Medical Bulletin 03/ December/ 2024

The team of investigators, led by Professor Ben Goult at the University of Liverpool, have examined the role of two proteins found in the brain and suggest the stability of their relationship to one another is crucial for memory formation and maintenance.

The new study represents a significant step forward in scientists' understanding of Alzheimer's disease. Researchers have shed light on how mechanical signalling in the brain is disrupted and could lead to the condition which accounts for 60-80% of dementia cases worldwide. Disruptions in this mechanical signalling pathway could lead to the disease.

The study proposes that Amyloid Precursor Protein (APP), known for its role in the formation of the amyloid plaques in the brain, that are a characteristic feature in Alzheimer's disease (AD), directly interacts with talin, a synaptic scaffold protein.

The study suggested the talin- Amyloid Precursor Protein interaction is crucial for the mechanical integrity of synapses in the brain and that the misprocessing of Amyloid Precursor Protein observed in Alzheimer's, disrupts mechanical signalling pathways, leading to synaptic degeneration and memory loss, thereby contributing to the progression of Alzheimer's disease. The paper further shows that if talin is removed from cells in culture then the processing of Amyloid Precursor Protein is dramatically altered.

Professor Ben Goult, University of Liverpool said:

"Our paper outlines that Amyloid Precursor Protein is fundamental for the mechanical coupling of synapses in the brain and how the processing of Amyloid Precursor Protein is part of a mechanical signalling pathway that maintains synaptic integrity. However, misprocessing of Amyloid Precursor Protein, due to altered mechanical cues, disrupts this pathway, leading to the synaptic degeneration observed in Alzheimer's and could explain the memory loss associated. What's most exciting is our paper highlights the intriguing possibility that repurposing currently available cancer drugs that stabilize focal adhesions might represent a way to restore mechanical integrity at synapses. Whilst currently this is only a theoretical prediction, our current research is focussed on testing whether this represents a novel approach to slow the progression of Alzheimer's.

Reference: https://news.liverpool.ac.uk/2024/11/27/new-discovery-could-offer-significant-answers-on-alzheimers-disease/

Intestinal infections can change the composition of liver bile, leading to changes in immune function and gut bacteria, potentially helping fight off harmful bacteria.

Researchers have identified a new axis of host defense by studying what happens during enteric infection -- a term that encompasses all types of intestinal infections including so called "stomach flu." A new study from infectious disease investigators at Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, uncovers how bile, a solution produced by the liver and responsible for the absorption of fat, plays a role in the fight against infections. Results are published in Nature Microbiology.

"The changes we detected in the composition of bile with infection are beneficial for the intestine to clear infection," said Matthew Waldor, MD, PhD, of the Brigham's Division of Infectious Diseases.

"Our findings reveal the intricate and dynamic nature of bile composition, shedding new light on the liver's critical role in defending the intestine from infection. These insights enhance our understanding of the liver's broader functions in regulating physiological stability and metabolic processes."

The researchers hypothesized that during infection, there is a shift in the composition and function of bile, given that it is an important part of communication between the liver and gut.

Using a mouse model, this study used global metabolic analysis to investigate changes in metabolites during an enteric infection. The mice were infected with one of two pathogens, L. monocytogenes, which replicates in the intestine, liver and gall bladder, or C. rodentium, which replicates in the caecum and colon. The different infection groups led to both shared and specific changes in bile metabolites. Moreover, hundreds of new metabolites that are in the bile metabolome were described. More specifically, the researchers found that enteric infection dynamically changes the composition of bile in order to provide intestinal defense. While these findings bridge a large gap in knowledge regarding bile composition, the researchers note that the 812 bile metabolites identified in this study likely only represent a subset of all bile metabolites. They predict that more will be discovered as tandem mass spectrometry techniques improve.

Reference: https://www.brighamandwomens.org/about-bwh/newsroom/research-briefs-detail?id=4833

Nearly five years since COVID-19 was first reported, a new global report on infection prevention and control (IPC) by the World Health Organization (WHO) shows there has been slow progress in addressing critical gaps to prevent healthcare-associated infections (HAIs).

A large proportion of healthcare-associated infections can be prevented with improved infection prevention and control practices and basic water, sanitation and hygiene (WASH) services, which are also a highly cost-effective "best buy" to reduce antimicrobial resistance (AMR) in health-care settings. This report, launched at a G7 side-event hosted by Italy, provides a baseline assessment for policymakers, infection prevention and control professionals, health care workers and stakeholders to guide action.

The report finds that though 71% of countries now have an active infection prevention and control programme, just 6% met all of the WHO infection prevention and control minimum requirements in 2023-2024. This is well behind the target of more than 90% by 2030 set in the WHO Global action plan and monitoring framework on infection prevention and control. The report also highlights that patients in low- and middle-income countries (LMICs) have up to 20 times higher risk of acquiring infections during health-care delivery than in high-income countries (HICs).

“The COVID-19 pandemic, along with outbreaks of Ebola, Marburg and mpox are the most dramatic demonstrations of how pathogens can spread rapidly and be amplified in health care settings. These healthcare-associated infections are a daily threat in every hospital and clinic, not only during epidemics and pandemics,” said WHO Director-General, Dr Tedros Adhanom Ghebreyesus. “Every country can and must do more to prevent infections in health facilities, and control them when they strike.”

Healthcare-associated infections prolong hospital stays and result in complications such as sepsis and in some cases disability or death. Addressing HAIs through improved infection prevention and control is also critical to reduce the risk of antimicrobial resistance, as recent estimates indicate that 136 million antibiotic resistant healthcare-associated infections occur each year.

The report found that health-care facilities face significant financial and resource challenges, including a lack of infection prevention and control professionals and budgets, especially in low- and middle-income countries. Nearly a quarter of countries reported shortages in their supply of personal protective equipment in 2023.

New data from WHO and the Organisation for Economic Cooperation and Development (OECD) estimates that up to 3.5 million patients could die each year from healthcare-associated infections without urgent action. Improving infection prevention and control measures at every level will help to reduce the number of deaths. The modelling estimated that IPC interventions at the point of care in health facilities, coordinated by Ministries of Health or established networks, could avert up to 821 000 deaths per year by 2050. Such an intervention would also yield annual savings in health-care expenditure as high as US$ 112 billion and generate economic gains of up to US$ 124 billion.

“WHO is committed to supporting countries to ensure that by 2030, everyone accessing and providing health care is safe from healthcare-associated infections,” said Dr Bruce Aylward, WHO Assistant Director-General, Universal Health Coverage, Life Course. “Fulfilling all infection prevention and control minimum requirements at the national and healthcare-facility levels should be a priority for all countries, to protect patients and health-care workers, and prevent unnecessary suffering”.

Reference: https://www.who.int/news/item/29-11-2024-new-report-highlights-need-for-sustained-investment-in-infection-prevention-and-control-programmes

Data from the National Family Health Survey in India indicate higher risks of stunting, wasting, and underweight among children born via C-section compared to those delivered vaginally. The analysis, which included 200,794 births, also found an increased likelihood of neonatal mortality in C-section births.

Additionally, children born to mothers with third or higher-order pregnancies faced greater risks of both neonatal and infant mortality. These findings, published in BMC Pediatrics, highlight the need to address delivery methods and maternal factors in improving child health outcomes.

Researchers from Fakir Mohan University, Balasore, Odisha, India, examined the impact of delivery methods on child health in children aged 0–59 months in India.

For this purpose, the researchers used 200,794 samples in the study. Of these, 45,784 births were delivered by C-section, while the remaining 150,010 were delivered through normal vaginal delivery. To assess the association between child health and mode of delivery, life table estimation of mortality and bivariate and multivariate logistic regression were applied to data from the fifth round of the National Family Health Survey conducted in 2019-21.

The study led to the following findings:

Children born via normal delivery had significantly lower rates of stunting, wasting, and underweight compared to those born by C-section.

The likelihood of neonatal death was higher for newborns delivered by C-section than for those delivered vaginally, across various background characteristics.

Mothers with a third or higher-order birth who deliver via C-section face a higher risk of neonatal and infant mortality compared to those with a second-order birth.

The study highlights that C-section deliveries are linked to delayed breastfeeding, higher financial burdens, and shorter breastfeeding durations compared to vaginal births. Additionally, C-sections increase the risk of child undernutrition, mortality, and complications, especially in emergency C-sections and those with previous C-sections. Neonatal and infant mortality rates are higher among C-section births.

"These findings stress the importance of antenatal and postnatal care visits. Low maternal healthcare coverage in rural areas exacerbates these issues. Health policies should focus on improving obstetric care quality and promoting vaginal deliveries to reduce mortality and improve child health outcomes," the researchers concluded.

Reference: Das, U., Rout, N.R. Impact of normal vs. caesarean deliveries on child nutritional status and mortality in India: insights from NFHS-5 data. BMC Pediatr 24, 781 (2024). https://doi.org/10.1186/s12887-024-05149-4