Combining Antibiotics Changes How Effective They Are

The implications from this should be studied more in light of the major antibiotic resistance problem this century. Among other things, the research found that the compound vanillin (which gives vanilla its taste) combined with an antibiotic that has mostly stopped being used (spectinomycin) increased the effectiveness of the antibiotic.

The effectiveness of antibiotics can be altered by combining them with each other, non-antibiotic drugs or even with food additives. Depending on the bacterial species, some combinations stop antibiotics from working to their full potential whilst others begin to defeat antibiotic resistance, report EMBL researchers and collaborators in Nature on July 4.

In the first large-scale screening of its kind, scientists profiled almost 3000 drug combinations on three different disease-causing bacteria. The research was led by EMBL group leader Nassos Typas.

Overcoming antibiotic resistance

Overuse and misuse of antibiotics has led to widespread antibiotic resistance. Specific combinations of drugs can help in fighting multi-drug resistant bacterial infections, but they are largely unexplored and rarely used in clinics. That is why in the current paper, the team systematically studied the effect of antibiotics paired with each other, as well as with other drugs and food additives in different species.

Whilst many of the investigated drug combinations lessened the antibiotics’ effect, there were over 500 drug combinations which improved antibiotic outcome. A selection of these positive pairings was also tested in multi-drug resistant bacteria, isolated from infected hospital patients, and were found to improve antibiotic effects.

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According to Nassos Typas, combinations of drugs that decrease the effect of antibiotics could also be beneficial to human health. “Antibiotics can lead to collateral damage and side effects because they target healthy bacteria as well. But the effects of these drug combinations are highly selective, and often only affect a few bacterial species. In the future, we could use drug combinations to selectively prevent the harmful effects of antibiotics on healthy bacteria. This would also decrease antibiotic resistance development, as healthy bacteria would not be put under pressure to evolve antibiotic resistance, which can later be transferred to dangerous bacteria.”

General principles

This research is the first large-scale screening of drug combinations across different bacterial species in the lab. The compounds used have already been approved for safe use in humans, but investigations in mice and clinical studies are still required to test the effectiveness of particular drug combinations in humans. In addition to identifying novel drug combinations, the size of this investigation allowed the scientists to understand some of the general principles behind drug-drug interactions. This will allow more rational selection of drug pairs in the future and may be broadly applicable to other therapeutic areas.

Health Benefits of ASMR Found in First Study of Its Kind

ASMR provides calming and stimulating sensation with no downsides currently known. It’s worth noting that the phenomenon hasn’t been researched much yet though — there may be more positives or negatives discovered in the future. There’s still an amazing amount that isn’t scientifically known about various aspects of the human mind.

Autonomous Sensory Meridian Response (ASMR) — the relaxing ‘brain tingles’ experienced by some people in response to specific triggers, such as whispering, tapping and slow hand movements — may have benefits for both mental and physical health, according to new research.

Developing Drug Impairs Process Cancer Cells Use for Growth

It looks like this will be useful later on.

A drug discovered and advanced by The University of Texas MD Anderson Cancer Center’s Institute for Applied Cancer Science (IACS) and the Center for Co-Clinical Trials (CCCT) inhibits a vital metabolic process required for cancer cells’ growth and survival.

IACS-10759 is the first small molecule drug to be developed from concept to clinical trial by MD Anderson’s Therapeutics Discovery team, which includes IACS and the CCCT. Therapeutics Discovery is a unique group of clinicians, researchers and drug development experts working collaboratively to create new treatment options, including small molecules, biologics, and cell-based therapies.

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Metabolic reprogramming is an emerging hallmark of tumor biology where cancer cells evolve to rely on two key metabolic processes, glycolysis and oxidative phosphorylation (OXPHOS), to support their growth and survival. Extensive efforts have focused on therapeutic targeting of glycolysis, while OXPHOS has remained largely unexplored, partly due to an incomplete understanding of tumor contexts where OXPHOS is essential.

“Through a comprehensive translational effort enabled by collaboration across MD Anderson, we have identified multiple cancers that are highly dependent on OXPHOS,” said Marszalek.

This effort inspired the discovery and development of IACS-10759, a potent and selective inhibitor of OXPHOS. Its advancement to clinical trials was made possible by a multidisciplinary team of more than 25 scientists across Therapeutics Discovery.

“Through this collaborative, 18-month process, we identified and rapidly advanced IACS-10759 as the molecule for clinical development,” said Di Francesco. “We believe IACS-10759 will provide a promising new therapy for cancer patients.”

Noninvasive Technique to Correct Vision Shows Promise in Early Trials

A potentially safer and more effective solution to a widespread problem.

But, while vision correction surgery has a relatively high success rate, it is an invasive procedure, subject to post-surgical complications, and in rare cases permanent vision loss. In addition, laser-assisted vision correction surgeries such as laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) still use ablative technology, which can thin and in some cases weaken the cornea.

Columbia Engineering researcher Sinisa Vukelic has developed a new non-invasive approach to permanently correct vision that shows great promise in preclinical models. His method uses a femtosecond oscillator, an ultrafast laser that delivers pulses of very low energy at high repetition rate, for selective and localized alteration of the biochemical and biomechanical properties of corneal tissue. The technique, which changes the tissue’s macroscopic geometry, is non-surgical and has fewer side effects and limitations than those seen in refractive surgeries. For instance, patients with thin corneas, dry eyes, and other abnormalities cannot undergo refractive surgery. The study, which could lead to treatment for myopia, hyperopia, astigmatism, and irregular astigmatism, was published May 14 in Nature Photonics.

“We think our study is the first to use this laser output regimen for noninvasive change of corneal curvature or treatment of other clinical problems,” says Vukelic, who is a lecturer in discipline in the department of mechanical engineering. His method uses a femtosecond oscillator to alter biochemical and biomechanical properties of collagenous tissue without causing cellular damage and tissue disruption. The technique allows for enough power to induce a low-density plasma within the set focal volume but does not convey enough energy to cause damage to the tissue within the treatment region.

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“Refractive surgery has been around for many years, and although it is a mature technology, the field has been searching for a viable, less invasive alternative for a long time,” says Leejee H. Suh, Miranda Wong Tang Associate Professor of Ophthalmology at the Columbia University Medical Center, who was not involved with the study. “Vukelic’s next-generation modality shows great promise. This could be a major advance in treating a much larger global population and address the myopia pandemic.”

Vukelic’s group is currently building a clinical prototype and plans to start clinical trials by the end of the year. He is also looking to develop a way to predict corneal behavior as a function of laser irradiation, how the cornea might deform if a small circle or an ellipse, for example, were treated. If researchers know how the cornea will behave, they will be able to personalize the treatment — they could scan a patient’s cornea and then use Vukelic’s algorithm to make patient-specific changes to improve his/her vision.

“What’s especially exciting is that our technique is not limited to ocular media — it can be used on other collagen-rich tissues,” Vukelic adds. “We’ve also been working with Professor Gerard Ateshian’s lab to treat early osteoarthritis, and the preliminary results are very, very encouraging. We think our non-invasive approach has the potential to open avenues to treat or repair collagenous tissue without causing tissue damage.”

People Who Have Alcoholism Run in the Family Release More Dopamine in Expectation of Alcohol

Interesting findings that should be included in future treatments of alcohol use disorders. Forming situations where alcohol use isn’t expected could allow people to avoid a bad structure of incentives.

People with a family history of alcohol use disorder (AUD) release more dopamine in the brain’s main reward center in response to the expectation of alcohol than people diagnosed with the disorder, or healthy people without any family history of AUD, reports a new study in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.

“This exaggerated reward center stimulation by expectation of alcohol may put the [individuals with family history] at greater risk of alcohol use disorder, and could be a risk factor in itself,” said first author Lawrence Kegeles, MD, PhD, of Columbia University.

The study examined a range of risk for AUD, including 34 healthy participants with no family history of AUD, 16 healthy participants with a family history of the disorder (referred to as the family-history positive, or FHP, group), and 15 participants diagnosed with AUD. Dr. Kegeles and colleagues used PET brain scanning to measure the amount of dopamine release in areas of the brain important for reward and addiction. The participants underwent the brain scans after receiving either an alcohol drink — a cocktail of vodka, tonic, and cranberry — or a placebo drink without the vodka. Although the participants didn’t know the order in which they would receive the drinks, if they received the placebo drink first they were cued into expecting the alcohol drink next.

All three groups had similar dopamine release-levels in response to the alcohol, suggesting that alcohol-induced dopamine release is normal in AUD. However, “we found that the FHP participants had a much more pronounced response to the placebo drink than the other groups, indicating that expectation of alcohol caused the FHP group to release more reward center dopamine,” said Dr. Kegeles. The release of dopamine into the reward center is thought to reinforce alcohol consumption and possibly contribute to risk of AUD.

Study: Leg Exercise is Crucial to Brain and Nervous System Health

The relation between having both a strong mind and body is shown again, this time with reasoning as to why leg day shouldn’t be skipped at the gym.

Groundbreaking research shows that neurological health depends as much on signals sent by the body’s large, leg muscles to the brain as it does on directives from the brain to the muscles. Published today in Frontiers in Neuroscience, the study fundamentally alters brain and nervous system medicine — giving doctors new clues as to why patients with motor neuron disease, multiple sclerosis, spinal muscular atrophy and other neurological diseases often rapidly decline when their movement becomes limited.

“Our study supports the notion that people who are unable to do load-bearing exercises — such as patients who are bed-ridden, or even astronauts on extended travel — not only lose muscle mass, but their body chemistry is altered at the cellular level and even their nervous system is adversely impacted,” says Dr. Raffaella Adami from the Università degli Studi di Milano, Italy.

The study involved restricting mice from using their hind legs, but not their front legs, over a period of 28 days. The mice continued to eat and groom normally and did not exhibit stress. At the end of the trial, the researchers examined an area of the brain called the sub-ventricular zone, which in many mammals has the role of maintaining nerve cell health. It is also the area where neural stem cells produce new neurons.

Limiting physical activity decreased the number of neural stem cells by 70 percent compared to a control group of mice, which were allowed to roam. Furthermore, both neurons and oligodendrocytes — specialized cells that support and insulate nerve cells — didn’t fully mature when exercise was severely reduced.

The research shows that using the legs, particularly in weight-bearing exercise, sends signals to the brain that are vital for the production of healthy neural cells, essential for the brain and nervous system. Cutting back on exercise makes it difficult for the body to produce new nerve cells — some of the very building blocks that allow us to handle stress and adapt to challenge in our lives.

“It is no accident that we are meant to be active: to walk, run, crouch to sit, and use our leg muscles to lift things,” says Adami. “Neurological health is not a one-way street with the brain telling the muscles ‘lift,’ ‘walk,’ and so on.”

The researchers gained more insight by analyzing individual cells. They found that restricting exercise lowers the amount of oxygen in the body, which creates an anaerobic environment and alters metabolism. Reducing exercise also seems to impact two genes, one of which, CDK5Rap1, is very important for the health of mitochondria — the cellular powerhouse that releases energy the body can then use. This represents another feedback loop.

These results shed light on several important health issues, ranging from concerns about cardio-vascular impacts as a result of sedentary lifestyles to insight into devastating diseases, such as spinal muscular atrophy (SMA), multiple sclerosis, and motor neuron disease, among others.

Link Between Local Temperature Increases and More Antibiotic Resistance Found

A significant note with the threat of climate change looming.

Seeking to better understand the distribution of antibiotic resistance across the U.S., a multidisciplinary team of epidemiologists from Boston Children’s Hospital and the University of Toronto have found that higher local temperatures and population densities correlate with a higher degree of antibiotic resistance in common bacterial strains. The findings were published today in Nature Climate Change.

“The effects of climate are increasingly being recognized in a variety of infectious diseases, but so far as we know this is the first time it has been implicated in the distribution of antibiotic resistance over geographies,” says the study’s lead author, Derek MacFadden, MD, an infectious disease specialist and research fellow at Boston Children’s Hospital. “We also found a signal that the associations between antibiotic resistance and temperature could be increasing over time.”

“Estimates outside of our study have already told us that there will already be a drastic and deadly rise in antibiotic resistance in coming years,” says the paper’s co-senior author John Brownstein, PhD, who is Chief Innovation Officer and director of the Computational Epidemiology Group at Boston Children’s and professor of pediatrics at Harvard Medical School (HMS). “But with our findings that climate change could be compounding and accelerating an increase in antibiotic resistance, the future prospects could be significantly worse than previously thought.”

During their study, the team assembled a large database of U.S. antibiotic resistance information related to E. coli, K. pneumoniae, and S. aureus, pulling from various streams of hospital, laboratory and disease surveillance data documented between 2013 and 2015. Altogether, their database comprised more than 1.6 million bacterial pathogens from 602 unique records across 223 facilities and 41 states.

Not surprisingly, when looking at antibiotic prescription rates across geographic areas, the team found that increased prescribing was associated with increased antibiotic resistance across all the pathogens that they investigated.

Then, comparing the database to latitude coordinates as well as mean and medium local temperatures, the team found that higher local average minimum temperatures correlated the strongest with antibiotic resistance. Local average minimum temperature increases of 10 degrees Celsius were found to be associated with 4.2, 2.2 and 3.6 percent increases in antibiotic resistant strains of E. coli, K. pneumoniae, and S. aureus, respectively.

More unsettling still, when looking at population density, the team found that an increase of 10,000 people per square mile was associated with three and six percent respective increases in antibiotic resistance in E. coli and K. pneumoniae, which are both Gram-negative species. In contrast, the antibiotic resistance of Gram-positive S. aureus did not appear to be significantly affected by population density.

“Population growth and increases in temperature and antibiotic resistance are three phenomena that we know are currently happening on our planet,” says the study’s co-senior author Mauricio Santillana, PhD, who is a faculty member in the Computational Health Informatics Program at Boston Children’s and an assistant professor at HMS. “But until now, hypotheses about how these phenomena relate to each other have been sparse. We need to continue bringing multidisciplinary teams together to study antibiotic resistance in comparison to the backdrop of population and environmental changes.”

MacFadden says the transmission factor is of particular interest for further scientific research.

“As transmission of antibiotic resistant organisms increases from one host to another, so does the opportunity for ongoing evolutionary selection of resistance due to antibiotic use,” MacFadden says. “We hypothesize that temperature and population density could act to facilitate transmission and thus increases in antibiotic resistance.”