Day: June 15, 2021

Categories : Mental Health PaediatricsTags :

Spotting Self-harming Risk for Adolescents a Decade in Advance

On By ModernMedia
Photo by Andrew Neel on Unsplash

Researchers have revealed two subgroups of self-harming adolescents and have shown that those self-harming risk can be identified almost a decade before they begin self-harming.

The team, based at the MRC Cognition and Brain Sciences Unit, University of Cambridge, found that while sleep problems and low self-esteem were common risk factors, there were two distinct profiles of young people who self-harm – one with emotional and behavioural difficulties and a second group with different risk factors.

Between one in five and one in seven adolescents in England self-harms, such as by cutting themselves. Though self-harm is a significant risk factor for later suicide attempts, many do not plan suicide but face other harmful outcomes, including repeatedly self-harming, poor mental health, and risky behaviours like substance abuse. 

Despite its prevalence and lifelong consequences, there has been little progress in the accurate prediction of self-harm, and until recently, little research in the area.

Drawing from a nationally representative UK birth cohort of approximately 11 000 individuals, the Cambridge team picked out adolescents who reported self-harm at age 14. With machine learning analysis, they were able to establish profiles of self-harming young people, with different emotional and behavioural characteristics. This information enabled them to identify risk factors present in early and middle childhood. 

Since the data tracked the participants over time, the researchers could distinguish factors that appear at the same time reported self-harm, such as low self-esteem, from those that came before it, such as bullying.

The analysis showed that there were two distinct subgroups among young people who self-harm, with significant risk factors manifesting as early as age five, almost a decade before self-harming. Both groups were likely to experience sleep difficulties and low self-esteem reported at age 14, but other risk factors differed between the two groups.

The first group tended to have a long history of poor mental health, as well as bullying before self-harming. Their caregivers were also more likely to have their own mental health issues.

With the second group, however, self-harming was harder to predict early in childhood. One of the key signs was a greater willingness to take part in risk-taking behaviour, linked to impulsivity. Research suggests that these tendencies may make the individuals less likely to consider alternatives to self-harm. Relationship factors with their peers were also important for this subgroup, including feeling less secure with friends and family at age 14 and worrying more about the feelings of others as a risk factor at age 11.

First author Stepheni Uh, a Gates Cambridge Scholar, explained: “Self-harm is a significant problem among adolescents, so it’s vital that we understand the nuanced nature of self-harm, especially in terms of the different profiles of young people who self-harm and their potentially different risk factors.

“We found two distinct subgroups of young people who self-harm. The first was much as expected – young people who experience symptoms of depression and low self-esteem, face problems with their families and friends, and are bullied. The second, much larger group was much more surprising as they don’t show the usual traits that are associated with those who self-harm.”

The findings suggest the possibility of predicting who is most at risk of self-harm up to a decade in advance, creating a window of opportunity for intervention.

Principal investigator Dr Duncan Astle said: “The current approach to supporting mental health in young people is to wait until problems escalate. Instead, we need a much better evidence base so we can identify who is at most risk of mental health difficulties in the future, and why. This offers us the opportunity to be proactive, and minimise difficulties before they start.

“Our results suggest that boosting younger children’s self-esteem, making sure that schools implement anti-bullying measures, and providing advice on sleep training, could all help reduce self-harm levels years later.

“Our research gives us potential ways of helping this newly-identified second subgroup. Given that they experience difficulties with their peers and are more willing to engage in risky behaviours, then providing access to self-help and problem-solving or conflict regulation programmes may be effective.”

Source: University of Cambridge

Journal information: Uh, S et al. Two pathways to self-harm in adolescence. Journal of the American Academy of Child and Adolescent Psychiatry; DOI: 10.1016/j.jaac.2021.03.010

Categories : PaediatricsTags :

Earliest Childhood Memories Date Back to Two and a Half

On By ModernMedia
Photo by Caroline Hernandez on Unsplash

People’s earliest childhood memories they can recall are on average from just two-and-a-half years old, according to a new study published in the journal Memory.

It was previously held that the earliest memories are from three-and-a-half years old. Research on earliest memories dates back to the late 1800s, when it was first noted that most adults lack memories from the first 3 to 4 years of their lives, a phenomenon later termed infantile or childhood amnesia.

The evidence for the lower age of earliest memories is presented in a new 21-year study, which followed on from a review of already-existing data.

“When one’s earliest memory occurs, it is a moving target rather than being a single static memory,” explained lead author Dr Carole Peterson, a childhood amnesia expert from Memorial University of Newfoundland.

“Thus, what many people provide when asked for their earliest memory is not a boundary or watershed beginning, before which there are no memories. Rather, there seems to be a pool of potential memories from which both adults and children sample.

“And, we believe people remember a lot from age two that they don’t realise they do.

“That’s for two reasons. First, it’s very easy to get people to remember earlier memories simply by asking them what their earliest memory is, and then asking them for a few more. Then they start recalling even earlier memories – sometimes up to a full year earlier. It’s like priming a pump; once you get them started its self-prompting.

“Secondly, we’ve documented those early memories are systematically misdated. Over and over again we find people think they were older than they actually were in their early memories.”

Dr Peterson has conducted studies on memory for over two decades, focusing on the ability of children and adults to recall their earliest years.

This latest study reviewed 10 of her research articles on childhood amnesia followed by analyses of both published and unpublished data collected in Dr Peterson’s laboratory since 1999. This comprised 992 participants, and memories of 697 participants were then compared to the recollections of their parents.

The finding shows that children’s earliest memories date from before when they think it happened, backed up by their parents.

‘Telescoping’ memories

The evidence from this research to move our potential memory clock is “compelling”. For example, when reviewing a study which interviewed children after two and eight years had passed since their earliest memory they were able to recall the same memory, however in the subsequent interviews reported a later age as to when they occurred.

“Eight years later many believed they were a full year older. So, the children, as they age, keep moving how old they thought they were at the time of those early memories,” explained Dr Peterson, from the Department of Psychology at Memorial University.

The finding is due to something in memory dating called ‘telescoping’, she believes.

“When you look at things that happened long ago, it’s like looking through a lens.

“The more remote a memory is, the telescoping effect makes you see it as closer. It turns out they move their earliest memory forward a year to about three and a half years of age. But we found that when the child or adult is remembering events from age four and up, this doesn’t happen.”

She says, after combing through all of the data, it clearly shows that people recall much more of their early childhood, a lot farther back, than they think they do, and helping to access those memories is fairly simple.

“When you look at one study, sometimes things don’t become clear, but when you start putting together study after study and they all come up with the same conclusions, it becomes pretty convincing.”

This lack of clarity is a limitation of her research, she acknowledges, one which is also common to all research done to-date in the subject area.

“What is needed now in childhood amnesia research are independently confirmed or documented external dates against which personally derived dates can be compared, as this would prevent telescoping errors and potential dating errors by parents,” Dr Peterson said.

She is currently doing research on this with verified dating, both in her laboratory and elsewhere to further confirm the answer to this long-debated question.

Source: Taylor & Francis Group

Journal information: Peterson, C., (2021) What is your earliest memory? It depends. Memory. doi.org/10.1080/09658211.2021.1918174.

Categories : Gastrointestinal HospitalsTags :

High Risk for Upper GI Bleeding Developed During Hospital Stay

On By ModernMedia
Photo by Anna Shvets from Pexels

Patients who developed upper gastrointestinal (GI) bleeding during a hospital stay experienced worse adverse outcomes than those admitted for upper GI bleeding alone, according to a new study from France.

Currently hospitalised patients (inpatients) with upper GI bleeding showed a significantly higher mortality rate at 6 weeks than patients hospitalised for GI bleeding alone (outpatients), at 21.7% versus 8.8%, respectively, as well as increased frequency of rebleeding .

Upper GI bleeding is a common problem that occurs in 80 to 150 out of 100 000 people annually, with mortality rates between 2 and 15%. The condition is described as blood loss from a gastrointestinal source above the ligament of Treitz. 

Though upper GI bleeding in patients has fallen over the past decades, rates of rebleeding and mortality remained stable or risen slightly. The authors said that modifiable risk factors need to be identified to help reduce this.

Researchers investigated the outcomes among inpatients and outpatients with upper GI bleeding, collecting data on 2498 patients with upper GI bleeding from 46 hospitals. Inpatients were defined as patients who developed variceal or non-variceal bleeding at least 24 hours after hospitalisation, and outpatients (75% of participants) were defined as presenting with bleeding upon admission.

Primary outcomes included mortality and rebleeding rates, assessed at 6 weeks from onset. Hospital stay duration, and the requirement for radiological or surgical intervention were secondary outcomes.

Outpatients were younger (average age 67), more likely to be smokers and consumed more alcohol than inpatients. Inpatients had a significantly higher rate of comorbidities (39% vs 27%, respectively), and more inpatients had a Charlson score above 3 than outpatients (38.9% vs 26.6%). There was no difference in sex or body weight.

Outpatients had a shorter hospital stay of 9 days compared to 16 for inpatients. The  authors noted that the groups did not differ in needing radiological or surgical intervention.

More inpatients were taking aspirin, steroids, and heparin, while more outpatients were taking oral anticoagulants and NSAIDs. At bleeding onset, more inpatients were on proton pump inhibitors (PPIs) than outpatients (41.6% vs 27.5%). However, more outpatients received intravenous PPIs than inpatients (87% vs 79%).

“Despite the more prevalent use of PPI among inpatients, their [upper gastrointestinal bleeding] was mainly related to peptic ulcer disease (PUD) and [esophagitis],” the authors explained. “This may be explained by the higher intake of aspirin and steroids, known to increase PUD-related haemorrhage risks especially in the elderly and hospitalized patients.”

For all patients, risk factors associated with 6-week mortality were rebleeding, Charlson score > 3, haemodynamic instability, pre-Rockall score > 5 and being an inpatient.

Independent  mortality risk factors for inpatients were prothrombin < 50% and rebleeding, though bleeding-related mortality was lower among inpatients compared to outpatients (10.8% vs 20.6%).

“We found that mortality in outpatients was more likely to be directly related to [upper gastrointestinal bleeding] as opposed to inpatients where death resulted more commonly from other causes,” the authors stated.

When looking at patient groups separately, cirrhosis and antiplatelets were independent outcome predictors among outpatients, in addition to rebleeding, comorbidities, haemodynamic instability and severity of bleeding.

Difficulty in comparability of results to previous studies is a limitation to this study due to the 6-week mortality timeline versus the 28-day one for previous studies. The reason for inpatient hospitalisation also was not recorded, which could impact the results.

Source: MedPage Today

Journal information: El Hajj W, et al “Prognosis of variceal and non-variceal upper gastrointestinal bleeding in already hospitalised patients: Results from a French prospective cohort” United European Gastroenterol J 2021; DOI: 10.1002/ueg2.12096.

Categories : Cancer GeneticsTags :

Novel Approach Targets Pancreatic Cancers Which Depend on Mutant KRAS Gene

On By ModernMedia
KRAS Protein Structure. RAS is a family of related proteins that is expressed in all animals. KRAS is one of three RAS genes found in humans. RAS genes are mutated in approximately one-third of all human cancers. Photo by National Cancer Institute on Unsplash

Researchers have identified a novel drug that effectively thwarts pancreatic tumours that are addicted to the cancer-causing mutant KRAS gene.

Because early detection of pancreatic cancer is difficult, it has a low survival rate, accounting for just over 3% of all new cancer cases in the US, but leading to nearly 8% of all cancer deaths, according to the National Cancer Institute.

The KRAS gene was recognised more that 25 years ago as the component of Kirsten sarcoma virus responsible for oncogenesis. Since then, mutations of KRAS have been described in a large proportion of solid tumors ranging from more than 90% of pancreatic carcinomas to 20% to 30% of pulmonary adenocarcinomas.

Through a pre-clinical study, Said Sebti, PhD, associate director for basic research at VCU Massey Cancer Center, identified a novel drug that effectively thwarts pancreatic tumors that are addicted to the cancer-causing mutant KRAS gene. 

“We discovered a link between hyperactivation of the CDK protein and mutant KRAS addiction, and we exploited this link preclinically to counter mutant KRAS-driven pancreatic cancer, warranting clinical investigation in patients afflicted with this deadly disease,“ said Dr Sebti, who is also the Lacy Family Chair in Cancer Research at Massey and a professor of pharmacology and toxicology at the VCU School of Medicine. “Our findings are highly significant as they revealed a new avenue to combat an aggressive form of pancreatic cancer with very poor prognosis due mainly to its resistance to conventional therapies.”

In 90 percent of pancreatic cancers, KRAS is mutated. Prior studies have shown that some tumours harbouring mutant KRAS are in fact addicted to the mutant gene, meaning they cannot survive or grow without it. Sebti set out to discover if there is a drug that can specifically kill those tumours with a mutant KRAS addiction.

Searching for a suitable drug

Dr Sebti and colleagues used a three-pronged approach to tackle this question.

First of all, they mapped the blueprint of pancreatic cancer cells through global phosphoproteomics, showing them how the addicted and non-addicted tumours differ at the phosphoprotein level. They found two proteins, CDK1 and CDK2, which signalled which cells were addicted to mutant KRAS.

Additionally, they analysed a comprehensive database from the Broad Institute of MIT and Harvard which contains genome-wide CRISPR gRNA screening datasets. They discovered that CDK1 and CDK2 as well as CDK7 and CDK9 proteins were associated with mutant KRAS-addicted tumors.

Finally, they evaluated 294 FDA drugs to selectively kill mutant KRAS-addicted cancer cells over non-KRAS-addicted cancer cells in the lab. They determined the most effective drug in preclinical experiments was AT7519, an inhibitor of CDK1, CDK2, CDK7 and CDK9.

“Using three entirely different approaches, the same conclusion presented itself clearly to us: pancreatic cancer patients whose tumors are addicted to mutant KRAS could benefit greatly from treatment with the CDK inhibitor AT7519,” Dr Sebti said.

To further validate these findings in fresh tumours taken from pancreatic cancer patients the researchers found that AT7519 suppressed the growth of xenograft cells from five mutant KRAS pancreatic cancer patients who relapsed on chemotherapy and/or radiation therapies.

Though AT7519 had previously been tested unsuccessfully in a number of clinical trials, none of the trials were for pancreatic cancer.

“If our findings are correct and translate in humans, then we should be able to see a positive response in pancreatic cancer patients whose tumors are addicted to mutant KRAS,” Dr Sebti said.

As well as pancreatic cancer, the study authors believe these findings may also have clinical implications for colorectal and non-small cell lung cancer patients with prevalent KRAS mutations.

Source: Virginia Commonwealth University

Journal information: Kazi, A., et al. (2021) Global Phosphoproteomics Reveal CDK Suppression as a Vulnerability to KRas Addiction in Pancreatic Cancer. Clinical Cancer Research. doi.org/10.1158/1078-0432.CCR-20-4781.

Categories : NeurologyTags :

Call for More Neuroscience Research in Africa

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Photo by MART PRODUCTION from Pexels

A team of neuroscientists are calling for greater support of neuroscience research in Africa based on an analysis of the continent’s past two decades of research outputs.  

The findings reveal important information about the nature of funding and international collaboration comparing activity in the continent to other countries, mainly the US, UK and areas of Europe. It is hoped that the study will provide useful data to help further develop science in Africa.  

The greatest human genetic diversity is found in Africa, and Eurasian genomes have less variation than African ones; in fact, Eurasian genomes can be considered a subset of African ones. This carries important implications for understanding human diseases, including neurological disorders.

Co-lead senior author Tom Baden, Professor of Neuroscience in the School of Life Sciences and the Sussex Neuroscience research group at the University of Sussex said: “One beautiful thing about science is that there is no such thing as a truly local problem. But that also means that there should be no such thing as a local solution – research and scientific communication by their very nature must be a global endeavour.  

“And yet, currently the vast majority of research across most disciplines is carried out by a relatively small number of countries, located mostly in the global north. This is a huge waste of human potential.”  

The team, made up of experts from the University of Sussex, the Francis Crick Institute and institutions from across Africa, analysed the entirety of Africa’s outputs in neuroscience over two decades. A lot of early neuroscience research took place in Egypt, it was pointed out.

Lead author Mahmoud Bukar Maina, a Research Fellow in the School of Life Sciences and the Sussex Neuroscience research group at the University of Sussex and visiting scientist at Yobe State University, Nigeria, explained: “Even though early progress in neuroscience began in Egypt, Africa’s research in this area has not kept pace with developments in the field around the world. There are a number of reasons behind this and, for the first time, our work has provided a clear picture of why – covering both strengths and weaknesses of neuroscience research in Africa and comparing this to other continents.  

“We hope it will provide useful data to guide governments, funders and other stakeholders in helping to shape science in Africa, and combat the ‘brain drain’ from the region.”  

Co-lead senior author Lucia Prieto-Godino, a Group Leader at the Francis Crick Institute, said: “One of the reasons why this work is so important, is that the first step to solve any problem is understanding it. Here we analyse key features and the evolution of neuroscience publications across all 54 African countries, and put them in a global context. This highlights strengths and weaknesses, and informs which aspects will be key in the future to support the growth and global integration of neuroscience research in the continent.” 

The study identifies the African countries with the greatest research outputs, revealing that most research funding originates from external sources such as the USA and UK.  

The researchers argue that a sustainable African neuroscience research environment needs local funding, suggesting that greater government backing is needed as well as support from the philanthropic sector.  
Professor Baden added: “One pervasive problem highlighted in our research was the marked absence of domestic funding. In most African countries, international funding far predominates. This is doubly problematic.  

“Firstly, it takes away the crucial funding stability that African researchers would need to meaningfully embark on large-scale and long-term research projects, and secondly, it means that the international, non-African funders essentially end up deciding what research is performed across the continent. Such a system would generate profound outrage across places like Europe – how then can it be acceptable for Africa?”

A number of the researchers involved in the study are members of TReND Africa, a charity supporting scientific capacity building in Africa.  

Source: University of Sussex

Journal information: M. B. Maina et al, Two decades of neuroscience publication trends in Africa, Nature Communications (2021). DOI: 10.1038/s41467-021-23784-8 , www.nature.com/articles/s41467-021-23784-8

Categories : Cancer General InterestTags :

CNN Anchor Christiane Amanpour Reveals Her Ovarian Cancer Diagnosis

On By ModernMedia
Photo by Obi Onyeador on Unsplash

CNN anchor Christiane Amanpour told viewers on Monday that she has been diagnosed with ovarian cancer.

The 63 year-old international news veteran told viewers she had had “major successful surgery to remove it” and will now undergo several months of chemotherapy, adding that she was “very confident”.

Amanpour, who works in CNN’s London studio, said she feels “fortunate to have health insurance through work and incredible doctors who are treating me in a country underpinned by, of course, the brilliant NHS,” referencing the UK’s National Health Service.

After four weeks off, she said in Monday’s announcement, “I’m telling you this in the interest of transparency but in truth really mostly as a shoutout to early diagnosis.” Pointing out “millions of women around the world”, she added that she wanted to “urge women to educate themselves on this disease; to get all the regular screenings and scans that you can; to always listen to your bodies; and of course to ensure that your legitimate medical concerns are not dismissed or diminished.”

Amanpour has decades of experience reporting around the world, covering a wide range of conflicts and crises.

Ovarian cancer is the leading cause of death in women diagnosed with gynaecological cancers. It is also the fifth most frequent cause of death in women, in general. The symptoms, such as bloated, swollen or painful stomach, are easily mistaken for less serious health problems, making diagnosis difficult. Most cases are only diagnosed at an advanced stage, leading to poor outcomes. Existing screening tests unfortunately have a low predictive value.

Standard care treatment includes surgery and platinum-based chemotherapy; however, anti-angiogenic bevacizumab and Poly(ADP-ribose) polymerase (PARP) inhibitors are gaining ground in the treatment of this disease.

Source: BBC News