Tag: 12/12/23

Categories : NeurologyTags :

What Happens When the Brain Loses a Hub?

On By ModernMedia
Photo by Jafar Ahmed on Unsplash

A University of Iowa-led team of international neuroscientists have obtained the first direct recordings of the human brain in the minutes before and after a brain hub crucial for language meaning was surgically disconnected. The results reveal the importance of brain hubs in neural networks and the remarkable way in which the human brain attempts to compensate when a hub is lost, with immediacy not previously observed. The findings were reported recently in the journal Nature Communications.

Hubs are critical for connectivity

The human brain has hubs – the intersection of many neuronal pathways that help coordinate brain activity required for complex functions like understanding and responding to speech. But debate has reigned as to whether highly interconnected brain hubs are irreplaceable for certain brain functions. By some accounts the brain, as an already highly interconnected neural network, can in principle immediately compensate for the loss of a hub, in the same way that traffic can be redirected around a blocked-off city centre.

With a rare experimental opportunity, the UI neurosurgical and research teams led by Matthew Howard III, MD, professor and DEO of neurosurgery, and Christopher Petkov, PhD, professor and vice chair for research in neurosurgery, have achieved a breakthrough in understanding the necessity of a single hub. By obtaining evidence for what happens when a hub required for language meaning is lost, the researchers showed both the intrinsic importance of the hub as well as the remarkable and rapid ability of the brain to adapt and at least partially attempt to immediately compensate for its loss.

Evaluating the impact of losing a brain hub

The study was conducted during surgical treatment of two patients with epilepsy. Both patients were undergoing procedures that required surgical removal of the anterior temporal lobe – a brain hub for language meaning – to allow the neurosurgeons access to a deeper brain area causing the patients’ debilitating epileptic seizures. Before this type of surgery, neurosurgery teams often ask the patients to conduct speech and language tasks in the operating room as the team uses implanted electrodes to record activity from parts of the brain close to and distant from the planned surgery area. These recordings help the clinical team effectively treat the seizures while limiting the impact of the surgery on the patient’s speech and language abilities.

Typically, the recording electrodes are not needed after the surgical resection procedure and are removed. The innovation in this study was that the neurosurgery team was able to safely complete the procedure with the recording electrodes left in place or replaced to the same location after the procedure. This made it possible to obtain rare pre- and post-operative recordings allowing the researchers to evaluate signals from brain areas far away from the hub, including speech and language areas distant from the surgery site. Analysis of the change in responses to speech sounds before and after the loss of the hub revealed a rapid disruption of signaling and subsequent partial compensation of the broader brain network.

“The rapid impact on the speech and language processing regions well removed from the surgical treatment site was surprising, but what was even more surprising was how the brain was working to compensate, albeit incompletely within this short timeframe,” says Petkov, who also holds an appointment at Newcastle University Medical School in the UK.

The findings disprove theories challenging the necessity of specific brain hubs by showing that the hub was important to maintain normal brain processing in language.

“Neurosurgical treatment and new technologies continue to improve the treatment options provided to patients,” says Howard, who also is a member of the Iowa Neuroscience Institute.

“Research such as this underscores the importance of safely obtaining and comparing electrical recordings pre and post operatively, particularly when a brain hub might be affected.”

According to the researchers, the observation on the nature of the immediate impact on a neural network and its rapid attempt to compensate provides evidence in support of a brain theory proposed by Professor Karl Friston at University College London, which posits that any self-organising system at equilibrium works towards orderliness by minimising its free energy, a resistance of the universal tendency towards disorder.

These neurobiological results following human brain hub disconnection were consistent with several predictions of this and related neurobiological theories, showing how the brain works to try to regain order after the loss of one of its hubs.

Source: University of Iowa Health Care

Categories : Metabolic Disorders Obstetrics & GynaecologyTags :

Newer Diabetes Drugs don’t Increase Risk to Foetus

On By ModernMedia
Photo by SHVETS production

Newer diabetes medicines do not appear to increase the risk of birth defects. The largest comparative study to date found no increased risk compared to treatment with insulin, which is considered safe during pregnancy. The study was published in JAMA Internal Medicine.

Newer diabetes drugs such as sulfonylureas, DPP-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors are being increasingly used, both in the treatment of diabetes, but also extended indications for several of the preparations. 

However, knowledge of the foetal effects of these drugs is still low, so women with type 2 diabetes are often advised to switch to insulin before a planned pregnancy because it is considered safe. However, not all pregnancies are planned and more and more people are becoming pregnant while being treated with these drugs.

An international research team has now investigated whether the use of these drugs during pregnancy increases the risk of birth defects. The researchers used health data from 3.5 million pregnancies in six different countries (Sweden, Norway, Finland, Iceland, USA and Israel) between 2009 and 2021. Among these 3.5 million women, nearly 52 000 were diagnosed with type 2 diabetes and more than 8000 took one of the newer diabetes drugs in the three months before or after their last menstrual period.

Diabetes itself poses a risk of birth defects. High blood sugar levels in early pregnancy, which are more common in people with diabetes, increase the risk of foetal malformations. Therefore, the researchers were not surprised to see a slightly elevated risk in this group.

Among women diagnosed with type 2 diabetes before pregnancy, 5.3% of babies were born with severe birth defects, including 2.2% with heart defects, compared to the overall group where 3.8% had severe birth defects and 1.3% with heart defects. 

No increased risk of birth defects

However, the researchers found that the women with diabetes treated with the newer diabetes drugs did not have a higher risk of giving birth to children with birth defects than the women with diabetes treated with insulin.

“It has already been shown that insulin is safe to use during pregnancy and that it does not cross the placenta. The increased risk of birth defects in the children of women with type 2 diabetes using the newer diabetes drugs is therefore very likely caused by the disease,” says first author Carolyn Cesta, Associate Professor at the Center for Drug Epidemiology at Karolinska Institutet.

Despite being the largest study in this field to date, covering more than 3.5 million pregnancies, relatively few women used the new diabetes drugs, and the researchers stress that further studies are needed to confirm the results. However, they note that the study still shows that these drugs do not pose a major risk of birth defects.

As type 2 diabetes becomes more common among women of childbearing age and as GLP-1 receptor agonists such as semaglutide (Wegovy, Ozempic) are approved to treat obesity, the number of exposed pregnancies is likely to increase. 

“Our findings provide a first indication of the safety of infants exposed to these medications during pregnancy,” says Carolyn Cesta.

Source: Karolinska Institutet

Categories : Diet and Nutrition Neurodegenerative DiseasesTags :

Explaining the Parallels between Vitamin B12 Deficiency and Multiple Sclerosis

On By ModernMedia
This is a pseudo-colored image of high-resolution gradient-echo MRI scan of a fixed cerebral hemisphere from a person with multiple sclerosis. Credit: Govind Bhagavatheeshwaran, Daniel Reich, National Institute of Neurological Disorders and Stroke, National Institutes of Health

For decades, scientists have noted an intriguing similarity between a deficiency in vitamin B12 – an essential nutrient that supports healthy development and functioning of the central nervous system (CNS) – and multiple sclerosis (MS), a chronic disease in which the body’s immune system attacks the CNS and which can produce neurodegeneration.

Both vitamin B12 deficiency and MS produce similar neurological symptoms, including numbness or tingling in hands and feet, vision loss, difficulty walking or speaking normally and cognitive dysfunction, such as problems with memory.

In a new study, published in Cell Reports, researchers at Sanford Burnham Prebys, with collaborators elsewhere, describe a novel molecular link between vitamin B12 and MS that takes place in astrocytes – important non-neuronal glial cells in the brain.

The findings by senior study author Jerold Chun, MD, PhD, professor and senior vice president of neuroscience drug discovery, and Yasuyuki Kihara, PhD, research associate professor and co-corresponding author, and colleagues suggest new ways to improve the treatment of MS through CNS-B12 supplementation.

“The shared molecular binding of the brain’s vitamin B12 carrier protein, known as transcobalamin 2 or TCN2, with the FDA-approved MS drug fingolimod provides a mechanistic link between B12 signaling and MS, towards reducing neuroinflammation and possibly neurodegeneration,” said Chun.   

“Augmenting brain B12 with fingolimod or potentially related molecules could enhance both current and future MS therapies.”

In their paper, the team at Sanford Burnham Prebys, with collaborators at University of Southern California, Juntendo University in Japan, Tokyo University of Pharmacy and Life Sciences and State University of New York, focused on the molecular functioning of FTY720 or fingolimod (Gilenya®), a sphingosine 1-phosphate (S1P) receptor modulator that suppresses distribution of T and B immune cells errantly attacking the brains of MS patients.

Working with an animal model of MS as well as human post-mortem brains, the researchers found that fingolimod suppresses neuroinflammation by functionally and physically regulating B12 communication pathways, specifically elevating a B12 receptor called CD320 needed to take up and use needed B12 when it is bound to TCN2, which distributes B12 throughout the body, including the CNS.  This known process was newly identified for its interactions with fingolimod within astrocytes. Importantly, the relationship was also observed in human MS brains.

Of particular note, the researchers reported that lower levels of CD320 or dietary B12 restriction worsened the disease course in an animal model of MS and reduced the therapeutic efficacy of fingolimod, which occurred through a mechanism in which fingolimod hitchhikes by binding to the TCN2-B12 complex, allowing delivery of all to the astrocytes via interactions with CD320, with component losses disrupting the process and worsening disease.

These new findings further support to the use of B12 supplementation – especially in terms of delivering the vitamin to astrocytes within the brain – while revealing that fingolimod can correct the impaired astrocyte-B12 pathway in people with MS. 

The scientists said it is possible that other S1P receptor modulators on the market, such as Mayzent®, Zeposia® and Ponvory®, may access at least parts of this CNS mechanism.  The study supports B12 supplementation with S1P receptor modulators with the goal of improving drug efficacy for this class of medicines.

The study also opens new avenues on how the B12-TCN2-CD320 pathway is regulated by sphingolipids, specifically sphingosine, a naturally occurring and endogenous structural analogue of fingolimod, toward improving future MS therapies, Chun said. 

“It supports creating brain-targeted B12 formulations. In the future, this mechanism might also extend to novel treatments of other neuroinflammatory and neurodegenerative conditions.”

Source: Sanford-Burnham Prebys

Categories : General Interest Healthcare Politics and RegulationsTags :

Universal Healthcare is Possible in Our Lifetime

On By ModernMedia

Universal Health Coverage Day calls on us to reflect on the progress that we have achieved in providing healthcare for all. As the health and pharmaceutical industries, it is time to question if our strides in achieving healthcare for all are successful and identify areas for improvement. The theme “A Time for Action”, speaks to the urgency of healthcare access regardless of socioeconomic status, age, race or demographic. It is not an ambitious dream and can be attained in our lifetime, writes Bada Pharasi, CEO of the Innovative Pharmaceutical Association of South Africa (IPASA). 

Universal Health Coverage (UHC) means access to primary healthcare for everyone. In South Africa, this is referred to as  National Health Insurance (NHI). Regardless of its name, the objective remains the same – to ensure that all citizens, regardless of where they live or their socioeconomic status, have access to healthcare.

A 2021 report released at the Africa Health Agenda International Conference (AHAIC) revealed that 615 million, or 52%, of the people in Africa, did not have access to the healthcare that they needed¹. It was also estimated that 97 million Africans face catastrophic healthcare costs, which push 15 million people into poverty every year¹. 

The effective implementation of UHC would mean that no person would have to go without appropriate healthcare. It would also mean that no person would have to undergo financial strain to receive treatment for ill health.

UHC covers a spectrum of health needs from health promotion to prevention, treatment, rehabilitation, and palliative care across the life course². In 2015, 193 United Nations (UN) member states agreed on the 2030 Sustainable Development Goals (SDG). These goals are aimed at seeing an end to poverty and a sustainable future by 2030², and ensuring health coverage for all is an integral part of reaching these goals. 

The World Health Organization (WHO) believes that UHC can be achieved by using the primary healthcare approach as it remains the most accessible, inclusive and cost-effective method to reach the majority of the population². 

Globally, as many as 72 countries have included UHC in their national healthcare systems. The countries where UHC has been the most successful include Canada, Australia, and several European countries, such as Switzerland and Sweden. It is from these countries that we can glean valuable lessons on the importance of strong healthcare systems, well-trained healthcare professionals and a cohesive relationship between governments and the private sector³. 

Ensuring a healthier nation may seem like an exorbitant mission. However, when we consider that a healthier population will be beneficial to the economy, it makes for a worthwhile investment. The World Bank adds that UHC allows countries to make the most of their strongest asset: human capital. A nation in good health is one where children can go to school and adults can go to work⁴. 

There is a common perspective that for a country’s overall health to improve, its economy must improve first. This idea fuels the understanding of why low- to middle-income countries have such poor healthcare infrastructure. The World Bank offers an alternative perspective, suggesting that when a country’s overall health improves, so will its economy. This as more citizens will be able to contribute to its economic growth and the workplace⁵.  

Some of the reasons why the adoption of UHC in African countries has seemed to stall include inadequate financial and technology support, limited pharma manufacturing companies, and unclear policies and regulatory frameworks⁶. 

In South Africa, the greatest hindrance to people receiving the healthcare they require boils down to numbers. With a population of more than 60 million people, there is a greater need for healthcare than there is capacity to meet the demand⁷. 

At IPASA, we believe that healthcare is a basic right and that citizens in any given country should be given the necessary access to healthcare. We understand that working with key stakeholders, such as the government, is critical to the success of universal healthcare. Our ongoing work with patient advocacy groups ensures we understand what patients need from a treatment perspective.

We recently attended the Access Dialogue conference with patient advocacy groups including Rare Diseases South Africa and Campaigning for Cancer to gain an understanding of some of the concerns faced by patients and share insights on the proposed NHI Bill. 

IPASA believes that an adequate supply of medicines is a critical pillar of any healthcare scheme, and the NHI is no different. For the NHI to succeed, it must be backed by a sustainable healthcare sector to ensure the security of healthcare provision and medicine supply.

To this end, the NHI must allow for a flexible, responsive pricing model that includes alternative/innovative reimbursement models to cover the cost of medicines and health products. This allows responsiveness to the needs of geographical areas, quality and levels of care, and negotiations directly with healthcare providers.

Healthcare for all can only be achieved by the joint commitment of the health and pharmaceutical industries, government stakeholders and patient advocacy groups for the benefit of patients. No person should be faced with the obstacle of finance at a time when they need healthcare: providing healthcare for all results in a healthier society and healthier world for us all. 

References:

  1. https://healthpolicy-watch.news/only-half-of-africans-have-access-to-health-care/ 
  2. https://www.who.int/news-room/fact-sheets/detail/universal-health-coverage-(uhc) 
  3. https://wisevoter.com/country-rankings/countries-with-universal-healthcare/#:~:text=The%20countries%20with%20the%20highest,comprehensive%20coverage%20of%20healthcare%20services.
  4. https://www.worldbank.org/en/topic/universalhealthcoverage 
  5. https://widgets.weforum.org/outlook15/10.html 
  6. https://www.iqvia.com/locations/middle-east-and-africa/blogs/2023/01/getting-quality-medicines-to-patients-faster-in-africa-how-to-solve-for-access-issues 
  7. https://www.wits.ac.za/covid19/covid19-news/latest/healthcare-in-south-africa-how-inequity-is-contributing-to-inefficiency.html