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The connection between cannabis use and psychosis has long been a topic of interest for researchers. A recent study led by McGill University sheds light on the brain’s dopamine system as a possible explanation for why cannabis use increases the risk of hallucinations and delusions, key symptoms of schizophrenia and other psychotic disorders.

Dopamine is a neurotransmitter that regulates mood and motivation, and an excess is associated with psychosis. The study reveals that individuals with cannabis use disorder (CUD) have elevated dopamine levels in a brain region linked to psychosis. This finding could help explain why cannabis use increases the risk of hallucinations and delusions.

The study involved 61 participants, including those with and without CUD, as well as individuals with early-stage schizophrenia, some of whom also had CUD. Using a specialized brain scan called neuromelanin-MRI, researchers measured their neuromelanin signal, which reflects dopamine activity. The results showed that people with CUD had an abnormally high neuromelanin signal, and the elevation was tied to the severity of their cannabis use.

These findings have significant implications for educating youth about the risks associated with frequent cannabis use. In Canada, about one-in-five youth are cannabis users, consuming it daily or almost daily. Understanding the potential impact on mental health remains a pressing question.

The study’s lead author, Jessica Ahrens, notes that “for a long time, clinical researchers across the world have been searching for a link showing that cannabis affects the brain mechanism behind psychosis. We now show that a shared dopamine pathway could be the answer.”

Future research will explore whether long-term cannabis use leads to lasting dopamine changes and whether these effects reverse after quitting. As Dr. Lena Palaniyappan, Professor of Psychiatry at McGill and Psychiatrist at the Douglas Mental Health University Institute, suggests, “our findings could help doctors and mental health professionals better educate patients about the potential risks of frequent cannabis use, especially for those with a family history of psychosis.”

The study’s publication in Jama Psychiatry provides valuable insights into the link between cannabis use and psychosis, and its findings have important implications for public health and education.

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Controlled Substances

Potential Biomarkers for Schizophrenia Identified in Cannabis Users

A new study has analyzed and compared the fatty acids in the blood of individuals with schizophrenia, of those with cannabis use disorder and of those with both diagnoses, with the aim of shedding light on new biomarkers and improving the understanding of the biological relationship between the two disorders. The study also offers a powerful tool for identifying new biomarkers.

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A new study published in Scientific Reports has made a significant breakthrough in understanding the potential risk factors for developing schizophrenia due to cannabis use. Researchers from the University of the Basque Country (UPV/EHU) have identified biomarkers in the blood that could help predict the risk of some individuals developing a psychiatric disorder like schizophrenia if they use cannabis.

Cannabis is one of the most widely used substances globally, with an estimated 228 million users between the ages of 15 and 64. However, the risk of developing schizophrenia increases significantly with cannabis use, especially when it starts at a young age. According to estimates, approximately 10% of cannabis users will develop cannabis use disorder during their lifetime.

The research team compared the fatty acid content in the blood samples taken from individuals with schizophrenia who did not use cannabis, those who used cannabis and developed a cannabis use disorder, and a control group with neither a psychiatric disorder nor drug use. They found considerable differences between these groups, indicating an altered metabolism.

Specifically, they detected that some fatty acids differentiated between the cannabis-using group and the groups with schizophrenia and dual-diagnosis patients. These molecules could potentially be biomarkers for predicting the risk of developing a psychiatric disorder like schizophrenia due to cannabis use.

The study’s findings are promising, as it paves the way forward in identifying blood biomarkers that can help predict the risk of developing a psychiatric disorder. While more research is needed to confirm these results, this study has opened up new avenues for investigation and could lead to the development of more effective prevention strategies.

Dr. Leyre Urigüen, coordinator of the study, expressed optimism about the findings: “I think it’s essential to be capable of finding blood biomarkers that can help predict the risk of developing a psychiatric disorder like schizophrenia due to cannabis use. This study has proven to be the start of this way forward.” The research team is hopeful that these findings will lead to more targeted and effective interventions for individuals at risk of developing schizophrenia due to cannabis use.

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