Year: 2023

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags :

Ground-breaking Progress in Identifying the Root Cause of Preeclampsia

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Photo by Shvets Production on Pexels

Researchers report in Nature Communications that they have made ground-breaking progress towards identifying the root cause and potential therapy for preeclampsia. They identified a toxic protein, cis P-tau, in the blood and placenta of preeclampsia patients. This protein is also linked to the development of memory loss after brain injury or Alzheimer’s.

The pregnancy complication affects up to 8% of pregnancies globally and is the leading cause of maternal and foetal mortality due to premature delivery, complications with the placenta and lack of oxygen. It also disproportionately affects women of certain races.

According to the study, led by Drs Kun Ping Lu and Xiao Zhen Zhou at the University of Western Ontario, and Drs Surendra Sharma and Sukanta Jash at Brown University, cis P-tau is a central circulating driver of preeclampsia.

“The root cause of preeclampsia has (so far) remained unknown, and without a known cause there has been no cure. Preterm delivery is the only life-saving measure,” said Lu, professor of biochemistry and oncology at Schulich School of Medicine & Dentistry.

“Our study identifies cis P-tau as a crucial culprit and biomarker for preeclampsia. It can be used for early diagnosis of the complication and is a crucial therapeutic target,” said Sharma.

In 2016, Sharma, a leading preeclampsia researcher, and his team had identified that preeclampsia and diseases like Alzheimer’s had similar root causes related to protein issues. This research builds on that finding.

Until now, cis P-tau was mainly associated with neurological disorders like Alzheimer’s disease, traumatic brain injuries (TBI) and stroke. This association was discovered by Lu and Zhou in 2015 as a result of their decades of research on the role of tau protein in cancer and Alzheimer’s.

An antibody developed by Zhou in 2012 to target only the toxic protein while leaving its healthy counterpart unscathed is currently undergoing clinical trials in human patients suffering from TBI and Alzheimer’s Disease. The antibody has shown promising results in animal models and human cell cultures in treating the brain conditions.

The researchers were curious whether the same antibody could work as a potential treatment for preeclampsia. Upon testing the antibody in mouse models they found astonishing results.

“In this study, we found the cis P-tau antibody efficiently depleted the toxic protein in the blood and placenta, and corrected all features associated with preeclampsia in mice. Clinical features of preeclampsia, like elevated blood pressure, excessive protein in urine and foetal growth restriction, among others, were eliminated and pregnancy was normal,” said Sharma.

Sharma and his team at Brown have been working on developing an assay for early detection of preeclampsia and therapies to treat the condition. He believes the findings of this study have brought them closer to their goal.

Preeclampsia, genetics and the brain

Recent research has also thrown light on preeclampsia’s long-term impacts and possible links to brain health.

“Research has shown that women of certain races have genes that could possibly lead to higher than average blood pressure levels, eventually creating conditions for preeclampsia during pregnancy. However, it’s also true that in many low socio-economic countries there’s no registry to record PE cases. So, its link to other environmental factors is still unclear,” said Sharma.

“Preeclampsia presents immediate dangers to both the mother and foetus, but its long-term effects are less understood and still unfolding,” said Sharma. “Research has suggested a heightened risk of dementia later in life for both mothers who have experienced preeclampsia and their children.” However, the causal link between preeclampsia and dementia is not known.

The researchers say this new study has pinpointed a potential underlying cause of the complex relationship between preeclampsia and brain health.

“Our study adds another layer to this complexity. For the first time, we’ve identified significant levels of cis P-tau outside the brain in the placenta and blood of preeclampsia patients. This suggests a deeper connection between preeclampsia and brain-related issues,” said Jash, the lead author of the study.

As researchers delve deeper, how our bodies respond to stress is also emerging as a potential factor in the onset of preeclampsia.

“Although genetics play a role, factors like stress could be an important piece of the puzzle. Understanding how stress and other environmental factors intersect with biological markers like cis P-tau may offer a more complete picture,” said Jash, assistant professor of molecular biology, cell biology and biochemistry (research) and paediatrics (research) at Brown.

A stress-response enzyme called Pin1

In 1996 and 1997, Lu and Zhou made the ground-breaking discovery of Pin1, which turns out to be a stress-response enzyme. This is a specific protein in the cells that becomes active or changes its behaviour in response to stressors, such as environmental challenges, toxins or physiological changes.

“Pin1 plays a pivotal role in keeping proteins, including the tau protein, in the functional shape during stress. When Pin1 becomes inactivated, it leads to the formation of a toxic, misshapen, variant of tau — cis P-tau,” said Zhou, associate professor, pathology and laboratory medicine at Schulich Medicine & Dentistry.

Interestingly, Pin1 is a key player in cancer signalling networks, turning on numerous cancer-causing proteins and turning off many cancer-suppressing ones. Found in high levels in most human cancers, it’s particularly active in cancer stem cells, which are thought to be central to starting and spreading tumours and are hard to target with existing treatments.

“Essentially, when Pin1 is activated, it can lead to cancer. On the other hand, when there’s a decrease or deactivation in Pin1, it results in the formation of the toxic protein cis P-tau, which leads to memory loss in Alzheimer’s and after TBI or stroke. Now, we’ve uncovered its connection to preeclampsia as well,” said Zhou.

“The results have far-reaching implications. This could revolutionise how we understand and treat a range of conditions, from pregnancy-related issues to brain disorders,” said Lu.

Source: University of Western Ontario

Categories : Immune SystemTags :

A Cellular Switch to Shut off Cytokine Storms

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Signalling from inflammatory cytokines activates several protein kinases in a chain – at the end of this process MKK6 (yellow) ‘switches on’ p38α (green) by binding it and adding phosphates. The combination of computer simulations, SAXS, and cryo-EM has shown how the two proteins interact and bind to each other to transmit the signal. Credits: Ella Marushchenko, Isabel Romero Calvo/EMBL

Cytokine storms, where inflammatory cascades during an infection that can spiral out of control and lead to severe disease and even death, were recently highlighted during the COVID-19 pandemic. In a new paper published in Science, researchers report their discovery of a cellular ‘switch’ which may lead to new drugs to prevent deadly cytokine storms.

EMBL Grenoble and University of Geneva researchers provide essential insights on a protein called p38α which is an important cellular ‘switch’ triggering the inflammatory response. They have obtained the first structure of p38α being activated by another regulatory protein kinase, MKK6, opening up new directions to develop drugs to stop cytokine storms.

The final switch: a drug target

Matthew Bowler, a researcher at EMBL Grenoble, has been studying kinases for more than a decade. This group of enzymes plays an important role in regulating complex processes in the cell by acting as a ‘switch’ to transmit signals and activate gene expression. They do so by phosphorylation, in which phosphate is added to other molecules to modulate their function.

Bowler’s work particularly focuses on belonging to the Mitogen Activated Protein (MAP) family of kinases, key players involved in the inflammatory response. Inflammation is switched on via a series of kinases, which activate each other in a cascade of reactions, the final kinase in the series being responsible for activating gene transcription required for inflammation. This process releases cytokines, pro-inflammatory signalling molecules, which, in case of overactivation, can lead to cytokine storms.

This kinase chain reaction is well regulated and is similar to a logic circuit: the inflammation response requires specific buttons to be switched on, ultimately activating p38α – the convergence point for all the signals and the last switch of the inflammatory process.

Because the kinase chain reaction can come from different ‘branches’ of the logic circuit, this last switch is a particularly relevant drug target. The inflammatory response is regulated by p38α and is highly activated during a cytokine storm. Inactivating it could prevent inflammation from occurring, instead of trying to treat it while it is already underway.

Protein kinases, including p38α, have therefore been heavily studied. The first protein kinase structure was solved 30 years ago and many more structures have followed, with over 7000 structures now available in the Protein Data Bank.

However, important parts of the puzzles are still missing. “Structural biologists have obtained detailed information on the structure and functions of protein kinases, but mostly in isolation. So we don’t really know how these enzymes are activated along the chain reaction,” explained Bowler.

Without this essential information about how the activation is triggered, drugs have mostly targeted the kinases’ nucleotide-binding site – a common and well-known pocket present in all kinases, where the phosphate transfer occurs. The lack of drug specificity due to a common binding site across kinases means that a drug designed to stop one kinase from signalling could also stop others. This presents a problematic side effect, considering the essential role of kinases as key regulators in cellular processes.

“There are many molecules that have been designed to target p38α, especially its nucleotide-binding site, but none have yet made it past clinical trials due to this lack of specificity,” added Bowler.

Cracking the activation mechanism

Since 2009, Bowler and a former PhD student in his lab, Erika Pellegrini, have therefore been investigating the interactions between p38α and MKK6, the kinase which activates it. But studying the interaction between kinases proves to be extremely complex. “These enzymes are very dynamic molecules; they transmit important signals and need to act quickly. In the case of p38α, it has to go into the nucleus and activate lots of other different proteins,” said Bowler.

They were hampered by the fact that the interactions of the MKK6-p38α complex cannot be determined by macromolecular crystallography, a structural biology technique often employed to investigate proteins but that is particularly challenging to apply in the case of such dynamic proteins.

Recent developments in cryo-electron microscopy (cryo-EM), particularly during the last decade, raised new hopes. In 2016, Bowler and new PhD student and first author of the paper, Pauline Juyoux, decided to switch to this technique – even though the protein complex was at the time considered too small for cryo-EM analysis. They were supported by Pellegrini, who had acquired expertise in this technique.

Using cryo-EM and complementary techniques, such as X-ray crystallography and small-angle X-ray scattering (SAXS), the team managed to obtain the 3D structure of the complex and identify a previously unknown docking site where the two enzymes interact – crucial information for understanding how p38? is activated. “This could be an interesting target for inhibitors that block this specific interaction, and consequently the signal triggering the inflammatory response,” explained Juyoux.

A collaboration with the Gervasio Lab from the University of Geneva, which uses molecular dynamics simulations, provided further insight into how the two kinases interact. “They showed that the model we had generated was compatible with the enzymatic activity and that the phosphorylation site was at the right distance from the active site,” explained Juyoux. “They also classified the different types of conformations of the complex to show how they assemble.”

Crucially, by comparing these simulations with the SAXS data they were able to model how the two proteins interact prior to catalysis. “The beauty of combining the state-of-the-art simulations with SAXS and cryo-EM data through advanced statistical approaches is that we can ‘see’ the dance of the two kinases approaching one another, while knowing that what we see in the computer is fully supported by all the experimental data available,” explained Francesco Gervasio. “The simulations required several months of supercomputing time generously allocated by the Swiss National Supercomputing Centre,” he continued, “But it was well worth it, given the relevance of the final results.”

These results provide an alternative drug target site to explore and also open the door to studying similar processes in two other families of MAP kinases: ERK kinases, which are involved in cancer, and JNK kinases, which are also involved in inflammation, especially in Alzheimer’s disease.

“Kinases are very similar to one another in terms of sequence and structure, but we don’t know how and why they respond or send a specific signal,” said Juyoux, whose current research project as a postdoctoral fellow at Institut de Biologie Structurale in Grenoble focuses on JNK kinases. “Comparing these different families of kinases could help explain the specificity of interactions and lead the way to new therapeutic approaches.”

Source: European Molecular Biology Laboratory

Categories : Ethics and LawTags :

Elevating Patients’ Voices for Greater Healthcare Safety

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With four in ten patients injured in primary and outpatient healthcare and 134 million adverse events occurring on the back of unsafe care in hospitals globally every year,1 World Patient Safety Day aims to address the avoidable challenges that will bolster patient safety across the healthcare spectrum.

Even in an era marked by incredible innovation and advancements in medical science, the reality is that within the four walls of the hospital environment, patients continue to face preventable challenges that could potentially threaten their health and well-being.

Recognising the seriousness of this, the World Health Organization (WHO) launched its World Patient Safety Day initiative in 2005 to increase awareness of unsafe healthcare, and to drive high-level support and commitment to address patient safety issues across all parts of the world.2

Bada Pharasi, CEO of the Innovative Pharmaceutical Association of South Africa, adds that under the theme of “engaging patients for patient safety”, World Patient Safety Day 2023 is positioned to recognise the crucial role that patients, families and caregivers play in safety in the healthcare sector.3

“Patients are the core of all healthcare systems, and evidence shows that when patients are treated as partners in their care, significant gains are made in safety, patient satisfaction and overall health outcomes,” explains Pharasi.

Patient safety is fundamental to delivering quality and essential health services and prevents and reduces risks, errors and harm to patients. A cornerstone of this lies in continuous improvement based on learning from errors and previous adverse events that have impacted patient well-being.  

More than 10% of patients have experienced harm due to negligence during treatment, and alarmingly, this has resulted in over three million deaths globally every year.5 Even more concerning is that up to 80% of these instances are avoidable, with the most significant factors accounting for these errors being related to misdiagnosis and the prescribing and use of incorrect medications.1

“An integral part of addressing this plight is to elevate patients’ voices,” adds Pharasi. “This can be accomplished by ensuring that patients are involved in policy formulation, represented in governance structures, engaged in co-designing safety strategies, and are active partners in their own care.”3

Here, patients should enquire why the medication has been prescribed, how long the medication will take to resolve symptoms if the medication can be taken with others, and what are the potential side effects of the medication.6

Furthermore, patients should be cognisant of not taking medication prescribed to someone else, discarding medicines that have passed their expiry date, never exceeding dosage recommendations, carefully reading the patient information leaflets included with medications, and being aware that some medications may contain addictive substances.

For patient safety strategies to be successful, patients need to report instances where they have been prescribed the incorrect medication and the adverse effects it may have caused. To report these, patients can record their complaints on the Med Safety app, the SAHPRA e-reporting portal on its website, or via email or telephone.7

“As IPASA, we are committed to a healthier South Africa and a patient-centred healthcare system. We support the WHO mandate to ensure safer patient treatments and outcomes, and strive to continue informing healthcare professionals and patients about the benefits and risks of pharmaceutical products. In doing so, we believe we can make a notable difference in ensuring patient safety across all facets of the South African healthcare sector,” concludes Pharasi.  

References:

Categories : Diseases, Syndromes and ConditionsTags :

An Antibacterial for Livestock may be a Magic Bullet for Acne

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Photo by cottonbro studio

In a study published in the journal Nanoscale, researchers encased Narasin, a new antibacterial compound, in tiny, soft nanoparticles 1000 times smaller than a single strand of human hair and applied in a gel form to targeted acne sites. The University of South Australia (UniSA)-led research team found that the drug proved successful against drug-resistant acne bacteria and delivered via nanocarriers achieved a 100-fold increase in absorption than simply taken with water.

Lead author UniSA PhD student Fatima Abid says this is the first time that nano-micelle formulations of Narasin have been developed and trialled.

“Acne severely impacts approximately 9.4% of the world’s population, mainly adolescents, and causes distress, embarrassment, anxiety, low self-confidence and social isolation among sufferers,” Abid says.

“Although there are many oral medications prescribed for acne, they have a range of detrimental side effects, and many are poorly water soluble, which is why most patients and clinicians prefer topical treatments.”

Abid’s supervisor, pharmaceutical scientist Professor Sanjay Garg, says a combination of increasing antibiotic resistance and the ineffectiveness of many topical drugs to penetrate hair follicles in acne sites means there is a pressing need to develop new antibacterial therapies that are effective and safe.

Narasin is commonly used for bacterial infections in livestock but has never been previously investigated as a viable treatment for acne.

Abid, Prof Garg and researchers from UniSA, the University of Adelaide, and Aix-Marseille Université in France also investigated how well Narasin encased in nanoparticles penetrated various layers of skin, using pig’s ear skin as a model.

“The micelle formulation was effective in delivering Narasin to acne targets sites, as opposed to the compound solution which failed to permeate through skin layers,” Prof Garg says.

Source: University of South Australia

Categories : Hospitals NeurologyTags :

New Evidence of Patients Recalling Death Experiences after Cardiac Arrest

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Up to an hour after cardiac arrest, some patients revived by cardiopulmonary resuscitation (CPR) had clear memories afterward of experiencing death and had brain patterns while unconscious linked to thought and memory, report investigators in the journal Resuscitation.

In a study led by researchers at NYU Grossman School of Medicine, some survivors of cardiac arrest described lucid death experiences that occurred while they were seemingly unconscious. Despite immediate treatment, fewer than 10% of the 567 patients studied, who received CPR in the hospital, recovered sufficiently to be discharged. Of the survivors, four in 10 recalled some degree of consciousness during CPR not captured by standard measures.

The study also found that in a subset of these patients, who received brain monitoring, nearly 40% had brain activity that returned to normal, or nearly normal, from a “flatline” state, at points even an hour into CPR. As captured by EEG, the patients saw spikes in the gamma, delta, theta, alpha, and beta waves associated with higher mental function.

Survivors have long reported having heightened awareness and powerful, lucid experiences, say the study authors. These have included a perception of separation from the body, observing events without pain or distress, and a meaningful evaluation of their actions and relationships. This new work found these experiences of death to be different from hallucinations, delusions, illusions, dreams, or CPR-induced consciousness.

The study authors hypothesise that the “flatlined”, dying brain removes natural inhibitory (braking) systems. These processes, known collectively as disinhibition, may open access to “new dimensions of reality,” they say, including lucid recall of all stored memories from early childhood to death, evaluated from the perspective of morality. While no one knows the evolutionary purpose of this phenomenon, it “opens the door to a systematic exploration of what happens when a person dies.”

Senior study author Sam Parnia, MD, PhD, associate professor in the Department of Medicine at NYU Langone Health and director of critical care and resuscitation research at NYU Langone, says, “Although doctors have long thought that the brain suffers permanent damage about 10 minutes after the heart stops supplying it with oxygen, our work found that the brain can show signs of electrical recovery long into ongoing CPR. This is the first large study to show that these recollections and brain wave changes may be signs of universal, shared elements of so-called near-death experiences.”

Dr Parnia adds, “These experiences provide a glimpse into a real, yet little understood dimension of human consciousness that becomes uncovered with death. The findings may also guide the design of new ways to restart the heart or prevent brain injuries and hold implications for transplantation.”

The AWAreness during REsuscitation (AWARE)-II study followed 567 adults who suffered in-hospital cardiac arrest between May 2017 and March 2020 in the US and UK. Only hospitalised patients were enrolled to standardise the CPR and resuscitation methods used, as well as recording methods for brain activity. A subset of 85 patients received brain monitoring during CPR. Additional testimony from 126 community survivors of cardiac arrest with self-reported memories was also examined to provide greater understanding of the themes related to the recalled experience of death.

The study authors conclude that research to date has neither proved nor disproved the reality or meaning of patients’ experiences and claims of awareness in relation to death. They say the recalled experience surrounding death merits further empirical investigation and plan to conduct studies that more precisely define biomarkers of clinical consciousness and that monitor the long-term psychological effects of resuscitation after cardiac arrest.

Source: Elsevier

Categories : Medical Industry Mental HealthTags :

Stress, Overwork, Understaffing Driving Healthcare Workers from NHS

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Photo by Usman Yousaf on Unsplash

Work stress, high workload, and understaffing are the primary factors driving health professionals out of the NHS, suggest the results of a survey published in the open access journal BMJ Open.

The findings prompt the researchers to suggest that pay increases alone may not be sufficient to fix NHS staff retention. The NHS is short of well over 100 000 staff and fallout from COVID-19 has seen worsening retention.

The researchers investigated the ‘push’ factors behind decisions to leave the NHS, and whether these were ranked differently by profession and NHS setting, a year after exposure to the effects of the pandemic.

In 2021, NHS health professionals completed an online survey to determine the relative importance they gave to 8 factors as the key reasons for leaving NHS employment.

The respondents included 227 doctors; 687 nurses/midwives; 384 healthcare assistants and other nursing support staff; 417 allied health professionals, such as physiotherapists and occupational therapists; and 243 paramedics from acute, mental health, community, and ambulance services.

Using the paired comparison technique, whereby two push factors at a time were presented at a time, respondents were asked: ‘Which of these two factors is the bigger influence on why staff in your profession/job role leave the NHS’?’

Photo by Pavel Danilyuk

Compared to other professions, paramedics gave a much higher relative weighting to work stress, work-life balance, work intensity and pay higher relative weighting.

The factors compared were: staffing levels; working hours; mental health/stress; pay; time pressure; recognition of contribution; workload intensity; and work–life balance.

Compared to other professions, paramedics gave a much higher relative weighting to work stress, work-life balance, work intensity and pay higher relative weighting. Paramedics also ranked work-life balance as a stronger driver to leave the NHS. They ranked this second compared to a fourth or fifth ranking across the other professions.

Pay was considered more important by healthcare assistants and other nursing support staff and paramedics, but was generally ranked fourth or fifth by other professional groups. 

This contrasts with “some contemporary media and industrial relations accounts, and some academic research findings,” say the researchers, who nevertheless add: “While other variables appear to exert a stronger push than pay, this is not grounds to diminish it as a potential source of dissatisfaction in absolute terms.” 

Overall, health professionals ranked work-related stress, workload intensity, and staffing levels as the primary ‘push factors’ underpinning decisions to leave the NHS. Recognition of effort and working hours were ranked lowest. But there were differences in the order of importance and relative weighting given to the push factors among the different health professions.

Work intensity in acute care hospitals and community services; time pressure in community services; and recognition of effort in mental health services were given higher relative weightings.

“In common with the NHS annual staff survey and all other voluntary participation employee surveys, the potential for self-selection response bias cannot be discounted,” emphasise the researchers. 

But they conclude: “Excepting paramedics, rankings of leave variables across the different health professional families exhibit a high degree of alignment, at the ordinal level, and highlight the primacy of psychological stress, staff shortages, and work intensity.”

They add: “While increases in pay are transparently important to NHS staff, findings from this research suggest that enhancements in that domain alone may produce a modest impact on retention.

“An equivalent conclusion might be drawn with respect to the current high-profile emphasis on increased access to flexible working hours as a solution within contemporary NHS staff retention guidance to employers. 

“Both have potential to do good, but there are grounds for inferring there is a risk that neither may deliver sufficient good to redress the high and rising exodus in the absence of attention to what present as more fundamental factors driving exit.” 

Source: BMJ Open

Categories : Injury & TraumaTags :

SA’s Injury Statistics are not Accurate, Experts Warn

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Photo by Maxim Hopman on Unsplash

By Sonia A. Rao for GroundUp

Reporting of gun crime in South Africa is wildly inaccurate, work by the South African Medical Research Council (SAMRC) suggests. This is because the official death notification form does not distinguish between gun deaths from accidents and gun deaths from homicide.

The SAMRC has called on the government to update the country’s official death notification form. In a September 2023 South African Medical Journal (SAMJ) editorial, researchers and scientists Pam Groenewald, Richard Matzopoulos, Estevão Afonso and Debbie Bradshaw, say the form does not comply with international standards. While the World Health Organisation recommends reporting manner of death on the medical certificate for cause of death, South Africa’s form does not allow this, they say.

As a result, South Africa does not have accurate information on injury statistics, says Groenewald, a specialist scientist at SAMRC.

“Given that South Africa has got a really high injury burden, this is really not acceptable,” she said.

The SAMRC has pointed out that accurate, timely mortality data for natural and non-natural deaths is especially important after the Covid pandemic.

In a press release, the SAMRC said natural deaths had spiked during Covid waves, while injuries had fallen during government-imposed lockdowns and alcohol sales bans. “Of particular concern is the significant impact of alcohol bans on injury-related deaths,” the council said.

The release also said the statistics are necessary to develop and monitor programs to reduce injuries and violence, and track Sustainable Development Goals of road traffic injury reduction, gender equality and reducing violence-related death rates.

South Africa’s official mortality statistics overestimate accidental injuries and underestimate homicides, transport and suicide deaths, according to a research report also published in the September 2023 SAMJ.

In official death notification form data from Stats SA for 2017, nearly 99% of firearm deaths were classified as accidental and only 1% as homicide. But the SAMRC’s National Cause-of-Death Validation Project (NCoDV) found more than 88% of firearm deaths were homicide, and its Injury Mortality Survey (IMS) found more than 93%.

Similar differences occurred for suicides. Only 0.3% of firearm deaths were recorded as suicide in the 2017 Stats SA data, but they were recorded as 7% in NCoDV and IMS data.

The research report says NCoDV and IMS provide more detailed and consistent data on causes of injury than the death notification form, but they are costly and time-consuming, and not feasible for routine surveillance.

“It costs a lot of money, when we could be getting this data in with every death certificate that gets completed,” Groenewald says.

She says the SAMRC has been asking for an updated death certificate form since 2012.

No annual mortality report since 2018

Also, Stats SA has not published an updated mortality report since the pandemic. The last official report was released in 2021 for the year 2018.

“We’ve got no cause-of-death data at all, not just injuries, nothing. We haven’t seen a death certificate from during the Covid period; we don’t know what doctors have reported,” she said. “It’s mind boggling.”

Felicia Sithole, deputy director of media relations for Stats SA, said in a statement that the Mortality and Causes of Death report had been delayed by a backlog of processing death notification forms as a result of the Covid lockdown, and because of Census 2022 work.

Sithole said Stats SA is committed to publishing the 2019 and 2020 Mortality and Causes of Death reports by the end of March 2024.

“Stats SA fully comprehends the importance of the Mortality and Causes of Death release, especially during the Covid-19 pandemic, and acknowledges that our data must conform to international standards,” she said.

The SAMRC report also calls for the dormant National Forensic Pathology Services Committee to be reactivated. This would help improve data quality, the report says. The committee, established in 2014, has been inactive since 2018/9.

Foster Mohale, a media officer for the Department of Health, said the Minister of Health is in the process of appointing a new National Forensic Pathology Services Committee.

The Department of Home Affairs had not responded to requests for comment at the time of publication.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Source: GroundUp

Categories : Injury & TraumaTags :

Students Develop an AI Tool that Predicts Survival of Brain Injury in ICU

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Photo by Anna Shvets on Pexels

A pair of postgraduate students have developed a ground-breaking method for predicting which intensive care unit (ICU) patients will survive a severe brain injury. The two researchers combined functional magnetic resonance imaging (fMRI) with state-of-the art machine learning techniques to tackle one of the most complex issues in critical care. They describe the new technology in the Journal of Neurology.

Whether it is the result of a stroke, cardiac arrest or traumatic brain injury, lives can forever be changed by a serious brain injury. But the potential of a good recovery is highly uncertain.

The University of Western Ontario researchers, Matthew Kolisnyk and Karnig Kazazian, are PhD candidates at Schulich School of Medicine & Dentistry in the lab of neuroscientist Adrian Owen.

“For years we’ve lacked the tools and techniques to know who is going to survive a serious brain injury,” said Owen.

An interdisciplinary team of researchers from Western, in collaboration with neurologists at London Health Sciences Centre and Lawson Health Research Institute sought to find a solution to this problem. They were led by Loretta Norton, a psychology professor at King’s University College at Western, who was one of the first researchers in the world to measure brain activity in the ICU.

The team measured brain activity in 25 patients at one of London’s two ICUs in the first few days after a serious brain injury and tested whether it could predict who would survive and who would not.

“We previously found that information about the potential for recovery in these patients was captured in the way different brain regions communicate with each other,” said Norton. “Intact communication between brain regions is an important factor for regaining consciousness.”

The breakthrough occurred when the team realized they could combine this imaging technique with an application of AI known as machine learning. They found they could predict patients who would recover with an accuracy of 80 per cent, which is higher than the current standard of care.

“Modern artificial intelligence has shown incredible predictive capabilities. Combining this with our existing imaging techniques was enough to better predict who will recover from their injuries,” said Kolisnyk.

While encouraging, the researchers say the prediction was not perfect and needs further research and testing.

“Given that these models learn best when they have lots of data, we hope our findings will lead to further collaborations with ICUs across Canada,” said Kazazian.

Source: University of Western Ontario

Categories : Implants and Prostheses NeurologyTags :

A New Way to Map the Human Auditory Pathway

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Photo by Brett Sayles

Researchers have developed a non-invasive method for mapping the human auditory pathway, which could potentially be used as a tool to help clinicians decide the best surgical strategy for patients with profound hearing loss. The findings, published online in the journal eLife, highlight the importance of early interventions to give patients the ability to hear and understand speech, so that their auditory-language network can develop properly and their long-term outcomes are improved.

Sensorineural hearing loss (SNHL) occurs when the sensitive hair cells inside the cochlea are damaged, or when there is damage to the auditory nerve which transmits sound to the brain. A person with profound hearing loss is typically unable to hear any sounds, or at best, only very loud sounds. Congenital SNHL has increased in prevalence over the past two decades, from 1.09 to 1.7 cases per 1000 live births.

The sound of speech is carried through the brain by nerve fibres in regions known as the auditory pathway, and are processed in a region called the language network. In cases of congenital SNHL, the lack of speech inputs reaching the language network may hinder its proper development, leading to poorer spoken language skills.

Currently, the primary treatments for profound SNHL are cochlear and auditory brainstem implantation, where a device is used to stimulate the peripheral cochlea or the central cochlear nucleus, respectively. Both techniques can partially restore hearing in patients, but their language development outcomes can vary. This is especially true for patients with inner ear malformations (IEM) or cochlear nerve deficiencies (CND), which contribute to 15-39% of congenital SNHL cases.

“Where SNHL is caused by CNDs and/or IEMs, there is a great deal of uncertainty around the best method of treatment. This is due to the difficulty of assessing the condition of the cochlear nerve and distinguishing between certain types of IEM, both of which impact surgical decision making,” says senior authors Hao Wu, a professor and Chief Physician specialising in Otolaryngology at Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, China. Wu also serves as the Hospital Administrator and the Clinical and Academic Lead for the department. “We therefore need a more effective method for mapping the auditory pathway and diving deeper into how IEMs and CNDs affect the development of the auditory-language network.”

In their study, professor Wu’s team investigated the auditory and language pathways in 23 children under the age of six. They included 10 children with normal hearing, and 13 with profound SNHL. In the latter group, seven children had received cochlear implantations, two had received auditory brainstem implantations, and four were candidates for auditory brainstem implantations.

The human auditory pathway is difficult to investigate non-invasively due to its delicate and intricate subcortical structures located deep within the brain. To navigate this, the team developed a new methodology to reconstruct the pathway. First, they segmented the subcortical auditory structures using track density imaging, which are reconstructed from a specific type of MRI scan and provide much greater detail and information on the structural connectivity of the brain. This allowed them to delineate the cochlear nucleus and the superior olivary complex of the auditory pathway. They then tracked the auditory and language pathways using a neuroimaging technique called probabilistic tractography, which uses the information from an MRI scan to provide the most likely view of structural brain connectivity. Next, the team assessed the density and cross-section of the nerve fibres in the auditory and language pathways.

This combined methodology allowed them to investigate three key areas to inform surgical decision making: the condition of the nerve fibres in the auditory-language network of children with profound SNHL; the potential impact of IEMs and CNDs on the development of the network before surgical intervention; and the relationship between the pre-implant structural development of the network and the auditory-language outcomes following implantation.

The team’s observations revealed a lower nerve fibre density in children with profound SNHL, in comparison to those with normal hearing. This reduction was most pronounced in two regions of the inferior central auditory pathway, as well as the left language pathway.

In addition, the findings revealed that the language pathway is more sensitive than the central auditory system to IEMs and/or CNDs, implying that the structural development of the language pathway is more negatively impacted by the condition of the peripheral auditory structure. However, the authors caution that further study is required to validate this finding. As it is more difficult to image the central auditory pathway than the language pathway, this difference could have arisen due to the limitations of current neuroimaging technologies.

The authors say the study is also limited by a relatively small cohort of patients and an incomplete genetic dataset, so more studies with a more diverse patient population will also be needed. But with further validation, they add that the methodology could be used more widely for informing decisions in treating profound SNHL.

Source: eLife

Categories : Gender Mental HealthTags :

Inflammatory Markers of Depression Risk Differ in Boys and Girls

On By ModernMedia
Photo by Daniil Onischenko on Unsplash

New research led by King’s College London researchers has found that depression and the risk of depression are linked to different inflammatory cytokines in boys and girls. Previous research has shown that higher levels of inflammatory cytokines are associated with depression in adults, but little is known about this relationship in adolescence.

This study, published in the Journal of Affective Disorders, found that different cytokines were implicated in depression risk and severity in boys compared to girls. The research was part of the IDEA (Identifying Depression Early in Adolescence) project funded by MQ Mental Health Research.

To assess inflammation, researchers measured the blood cytokine levels in 75 adolescent boys and 75 adolescent girls (aged 14–16 years) from Brazil. The 150 participants had been recruited into three groups with equal numbers (50 participants in each group: 25 girls and 25 boys). The groups were those at low-risk for depression and not depressed, those at high risk of depression and not depressed, and those currently experiencing major depressive disorder (MDD).

The findings indicated that there are sex differences between the individual cytokines that are associated with depression in adolescents. Higher levels of the cytokine interleukin-2 (IL-2) were associated with both increased risk for depression and the severity of depressive symptoms in boys, but not in girls. However, higher levels of IL-6 were associated with severity of depression in girls, but not boys. In boys the levels of IL-2 were higher in the high-risk than the low-risk group and even higher in the group diagnosed with depression, indicating that in boys IL-2 levels in the blood could help indicate the onset of future depression.

Dr Zuzanna Zajkowska, Postdoctoral Researcher at King’s IoPPN and first author of the study, said: “This is the first study to show differences between boys and girls in the patterns of inflammation that are linked to the risk and development of adolescent depression.

“We found that the severity of depressive symptoms was associated with increased levels of the cytokine interleukin-2 in boys, but interleukin-6 in girls. We know more adolescent girls develop depression than boys and that the disorder takes a different course depending on sex so we hope that our findings will enable us to better understand why there are these differences and ultimately help develop more targeted treatments for different biological sexes.”

Researchers recruited adolescents from public schools in Brazil. Risk of depression was assessed by a composite risk score for depression based on 11 sociodemographic variables that had been developed as part of the IDEA project. Adolescents completed several questionnaires, self-reporting their emotional difficulties, relationships, experiences, and mood. They also completed a clinical assessment with a child and adolescent psychiatrist.

Senior author on the study Professor Valeria Mondelli, Clinical Professor of Psychoneuroimmunology at King’s IoPPN and theme-lead for Psychosis and Mood Disorders at the NIHR Maudsley BRC, said:

“Our findings suggest that inflammation and biological sex may have combined contribution to the risk for depression. We know that adolescence is a key time when many mental disorders first develop and by identifying which inflammatory proteins are linked to depression and how this is different between boys and girls we hope that our findings can pave the way to understanding what happens at this critical time in life. Our research highlights the importance of considering the combined impact of biology, psychology, and social factors to understand the mechanisms underlying depression.”

Source: King’s College London