Day: June 3, 2022

Supplementation Effective in Slowing Age-related Macular Degeneration

Credit: National Eye Institute

A pair of major studies established that dietary supplements can slow progression of age-related macular degeneration (AMD). In a new report published in JAMA Ophthalmology, scientists went through 10 years of Age-Related Eye Disease Studies (AREDS2) data and showed that the AREDS2 formula, which substituted antioxidants lutein and zeaxanthin for beta-carotene, not only reduces risk of lung cancer due to beta-carotene, but is also more effective at reducing risk of AMD progression, compared to the original formula.

“Because beta-carotene increased the risk of lung cancer for current smokers in two NIH-supported studies, our goal with AREDS2 was to create an equally effective supplement formula that could be used by anyone, whether or not they smoke,” said Emily Chew, MD, lead author of the study report. “This 10-year data confirms that not only is the new formula safer, it’s actually better at slowing AMD progression.”

AMD is a degenerative disease of the retina, the light-sensitive tissue at the back of the eye. Progressive death of retinal cells in the macula, the part of the retina that provides clear central vision, eventually leads to blindness. Treatment can slow or reverse vision loss; however, no cure for AMD exists.

The original AREDS study, launched in 1996, showed that a dietary supplement formulation (50 mg vitamin C, 400 international units vitamin E, 2mg copper, 80mg zinc, and 15mg beta-carotene) could significantly slow the progression of AMD from moderate to late disease. However, two concurrent studies also revealed that people who smoked and took beta-carotene had a significantly higher risk of lung cancer than expected.

In AREDS2, begun in 2006, Dr Chew and colleagues compared the beta-carotene formulation to one with 10 mg lutein and 2 mg zeaxanthin instead. Like beta-carotene, lutein and zeaxanthin are antioxidants with activity in the retina. The beta-carotene-containing formation was only given to participants who had never smoked or who had quit smoking.

At the end of the five-year AREDS2 study period, the researchers concluded that lutein and zeaxanthin did not increase risk for lung cancer, and that the new formation could reduce the risk of AMD progression by about 26%. After the completion of the five-year study period, the study participants were all offered the final AREDS2 formation that included lutein and zeaxanthin instead of beta-carotene.

In this new report, the researchers followed up with 3883 of the original 4203 AREDS2 participants an extra five years from when the AREDS2 study ended in 2011, collecting information AMD progression, and lung cancer diagnosis. Even though all the participants had switched to the formula containing lutein and zeaxanthin after the end of the study period, the follow up study continued to show that beta-carotene increased risk of lung cancer for people who had ever smoked by nearly double. No increased risk for lung cancer was seen in those receiving lutein/zeaxanthin. In addition, after 10 years, the group originally assigned to receive lutein/zeaxanthin had an additional 20% reduced risk of progression to late AMD compared to those originally assigned to receive beta-carotene.

“These results confirmed that switching our formula from beta-carotene to lutein and zeaxanthin was the right choice,” said Dr Chew.

Source: NIH/National Eye Institute

Newly Discovered Neuron Type may Help Explain Memory Formation

A healthy neuron.
A healthy neuron. Credit: NIH

Scientists publishing in Neuron have described how a newly discovered neuron type may be involved with the formation of memory in the hippocampus, which is marked by high-frequency electrical events.

It is known that memory is represented by changes in the hippocampus. One of the well-established changes in the hippocampus that has been associated with memory is the presence of so-called sharp wave ripples (SWR). These are brief, high-frequency electrical events generated in the hippocampus, and they are believed to represent a major event occurring in the brain in the so-called episodic memory, such as recalling a life event or a friend’s phone number.

However, what happens in the hippocampus when SRWs are generated has not been well understood.

Now a new study sheds light on the existence of a neuron type in the mouse hippocampus that might be a key to better understanding of episodic memory.

Professor Marco Capogna and Assistant professor Wen-Hsien Hou have contributed to the discovery of the novel neuron that is associated with sharp wave ripples and memory.

Possible disruption in dementia and Alzheimer’s

The study describes the novel neuron type in the hippocampus.

“We have found that this new type of neuron is maximally active during SWRs when the animal is awake – but quiet – or deeply asleep. In contrast, the neuron is not active at all when there is a slow, synchronized neuronal population activity called “theta” that can occur when an animal is awake and moves or in a particular type of sleep when we usually dream,” Prof Capogna said.

Because of this dichotomic activity, this novel type of neuron is named theta off-ripples on (TORO).

“How come, TORO-neurons are so sensitive to SWRs? The paper tries to answer this question by describing the functional connectivity of TORO-neurons with other neurons and brain areas, an approach called circuit mapping. We find that TOROs are activated by other types of neurons in the hippocampus, namely CA3 pyramidal-neurons and are inhibited by inputs coming from other brain areas, such as the septum,” Prof Capogna explained.

“Furthermore, the study finds that TOROs are inhibitory neurons that release the neurotransmitter GABA. They send their output locally – as most GABAergic neurons do – within the hippocampus, but also project and inhibit other brain areas outside the hippocampus, such as the septum and the cortex. In this way, TORO-neurons propagate the SWR information broadly in the brain and signal that a memory event occurred,” he concluded.

The team has monitored the activity of the neuron by using electrophysiology – a technique that detects activity of the neurons by measuring voltage versus time, and by using imaging that detects activity by measuring changes in calcium signalling inside the neurons.

Demonstrating a causal link between the activity of TORO-nerve cells and memory will be the next step, and exploring whether inhibition of TORO-neurons and sharp wave ripples occurs in dementia and Alzheimer’s diseases. 

Source: Aarhus University

IBD and Depression is a Two-way Street

Photo by Andrea Piacquadio on Pexels

While irritable bowel disease (IBD) and depression are known to occur together, scientists report a clinical overlap of these conditions in the Journal of Gastroenterology and Hepatology, implying the existence of a two-way relationship. Patients diagnosed with IBD were nine times as likely to develop depression than the general population. Their siblings who did not suffer from IBD were almost two times as likely to develop depression.

Conversely, patients with depression were two times as likely to develop IBD, and their siblings without depression were more than one and a half times as likely to develop IBD.

“This research reveals a clinical overlap between both conditions, and is the first study to investigate the two-way association between IBD and depression in siblings,” said Bing Zhang, MD, a gastroenterologist with Keck Medicine and co-lead author of the study.

The researchers drew on the data of more than 20 million people from Taiwan’s National Health Insurance Research Database. For 11 years, they tracked patients with either IBD or depression and their siblings without either condition, comparing onset of depression or IBD with a control group of people without either condition, but with similar age, sex and socioeconomic status.

Zhang hypothesises that many factors may contribute to the bidirectional nature of the disorders, including environmental stressors, the gut microbiome and genetics.

“The finding that people with IBD are more prone to depression makes sense because IBD causes constant gastrointestinal symptoms that can be very disruptive to a patient’s life,” he said. “And the elevated depression risk among siblings of IBD patients may reflect caregiver fatigue if the siblings have a role in caring for the patient.”

What surprised researchers was that patients with depression were prone to IBD. Zhang speculates that this discovery may have to do with what is known as the gut-brain axis, a scientifically established connection between the gastrointestinal system and the central nervous system, which consists of the spinal cord and the brain.

For example, he said, inflammation of the brain, which plays a role in depression, may be linked to the inflammation of the gastrointestinal tract, a hallmark of IBD.

The researchers are not sure why siblings of patients with depression are more likely to be diagnosed with IBD. Zhang surmises that there may be a shared genetic susceptibility for either disease that presents differently in family members.

Zhang hopes that the study findings will encourage health care professionals to take both family history and the relationship between gastrointestinal and mood disorders into consideration when evaluating or treating patients with either IBD or depression.

Through more research and better understanding of the gut-brain axis, he envisions leveraging the newfound connection between the conditions to improve the prevention, diagnosis and treatment of IBD and mental disorders.

Source: University of Southern California – Health Sciences

Faecal Microbiota Transplantation is Effective for Recurrent C. Diff

C difficile. Source: CDC

Research just published in Clinical Infectious Diseases has found that Faecal Microbiota Transplantation, or FMT, is an optimal cost-effective treatment for first recurrent Clostridioides difficile infection (CDI).

“The most effective therapies for CDI are also the cost effective therapies,” said co-investigator Radha Rajasingham, MD. “FMT should be moved earlier in the treatment algorithm for CDI. Our model suggests it is effective and cost effective when used in patients after a single episode of recurrent CDI.”

Mathematical modelling was used to understand both the effectiveness and cost effectiveness of earlier use of FMT in the treatment of CDI, which normally arises from the disruption of healthy gut bacteria.

While this disease is caused by antibiotics, it is often treated with antibiotics, including fidaxomicin for initial, non-severe CDI or vancomycin for severe CDI, followed by FMT for any recurrent CDI.s. Unfortunately in many cases, CDI recurs in the same person again. This cycle of infection is called recurrent CDI.

Current guidelines recommend using FMT as a last resort for people with recurrent CDI. The goal of this research was to examine the benefits of using FMT earlier in the cycle of CDI.

“Based on this analysis, we would recommend that rather than waiting for multiple recurrent CDI, providers should consider FMT use for any recurrent CDI,” said co-author Byron Vaughn, MD, MS.

The authors suggest future research examine the role of FMT to prevent all recurrent CDI or even as primary prevention of CDI in high risk individuals.

Source: University of Minnesota Medical School

Audit Finds Women are Uninformed of Common Anaesthetic’s Effect on Contraception

Women undergoing operations are not being routinely informed that a common anaesthetic may reduce their contraception’s effectiveness, putting them at risk of an unplanned pregnancy, suggests new research which is being presented at Euroanaesthesia, the annual meeting of the European Society of Anaesthesiology and Intensive Care (ESAIC).

The drug sugammadex is widely used in anaesthesia.  Administered towards the end of the operation, ahead of waking the patient up, it reverses the action of the neuromuscular blocking drugs rocuronium and vecuronium given earlier in the procedure to relax the patient’s muscles.

Sugammadex is known to interact with progesterone, possibly reducing the effectiveness of hormonal contraceptives, including the progesterone-only pill (mini-pill), combined pill, vaginal rings, implants and intra-uterine devices.

Current guidance is to inform women of child-bearing age (WCBA) that they have received the drug and, due to increased risk of contraceptive failure, advise those taking oral hormonal contraceptives to follow the missed pill advice in the leaflet that comes with their contraceptives and advise those using other types of hormonal contraceptive to use an additional non-hormonal means of contraception for seven days.

However in the experience of the authors, robust methods for identifying at-risk patients and informing them of the associated risk of contraceptive failures is not common practice across anaesthetic departments within the UK, and likely further afield. 

To find out more, Dr Neha Passi, Dr Matt Oliver and colleagues at the University College London Hospitals NHS Foundation Trust surveyed anaesthetists at their hospital trust on their use of sugammadex and carried out a retrospective audit of sugammadex use in the Trust.

A seven-question survey was sent to all anaesthetists at the Trust.  Including consultants, junior doctors and physician assistants, this numbered almost 150 professionals.

Of the 82 anaesthetists who responded, 94% said they were aware of the risk of contraceptive failure – but 70% of respondents reported they do not routinely discuss sugammadex with patients who received it.

During the audit, 65 WCBA patients were given sugammadex, and 48 of these should have received advice on the risks of contraceptive failure.  There was no record of it, however, in the medical notes of any of the 48 women. (The other 17’s medical history meant they weren’t at risk of pregnancy and so not eligible for the advice.)

Dr Passi said: “It is concerning that we are so seldom informing patients of the risk of contraceptive failure following sugammadex use.

“Use of sugammadex is expected to rise as it becomes cheaper in the future and ensuring that women this receiving medicine are aware it may increase their risk of unwanted pregnancy must be a priority.”

Dr Oliver added: “We only studied one hospital trust but we expect the results to be similar in elsewhere in the UK.”

Dr Passi adds: “It is important to note, however, that most patients receiving an anaesthetic do not need a muscle relaxant2 and that sugammadex is one several drugs available to reverse muscle relaxation.”

In response to their findings, the study’s authors have created patient information leaflets and letters and programmed the Trust’s electronic patient record system to identify ‘at-risk’ patients and deliver electronic prompts to the anaesthetists caring for them in the perioperative period.

Sugammadex is the only anaesthetic drug known to have this effect.

Source: EurekAlert!