Daily Archives: February 15, 2022

In part 2 of this video, Vladimir Maletic, MD, MS, clinical professor of neuropsychiatry and behavioral science, University of South Carolina School of Medicine, Greenville, interviews Bernadette DeMuri-Maletic, MD, medical director of Associated Mental Health Consultants and the TMS center of Wisconsin, Milwaukee, about the impact of loneliness on general health, including disease development such as depression or Alzhiemer, and the brain-body impact of marital connections. The pair recently co-presented a session titled "Love and Loneliness in the Time of COVID-19: Clinical Relevance of Relationships" at Psych Congress 2021 in San Antonio, Texas.

In the previous part 1, Dr Maletic, who is also Psych Congress Networks attention-deficit/hyperactivity disorder (ADHD) Section Editor, and Dr DeMuri-Maletic, explore the effects of social relationships, including loneliness and isolation, on the brain and the body.

In the upcoming part 3, they discuss the role relationships play in prevention psychiatry and the impact dyadic relationships have on the treatment of major depressive disorder.

Read the transcript:

Dr Vladimir Maletic: It appears that disruption of social relationships reverberates as a threat danger signal in the brain and that it causes changes in endocrine regulation, immune regulation, autonomic regulation.

One would suppose that it might have some impact on general health. I know you have recently reviewed the literature on the impact of loneliness on general health. What can you tell us about it?

Dr Bernadette DeMuri-Maletic: Vlad, there certainly is an impact both on physical and mental health. We see it in all areas. We see it in endocrine dysfunction.

Believe it or not, we can see an impact of relationships on things as specific as artery width and artery thickness. For example, in one study, they looked at the quality of dyadic relationships in married couples. They rated their interactions as positive or negative. Then they looked at artery width.

What they found was that those individuals who had negative interactions had thicker artery walls. That's affiliated with risk for stroke. You could draw from that study that perhaps bad marital relationships could put someone at higher risk for stroke. Interestingly, the converse was true.

Vladimir: That's pretty scary.

Bernadette: It is scary. The converse was true, if individuals had good relationships, good marital connection, they got along, they had thinner diameters of the carotid artery.

Also, the cardiovascular system is impacted. There was a study that looked at women who had more social support and more social integration, so to speak. They found that those women were at lower risk for cardiovascular disease and for cerebrovascular disease as well.

Vladimir: One aspect of mental health is a little bit awkward to talk about. We're both psychiatrists. We see patients with a variety of mental health issues but especially mood disorders. Asking about their intimacy is not always easy. Is that an important question? Does the quality of physical relationship have anything to do with mental health outcomes and overall physical health?

Bernadette: That's a great question. I agree that oftentimes we forget to discuss that. We forget to go deeper into our relationship history to look at people's physical intimacy and their connection in that area.

There was one study that looked at younger women. They were all moms. They were between ages 20 and 50. They corrected for their general health and also for their perceived stress.

They measured their telomere length. They found that women who had more physical intimacy the week before the study had longer telomeres. We know that shortened telomeres are affiliated with oxidative stress, with aging, with general poor health.

You could draw conclusion from that perhaps that physical intimacy can lead to overall better health, longevity, and improved health function. Vlad, to your question, we often forget to ask about physical intimacy in older adults in particular. There's been a strong link with physical intimacy and cognition in the older adult population.

They looked at individuals who were 57 to 83. They gave them questionnaires about their physical contact with their partners. Then they gave them a cognitive assessment, the ACE III. There was a clear correlation with frequency of sexual intimacy and their scores. They had higher scores on their cognitive evaluations suggesting the maintenance of physical relationships later in life.

Vladimir: That is really interesting. You also quoted a study that looked at the relationship between physical intimacy and the risk for developing Alzheimer's. I'm sorry. It's not physical intimacy if my memory serves me. It is more, did one have a partner in different phases in one's life? Can you remind us what the finding of that study was?

Bernadette: That was a very interesting study where they looked at partner status at midlife and then later in life. They found that individuals who were partnered at midlife but lost a partner due to divorce, to breakup, to death of a partner, those individuals had twice the risk of developing Alzheimer's disease overall.

Individuals who were not partnered, who lived alone both at midlife and later in life, had three times the risk of Alzheimer disease. The most remarkable thing to me in that study was they also factored in for the APOE4 risk gene for Alzheimer's.

Vladimir: That's apolipoprotein E4, right? It's one of the major risk genes.

Bernadette: Absolutely.

Vladimir: What do relationships have to do with genetic risk for Alzheimer?

Bernadette: This speaks to epigenetics. Those individuals even who had the risk gene, if they were partnered both at midlife and later in life, they had a much lower chance of developing Alzheimer's almost to the point where it negated the impact of that risk gene.

It's very interesting epigenetic phenomena that shows us that being partnered can influence our risk for developing Alzheimer's later in life.

Vladimir: That is amazing. Can you tell us a little bit about health hazards associated with being alone and lonely? Sometimes loneliness is not a choice. What can we do to help these individuals who are lonely? First, what are some of the risks of being lonely? Then, what can be done about it?

Bernadette: We've seen from multiple studies that we discussed in our talk that loneliness can have an impact on mental health, certainly, individuals, say, for example, health workers in general during the pandemic, they were at higher risk of developing mental health issues, depression and anxiety, if they perceived themselves as experiencing loneliness.

We also saw that loneliness can lead to cognitive dysfunction as we discussed earlier and also has a risk in cardiovascular and cerebrovascular health. The first thing we need to be aware of is, how do we diagnose loneliness? People can be alone and not feel lonely. What kind of interventions can we have to address that?

I've been using the UCLA loneliness screener or questionnaire. That's the screener that's been used in a lot of our studies that we've quoted today. It's a threequestion screener. It's very simple to use. It's downloadable on the Internet. It's free to use and it's quite reliable.

Once we've identified someone with loneliness, then we need to figure out what we can do to address that and how do we treat it?

Vladimir: There are different levels of loneliness from what I understood from your presentation.

Bernadette: There are. People can just be atrisk. Those individuals, we can intervene early and prevent them from having some of the health effects. There are some individuals who are quite isolated, but they're not quite at severe risk.

Then we have the people who are very isolated. Those individuals, we can see oftentimes who have more significant mental health problems who are living alone, who never leave their home. They're at very high risk.

In terms of treatment, we generally talk about things like CBT, looking at individuals who have cognitive distortions about how they interact with others, maybe referring them to a cognitivebehavioral therapist or doing some cognitive work in our own practices to help them look and change those distorted cognitions can be one treatment for loneliness.

Another treatment for loneliness is simple social skills training. We can do that in terms of our own practice or send them out to an outside therapist. We can look at something called supported socialization where you pair an individual up with someone out in the community and encourage them to do social activities either individually or in larger groups.

Then there are group activities that we can look at. For instance, in individuals who are more severely mentally ill, individuals maybe in community mental health settings, there is the Clubhouse phenomena, the Clubhouse movement. You can go online to Clubhouse International and find a Clubhouse in your area.

These centers have a lot of socialization. They have activities. It's a way for people who have more severe mental illness to get increase in their socialization.

Otherwise, other group activities such as group exercise, group gardening, interest groups, we found that group exercise is beneficial even without the intensity of exercise. Studies that looked at intensity of exercise going down, there was still significant benefit from the group activity.

What I do in my own practice is I often recommend going out for a friend for a walk in the morning or going out with someone, a coworker at work, and making a commitment with someone to do group exercise.

Vladimir: What are you hearing from your patients? If there is a change in the level of their social interaction, does it have some bearing in how they're doing?

Bernadette: Yes, I think so. The studies bear that out and anecdotally, I've seen that with my patients. They get double benefit, especially with exercise. In terms of working out with someone, there's more adherence because they have someone else that they have to really be accountable to, and so, it's been quite successful actually.

Vladimir: Great answer. Thank you.

Vladimir Maletic, MD, MS, is a clinical professor of psychiatry and behavioral science at the University of South Carolina School of Medicine in Greenville, and a consulting associate in the Division of Child and Adolescent Psychiatry, Department of Psychiatry, at Duke University in Durham, North Carolina. Dr Maletic received his medical degree in 1981 and his masters degree in neurobiology in 1985, both from the University of Belgrade in Yugoslavia. He went on to complete a residency in psychiatry at the Medical College of Wisconsin in Milwaukee, followed by a residency in child and adolescent psychiatry at Duke University.

Bernadette DeMuri-Maletic, MD, received her medical degree from the Medical College of Wisconsin. She completed residencies in both Psychiatry and Neurology at the Medical College of Wisconsin Affiliated Hospitals. Dr DeMuri is the medical director of associated mental health consultants and The TMS center of Wisconsin, both located in Milwaukee. She is an assistant clinical professor at the Medical College of Wisconsin. Dr DeMuri has a special interest in the treatment of mood disorders including treatment-resistant depression.

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The Impact of Loneliness on Disease Development - Consultant360

Pseudomonas aeruginosa, an organism responsible for thousands of deaths.

University of South Australia scientists have made a surprising discovery in the origins of an antibiotic-resistant gene previously thought to have been confined to Adelaide.

The gene, first detected in Adelaide in 2006, is carried by the nasty bacterium Pseudomonas aeruginosa, an organism responsible for thousands of deaths among immunocompromised, surgical, and burns patients due to its resistance to last resort antibiotics.

This gene makes infections resistant to the most potent antibiotics used in medicine imipenem and meropenem. Antibiotic resistant P. aeruginosa is now listed by the World Health Organization as a critical priority pathogen, one of 12 families of bacteria that pose the greatest threat to human health.

Until now, it was believed that the Adelaide Imipenemase (AIM-1) gene was only found in the South Australian capital city after being detected in clinical samples and healthcare-associated wastewater.

But a group of scientists led by UniSA microbiologist Associate Professor Rietie Venter has shown evidence of it worldwide, pinpointing its source in a harmless environmental organism present in soil, groundwater, wastewater, and even in plants.

The findings have been published in the journal Microbial Genomics.

The discovery suggests that the gene has mobilized at some stage and jumped from a harmless organism to a nasty pathogen.

Its an opportunistic pathogen which is ubiquitous and very resilient, says Assoc Prof Venter.

The team used innovative ways to track and characterize antimicrobial resistance, making their discovery through wastewater analysis. Their research revealed the AIM-1 gene was prevalent at many sites throughout Adelaide and South Australia, including in every wastewater sample and river water, hinting at a wider spread of the gene than originally thought.

We then investigated the possibility of a global distribution of the AIM-1 gene. Through extensive nucleotide and protein data base searching, we discovered the gene was also present in Asia, North America, and Europe.

However, AIM-1 was predominantly found in harmless environmental organisms and has only made the jump to the pathogen P. aeruginosa in two other locations so far (Iran and Iraq).

Genes that are mobile jump around all the time, but the scenario described in this study is much rarer, says Assoc Prof Venter.

However, as microbes are a great source of antibiotics and very competitive, it is highly likely that many bacterial resistant genes evolve in unknown organisms before making their way to dangerous pathogens, especially P. aeruginosa, which shares a habitat with harmless environmental organisms.

Assoc Prof Venter says the AIM-1 gene requires carefully monitoring.

If we can better understand why genes jump from environmental into human pathogens, we might be able to prevent it from happening more often, she says.

Reference: Worldwide distribution and environmental origin of the Adelaide imipenemase (AIM-1), a potent carbapenemase in Pseudomonas aeruginosa by Anteneh Amsalu, Sylvia A. Sapula, Jonathan J. Whittall, Bradley J. Hart, Jan M. Bell, John Turnidge and Henrietta Venter, 17 December 2021, Microbial Genomics.DOI: 10.1099/mgen.0.000715

P. aeruginosa that are resistant to carbapenems the best available antibiotics used for treating multi-drug resistant bacteria poses a particular threat in hospitals, nursing homes, and among patients whose care requires devices such as ventilators and blood catheters.

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Surprising Discovery Proves That Deadly Gene Has Jumped From a Harmless Organism to a Deadly Pathogen - SciTechDaily

The last few decades have seen a genomic revolution. Researchers like us have interrogated the genomes of millions of people and uncovered gene variants that increase risks of diseases such as breast cancer, kidney disease, diabetes and schizophrenia. These help us understand the causes of the conditions, identify people at risk and develop new drugs.

However, currently in genomic research there is a drastic lack of diversity. In our new perspective piece, published this week in Nature Medicine, we show that 86 per cent of genomics studies use data from people of European descent despite only making up 16 per cent of the worlds population. Although this is usually defined by genetic ancestry, it overlaps strongly with people who identify with the white ethnic group.

Despite repeated calls for more diversity over recent years, progress has been limited and the eurocentric bias has actually risen. The proportion of studies conducted in African populations have, painfully, dropped from three per cent in 2016 to 1.1 per cent now.

What does this mean in practice? Imagine that a doctor looks at your genetic information and finds out that you are at risk of getting heart disease, although currently you do not have any symptoms. With this knowledge, a medic could recommend strategies to prevent or delay the disease onset.

But whether this prediction is accurate largely depends on your background. A previous study showed that genetic risk predictions based on eurocentric data are 4.5 times more accurate in individuals of European than African ancestry, meaning that in most cases genetics cannot be used to identify people at risk of disease if they are black.

The lack of diversity has led to major missed scientific opportunities. For example, by including people of African descent in one study, researchers found that a gene called PCSK9 affects cholesterol, which has led to new drugs for heart disease that benefit everyone.

So how can we overcome this and ensure representative data and health equity?

It is first important to understand how we got here. The dominance of European and American scientists in genomic research is a consequence of structural advantages, some of which are related to historical and present-day exploitation. The lack of diversity among researchers is a crucial driver of bias in genetic studies.

We believe that we can and should address this issue now. Together with four other international researchers we looked back at our own experiences in running global genomic studies in underrepresented populations, in an attempt to understand the current barriers and find ways to overcome them. We think that these are the most important areas in our roadmap towards genomic equity:

This is certainly doable. The success of some diverse studies illustrate indigenous groups and those at institutions in low- and middle-income countries can scale up in resources and skills to enable high-quality genomics research. For example, PARKH (the Pakistan Alliance for genetic RisK factors for Health) is a study of 45,000 people from Pakistan to identify genetic causes of mental illness. Such research helps to highlight the contribution of heritable physiological causes and reduce the stigma of mental illness.

Genomic research has received billions of pounds in funding to improve the health of people. But it is now clear that some of the benefits will be exclusive to white people this must change.

We have to fundamentally alter the way we do research, including leading roles for diverse global researchers, genuine partnerships with the communities and strategic funding that is tied to capacity building. Only then can all benefit from the genomic revolution.

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Why the world's genomic revolution is incomplete - Telegraph.co.uk

Nucleome Therapeutics appoints Nigel Clark as Chief Business Officer

Nigel brings 20+ years of commercial and senior managerial experience in the biotech and pharma industry

Oxford, UK, 15 February 2022 Nucleome Therapeutics, a biotechnology company decoding the dark matter of the human genome to uncover novel ways to treat disease, today announces the appointment of Dr Nigel Clark as Chief Business Officer with immediate effect. Nigel has more than 20 years of deal-making experience from negotiating and executing over 20 major transactions worth over $1.6bn.

Most recently, Nigel served as Senior Vice President of Business Development at Kymab, which was acquired by Sanofi in 2021. In his role at Nucleome, Nigel will serve on the executive leadership team and will shape and oversee Nucleomes business and corporate development strategy.

Nigel has broad commercial experience, an impressive record of high value transactions and long-standing relationships across the life sciences industry. I am thrilled to welcome him to our executive team, commented Dr Danuta Jeziorska, Chief Executive Officer and Founder of Nucleome. He joins us at an incredibly exciting stage as we continue to decode the dark genome to uncover precision medicines and began biological validation of our first targets with the ambition to progress them to discovery programmes for the treatment of autoimmune diseases.

Dr Nigel Clark, Chief Business Officer of Nucleome, said: The opportunity to join Nucleome Therapeutics, a company with real potential to transform drug discovery and translational medicine, is truly exciting. I have been privileged in my career to date to work with the very best in the industry and I look forward to working with the exceptional executive and scientific team at Nucleome to realise a paradigm shift in the research and development of novel therapeutics to improve patient's lives.

Dr Nigel Clark most recently served as SVP Business Development and a member of the executive team at Kymab which was divested in 2021 to Sanofi for $1.1bn upfront and a further $300M of success-based milestones. Previous roles include Chief Business Officer at Syntaxin (divested to Ipsen Pharma), VP of Business Development at Vernalis and a member of the senior executive committee as well as President, Vernalis Canada. Nigel has also held leadership roles at Ribotargets and British Biotech and was co-head of the biotech business unit at Datamonitor. He was awarded a Ph.D. from the University of Reading for research conducted into HIV gene regulation and completed his scientific training as a post-doctoral scientist at the department of biochemistry, University of Oxford.

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About Nucleome Therapeutics Nucleome Therapeutics is decoding the dark matter of the human genome to uncover novel ways to treat disease. The dark genome holds more than 90% of disease-linked genetic variants whose value remains untapped, representing a significant opportunity for drug discovery and development. We have the unique ability to link these variants to gene function and map disease pathways. Our cell type-specific platform creates high resolution 3D genome structure maps and enables variant functional validation at scale in primary cell types. This enables us to discover and develop novel, better and safer drugs. The initial focus of the company is on lymphocytes and related autoimmune disease. Our ambition is to build a robust pipeline of drug assets, with corresponding biomarkers. Nucleome Therapeutics was founded by leading experts in gene regulation from the University of Oxford and backed by investment from Oxford Sciences Innovation. For more information, please visit http://www.nucleome.com.

For more information, please contact:

Nucleome TherapeuticsDr Danuta Jeziorska, Chief Executive Officer & Foundercontact@nucleome.com

Consilium Strategic CommunicationsMary-Jane Elliott/ Sukaina Virji/ Lindsey NevilleNucleome@consilium-comms.com

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Nucleome Therapeutics appoints Nigel Clark as Chief Business Officer - GlobeNewswire